#38861: Pathophysiology: The Renal System

An adult typically has two kidneys, which are reddish-brown and bean-shaped (Image 1). Although their size can vary, the length of the average kidney is about 11 cm, the thickness about 2.5 cm, and the width is about 5 cm. The average weight of a single kidney is 15 g. The kidney's lateral border is convex, whereas the medial border is concave and indented in a depression called the renal hilus. All related structures enter or leave the kidney at the hilus [2,3].

ANATOMY OF THE KIDNEY

Image 1

Source: National Cancer Institute

The kidneys lie in the retroperitoneal space of the posterior abdominal cavity (Image 2). Thus, they can be exposed without opening the peritoneal cavity. One kidney lies on either side of the vertebral column. Layers of muscle surround the posterior surfaces of the kidneys, and abdominal organs surround their anterior surfaces. The peritoneal membrane covers most of the anterior surface of each kidney.

EXCRETORY SYSTEM ANATOMY

Image 2

Source: National Cancer Institute

The kidneys are protected and supported by renal fascia and layers of perirenal fat. Posteriorly, the psoas, quadratus lumborum, and transverse abdominis muscles provide support. The position of the kidneys is not fixed but varies somewhat with an individual's position. When a patient is in the supine position, the kidneys lie between the 12th thoracic and 3rd lumbar vertebrae. When the patient is standing, the kidneys may descend to the top of the iliac crest. For a patient in Trendelenburg position, the kidneys ascend to the 10th intercostal space [4,5].

The left kidney, which lies near the tail of the pancreas and the splenic flexure of the colon, is normally slightly longer and narrower than the right kidney. The right kidney is lower in the abdomen than the left because of the presence of the liver in the right upper quadrant. The superior pole of the right kidney lies beneath the liver in an area referred to as the renal bed. The right kidney's anterior surface is adjacent to the hepatic flexure of the colon, the duodenum, and the liver. The lower portion of each kidney descends beneath the lower portion of the rib cage [2,6].

Each kidney is surrounded by three layers of tissue. The fibrous renal capsule (the innermost layer) covers the surface of the kidney. The adipose capsule, a mass of perirenal fat, surrounds the renal capsule. The third layer, the renal fascia, surrounds and encloses the kidney and anchors the kidney to the posterior abdominal wall [2,6].

There are essentially three general regions of each kidney: the cortex, the medulla, and the pelvis. These structures are located inside the renal capsule. Two of them—the cortex and the medulla—are often referred to collectively as the renal parenchyma. The cortex is directly beneath the renal capsule. This highly vascularized area of tissue is very sensitive to changes in blood flow. The medulla, located deep in the cortex, consists of 8 to 18 triangular renal pyramids. The renal pyramids are composed of collecting ducts that drain urine into the calyces. The cortex covers the base of the pyramids, and the tips (or papillae) project toward the renal pelvis. Cortical tissue known as renal columns dips into the medulla to separate the pyramids, and blood vessels that supply the cortex and medulla pass through these columns. Urine flows from the papillae into a minor calyx, and several of the funnel-shaped minor calyces emerge to form a major calyx. The major calyces join to form the renal pelvis, which is the expanded upper end of the ureter. At times, a catheter is positioned in the renal pelvis and must be irrigated with 4–6 mL of fluid (as ordered) to maintain catheter patency [7].

The Nephron

The nephron (Image 3) is the functional unit of the kidney and is primarily responsible for most of the mechanisms that provide internal homeostasis. Each kidney contains approximately 1.25 million nephrons, and each nephron in turn is composed of a vascular and tubular system that allows for the formation of urine. The nephrons are located in the renal parenchyma. Most nephrons are in the cortex (referred to as cortical nephrons), but juxtamedullary nephrons begin in the cortex and extend deep into the medulla [7].

THE NEPHRON

Image 3

Source: National Cancer Institute

The vascular system of the nephron consists of the glomerulus and the Bowman capsule, both located in the cortex of the kidney. The glomerulus is composed of a knot of capillaries. The Bowman (or glomerular) capsule surrounds the glomerulus. The glomerulus derives its blood flow from the renal artery of the abdominal aorta. Each renal artery branches into segmental arteries and increasingly smaller arteriole, arcuate (or arciform), and interlobular (or cortical radial) arteries, which supply progressively smaller areas of renal parenchyma. The smallest branch, the afferent arteriole, feeds blood to the glomerulus. After passing through the capillaries in the glomerulus, the blood exits the glomerulus, not through a venule but via the efferent arteriole. From the efferent arteriole, the blood enters the peritubular capillaries of the cortical nephron or the vasa recta of the juxtamedullary nephron. This plexus of capillaries surrounds the proximal tubule, the Henle loop, and the distal tubule. Finally, blood enters the venous system from either the peritubular capillaries or the vasa recta and returns to the general circulation through a series of renal venules and veins that drain all portions of the kidney. The renal vein of each kidney returns blood into the inferior vena cava [7].

The tubular system of the nephron begins with the Bowman capsule, which is invaginated around each glomerular tuft to form a sac. The Bowman capsule narrows into the proximal convoluted tubule, which changes directions many times until it straightens into the descending limb of the Henle loop and angles downward toward the pelvis of the kidney. The proximal convoluted tubule is largely responsible for the conservation of fluids and electrolytes. The loops of tubular tissue are much longer in juxtamedullary nephrons than in cortical nephrons and are contained within the pyramids of the medulla. The ascending limb of the Henle loop then becomes the distal convoluted tubule. The distal convoluted tubules of several nephrons enter a collecting duct with a pyramid of the medulla; these ducts are responsible for the drainage of formed urine from the nephrons. Pyramids then are drained into the calyceal system of the renal pelvis through the tips of the papillae [1,8].

The important relation between the kidneys and the blood vascular system becomes apparent when considering the large size of the renal arteries that supply the kidneys. At rest, these vessels carry about 20% of the total cardiac output to the kidneys, or approximately 600 mL of blood per minute through each kidney. Little of this blood supplies the nutritive needs of the kidneys; the large blood flow is related to the fact that the kidneys can maintain homeostasis of the blood only if a large amount of the blood passes through them [10].

The vascular supply to the kidney consists of several microcirculations:

The urinary bladder is a muscular sac capable of significant distention that is used to store formed urine. The bladder rests on the floor of the pelvic cavity and is retroperitoneal. Its anterior surface lies just behind the pubic symphysis. In male individuals, the bladder is in front of the rectum, whereas in female individuals it lies just anterior to the uterus and the superior portion of the vagina [11,12].

The major anatomic areas of the bladder are the fundus, apex, neck, and trigone. The fundus is the upper portion of the bladder, and the apex is the bottom portion of the bladder closest to the pelvic floor. The bladder neck is the most inferior portion of the bladder and contains the internal sphincter. It is composed of a group of thickened fibers of the detrusor muscle that evolves into the smooth muscle of the urethra. The trigone is an area of the posterior wall of the bladder defined by the urethra and the two ureteral orifices or slits, where the ureters enter the bladder. This area of muscle is responsible for separating the upper urinary tract from the lower urinary tract during normal micturition [11,12].

As the bladder fills with urine, its internal pressure increases somewhat initially and then remains fairly constant up to a volume of about 300–400 mL. Beyond this point, the pressure rises rapidly. The bladder can hold 600–800 mL of urine, but it is generally emptied before it reaches this capacity [12].

The nerve supply to the bladder is both sensory and motor. Sympathetic, parasympathetic, and somatic nerves carry sensations to the central nervous system. Sympathetic fibers arise from T9 through L2, and parasympathetic and somatic nerves arise from S2 through S4. The motor nerves of the bladder involve parasympathetic supply to the detrusor muscle and sympathetic supply to the trigone. The pudendal nerves, which are under voluntary control, supply the external sphincter and the muscles of the pelvic floor [12].

The urethra is a muscular tube lined with mucous membranes that exits from the inferior surface of the urinary bladder and carries urine to the exterior of the body. At the junction of the urethra and bladder, the smooth muscle of the bladder surrounds the urethra and acts as a sphincter (the internal urethral sphincter) that keeps the urethra closed. During micturition, a contraction of the bladder opens the sphincter [11,12].

The male urethra is about 21 cm long, approximately the length of the penis, and about 8–9 mm in diameter. The urethra descending from the base of the bladder to the pelvic floor is surrounded by the prostate gland; this is referred to as the prostatic urethra. The portion of the urethra that extends through the pelvic floor is referred to as the membrane urethra, and the cavernous urethra traverses the length of the penis. In female individuals, the urethra is about 4-cm long and about 8 mm in diameter. Because of the close proximity of the anus and vagina to the urethra, micro-organisms found in those regions (most commonly Escherichia coli) may more easily migrate into the bladder in these patients [11,12,124].

The kidneys and urinary system sustain homeostasis of body fluids and their composition. A variety of mechanisms maintain this fluid and electrolyte balance, and the end result is the production of urine. Urine represents the work of the kidneys and results in the removal of nitrogenous waste products as well as the regulations of fluid, electrolyte, and acid-base balances. In addition, the kidneys produce hormones and substances that influence other metabolic and chemical processes [10].

Miscellaneous Hormonal and Metabolic Controls

The Department of Veterans Affairs Guideline Panel recommends against offering erythropoiesis-stimulating agents to patients with chronic kidney disease for the purpose of achieving a hemoglobin target greater than 11.5 g/dL due to increased risk of stroke and hypertension.

(https://www.healthquality.va.gov/guidelines/CD/ckd/VADoDCKDCPGFinal5082142020.pdf Last Accessed: July 27, 2023)

Strength of Recommendation: Strong against

Several other metabolic and hormonal functions of the kidneys have been identified, including the production of erythropoietin, the production of 1,25-dihydroxycholecalciferol, and the metabolism of insulin. Erythropoietin is a glycoprotein produced in the kidneys that influences red blood cell production. The site of erythropoietin production is in the peritubular cells of the kidney, specifically the renal cortex peritubular cells, while storage in the kidney has not been identified. However, the effects of bilateral nephrectomy and the subsequent decrease in erythropoiesis have been observed. Erythropoietin seems to increase both the rate of production and the rate of release of new red blood cells from the bone marrow and the spleen [16,17,125].

The kidneys also produce 1,25-dihydroxycholecalciferol, the active component of vitamin D. Without this substance, calcium cannot be absorbed properly from the intestines [16,17].

The kidneys play a role in insulin metabolism and excretion. Failure to excrete insulin results in an increased availability of insulin, which has important consequences for the management and control of diabetes. Most patients with diabetes have a decreased need for insulin as renal failure progresses. The reliability of urine testing to calculate insulin needs is limited, as the renal threshold changes constantly with decreasing renal function [16,17].

Micturition, also called urination or voiding, is a complex physical process under a variety of neural controls. For most healthy persons older than 5 years of age, urination is under voluntary control and can be interrupted or initiated upon cerebral command, as long as motor and sensory nerve pathways are intact. Micturition normally is a painless function that occurs five to six times per day and possibly once at night. The average person voids a total of about 1,500 mL of urine per 24 hours. This amount is affected by fluid intake, the ingestion of foods high in water content, diuretics, sweating, temperature, vomiting, and diarrhea [14,18].

Adults usually perceive an initial desire to empty the urinary bladder when about 150 mL of urine has accumulated. However, the bladder can distend to a much larger capacity, and it often does before there is a feeling of bladder fullness. Because urine accumulates gradually in the bladder, the slow distention of the muscular sac accommodates larger and larger quantities of urine. The capacity of the urinary bladder has been calculated at 450 mL, but much larger amounts may accumulate if there is an obstruction to outflow [14,18].

Micturition involves several responses that occur almost simultaneously. Initially, there is the felt need to void and an assessment of the environment. The individual must determine that the environment is appropriate to the release of urine or urination will be prevented [14,18].

After the person has determined that the conditions are satisfactory, a series of nerve impulses are activated to allow the release of urine. First, the muscles of the pelvic floor are relaxed, which opens the urethral opening and allows the descent of the urinary bladder. Next, the trigone contracts, which ensures closure of the ureterovesical junction and prevents the reflux of urine into the ureters. Trigonal contraction also causes contraction of the bladder neck, which makes the bladder more funnel-shaped. Finally, the detrusor muscle of the bladder, which is continuous with the urethral lining, contracts. Detrusor contraction increases the pressure within the bladder and results in bladder emptying [14,18].

The cerebral control mechanism can interrupt the voiding processes at any point. When the bladder is empty, the detrusor muscle relaxes, the bladder neck closes, and the trigone and perineal muscles resume their normal tone [18].

Enlargement of one or both kidneys is most commonly related to the invasion and multiplication of neoplastic cells. If a mass becomes very large, it can put pressure on abdominal nerves or displace other abdominal organs and cause discomfort or pain [1,15].

The kidneys may also become enlarged because of a blockage of the ureters, and occasionally the urethra, by either a stone, tumor, or enlargement of the prostate. This enlargement is due to a build-up of urine and is referred to as hydronephrosis. In these instances, urine backs up into the renal pelvis. The ureters and urethra also may enlarge in diameter as they fill with urine that cannot be voided. If enervation is interrupted, the bladder also can become overdistended with urine [1,15].

In most chronic diseases of the kidneys, the kidneys eventually atrophy because of the destruction of the renal parenchyma. In some instances, the cortex is most affected, whereas in others, the medulla is most affected. The kidneys may decrease to less than one-fifth of their normal size [1,15].

A major goal of renal function is the maintenance of fluid volume necessary to support metabolic and perfusion processes. As such, the inability to control fluid volume may have a variety of sequelae. For example, loss of the ability of the kidneys to concentrate urine may be the earliest sign of renal pathology. Conversely, continuous loss of dilute urine may result in volume depletion and low blood pressure. Hypovolemia (i.e., inadequate circulating blood volume) will eventually alter renal function, as adequate blood volume is required to establish a pressure gradient so glomerular filtration can occur [8,10].

Although the kidneys have the capacity for some autoregulation of blood flow, they will deprive the renal parenchyma of necessary blood volume if the demands are greater elsewhere. This capacity to severely limit renal blood flow is observed in severe shock or stress states. Fluid deficits can also occur with decreased fluid intake or excessive water losses, as with diarrhea, vomiting, or rapid dehydration [8,10].

Failure of the kidneys to excrete water and maintain normal fluid volume has serious consequences for the overall functioning of the body. Hypervolemia (i.e., an increase in circulating and total body water) manifests as an elevation of blood pressure, increased cardiac workload, and the development of fluid in the interstitial spaces and alveoli of the lungs or other body tissues. As such, it puts severe strain on the cardiovascular system. The associated hypertension can cause long-term problems related to ventricular hypertrophy and increased peripheral vascular resistance. More immediate changes due to fluid shifts, particularly into the lungs, can impair adequate gas exchange causing severe hypoxia [1,15].

Ischemia of renal tissue results in the liberation of renin and the stimulation of the renin-angiotensin-aldosterone system (RAAS). The release of renin is triggered to increase renal blood flow in response to hormonal mechanisms, but it is also associated with increased volume retention and volume expansion. Particularly, this can happen when kidney tissue is damaged, which affects the normal formation of urine while aldosterone and ADH are being produced normally. Therefore, overhydration is more common as the patient reaches end-stage renal disease (ESRD) [1,15].

As discussed, the kidneys maintain the normal osmolality of body fluids and, in conjunction with various endocrine mechanisms, control the appropriate balance of electrolytes in body fluids. Excesses and deficits of various electrolytes result in serious problems in the maintenance of normal nerve transmission and muscle conduction. Sodium, potassium, calcium, and magnesium are the major cations under the regulation of the kidneys. Some major anions (e.g., chloride, bicarbonate), as well as other anions such as sulfates, phosphates, and proteinate, are also under direction by the renal system [21,22].

Of the various electrolytes, potassium—the primary intracellular cation—has the most potential for causing harm if disrupted. Hyperkalemia is the most frequently encountered imbalance in chronic renal failure, and failure of the kidneys to excrete potassium will disturb the conduction system of the heart and, if untreated, can terminate myocardial contraction. The kidney tubules also may fail to conserve potassium correctly and thus excrete large amounts. Hypokalemia may result in altered cardiac muscle contractions and alter the medullary interstitium of the kidney, impairing renal function [21,22].

Sodium excesses (hypernatremia) can occur in patients with renal disease when urine volume drops to very low levels. In these cases, sodium and water retention, edema, and pump failure occur, even in patients with restricted salt intake. Because sodium conservation occurs primarily in the renal medulla, deterioration in this area produces excessive sodium loss (hyponatremia), which leads to decreased extracellular fluid. As circulating blood volume decreases, the GFR decreases and the renal function is further compromised [21,22].

Imbalances of calcium and phosphorus are related to the reciprocal relationship between electrolytes and the effect of parathyroid hormone, which regulates serum calcium levels. When the GFR decreases to around 30 mL/min/1.73 m², the renal excretion of phosphate also decreases. With increases in serum phosphate level (hyperphosphatemia), the body attempts to lower the level by binding phosphate with calcium. The resultant calcium phosphate may then precipitate in various tissues. This response causes the calcium level (non-protein-bound or ionized) to decrease, potentially leading to hypocalcemia. In response to the low calcium level, parathyroid hormone is released and stimulates the release of calcium from stores in bone in an attempt to increase the circulating calcium level. In renal insufficiency, this is compounded by the kidney's inability to produce 1,25-dihydroxycholecalciferol, which is necessary for the intestinal absorption and utilization of calcium in the diet. This further contributes to the development of hypocalcemia [21,22].

The ongoing process of hyperphosphatemia and hypocalcemia with subsequent production of parathyroid hormone results in secondary hyperparathyroidism. Untreated, this leads to serious bone pathology known as renal osteodystrophy [22].

When urine output is low and a normal magnesium intake continues, hypermagnesemia can occur. Hypermagnesemia typically occurs with acute kidney injury (AKI) or chronic kidney disease (CKD). Hypermagnesemia may be aggravated by the administration of magnesium-containing laxatives or antacids, proton pump inhibitors, malnourishment, and/or alcohol use disorder [22,127]. Early findings include diarrhea, nausea, and vomiting. When present, hypermagnesemia can lead to cardiovascular complications, with prolonged PR intervals and abnormal sinoatrial/atrioventricular node block, leading to cardiac arrest. Generalized muscle weakness and loss of deep tendon reflexes will also occur. Respiratory suppression and ultimately respiratory arrest will occur if it continues unaddressed [126].

The kidneys are responsible for excreting the acids produced by the metabolism of amino acids. The excretion of hydrogen ions by the kidneys is accomplished by the conservation of bicarbonate, the secretion of ammonia, and the excretion of hydrogen in exchange for sodium. The kidneys work with blood buffers and the pulmonary system to maintain a normal blood pH of 7.35–7.45. Blood buffers maintain this narrow range of acceptability; they almost instantaneously convert acids for either pulmonary excretion as carbon dioxide or for renal excretion through the conservation of bicarbonate or the exchange of sodium or potassium for hydrogen [23,24].

Without the renal regulation of hydrogen ion excretion, a diminished amount of bicarbonate is available to buffer the fixed acids. In addition, the ability to excrete hydrogen as ammonia or with phosphoric acid is limited. Thus, unless the pulmonary reserve compensates, the pH will fall and metabolic acidosis will result [23,24].

Several factors related to renal impairment cause impaired gas exchange. The problems of fluid overload cause pulmonary edema, ventricular hypertrophy, and hypertension, which can lead to impaired gas exchange in the lungs and at the cellular level. Potassium imbalances can cause cardiac arrhythmias, which also can lead to impaired gas exchange. The lungs of a patient with metabolic acidosis have to work hard to correct the acidosis; if they are not able to do so, gas exchange is impaired. Anemia may result from a decrease in erythropoietin produced by the kidney, and this deficiency makes gas exchange more difficult. Furthermore, patients may encounter bleeding problems as a result of decreased aggregation ability from a defect in platelet factor III [12,13,24].

Patients with impaired renal function are at increased risk for infection as a result of impaired immune responses. These patients may also experience delayed hypersensitivity to antigens. Alterations in immune function with ESRD can be a complex issue. Uremia presents with hypercytokinemia, due to the buildup of pro-inflammatory cytokines resulting from decreased renal elimination following oxidative stress, volume overload, or other comorbidities [128].

The kidneys remove nitrogenous waste products resulting from protein metabolism. The kidneys must continually filter and excrete creatinine and urea nitrogen, whether it is from endogenous protein sources (such as the metabolism of the amine creatinine in skeletal muscle) or from primarily exogenous sources (such as dietary protein) [14,18].

Azotemia is the accumulation of uremic toxins (urea, uric acid, and creatinine) in the blood. Uremia refers to azotemia with clinical symptoms. The accumulation of uremic toxins can result in neurologic complications, gastrointestinal bleeding, and skin changes resulting from urochrome pigments deposited in the skin. This pigmentation, combined with anemia, results in the pale yellow-gray skin color characteristic of patients with renal failure. Pruritus, also common, is thought to be the result of a buildup of the urochrome pigments in the skin as well as the crust of urate crystals that accumulates on the skin (called uremic frost). Increased parathyroid hormone production is also a possible cause of pruritus [14,18].

The accumulation of uremic toxins also causes neurologic changes that range from fatigue, decreased ability to concentrate, irritability, and insomnia to depression, peripheral neuropathy, and retinopathy. Coma, convulsions, and death can occur in the absence of treatment [14,18].

Uremic toxins and gastrointestinal bleeding cause nutrition-related problems. The gastrointestinal tract becomes inflamed and irritated with the accumulation of uremic toxins. This results in loss of appetite, nausea, vomiting, and diarrhea—problems that further complicate fluid and electrolyte imbalances. This inflammation, compounded by altered platelet function, causes gastrointestinal bleeding common in patients with impaired kidney function. The buildup of ammonia in the body results in characteristic uremic fetor—a urine-like odor of the patient's breath accompanied by a bad taste in the mouth (described by some as metallic) that alters the appeal of food. Associated pancreatitis may also impair digestion [25].

Urine output may greatly increase in certain situations, such as in the diuretic phase of acute renal failure. However, decreased urine output is the more common alteration. This may be temporary, as with the oliguria phase of acute renal failure, benign prostatic hyperplasia, or kidney stone obstruction of the urethra, or it may be a long-term sequela of acute tubular necrosis or chronic renal failure. Alterations in the pattern of urination result from the underlying pathologic conditions. Patients who are unable to completely void, at such times as following renal procedures or surgery, should be checked for residual volume of urine. Short-term catheterization may be used to completely empty the bladder. If the amount retained was in the range of 75–100 mL, an indwelling catheter should be placed [1,26].

Dry, pale, yellow-grey skin is characteristic of renal failure. Nails and hair are also brittle and dry. Increased parathyroid hormone secretion, uremic frost, and urochrome pigments cause pruritus, which may result in scratches and bleeding. This break in skin integrity increases patients' susceptibility to infection. Edema from sodium and water retention, as well as poor nutritional status, can also make the skin increasingly susceptible to breakdown. Pressure ulcers may form within hours if patients are not frequently repositioned [1,26].

The cardiovascular complications that may occur after a loss of renal function and the resulting uremia include pericarditis, accelerated atherosclerosis, fluid overload, anemia, and the potential for potassium abnormality-related arrhythmias [1,26].

Uremic pericarditis is fairly common for patients with ESRD. Although this condition usually develops within 12 months of the initiation of dialysis, a later onset has also been observed. This inflammatory response is believed to be related to nitrogenous waste products not removed by dialysis. Fluid accumulates within the pericardial sac (pericardial effusion). With increased membrane irritability and platelet aggregation problems, the effusion may be serosanguineous. Massive pericardial effusions (greater than 2,000 mL) may accumulate over a period of days to weeks, seriously altering cardiovascular hemodynamics. Cardiac tamponade (compression of the heart from excessive fluid in the pericardial sac) will result in death unless medical intervention, surgical intervention, or both relieve the fluid accumulation [1,26].

Accelerated atherosclerotic processes have been observed in patients with chronic renal failure. An increased incidence of death from coronary artery disease appears to be associated with the effects of chronic essential hypertension, ventricular hypertrophy, and possible alterations in lipid metabolism associated with urea. In addition, diffuse atherosclerotic processes that include cerebral, aortic, and peripheral vessels are not uncommon [1,26].

Uncontrolled hypertension, either from volume or hormonal response, greatly increases peripheral vascular resistance in small blood vessels throughout the body. The loss of elasticity of the arterioles in the kidney as well as other organs, such as the retina of the eye and the small vessel circulation of the brain, will seriously affect the long-term functioning of these organs [1,26].

As noted, the inter-relation of the renal and respiratory systems is important in maintaining an acid-base balance. Although this balance is partially restored by diet and lifestyle changes, these measures can accomplish only so much. Dialysis can assist, but the lungs must contribute to controlling this narrow range of imbalance minute to minute. Patients with obstructive lung disease have carbon dioxide retention with respiratory acidosis. Thus, when renal and respiratory diseases exist simultaneously, the ability to combat metabolic acidosis is severely impaired. Gas exchange is further hampered by pulmonary edema and anemia states [1,26].

The neurologic manifestations of uremia include uremic encephalopathy and peripheral neuropathy associated with azotemia and metabolic acidosis. Uremic encephalopathy (characterized by altered mentation/intellectual processes, tremors, and myoclonus) is associated with the onset of uremic manifestations. Asterixis (a flapping tremor of the hands) is an early manifestation caused by increased irritability of the central nervous system from elevated serum ammonia levels. This symptom is important, because tonic-clonic seizures may develop if the encephalopathic process is not corrected [1,26].

Peripheral neuropathies are common in patients with ESRD who require chronic dialysis. These neuropathies are neither clearly understood nor easily treated. Their improvement with dialysis is uncertain, and leg weakness and difficulty with ambulation and maintenance of comfort remain problems. Renal transplantation is potentially the best hope for relief of these symptoms [1,26].

Musculoskeletal manifestations of renal failure are collectively referred to as renal osteodystrophy. A variety of problems, including osteomalacia, osteoporosis, and osteitis fibrosa cystica, may result from the chronic release of parathyroid hormone, which results in elevated phosphorous and decreased calcium levels in the serum. Bone pain, increased fracture risk, and metastatic calcifications result from this imbalance [1,26].

CKD-associated sarcopenia results from the catabolic and anabolic imbalance and can be exacerbated by poor nutritional status [129]. Sarcopenia is associated with increased hospitalizations and mortality in CKD. Loss of skeletal muscle increases the likelihood of sedentary lifestyle, leading to frailty, poor quality of life, fractures, and hospitalizations.

Androgens, specifically testosterone, influence muscle formation and regeneration. Hypogonadism is common in patients with CKD and is associated with a further decrease in muscle mass and strength. Androgen supplementation has been explored in the treatment of CKD, but longer-term studies are needed to determine if the benefits (if any) outweight risks of adverse events [129].

Hematologic effects of uremia include chronic anemia and disorder of platelet aggregation. Each of these alterations can have a variety of effects on patients. Patients with renal failure have chronic normochromic, normocytic anemia. Hematocrit values fall to 20% to 30%, and hemoglobin values drop to 7–8 g/dL. Chronic fatigue is the most common symptom, but patients respond differently and some adjust reasonably well. For patients with coronary artery disease, decreased circulating red blood cells may exacerbate angina or increase the risk of arrhythmias, particularly if hypoxia occurs [1,26].

In general, platelet dysfunction is usually a problem with platelet aggregation—the platelet count is normal, and there is no alteration in the ability to produce platelets. In the uremic environment, however, the platelets do not promote the clotting mechanism as well. The results of other clotting tests (prothrombin time and partial thromboplastin time) are normal, but bleeding time may be prolonged. Impaired platelet function in the uremic environment is believed to be responsible for the frequent and easily induced bleeding into the skin and mucous membranes of the patient with either acute or chronic renal failure. Mucous membrane irritation, particularly of the gastrointestinal tract, along with the frequent presence of occult blood, indicates that a uremic environment persists despite dialysis therapy [1,26].

Uremia profoundly affects the gastrointestinal system. Anorexia, nausea, and vomiting are generally the most bothersome symptoms. Inability to eat or to retain food results in weight loss and breakdown of muscle and fat. Uncorrected, profound debilitation results, because the patient is less able to combat infections and mount appropriate immune responses [1,26].

The effects of uremia may be observed throughout the gastrointestinal system. As described, the patient may develop uremic fetor, a urine-like odor noted on the breath [130]. Hypogeusia may manifest as both loss of acuity and loss of ability to discriminate tastes. Thus, with significant changes in the ability to taste foods, eating is less pleasurable [1,26].

Parotitis, gastritis, pancreatitis, and colitis may occur at varying stages in the development of uremia. The parotid glands may become infected and inflamed. Irritation of the gastric and intestinal mucosa is often accompanied by vague discomfort, nausea, vomiting, belching, and diarrhea. Bleeding from the gastrointestinal lining is common due to platelet abnormalities alter the clotting mechanism. The bleeding generally is occult, but gross bleeding with severe gastritis may also occur [1,26].

The loss of renal function and the development of uremia also affect the reproductive systems of men and women. Both experience a loss of libido, and men frequently become impotent. Fertility is affected as well. Men have lower testosterone levels and a decrease in sperm formation, whereas women ovulate and menstruate less often, if at all. Successfully carrying a pregnancy to term is rare [1,26].

Sex influences the structure of the urinary system in an important way. Because the urethra is shorter in women, they are more prone to cystitis (bladder infection) than men. Stress urinary incontinence is not uncommon in women who have experienced relaxation of the pelvic muscles as a result of pregnancy [27,28].

Sexual dysfunction occurs frequently in CKD and can be the result of a combination of effects of the disease, comorbidities (e.g., diabetes), and sociopersonal factors (e.g., poor self-image). Approximately 71% of those with erectile dysfunction have estimated glomerular filtration rates (eGFR) below 60 mL/min/1.73 m² [130]. Further, up to 92% of men undergoing dialysis report erectile dysfunction. Patients may be prescribed phosphodiesterase-5 inhibitors (e.g., sildenafil, vardenafil, tadalafil) to improve erectile response [130].

In addition, 56% of women with CKD report decreases and in sexual desire and difficulty achieving orgasm [130]. Estrogen deficiency is believed to be an underlying factor in dysfunctions of sexual drive, as a hypoestrogenic state leads to decreased blood flow to the vulva and vagina, resulting in less vaginal lubrication and dyspareunia. Transdermal estradiol treatments have improved sexual function in these patients [130].

Dietary habits can also affect the function of the kidneys and urinary system. For example, a high-salt diet can contribute to the development of hypertension, which can lead to or exacerbate renal disease. For people with diagnosed renal dysfunction, salt and protein restrictions may limit the pleasure of eating. Individuals can avoid certain foods and beverages in their own homes with some discipline, but visiting friends or dining in restaurants presents difficulties that may not be controlled so easily. People who must strictly limit fluid intake may experience questioning or stigma. Participation and sharing are social expectations, and some people prefer to avoid these situations rather than not do what is expected [27,28].

Among medications that may have a toxic effect on the kidneys, are a number of common antibiotics (e.g., penicillin, neomycin, kanamycin, amphotericin). Probably the most nephrotoxic category of antibiotics is the aminoglycosides (e.g., gentamicin, vancomycin, tobramycin). Other nephrotoxic drugs include sulfonamides, salicylates, thiazides, and furosemide [29,30].

The costs of renal dialysis and transplantation are high. Moreover, a loss of income may result if the patient is a wage earner [31]. Lower rates of transplantation wait list participation and increased risk of mortality is associated with lower socioeconomic status and Medicare/Medicaid insurance (rather than private insurance) [131]. Higher rates of neighborhood poverty are also associated with worsening ESRD and mortality, especially in the Black communities [131].

Certain occupations and hobbies are associated with exposure to nephrotoxic chemicals. Carbon tetrachloride, used in dry-cleaning and various industrial processes, is nephrotoxic, as are methyl alcohol, phenols, and ethylene glycol. Several metals used in the fabrication of jewelry and some electronic components are nephrotoxic, including gold, lead, copper, uranium, arsenic, mercury, and cadmium [31]. Commercially available hair dyes often contain paraphenylenediamine, a chemical linked to acute renal failure [32].

The development of renal disease may severely influence the patient's occupational performance. Jobs requiring travel, flexible hours, or physical energy may be difficult to maintain. The need to change careers or develop new skills, in addition to coping with physical illness, may be an enormous challenge or impossible for patients with renal disease [31]. Patients with higher education levels and/or white-collar jobs with disability benefits were more likely to retain employment than those with lower education and/or blue- or pink-collar jobs. Peritoneal dialysis can provide more flexibility in employment opportunities, with less danger of inadvertent removal of the dialysis catheters. Individuals undergoing dialysis may need to alter work schedules to accommodate appointments [132]. Improving access to care, including early intervention and vocational rehabilitation in patients with ESRD or dialysis, can help to ensure patients remain in the workforce as long as they desire or are medically able to do so [132].

For patients with serious kidney dysfunction, as in ESRD, the psychosocial effects are numerous. Lifestyle, family life, and work commitments usually are interrupted, often in substantial ways. Patients often must make major adjustments in various roles. Stress accompanies the effort to maintain the existing lifestyle in the face of vast uncertainty about the future, and patients and their families (especially spouses and children). Powerlessness, helplessness, and hopelessness are part of the experiences of patients with renal failure [31].

Disorders of the urinary system may profoundly affect the expression of sexuality. Procedures such as urinary diversion may require the placement of an ostomy bag, and patients with such appliances may be reluctant to participate in sexual activity. They and their partners may find it necessary to alter their sexual behaviors to accommodate a catheter or a dialysis fistula. Patients and their sexual partners may have to discuss and experiment with alternate positions for sexual intercourse, and intercourse may be somewhat unpleasant or even uncomfortable or painful [31].

Patients' reproductive ability may also be altered. For example, certain surgical procedures (such as radical cystectomy) may cause impotence. Because hormone levels are not regulated in the presence of chronic renal failure, many female patients have amenorrhea and are unlikely to become pregnant. In men with renal failure, low testosterone levels and oligospermia significantly reduce the ability to fertilize an ovum. Active prevention of pregnancy in women receiving dialysis is indicated for a number of reasons. For one, pregnancy increases the circulating blood volume. In addition, the low hemoglobin values of most patients with chronic renal failure are inadequate to support a healthy fetus. Attempting to conceive while on dialysis can be harmful to both mother and fetus. If the renal problem is genetically transmitted, as in polycystic kidney disease, reproduction may also be discouraged [31].

Because elimination is essentially culturally prescribed, it is intimately linked to our view of ourselves and to our self-concept. A person faced with the problem of disposing of a plastic bag full of urine or who finds that engaging in certain activities means that urine is likely to leak may feel unclean and out of control of basic body functions. The person may also worry about personal odors [31].

To conceal urinary diversion appliances or drainage tubes, patients may find their choice of clothing limited to nonrestrictive and comfortable styles. Not being able to wear a preferred style of clothing may provoke anxiety, depression, and self-isolation in some people. Being unclothed and seen in the nude may also cause great discomfort to the patient concerned about body changes [31].

Patients who have undergone renal transplantation may have concerns about having another person's organ in his or her own body. The knowledge that a donor has sacrificed a healthy kidney for the patient's benefit may become a burden of guilt. This guilt may be increased if the donor kidney is ultimately rejected [31].

Assessment of a patient's normal pattern of urination and discussion of changes in the pattern involves questioning the patient about the urinary volume, timing, characteristics, micturition control, and appearance of urine. Patients often experience anxiety discussing this aspect of their lives. Urination is typically private, and language referring to the process frequently involves colloquial expressions or terminology unique to a particular family or group. Thus, clear communication about the exact nature of the problem may be difficult. In addition, the proximity of the urethra to the organs of sexual functioning may cause further embarrassment or anxiety during assessment. Taking a calm, confident approach to the interview and examination may make the patient more comfortable [33,34].

It is important for nurses to question the patient about any changes in micturition. What color is the urine? Is there pain with urination? Does the patient have frequency, urgency, or hesitancy with voiding? Are there problems with incontinence? Does the patient void excessive amounts? Only a little? At night? These questions will elicit information about various alterations in micturition and the characteristics of the underlying problem [33,34].

Changes in the urine's appearance may be the presenting problem. Hematuria can be a serious sign, as it may be indicative of cancer. However, it also may be related to anticoagulant therapy, excessive exercise, infection, or trauma. If the urine is excessively alkaline, patients may describe it as being bright red or coffee-colored. If the urine is excessively acidic, blood can give the urine a cloudy or smoky appearance. In most cases, however, cloudy urine is the result of pus in the urine (pyuria). In severe pyuria, urine is also malodorous. Almost colorless urine usually results from excessive fluid intake, chronic renal disease, diabetes insipidus, or diabetes mellitus. Dark yellow-orange urine suggests dehydration or ingestion of medications or foods that discolor the urine. It is important to know when the change in urine color began and if it is constant, intermittent, or triggered by specific events [27,28]. Certain medications, such as phenazopyridine, can cause discoloration of the urine. It is important for history-taking to include any medications taken prior to urine testing. While dyes in medications can interfere with urine dip testing, they should not interfere with urine microscopy or urine culture [133].

Pain is not always present with chronic disorders of the kidneys and urinary tract; it is more common in acute conditions. If present, the patient's history should illicit descriptions of the character, location, distribution, onset, duration, and frequency of the discomfort [27,28]. Is it related to voiding? What brings it on? What relieves it?

Pain from within the kidney is typically described as a dull ache in the flank area (between the ribs and the ileum) and extending into the lower abdomen or the umbilical area. In most cases, the pain is always present and not interrupted with position changes. Renal and ureteral colic causes severe, excruciating pain of sudden onset. The pain, located in the flank area and radiating to the groin, is accompanied by nausea, vomiting, and paralytic ileus [27,28]. Some patients complain of sudden-onset lower back pain as the only symptom; this is reported primarily in postmenopausal women [134].

Feeling the constant need to void when catheterized is due to the pressure of the catheter in the urethra and spasms of the bladder. Bladder pain in the suprapubic area is usually the result of bladder spasms, which can be contractions of the detrusors muscle responsible for normal micturition. Urgency and burning on urination are also common in patients with cystitis or urethritis. Cystitis may produce burning both during and after urination, whereas urethritis usually causes burning during urination only. Strangury often accompanies severe urinary tract infection [27,28].

Some patients with symptoms of burning on urination may actually have a vaginal infection, so these patients should be assessed for signs of vaginal discharge. Has the patient noted any vaginal or perineal itching or dyspareunia (pain with sexual intercourse)? Pain at the urethral orifice or meatus results from irritation or trauma of the bladder neck or urethra. Renal and perineal fullness and pain suggest prostatitis. Metastasis of prostatic cancer to the pelvis can cause leg and back pain [27].

Questions regarding micturition frequency, dribbling, hesitancy, and incontinence are important. How many times per day does the patient void? Is there trouble initiating the stream or difficulty holding the urine? Does the patient get up at night to void? How many times? When did this begin?

Stress incontinence is a common problem for women. As noted, weakness can develop in the bladder-urethral sphincter mechanism through the stretching of pelvic muscles during childbirth or the pressure of the uterus on the bladder during pregnancy. In the elderly, relaxation of pelvic musculature also contributes to the incontinence. Frequent catheterizations and the use of forceps during delivery increase the chances for development of stress incontinence. When questioned, women may state that they need to wear sanitary pads or incontinence briefs [27].

Nurses should also determine if the patient maintains an adequate fluid intake (1,500–2,000 mL per day). If the patient has an excessive intake of milk and vitamin D, this could lead to hypercalciuria. Proteinuria, hematuria, or both can be a normal finding in people who exercise excessively. Immobility because of disability, fracture, thrombophlebitis, or surgery can predispose patients to the development of renal calculi [25,35].

Obtaining a medication history is essential, because many drugs can damage the kidney. Has the patient taken any prescription drugs recently? What over-the-counter medications does the patient routinely take? It is also important to determine if the patient has had any toxic exposures on their job or in their lives [36].

The patient's health history may be significant [28]. Has the patient ever had problems that could lead to nephropathy, such as frequent streptococcal infections, recurrent urinary tract infections, renal calculi, hyperuremia (as occurs in gout), or hypercalcemia (as occurs in hyperparathyroidism, sarcoidosis, or metastatic bone disease)? Has the patient ever had an indwelling catheter, cystoscopy, or x-rays of the renal system? Is there a history of trauma?

Family history of congenital disorders should also be determined, including polycystic kidney disease and congenital malformations of the urinary tract. A strong family history of diseases such as diabetes or hypertension is also significant because these diseases tend to cause renal problems [37].

Because of common autonomic and sensory nervous system innervation between the gastrointestinal and urinary tracts, as well as the anatomic proximity of the organs of the two systems, gastrointestinal symptoms often accompany renal system conditions. Some of these symptoms are nausea, vomiting, diarrhea, abdominal pain, gastrointestinal hemorrhage, and paralytic ileus. Conversely, urinary symptoms may accompany gastrointestinal conditions [27,28].

Renal biopsies are extremely helpful to pinpoint an exact diagnosis in a patient experiencing kidney disease. Lupus-like syndromes and types of tubular interstitial disorders may be diagnosed accurately by examination of kidney tissue. Cellular changes, atrophy, and neutrophil infiltration all may be seen by the pathologist, and these factors aid the nephrologist in treatment planning and prognosis. Renal biopsies are also performed to aid in tracking rejection after a kidney transplant. Some smaller hospitals send their renal specimens out to a laboratory that specializes in analysis of renal tissue because the care and examination of renal specimens are quite involved. The renal biopsy itself, however, may be performed in general interventional radiology departments.

Patients are positioned prone for kidney biopsies. Specimens are collected by means of long sampling needles. The procedure is usually safe, but some caveats apply, as in sampling for lupus [41]. Some referring physicians prefer to admit their patients for overnight observation, to closely monitor for excessive bleeding.

Long needles may also reach tumors of the adrenal gland. Due to the adrenal's location on the superior pole of the kidney, the technique for positioning is almost the same. The physician isolates the solid tumor by CT scan or ultrasound guidance and obtains a sample for analysis. Caution should be practiced with adrenal biopsies because the possibility always exists that the mass is a pheochromocytoma. This tumor consists of cells that secrete adrenaline and other catecholamines and can cause paroxysms of hypertension, tachycardia, headache, nausea, diaphoresis, and a multitude of similar symptoms [42]. Care is always taken not to stimulate a pheochromocytoma, so piercing it with a needle should be avoided.

Patients with renal calculi (stones in the kidneys, ureters, or bladder) may develop infections, as the stones are a continuing nidus of bacterial growth. Indwelling urinary catheters, stents, ureteral tubes, and nephrostomy tubes also increase the risk of infection. Urinary stasis associated with a neurogenic bladder increases the risk of ascending urinary tract infections, which can become systemic bacteremia. Any urinary instrumentation required for diagnosis or treatment (e.g., cystoscopy) may introduce pathogens, potentially leading to infection. In patients with uremia from either acute renal failure or ESRD, altered immune processes further contribute to the potential for infection [33,34].

Infections increase the workload of the kidneys, and the prevention of infection is a priority. It is important to maintain sterile technique during dressing changes and at sites where catheters have been inserted into the circulatory or urinary system. Intermittent catheterization is preferable to the placement of a continuous indwelling urinary catheter. If continuous urinary catheter drainage is necessary, however, the continuity of the system should not be disrupted. The tubing and bag should remain below the level of the bladder to ensure that urine does not ascend into the upper urinary tract. Vascular access routes for hemodialysis and catheters for peritoneal dialysis should all be cared for carefully [27,28].

Handwashing is an essential element of aseptic technique and care of patients with catheters. In addition, healthcare staff should be educated and trained in proper techniques of catheter insertion and care.

Patients with acute or chronic renal failure will have altered nutritional status. Nausea, vomiting, and anorexia are common effects of azotemia. Hypogeusia is also a common problem for patients with ESRD. Dietary modifications (e.g., low-salt, low-potassium diets) prescribed for patients with renal failure complicate efforts to maintain a good nutritional status. The loss of protein via peritoneal dialysis and loss of water-soluble vitamins via dialysis further complicate the issue. Patients with altered renal function who are acutely and critically ill from sepsis or other systemic disease will also experience nutritional deficits [25].

Patients with altered renal function generally require modified or restricted diets. Patients with hypertension should be given a diet of no added salt (generally <4 g sodium per day). If severe hypertension or heart failure is present, dietary sodium intake may be restricted to 2 g/day [25].

Patients who are losing excessive protein (e.g., patients with proteinuria secondary to nephritic syndrome, patients on peritoneal dialysis) require a high-protein diet (1.2–1.3 g/kg body weight/day). In contrast, patients with ESRD who are becoming uremic or are undergoing chronic hemodialysis generally require a protein-restricted diet (0.6–0.8 g/kg/day). Protein in foods should be of high biologic value (i.e., contain a high proportion of essential amino acids). Adequate protein and calories should be provided so the patient's muscle mass is not catabolized [25].

When patients stop excreting urine, potassium intake should be restricted to avoid fatal cardiac arrhythmias. Clinical manifestations of hyperkalemia are chiefly cardiac, although neuromuscular complications can also occur [44,45]. Electrocardiogram (ECG) changes associated with hyperkalemia include peaked T waves (often the first ECG finding), ST-segment depression, widening of the QRS and PR intervals, and loss of the P wave [44]. A late ECG sign is the appearance of a sine-wave pattern, which usually indicates impending ventricular fibrillation and asystole [44,46].

Although cardiac manifestations are obviously the most dangerous sequelae of hyperkalemia, neuromuscular complications, including paresthesias and fasciculations in the extremities, may be seen. Peripheral paralysis can occur, but paralysis of the respiratory muscles is rare [44].

Treatment of acute hyperkalemia with life-threatening symptoms (generally seen with potassium levels ≥7 mEq/L) is accomplished by the administration of IV calcium [44,46,47]. The usual recommended dose is 10 mL of a 10% calcium solution, such as calcium chloride [48]. The ECG should be monitored while calcium is administered, and calcium should be administered only when ECG changes, such as a widening QRS, have occurred [46,47]. Calcium does not correct the underlying hyperkalemia; it only counters the adverse neuromuscular effects [46]. Calcium infusion should always be followed by specific therapy aimed at lowering the plasma potassium level [45].

The administration of IV glucose and insulin is the quickest way to treat acute hyperkalemia that has not yet resulted in life-threatening sequelae [45,46,47]. This results in a shift of extracellular potassium into the cell [46]. Care should be taken in patients with diabetes and hyperkalemia, as glucose infusion that is not accompanied by a matching infusion of insulin can result in increased hyperkalemia due to extracellular hyperosmolarity [44].

When the individual can safely take medication orally and life-threatening sequelae have not developed, treatment with sodium polystyrene sulfate (Kayexalate) in sorbitol solution may be used [48]. This may be the treatment of choice in outpatients who are stable but have potassium levels in the 5.5–6.9 mEq/L range. In patients unable to tolerate oral administration, polystyrene sulfate may be given rectally [47,48]. Studies have raised the possibility of colonic complications from administration of polystyrene sulfate in sorbitol suspension, and there are no controlled studies of safety and efficacy for this use [49]. Due to this concern, concomitant use of sorbitol is no longer recommended [48]. Another strategy to avoid the use of polystyrene sulfate and associated adverse gastrointestinal events (e.g., ischemic colitis, bleeding, perforation, necrosis) would be the use of a loop or thiazide diuretic [50].

The most common cause of chronic hyperkalemia is renal failure; therefore, the most common management of chronic hyperkalemia is dialysis [45]. However, before resorting to dialysis, a combination of medications may be used to increase excretion of potassium, including sodium polystyrene sulfonate, furosemide, and/or IV calcium [51].

Renal dysfunction can lead to impairment of oxygen-carbon dioxide exchange and inadequate oxygenation. If kidneys fail to excrete hydrogen ions and regenerate adequate bicarbonate, the lungs compensate for the increased load of metabolic acids by increasing the rate and depth of breathing (i.e., Kussmaul respirations). Respiratory fatigue from continued compensation may lead to decreased oxygenation, especially if infection or cardiac problems are present.

Flank incisions or thoracoabdominal approaches for renal or urologic surgery also may limit respiratory movements. Hypoventilation following these surgical interventions may precipitate atelectasis or hypostatic pneumonia. Chronic anemia also impairs gas exchange and results in increased cardiac workload (evident as an increased heart rate) [21,22,28].

For patients with metabolic acidosis from acute or chronic renal failure, oxygen-carbon dioxide exchange may be improved with the administration of sodium bicarbonate or with the institution of dialysis. The major risk associated with IV administration of sodium bicarbonate is that it may further expand extracellular fluid volume and worsen problems of hypervolemia, if they are present. Because the correction of acidosis can lead to calcium deficits, it is important to observe for signs of tetany. Dialysate contains acetate, which converts to bicarbonate when absorbed. Thus, dialysis will provide for the replacement of depleted bicarbonate stores [27,28].

Patients with acute or chronic renal failure may experience a variety of changes in the pattern and amount of urine produced.

Severe blood loss, dehydration, or a shift of fluid may cause a decrease in renal tissue perfusion. This alteration in hemodynamics can result in prerenal azotemia. Uremic states also result in a decreased life span of red blood cells and an increased number of immature red blood cells [27,28]. If uncorrected, acute renal failure may result. Patients with chronic renal failure have decreased production of erythropoietin. Because the decrease is gradual, the situation is not life-threatening unless the value suddenly drops further.

Nursing interventions for patients with impaired tissue perfusion include careful monitoring of the patient's vital signs and urinary output. Fluid volume or blood replacement should occur at the prescribed rate, and the nurse should promptly report any inability to administer the fluid as prescribed. If severe hemorrhage is causing a lack of renal tissue perfusion, emergency surgery may be required [27,28].

For patients with renal failure, severe hemorrhage or fluid volume loss may significantly affect cardiac and cerebral tissue perfusion. Patients with ESRD have reduced available hemoglobin. Although patients experience chronic fatigue, vital processes are not typically impaired. If further hemoglobin loss occurs, however, cardiac dysrhythmias, angina, and hypotension may develop [27,28].

Chest pain or arrhythmias indicate alterations in perfusion. Adequate tissue perfusion may be verified through measurements of blood pressure and pulse in the patient's normal range. The patient should demonstrate orientation to person, place, and time [27,28]. Nonacute correction of impaired tissue perfusion may be achieved through the administration of iron supplements, folic acid, anabolic steroids, and judicious administration of blood transfusions [36,52].

Chronic kidney disease is defined as a reduction in kidney function or kidney damage that has been present for at least three months [53,54,55,56]. However, chronic kidney disease should not be viewed in simple mathematic terms. It is an ongoing process of renal injury that causes compensatory hyperfiltration in less-affected glomeruli, which eventually leads to the destruction of those glomeruli as well [53]. Left untreated, this ongoing destruction results in a steady decline in renal function, which eventually affects not just the renal system but almost every organ system in the body [53,54].

ESRD refers to a disease that requires either dialysis or transplantation services. In the United States, 98% of all patients receiving dialysis or transplantation have a GFR <15 mL/min/1.73 m² [57]. Therefore, the terms ESRD and kidney failure are often used interchangeably. Although ESRD is generally associated with a GFR of less than 15 mL/min/1.73 m², it is more importantly an administrative term, as patients receiving dialysis or transplantation services are covered by the Medicare ESRD program [58]. In some cases, ESRD is also used rather loosely to refer to patients who are experiencing progressive chronic kidney disease and are expected to begin dialysis in a matter of days or weeks.

The two leading causes of ESRD are diabetes (44% of new patients) and hypertension (29% of new cases) [59]. New cases of ESRD with diabetes or hypertension listed as the primary cause had been rising rapidly since 1980, but each has declined from 2010 to 2013 [60,61]. However, in 2019, 60.6% of those with ESRD had comorbid diabetes [138]. Approximately 6% of those with CKD and diabetes were hospitalized in 2020 [139]. Other less common causes of ESRD include glomerulonephritis, interstitial nephritis, autosomal dominant polycystic kidney disease (the leading genetic cause), and collagen vascular disease. Due to the prevalence of kidney transplantation, post-transplantation kidney disease has become the fourth largest cause of ESRD in the United States; however, these patients are reported within their original disease category for epidemiologic purposes [62]. New cases of diabetic ESRD are expectedly higher with increasing age in all racial groups, but generally stable or only slightly higher among younger individuals [63]. Statistically, non-White individuals are four times more likely to require dialysis. Compared with White patients, the prevalence of ESRD per million is 9.5 times greater in Native Hawaiians/Pacific Islanders, 3.7 times greater in Black/African Americans, 1.5 times greater in American Indians/Alaska Natives, and 1.3 times greater in Asian Americans [63]. The cost of treating ESRD was $35.4 billion in 2016 [63].

The pathophysiology of chronic kidney disease is dependent on the underlying cause, the most common of which are the disease processes of diabetes and hypertension. Diabetic nephropathy has various proposed hypotheses for mechanisms of kidney damage, though it is most often and broadly attributed to hyperglycemic end-organ damage to the glomerulus, eventually to the point of proteinuria. Experts have suggested that there may be disadvantaged nephron development in those born to mothers with diabetes, predisposing the offspring to chronic kidney disease during their lives. Some also posit that hyperglycemia sensitizes end-organs to hypertensive damage, and because diabetes and hypertension often occur together, this has an additive deleterious effect on the kidney [64]. The initial manifestation is often albuminuria and hyperfiltration (i.e., an elevation in GFR) [65]. Over time, albuminuria increases to the point of overt nephropathy, accompanied by a decline in GFR. Hyperglycemia-mediated overactivation of protein kinase C is also thought to be involved in progressive renal parenchymal damage, resulting in the loss of selective permeability in the glomerulus and an increase in local inflammation [66]. In addition to glomerular damage, thickening of the basement membrane and afferent and efferent arterioles may be noted [66].

Hypertensive nephropathy is another common cause of chronic kidney disease and induces renal damage through a variety of mechanisms. One mechanism is sympathetic nervous overactivity resulting in constriction of efferent arterioles and decreased outflow from the glomerulus, allowing for increased oncotic pressure in the nephron. Activation of the RAAS may also occur as a response to sympathetic nerve activity. Arterial stiffness, a central component of hypertension, is a contributing mechanism as well. Impaired salt and water excretion from sympathetic nervous overactivity or from RAAS activation serves to increase hypertension and thereby increase renal damage.

Other underlying causes of the renal damage leading to chronic kidney disease are generally associated with unique mechanisms, including immune complex deposition and interstitial damage from prolonged use of nephrotoxic drugs. Acute kidney injury may also lead to chronic kidney disease if the initial insult has not been removed or if the initial injury has not been completely reversed. Even in cases of full recovery after acute kidney injury, the risk of developing chronic kidney disease is increased [67]. Renal ischemia-reperfusion injury may also cause lasting damage [68].

Many of the complications and comorbidities associated with chronic kidney disease stem from this initial damage and begin to manifest as renal damage progresses. Hypertension, a common comorbidity of chronic kidney disease, can cause renal damage as well as be exacerbated by it, as discussed. Anemia is a common complication of chronic kidney disease and is likely due to reduced renal production of erythropoietin, though other factors, such as uremia-induced inhibition of erythropoiesis, shortened erythrocyte survival, and disordered iron homeostasis, also play a role [69]. A study of patients with stage 3 chronic kidney disease determined that renal anemia is associated with rapid progression to stage 4 and a higher risk of cardiovascular disease and hospitalization [70].

Alterations in bone and mineral metabolism are commonly seen in patients with chronic kidney disease, starting in early-stage disease. Hypocalcemia is common in these patients, often leading to parathyroid hyperplasia and secondary hyperparathyroidism [71]. The hypocalcemia is likely attributable to phosphate retention, skeletal resistance to parathyroid hormone, altered vitamin D metabolism, or a combination of these factors [72]. In line with altered vitamin D metabolism, patients with chronic kidney disease also have defective intestinal calcium absorption. Hyperphosphatemia is also common, and the resultant elevation in the plasma calcium-phosphate product often leads to precipitation of calcium phosphate in soft tissues and to calcific changes in the walls of arterioles and small arteries [72]. These electrolyte derangements are largely attributable to intrarenal damage and hormonal abnormalities, both of which affect electrolyte excretion and reabsorption. Activation of fibroblast growth factor 23 (FGF-23) and parathyroid hormone is implicated in the regulation of phosphate reabsorption in the tubules. FGF-23 also inhibits vitamin D production and promotes catabolism of vitamin D stores [73].

Clinical Manifestations

The Department of Veterans Affairs Guideline Panel suggest intensive blood pressure management (insufficient evidence to recommend a specific target) beyond a target of less than 140/90 mmHg, to reduce mortality in patients with estimated glomerular filtration rate below 60 mL/minute/1.73 m².

(https://www.healthquality.va.gov/guidelines/CD/ckd/VADoDCKDCPGFinal5082142020.pdf Last Accessed: July 27, 2023)

Strength of Recommendation: Weak for

The clinical presentation of chronic kidney disease is often subtle, and symptoms are uncommon with a GFR greater than about 35 mL/min/1.73 m². Therefore, suspicion for mild renal disease should be based on recognition of the primary pathologic mechanism responsible for renal injury, particularly in patients with diabetes and/or hypertension. It is equally important to begin early screening for the complications of renal disease to prevent morbidity and to establish a credible baseline for the individual patient.

After the GFR falls to less than 35 mL/min/1.73 m², a variety of metabolic, psychiatric, hematologic, cardiovascular, and acid-base regulatory problems occur. Clinical presentation at this point depends on the particular complication and the underlying cause of renal failure [44,53,54,55,75].

Therapeutic Measures

The management of chronic kidney disease is multifaceted, involving a series of tactical measures (including the effective management of comorbidities) designed to reduce the risk of further damage and slow the progression of kidney disease. The clinician should first seek to identify and treat reversible causes, such as lower urinary tract obstruction, which should be considered in any patient with unexplained deterioration in renal function. Optimal glucose control in the patient with diabetes and blood pressure control in those with hypertension, as well as initiation of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) therapy, are important to limit progression [76,77]. Certain nephrotoxic agents should be avoided if at all possible, especially in the patient with diabetes or receiving loop diuretics. These include nonsteroidal anti-inflammatory drugs, aminoglycoside antibiotics, and radiographic contrast material. Additional measures to protect the kidney and slow progression include smoking cessation, statin therapy to control hyperlipidemia, dietary protein restriction, and satisfactory treatment of metabolic acidosis.

The Department of Veterans Affairs Guideline Panel recommends against the use of combination renin-angiotensin-aldosterone system blockade (ACE inhibitor and ARB with or without a direct renin inhibitor) in patients with chronic kidney disease.

(https://www.healthquality.va.gov/guidelines/CD/ckd/VADoDCKDCPGFinal5082142020.pdf Last Accessed: July 27, 2023)

Strength of Recommendation: Strong against

For cases of chronic kidney disease that do progress to late-stage kidney disease, it is also important to anticipate and prepare patients for renal replacement therapy [76]. Patients with a GFR less than 30 mL/min/1.73 m² should be referred to a nephrologist to make preparations for impending end-stage disease and renal replacement therapy [76]. It is well to keep in mind, however, that acute, intercurrent declines in GFR are often due to reversible factors such as volume depletion, radiographic contrast or nephrotoxic drug use, and urinary tract obstruction; efforts should be made to correct these in order to appropriately address declines in GFR and determine whether true progression of the disease has occurred [76].

An intensive and multifactorial management approach is required for patients with renal disease in order to address all risk determinants. The mainstays of treatment are management of complications and/or comorbidities, lifestyle modification, and dialysis for patients with severe or late-stage disease. Some patients may be candidates for kidney transplant, although the wait for a non-related donor can be long. Psychosocial issues and patient education (primarily to ensure compliance with the established treatment plan) are important as well.

Nursing Measures

The Academy of Nutrition and Dietetics and the National Kidney Foundation recommends protein restriction with or without keto acid analogs, to reduce risk for end-stage kidney disease/death in adults with CKD 3–5 who are metabolically stable and under close clinical supervision. This includes a low-protein diet providing 0.55–0.60 g dietary protein/kg body weight/day, or a very low-protein diet providing 0.28–0.43 g dietary protein/kg body weight/day with additional keto acid/amino acid analogs to meet protein requirements (0.55–0.60 g /kg body weight/day).

(https://www.ajkd.org/article/s0272-6386(20)30726-5/pdf Last Accessed: July 27, 2023)

Level of Evidence: 1A (Very confident that the true effect lies close to that of the estimate of the effect)

An essential component of renal disease management is diet modification and dietary referral is beneficial for optimum care. This is especially true in patients with underlying diabetes and in patients who are under- or overweight, as the dietary recommendations must be modified in these cases. The American Dietetic Association has established guidelines for renal failure diets, which are published in the Manual of Clinical Dietetics [78].

Although the medical management of chronic kidney disease may seem overwhelming to even veteran healthcare providers, it is often devastating to patients. Therefore, it is essential to provide adequate social and psychiatric support. Patients with ESRD (especially patients on hemodialysis) are known to suffer from high rates of depression, insomnia, and anxiety [79]. Often ignored, sexual dysfunction occurs at high rates in both male and female patients with ESRD [79]. The treatment of these and other psychiatric complications should begin before the onset of ESRD, when possible, and continue as long as necessary.

Acute kidney injury is primarily a disease of hospitalized patients and often is the result of pre-existing chronic kidney disease [63]. Acute kidney injury in the Medicare population has reached an annual average of approximately 4.7%, compared with 1.5% in 2005 [63]. In 2020, the hospitalization rate for AKI was 6.2%, a 7% decrease compared with 2019; however, the hospitalization rate among those on Medicare was 34% [139]. Acute kidney injury rates are significantly associated with aging and with Black/African American race [63]. The most common causes of acute kidney injury vary according to pathophysiology, but possible etiologies include trauma, dehydration/volume depletion, tubulointerstitial disease, glomerulonephritis, and obstruction [53,80].

A neurogenic bladder occurs in patients whose normal neural innervation of bladder contraction is interrupted. The result may be sensory disruption, motor disruption, or both. A neurogenic bladder may have a variety of causes. Diabetes-related autonomic neuropathy may result in a sensory deficit. Neurologic disease (e.g., multiple sclerosis, amyotrophic lateral sclerosis), spinal cord injury, or central nervous system malignancy may also result in a neurogenic bladder [81,82].

Renal and urinary infections are a common clinical problem and may occur anywhere in the urinary tract.

In general, nursing interventions for patients with kidney or urinary tract cancers include providing comfort; providing emotional support during the diagnostic, therapeutic, and convalescent periods; and educating the patient in self-care and decision making. Patients should also be regularly assessed for potential complications related to cancer or therapeutic interventions (e.g., infection, urinary tract obstruction, acute renal failure) [18,86,88].

Obstructive disorders of the kidneys and urinary tract are fairly common in adults. The most common nonmalignant obstructive disorders result from the formation of calculi or the effects of their obstruction or from hyperplasia of prostatic tissue (benign prostatic hyperplasia) [18,86,88].

Nephrolithiasis and urolithiasis refer to the presence of calculi (stones) in the urinary tract. Calculi in the urinary tract are a relatively common problem, especially for men, and they often occur within the same family, indicating a possible heritable factor. There is also a high incidence of recurrence, with as many as 40% of patients reporting a recurrence within two years. Renal calculi are extremely painful, and individuals are incapacitated during an acute episode. When associated with infection or obstruction, renal calculi may be life-threatening [18,86].

Most calculi originate in the renal parenchyma (nephrolithiasis) and are passed out into the ureters or bladder (urolithiasis). Calculi are usually composed of calcium salts (calcium oxalate or phosphate, uric acid, or struvite [magnesium ammonium phosphate]). A number of factors contribute to the formation of calculi, primarily the degree to which the urine is supersaturated with a normally excreted element, the pH of the urine, the presence of substances that inhibit the formation of crystals, the stasis of urine, and the pre-existing environment [18; 86].

Immobilization, primary hyperparathyroidism, hypervitaminosis D, renal tubular acidosis, and dietary excess of foods containing calcium or purine may result in hypercalciuria. Medications or supplements taken in excess, such as antacids or vitamin C, may also result in hypercalciuria or excess calcium oxalate. However, most cases of calculus formation are idiopathic [93,94,95].

With infection and the consumption of some foods/beverages, the urine may become slightly alkaline or acidic. Uric acid and cystine calculi will form in acidic urine; calcium phosphate calculi will dissolve in acidic urine; and calcium oxalate calculi are not influenced by the pH of the urine. Urea-splitting bacteria (e.g., Proteus, Xanthomonas, Pseudomonas, Klebsiella, Staphylococcus, Mycoplasma) convert urea to ammonia, and the alkaline urine contributes to the formation of struvite calculi. Calculus formation is enhanced when there is urinary tract scarring (either from infection or surgical procedures in the urinary tract) or when urinary stasis or urinary crystallization is present [93,94,95].

Clinical Manifestations

The primary clinical manifestation of nephrolithiasis/urolithiasis is pain, and its location may suggest the location of the calculus. In some situations, there may be no discomfort at all. However, if the calculus descends into the ureters, the patient may describe the pain as excruciatingly severe (i.e., 10+ on a 10-point scale). The ureteropelvic junction, the point at which the ureter crosses anterior to the iliac vessels, and the ureterovesical junction—the narrowest points in the ureters—are the sites at which calculi are most likely to become lodged. Severe intermittent pain results as the musculature of the ureters goes into spasm (colic) in an attempt to move the calculus out of the ureters by peristalsis. The pain of urethral colic may traverse along the route of the ureter and extend into the lower abdomen, the vulva, or the testes. Patients commonly experience nausea and vomiting. They may also report blood in the urine and, if infection is present, chills and fever [93,94,95].

Therapeutic Measures

Opioids and NSAIDs are generally necessary to relieve pain associated with renal or urinary calculi; NSAIDs (e.g., ketorolac) are associated with fewer adverse effects. If analgesia is insufficient for pain management, referral to the emergency department with urology consultation is warranted [142]. Antispasmodics may also be prescribed to relax the urethral musculature. If infection is present or if instrumentation is necessary to remove the calculus, antibiotics will be prescribed. Other agents may be prescribed to alter the urinary pH to create the desired environment (e.g., sodium acid phosphate, potassium acid phosphates, or ascorbic acid to promote the formation of acidic urine). Thiazide diuretics increase calcium reabsorption and thus may be prescribed for patients who form calcium calculi. However, these diuretics may cause hyperuricemia, so agents to manage excess uric acid (e.g., allopurinol) may also be necessary. For patients who require more alkaline urine, 50% sodium citrate may be prescribed [93,94,95]. Other considerations for referral to the emergency department include suspected sepsis, anuria, or obstruction (particularly in those with a history of nephrectomy). When immediate referral is not indicated from exam, the provider should evaluate the urinalysis and culture, if necessary, to rule out infection. Non–contrast-enhanced computed tomography (CT) of the abdomen and pelvis has superior sensitivity and specificity and is commonly performed in the emergency department for concerns of renal calculi; it can also be ordered outpatient, if needed. In the outpatient setting, ultrasonography has acceptable performance and is more cost-effective [142]. Patients with a history of calculi should focus on producing high-volume, dilute urine. This may be achieved by consuming 4 L fluid (preferably water) per day. It is also important to void before bedtime and to awaken in the night to empty the bladder. When awakened, the patient should drink more water to ensure a constant dilution of urine [93,94,95].

Dietary modifications will depend on the content of the calculi. A low-calcium diet is only recommended for patients with active hypercalciuria. For patients who should limit calcium oxalate, foods to avoid include tea, cola, spinach, and citrus fruits.

Patients who are hyperuricosuric and form uric acid calculi may benefit from a diet low in purines. This means limiting intake of meat, fish, poultry, beer, and wine. Struvite calculi contain phosphates; therefore, a diet that limits phosphorus (from seafood, chicken, pork, nuts, dairy, and grains) may be indicated. Medications that alter urine composition are often more effective than dietary modification [25].

Patients with calculi too large to pass spontaneously may be candidates for extracorporeal shock wave lithotripsy. In this treatment, the patient is supported and suspended in lukewarm water or on a cushion or membrane. An extracorporeal shock wave lithotripter sends shock waves to the calculus, which shatters and is excreted within several days [93,94,95]. This procedure generally takes one hour and requires thousands of waves to be sent to the site of the calculi.

In percutaneous nephrolithotomy, a small incision is made and a scope is introduced to visualize the calculus. The stone(s) can then be pulverized with ultrasound vibration and flushed.

In some cases, the calculus may be retained and additional treatment necessary. A variety of surgical procedures may be used to remove the calculus; the method selected depends somewhat on its location [93,94,95].

Specific Nursing Measures

Care of the patient with renal or urinary calculi is primarily focused on comfort and the prevention of infection. In addition to measuring intake and output carefully, urine should be strained through fine mesh in order to obtain a calculus or calculus fragment that may be analyzed to determine its chemical characteristics [27,28,83].

Initially, patients may require IV administration of morphine to obtain pain relief. Antibiotics should be administered as prescribed. A high fluid intake (3–4 L/day) is usually recommended for the remainder of the patient's lifetime [25,36,52].

Direct or indirect injury to the organs of the urinary system can interrupt the structural integrity of the kidney(s), the ureter(s), and/or the bladder. A major interruption of vascular supply may occur concomitantly. Traumatic injuries are commonly classified as either penetrating or nonpenetrating (blunt) [93,94,95,96]. Abdominal gunshot or stab wounds are the most common sources of penetrating trauma. Automobile accidents, automobile-pedestrian accidents, motorcycle accidents, assault, and injuries from sporting events may result in blunt trauma [93,94,95,96].

Injuries to the renal system may significantly affect patients' overall health. Preservation of renal function is the primary goal. Loss of a single kidney from trauma may not be life-threatening, assuming the other kidney is functioning adequately, but it can have serious consequences. Patients who experience renal trauma are often victims of other abdominal trauma as well [93,94,95,96].

Obtaining a careful patient history is often the most important part of diagnosis. Gunshot or stab wounds are obvious, but the history may disclose less obvious traumatic events. Physical sports involving heavy direct contact, such as football or ice hockey, may result in injuries that did not seem significant at the time. A history of rib fractures, chest injuries, or abdominal injuries suggests the potential for renal trauma.

Physical assessment includes the collection of a urine specimen to determine the presence of blood. Flank pain or suprapubic tenderness may or may not be present. Alterations in urinary output and patterns of voiding are important [93,94,95,96].

Planning for access should occur well before the need for dialysis, as proper access may take months to properly heal. Up to 80% of patients presenting for initial dialysis are dialyzed via temporary venous catheters due to a lack of established access [63].

Hemodialysis can be provided via three major different types of access: an AV fistula, an AV graft, or a temporary venous catheter. The National Kidney Foundation endorsed a goal for at least 65% of all patients on hemodialysis to have a working AV fistula by 2009, but this goal was not met [97]. As of 2017, reporting institutions dialyzed 62.8% of all patients on hemodialysis via AV fistulas [63].

AV fistulas are created surgically by attaching an artery directly to a vein. Generally placed in the forearm, AV fistulas may be categorized as radial-cephalic, brachial-cephalic, or brachial-basilic based on the vein and technique used [55,98]. Generally, the radial-cephalic, having a lower anatomical position in the forearm, is preferred for first access as it preserves the higher veins for later use. After anastomosis, the resultant increase in blood flow to the vein results in thickening of the venous wall, allowing it to withstand the numerous punctures required for hemodialysis [98]. AV fistulas generally require at least three months to fully mature. AV fistulas are recommended as the first form of access, and they should be promoted in all eligible patients who choose hemodialysis, as they improve outcomes and reduce costs compared with central venous catheters [99]. They also offer the best access for longevity and have the lowest association with morbidity and mortality [100]. However, multiple studies suggest that certain subgroups of patients (i.e., the elderly and those with limited life-expectancy) may benefit from alternative forms of access. A patient-centered, individualized approach to the choice of access may indicate the use of a method other than AV fistula [101,102].

AV fistulas are not without complications, and the overall patency rate is only 50% after five years [98]. Fistula failure can be classified as early (in the first three months) or late (after three months) [98]. Early failure is generally due to infection, stenosis, or obstruction (either of inflow or outflow). Late failure is generally due to either venous stenosis or arterial lesions, with venous stenosis being the most common cause of late AV fistula failure [55,98]. Steal syndrome is another possible complication of AV fistulas and results in too high of a diversion of blood flow from the extremity distal to the fistula. Patients with steal syndrome may present with signs and symptoms of decreased blood flow to the affected extremity, particularly in the digits of the hand. Treatment of this complication includes the takedown of the fistula or placement of coils in the fistula to decrease diversion. Patients deemed at risk for imminent limb or digit loss should be referred immediately to the emergency department for evaluation by a vascular surgeon.

Fistula patency can be assessed by palpation of "thrill" and auscultation of bruit. A palpable motion in the surface of the fistula and a bruit when a stethoscope is placed over the fistula should both be present. The bruit should be loudest at the arterial side of the fistula. Patients found to have nonpatent grafts should be referred immediately to interventional radiology, as patency can often be restored by the use of antithrombotics (e.g., tissue plasminogen activators) and/or balloon angioplasty. Unfortunately, the use of contrast medium is usually necessary in order to restore patency. In these cases, the patient should be dialyzed within 24 hours of receiving the contrast. If the patient is to receive dialysis immediately after angioplasty, catheters may be left in place so it is not necessary to recannulate immediately after the procedure. If the patient is to return the following day for dialysis, temporary catheters should be removed to prevent potentially deadly hemorrhage. At no point should any patient with ESRD receive gadolinium-based contrast dye due to the risk of nephrogenic systemic fibrosis. Postexposure dialysis does not decrease the risk of developing nephrogenic systemic fibrosis in at-risk patients.

AV grafts are generally considered to be inferior to AV fistulas and superior to temporary catheters, but fewer than half are patent after five years [103]. These grafts are often used for patients who lack veins large enough to create fistulas. The determination of need for graft placement versus fistula is accomplished via vein mapping and clinical evaluation.

AV graft formation is accomplished by implantation of a synthetic tube that connects a vein and an artery. Dialysis is then performed by cannulating the synthetic graft. Synthetic grafts have higher rates of infection and clotting and, as noted, generally fail sooner than fistulas [104].

Both AV fistulas and grafts should be cannulated only by trained practitioners. Repeated same-site cannulation can result in destruction of grafts, aneurisms, and/or infiltrates. Although not all these complications are entirely preventable, trained inserters can minimize their occurrence.

Temporary catheters are the least preferred method of access for hemodialysis, but one of the most frequently used. However, according to data from the Centers for Medicare and Medicaid Services, catheter use in the United States declined slightly from approximately 28% in 2006 to 24% in 2007 [105]. Central venous catheters for dialysis (CVCDs) are generally tunneled catheters with two external access ports ("pigtails") and a tunneled lumen under the skin that extends into the vena cava; they may last up to one year. The introduction of advanced CVCDs has helped make temporary catheters a viable solution for patients with very poor vascular status. Patients often prefer the temporary catheters to other forms of access, as they do not involve the pain of subcutaneous cannulation and are often cosmetically more acceptable. Using a tunneled catheter helps reduce the risk of infection but does not eliminate it.

The peritoneal catheter is the only option for peritoneal dialysis. The invention of the Tenckhoff catheter in 1968 helped reduce high rates of peritonitis associated with peritoneal dialysis. It is made of silicone rubber and Dacron cuffs and can be coiled or straight. Compared with coiled cuffs, straight cuffs have higher catheter survival and fewer complications [106]. Coiled catheter use has been associated with lower rates of failure due to outward migration of the catheter [107,108]. Most catheters in use today have two cuffs: one in the musculature of the abdominal wall and one in the subcutaneous tissue nearer the exit. Placement is generally performed operatively and can now be accomplished laparoscopically. Other methods, such as blind insertion via Tenckhoff trocar or guidewire, are available.

After insertion, approximately 7 inches of catheter extend beyond the surface. The catheter will usually have an external suture in place for the first two weeks after implantation. An external flow switch that is capped when not in use is present at the end of the catheter.

Hemodialysis is a risk factor for a variety of complications, and patients must be closely monitored. Mortality rates for patients with ESRD are high in part due to uncontrolled complications associated with dialysis.

Patients on hemodialysis often experience hypotension during and after dialysis sessions. A fluid gain of 4 or more liters between sessions is not uncommon, and this same amount of fluid must then be removed over a four-hour dialysis session. Most of this fluid is situated in the extravascular space, and dialysis removes fluid only from the intravascular space. So, changes in osmotic pressure between the intravascular and extravascular must allow for fluid movement during dialysis. If the patient becomes acutely hypotensive, the dialysis may need to be interrupted and the patient placed in Trendelenburg (supine) position with elevated feet. Rarely, fluid replacement may be required.

Cramping is also common, especially at the end of the dialysis session after large amounts of fluid and electrolytes have been removed. Severe cramping may require administration of normal saline. For patients who are significantly bothered by cramping, hydromorphone (Dilaudid) 1–2 mg orally may be given one hour before the usual onset of cramping. Hydromorphone has the advantage of not being dialyzed out of the patient's system.

The indication for transplantation is ESRD, or a GFR of <15 mL/min/1.73 m² [57]. In recent years, the process for selection of a kidney transplant has liberalized, with larger numbers of elderly patients being accepted for transplantation. In 1991, 30% of kidney transplant recipients were older than 50 years of age; by 2016, this number had increased to more than 70% [63]. Transplant counts for recipients 65 years of age and older have been steadily increasing [63]. Only 3% of individuals older than 65 years of age on the waiting list received a kidney in 2017 [145].

One study assessed transplantation rates among 4,445 patients with a mean age of 52.2 years [146]. The survival time with transplant for all ages within a 10-year follow-up period was increased with transplantation versus dialysis only [146].

Guidelines for selection of patients for transplantation vary from program to program. Generally, metastatic disease or severe pulmonary or heart disease are exclusionary factors. Human immunodeficiency virus (HIV) is no longer considered an absolute contraindication, and studies have shown that patients with ESRD and HIV nephropathy have an increased life expectancy when treated with transplantation versus dialysis [110].

In January 2023, the Board of Directors of the Organ Procurement and Transplantation Network (OPTN) updated its policy on the use of eGFR to evaluate kidney function in candidates, increasing the cutpoint by approximately 16%. This update is meant to better reflect kidney function in Black/African American kidney candidates who were previously excluded [146].

Allocation of all transplants in the United States is managed by the UNOS. Kidney transplant guidelines place the highest considerations on histocompatibility and time spent on the transplant list [111]. Children suffering from ESRD will lose growth (and possibly other milestones) while on dialysis, so they are given priority. The median adult wait time for a cadaver kidney is four years [63].

One result of this method of allocation is a potential mismatch between grafts and patients. If a patient with a life expectancy of 10 to 20 years receives a kidney from a donor who is/was 20 years of age (with a potential for 50 to 60 years of function), the transplanted kidney will potentially be underutilized. Worse, if a patient with a 40- to 50-year life expectancy receives a kidney from an older donor, he or she will likely outlive the donated kidney. In fact, approximately 15% of all patients awaiting transplantation have already received at least one transplant [63].

To address these problems and others, in 2011, the UNOS released a concept document that proposes changes to the allocation system in order to more accurately match donors and recipients [112]. While this proposal has been met with some controversy, UNOS believes that it could actually increase the number of functioning years obtained from the current pool of donated kidneys. This gain would occur both from increased age matching as well as from eliminating the current designation of "expanded donor criteria" kidneys. These kidneys do not meet all donation criteria, either due to existing disease in the graft or risk factors of the donor. An estimated 12% of all donated kidneys are not used because they are classified as expanded donor criteria kidneys, meaning they have an increased potential for rejection [112].

A 2020 study reviewed data on kidneys discarded in the United States between 2015 and 2016. These kidneys underwent a "procurement biopsy" and were rejected based on abnormalities noted in the tissue. During this time, 1,103 kidneys were rejected; of these, 493 would have been matchable based on French criteria, which are less restrictive. The 493 kidneys that passed the French criteria had a one-year survival rate of 93%, a five-year survival rate of 81%, and a 10-year rate of 69%. This suggests that many donor kidneys in the United States are being discarded unnecessarily and may be worsening the already-severe deficiency of transplant-eligible kidneys [147]. An elderly recipient may be better off receiving a kidney with only 10 to 15 years of expected graft survival, as they are unlikely to live long without a transplant.

Transplanted kidneys are generally placed in the extraperitoneal space in the right iliac fossa. Pediatric patients can have their grafts placed in the intraperitoneal space. The major consideration for placement of the graft is surgical access to the renal arteries, renal veins, and the ureter. Failed kidneys are rarely removed unless infection or carcinoma is present. The donor's renal artery is usually anastomosed to the recipient internal iliac artery, and the donor renal vein is connected to the recipient external iliac vein. Lastly, the donor ureter is attached to the recipient bladder.

For patients experiencing acute rejection of a transplanted kidney, the National Kidney Foundation recommends biopsy first, unless the biopsy will substantially delay treatment.

(https://kdigo.org/wp-content/uploads/2022/09/KDIGO-2009-Transplant-Recipient-Guideline-English.pdf Last Accessed: July 27, 2023)

Strength of Recommendation/Level of Evidence: 1C (Recommended based on low quality of evidence)

Immediate postoperative care of the patient post-transplant involves all the usual issues involved in major surgery (e.g., bleeding, pain management, bowel function, infection, postoperative cardiac or pulmonary complications) as well as issues specific to kidney transplantation. These issues include graft function, acute rejection, urine leakage from the ureter anastomoses, and complications from immunosuppression. Acute rejection is not nearly the problem it was prior to the development of tacrolimus and cyclosporine, although chronic rejection remains a problem in long-term graft survival.

After transplantation, the graft may function immediately, have delayed graft function, or have complete non-function. Delayed graft function is a common problem in transplants, affecting up to 23% of cadaver transplants and 6% of living transplants [113]. The delay may last from days to weeks and may require temporary dialysis. Complete graft non-function, by definition, does not resolve and requires a return to dialysis.

Patient A, a man 27 years of age, presents to an outpatient clinic complaining of two days of facial and hand swelling. He first noticed swelling around his eyes, along with difficulty putting on his wedding ring because of swollen fingers. Around the same time, he began to notice that his urine appeared reddish-brown. He reports having less urine output over the past several days. He has no significant medical history. His only medication is ibuprofen, which he took more than one week ago for a fever and sore throat that have since resolved. On examination, he is afebrile, with a heart rate of 85 beats per minute and a blood pressure of 172/110 mm Hg. Patient A has periorbital edema; his funduscopic examination is normal, without arteriovenous nicking or papilledema. His chest is clear to auscultation. His heart rhythm is regular, with a nondisplaced point of maximal impulse, and he has no abdominal masses or bruits. The patient also has edema of his feet, hands, and face. A dipstick urinalysis in the clinic shows specific gravity of 1.025 with 3+ blood and 2+ protein but is otherwise negative. A fresh-spun urine specimen is positive for red blood cell casts.

The physician diagnoses acute (likely poststreptococcal) glomerulonephritis. This condition is most likely to affect children with a history of upper respiratory infection or a history of strep throat one to three weeks earlier, although adults may also be affected. Patients present with edema, hypervolemia, hypertension, hematuria, and oliguria. Red blood cell casts on urinalysis verify the diagnosis. Systemic lupus erythematosus is another possible cause, but this patient has no signs or symptoms indicating this etiology.

Treatment of poststreptococcal glomerulonephritis focuses on managing hypertension and edema. Patient A is placed on a low-salt diet and liquid intake is restricted. If the edema was more severe, loop diuretics would be prescribed. However, the edema begins to resolve, and his blood pressure begins to lower with conservative management. Additionally, Patient A is prescribed oral penicillin G at a dosage of 250 mg four times per day for 7 to 10 days to eradicate the nephritogenic strain. The patient is instructed to rest and avoid vigorous physical activity for a day or two.

Patient B, a man 40 years of age with no past medical history, presents to the clinic to establish care. He reports that he had a prior urinalysis that revealed blood as an incidental finding. The urinalysis was done as a standard screening test by his former employer. He denies ever seeing any blood in his urine and denies any voiding difficulties, dysuria, sexual dysfunction, or any history or risk factors for sexually transmitted infections. His review of systems is otherwise negative. He reports having smoked a half-pack of cigarettes per day for the past 10 years and jogging 15 minutes and lightweight training daily. On examination, his vital signs are normal, and the entire physical examination is unremarkable. A complete blood count and a chemistry panel (electrolytes, blood urea nitrogen, and creatinine) are normal. The results of the urinalysis are:

The likely diagnosis is determined to be asymptomatic microscopic hematuria. Repeat urinalysis is ordered to assess for risk factors. A urine culture is necessary to rule out infection. Imaging studies are also ordered. The primary concern is to rule out malignancy, including renal cell carcinoma and transitional cell carcinoma. The nurse counsels Patient B on the importance of an appropriate work-up but reassures him that the prevalence of renal cancers is low. Because the patient is a smoker, bladder cancer should be ruled out (or identified) as soon as possible.

Patient C, a Hispanic woman 48 years of age, presents to a medical office complaining of persistent swelling of her feet and ankles, to the degree that she cannot put on her shoes. She first noted mild ankle swelling approximately two to three months previously. She borrowed some diuretic pills from a friend, and the pills seemed to help, but now she has run out. She also reports that she has gained 20 pounds over the last few months, despite regular exercise and trying to adhere to a healthy diet. Her medical history is significant for type 2 diabetes, for which she takes a sulfonylurea agent. She neither sees a physician regularly nor monitors her blood glucose at home. She denies dysuria, urinary frequency, or urgency, but she does report that her urine has appeared foamy. She has had no fever, joint pain, skin rashes, or gastrointestinal symptoms.

Her physical examination is significant for mild periorbital edema, multiple hard exudates, and dot hemorrhages on funduscopic examination. She also has pitting edema of her hands, feet, and legs. Her heart rhythm is regular without murmurs, and her abdominal examination is benign. She has diminished sensation to light touch in her feet and legs to mid-calf. A urine dipstick performed in the office shows 2+ glucose, 3+ protein, and negative leukocyte esterase, nitrates, and blood.

The presumed diagnosis is nephrotic syndrome secondary to diabetic nephropathy. A 24-hour urine collection is taken to measure proteinuria and to verify the diagnosis. Usual causes in adults include diabetes, hepatitis B, amyloidosis, lupus erythematosus, and drugs such as penicillamine and captopril.

Maintenance of glycosylated hemoglobin (HbA1c) to 7.0% or lower is recommended, and Patient C is started on diabetes care (with regular follow-up and screening). To address the nephrotic syndrome, an ACE inhibitor is prescribed to control her blood pressure. In order to meet her blood pressure targets more quickly, a diuretic is also prescribed. Patient C is instructed to limit her intake of fluids and protein (to less than 2 g/day). She is asked to return in several weeks for additional screening and to call if the edema does not resolve.

The emergency resident calls up a new admission, describing a female patient, 84 years of age. Patient D was brought to the emergency department by ambulance from her long-term care facility for increased confusion, combativeness, and fever. Her medical history is significant for Alzheimer disease and well-controlled hypertension; otherwise, she has been healthy. The resident states that the patient is "confused" and combative with staff, which, per her family, is not her baseline mental status. Her temperature is 100° F, heart rate is 130 beats per minute, blood pressure 76/32 mm Hg, respiratory rate 24 breaths per minute, and oxygen saturation is 95% on room air. On examination, Patient D is lethargic but agitated when disturbed. Her neck veins are flat, her lung fields are clear, and her heart rhythm is tachycardia but regular, with no murmur or gallops. Her abdominal examination is unremarkable, and her extremities are warm and pink.

After administration of 2 L of normal saline over 30 minutes, her blood pressure is 95/58 mm Hg. The initial laboratory work indicates a white blood cell count of 14,000/mm3, with 67% neutrophils, 3% bands, and 24% lymphocytes. No other abnormalities are noted. The chest x-ray obtained in the emergency department is normal. Urinalysis of a catheterized sample shows 2+ leukocyte esterase, negatives nitrite, and trace blood. Microscopy shows 20–50 white blood cells per high-power field, 0 to 3 red blood cells, and many bacteria.

Patient D is diagnosed with urinary tract infection that has progressed to sepsis and possibly shock. She has several risk factors that predispose her to urinary tract infection, including older age, female sex, cognitive dysfunction, and fecal incontinence. Blood pressure support is continued, with IV fluids or vasopressors as necessary. Broad-spectrum antibiotics are started immediately. As the infection clears, the patient's combativeness resolves as well.

Patient E is a man, 42 years of age, who has driven to the mountains to hunt. While tramping through thick woods, a stray bullet (perhaps from another hunter) hits Patient E's thigh, tearing into muscles and blood vessels. He is thrown to the ground and temporarily loses consciousness. When he awakens a few minutes later, his leg is bleeding profusely. He yells for help, but there is no reply.

The patient slows the bleeding somewhat by tying his shirt around his leg and manages, with great effort, to get to a rural roadside where he again loses consciousness. A driver finds him a few hours later, pulls him into his car, and takes him to the hospital.

When he arrives, Patient E is immediately treated for hypovolemic shock that resulted from extensive blood loss. He is taken to surgery, and his leg is repaired. Although the patient's blood pressure increases and his pulse rate decreases with appropriate fluid replacement and cessation of blood loss, his urine output remains low.

Two days after admission, Patient E's total urine output has been 320 mL, with an average specific gravity of 1.013. His blood pressure is 150/95 mm Hg (an increase from his previous average of 125/80 mm Hg). His pulse is 90 beats per minute, and his respirations are 18 breaths per minute. He is complaining of nausea, which seems unrelated to the administration of his pain medication. Significant blood tests reveal a BUN of 48 mg/dL and elevations in serum creatinine and potassium. Urinalysis results are consistent with renal failure findings. A diagnosis of acute renal failure secondary to prolonged hypovolemic shock is made. Patient E's physicians administer trial doses of mannitol and furosemide (Lasix) in an effort to produce diuresis. Because no increase in urine results from this therapy, further diuretics are not employed. However, his physicians hope to manage him conservatively and avoid dialysis, if possible.

Patient F is a White woman, 35 years of age, with a history of frequent urinary tract infections who now presents with gross hematuria. On physical exam, she is thin with a palpably enlarged right kidney. On questioning, she states that her mother had some sort of "cyst disease" of the kidney. She further states that her mother died of a heart attack several years ago, at 62 years of age. A renal ultrasound reveals numerous large, fluid-filled cysts on the right kidney and several cysts on the left kidney. Further imaging also reveals a fluid-filled cyst visible on the liver. A consultation with nephrology and a geneticist results in a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).

ADPKD is the fourth leading cause and the leading genetic cause of ESRD, and the most common life-threatening hereditary disease in the United States. ADPKD occurs in approximately one of every 1,000 live births. Children of affected individuals have a 50% chance of inheriting the disorder.

Patients with ADPKD can present with flank pain, hematuria, and/or palpable kidneys. Individuals with a family history are considered to have ADPKD if ultrasound reveals two unilateral or bilateral cysts in patients 15 to 30 years of age, two or more cysts in each kidney for patients 30 to 59 years of age, or four or more cysts in each kidney in patients older than 60 years of age. For patients with no known genetic risks (either from family history or genetic testing), the diagnostic criteria are three or more unilateral or bilateral cysts in patients 15 to 39 years of age or two or more cysts in each kidney for patients 30 to 59 years of age.

While the predominant clinical feature of ADPKD is renal disease (50% of affected patients have ESRD by 60 years of age), extrarenal manifestations are also common, which suggests that the disease may involve a generalized collagen disorder. As well as liver and pancreatic cysts, patients have an increased risk of cerebral hemorrhage due to intracranial aneurysms, cardiac valve abnormalities, aortic root dilation, and abdominal hernias.