Renal System

 

Pathophysiologic manifestations
	Capillary pressure
	Interstitial fluid colloid osmotic pressure
	Plasma colloid pressure
	Structural variations
	Obstruction
Disorders
	Acute renal failure
	Chronic renal failure
	Glomerulonephritis
	Hypospadias and epispadias
	Nephrotic syndrome
	Neurogenic bladder
	Polycystic kidney disease
	Renal agenesis
	Renal calculi
	Vesicoureteral reflux

 

T he components of the renal system are the kidneys, ureters, bladder, and urethra. The kidneys, located retroperitoneally in the lumbar area, produce and excrete urine to maintain homeostasis. They regulate the volume, electrolyte concentration, and acid-base balance of body fluids; detoxify the blood and eliminate wastes; regulate blood pressure; and support red blood cell production (erythropoiesis). The ureters are tubes that extend from the kidneys to the bladder; their only function is to transport urine to the bladder. The bladder is a muscular bag that serves as reservoir for urine until it leaves the body through the urethra.

PATHOPHYSIOLOGIC MANIFESTATIONS

Wastes are eliminated from the body by urine formation ― glomerular filtration, tubular reabsorption, and tubular secretion ― and excretion. Glomerular filtration is the process of filtering the blood as it flows through the kidneys. The glomerulus of the renal tubule filters plasma and then reabsorbs the filtrate. Glomerular function depends on the permeability of the capillary walls, vascular pressure, and filtration pressure. The normal glomerular filtration rate (GFR) is about 120 ml/min. To prevent too much fluid from leaving the vascular system, tubular reabsorption opposes capillary filtration. Reabsorption takes place as capillary filtration progresses. When fluid filters through the capillaries, albumin, which doesn't pass through capillary walls, remains behind. As the albumin concentration inside the capillaries increases, the capillaries begin to draw water back in by osmosis. This osmotic force controls the quantities of water and diffusible solutes that enter and leave the capillaries.

Anything that affects filtration or reabsorption affects total filtration effort. Capillary pressure and interstitial fluid colloid osmotic pressure affect filtration. Interstitial fluid pressure and plasma colloid osmotic pressure affect reabsorption.

Altered renal perfusion; renal disease affecting the vessels, glomeruli, or tubules; or obstruction to urine flow can slow the GFR. The results are retention of nitrogenous wastes (azotemia), such as blood urea nitrogen and creatinine, which are consequent to acute renal failure.

Capillary pressure

The renal arteries branch into five segmental arteries, which supply different areas of the kidneys. The segmental arteries then branch into several divisions from which the afferent arterioles and vasa recta arise. Renal veins follow a similar branching pattern ― characterized by stellate vessels and segmental branches ― and empty into the inferior vena cava. The tubular system receives its blood supply from a peritubular capillary network. The ureteral veins follow the arteries and drain into the renal vein. The bladder receives blood through vesical arteries. Vesical veins unite to form the pudendal plexus, which empties into the iliac veins. A rich lymphatic system drains the renal cortex, kidneys, ureters, and bladder.

Capillary pressure reflects mean arterial pressure (MAP). Increased MAP increases capillary pressure, which in turn increases the GFR. When MAP decreases, so do capillary pressure and GFR. Autoregulation of afferent and efferent arterioles minimizes and controls changes in capillary pressure, unless MAP exceeds 180 mm Hg or is less than 80 mm Hg.

Sympathetic branches from the celiac plexus, upper lumbar splanchnic and thoracic nerves, and intermesenteric and superior hypogastric plexuses, which surround the kidneys, innervate the kidneys. Similar numbers of sympathetic and parasympathetic nerves from the renal plexus, superior hypogastric plexus, and intermesenteric plexus innervate the ureters. Nerves that arise from the inferior hypogastric plexus innervate the bladder. The parasympathetic nerve supply to the bladder controls urination.

Increased sympathetic activity and angiotensin II constrict afferent and efferent arterioles, decreasing the capillary pressure. Because these changes affect both the afferent and efferent arterioles, they have no net effect on GFR.

Inadequate renal perfusion accounts for 40% to 80% of acute renal failure. Volume loss (as with GI hemorrhage, burns, diarrhea, and diuretic use), volume sequestration (as in pancreatitis, peritonitis, and rhabdomyolysis), or decreased effective circulating volume (as in cardiogenic shock and sepsis) may reduce circulating blood volume. Decreased cardiac output due to peripheral vasodilatation (by sepsis or drugs) or profound renal vasoconstriction (as in severe cardiac failure, hepatorenal syndrome, or with such drugs as nonsteroidal anti-inflammatories [NSAIDs]) also diminish renal perfusion.

Hypovolemia causes a decrease in MAP that triggers a series of neural and humoral responses: activation of the sympathetic nervous system and renin-angiotensin-aldosterone system, and release of arginine vasopressin. Prostaglandin-mediated relaxation of afferent arterioles and angiotensin II�mediated constriction of efferent arterioles maintain GFR. GRF decreases steeply if MAP decreases to less than 80 mm Hg. Drugs that block prostaglandin production (such as NSAIDs) can cause severe vasoconstriction and acute renal failure during hypotension.

Prolonged renal hypoperfusion causes acute tubular necrosis. Processes involving large renal vessels, microvasculature, glomeruli, or tubular interstitium cause intrinsic renal disease. Emboli or thrombi, aortic dissection, or vasculitis can occlude renal arteries. Cholesterol-rich atheroemboli can occur spontaneously or follow aortic instrumentation. If they lodge in medium and small renal arteries, they trigger an eosinophil-rich inflammatory reaction.

Interstitial fluid colloid osmotic pressure

Few plasma proteins and red blood cells are filtered out of the glomeruli, so interstitial fluid colloid osmotic pressure (the force of albumin in the interstitial fluid) remains low. Large quantities of plasma protein flow through glomerular capillaries. Size and surface charge keep albumin, globulin, and other large proteins from crossing the glomerular wall. Smaller proteins leave the glomerulus but are absorbed by the proximal tubule.

Injury to the glomeruli or peritubular capillaries can increase interstitial fluid colloid osmotic pressure, drawing fluid out of the glomerulus and the peritubular capillaries. Swelling and edema occur in Bowman's space and the interstitial space surrounding the tubule. Increased interstitial fluid pressure opposes glomerular filtration, causes collapse of the surrounding nephrons and peritubular capillaries, and leads to hypoxia and renal cell injury or death. When cells die, intracellular enzymes are released that stimulate immune and inflammatory reactions. This further contributes to swelling and edema.

A CLOSER LOOK AT THE GLOMERULUS The normal internal structures separating the capillary lumen and the urinary space in the glomerulus are shown. <center>  </center> Adapted with permission from Harrison's 14th edition. Principals of Internal Medicine . New York: McGraw Hill, 1998.

The resulting increase in interstitial fluid pressure can interfere with glomerular filtration and tubular reabsorption. Loss of glomerular filtration renders the kidney incapable of regulating blood volume and electrolyte composition. Diseases that damage the tubules cause tubular proteinuria because small proteins can move from capillaries into tubules.

Normal glomerular cells, which are endothelial in nature, form a barrier that holds cells and other particles back. The basement membrane typically traps larger proteins. The channels of the basement membrane are coated with glycoproteins that are rich in glutamate, aspartate, and sialic acid. This produces a negative charge barrier that impedes the passage of such anionic molecules as albumin. (See A closer look at the glomerulus ).

Glomerular disease disrupts the basement membrane, allowing large proteins to leak out. Damage to epithelial cells permits albumin leakage. Hypoalbuminemia, as in nephrotic syndrome, is the result of excessive urine loss, increased renal catabolism, and inadequate hepatic synthesis. Plasma oncotic pressure decreases, and edema results as fluid moves from capillaries into the interstitium. Consequent activation of the renin-angiotensin system, AVP, and sympathetic nervous system increases renal salt and water reabsorption, which further contributes to edema. The severity of edema is directly related to the degree of hypoalbuminemia, and is exacerbated by heart disease or peripheral vascular disease.

CONGENITAL NEPHROPATHIES AND UROPATHIES The following congenital conditions can affect kidney function: Renal hypoplasia ― the kidney is small due to a reduction in the number of normally developed nephrons, and it may be unilateral or bilateral Renal dysplasia ― the kidney is abnormally shaped, and the involved areas are nonfunctional Renal malrotation ― the kidney is positioned abnormally Ectopic kidney ― the kidney is located in the pelvic or thoracic area, causing reflux from the bladder into the ureters Horseshoe kidney ― the lower poles of the kidneys are fused by an isthmus Obstructive uropathy ― renal outlet obstruction due to abnormal vasculature, adhesions, kinks, or masses, usually causing hydronephrosis Ureterocele ― a cystic dilation of the intravesicular ureter associated with duplication of the ureter. From Hansen, M. Pathophysiology: Foundations of Disease and Clinical Interventions . Philadelphia: W.B. Saunders Company, 1998.

Plasma colloid pressure

Protein concentration of the plasma determines the plasma colloid pressure (the pulling force of albumin in the intravascular fluid), the major force on reabsorption of fluid into the capillaries. Plasma protein levels can decrease as a result of liver disease, protein loss in the urine, and protein malnutrition.

As oncotic pressure decreases, less fluid moves back into the capillaries and fluid begins to accumulate in the tubular and peritubular areas. Swelling around the tubule causes collapse of the tubule and peritubular capillaries, hypoxia, and death of the nephrons.

Diminished plasma oncotic pressure and urinary protein loss stimulate hepatic lipoprotein synthesis, and the resulting hyperlipedemia manifests as lipid bodies (fatty casts, oval fat bodies) in the urine. Metabolic disturbances result as other proteins are lost in the urine, including thyroxine-binding globulin, cholecalciferol-binding protein, transferrin, and metal-binding proteins. Urine losses of antithrombin III, decreased serum levels of proteins S and C, hyperfibrinogenemia, and enhanced platelet aggregation lead to a hypercoagulable state, as in nephrotic syndrome. Some patients also develop severe immunoglobulin G deficiency, which increases susceptibility to infection.

Structural variations

Variations in normal anatomic structure of the urinary tract occur in 10% to 15% of the total population and range from minor and easily correctable to lethal. Ectopic kidneys, which result if the embryonic kidneys do not ascend from the pelvis to the abdomen, function normally. If the embryonic kidneys fuse as they ascend, the single, U-shaped or horseshoe kidney causes no symptoms in about one third of affected persons. The most common problems associated with horseshoe kidneys include hydronephrosis, infection, and stone formation.

 

AGE ALERT Structural abnormalities of the renal system account for about 45% of the renal failure in children.

Urinary tract malformations are commonly associated with certain nonrenal anomalies. These characteristics include low-set and malformed ears, chromosomal disorders (especially trisomies 13 and 18), absent abdominal muscles, spinal cord and lower extremity anomalies, imperforate anus or genital deviation, Wilms' tumor, congenital ascites, cystic disease of the liver, and positive family history of renal disease (hereditary nephritis or cystic disease). (See Congenital nephropathies and uropathies .)

SOURCES OF URINARY FLOW OBSTRUCTION Shown are the major sites of urinary tract obstruction. <center>  </center> From Hansen, M. Pathophysiology: Foundations of Disease and Clinical Interventions . Philadelphia: W.B. Saunders Company, 1998.

Obstruction

Obstruction along the urinary tract causes urine to accumulate behind the source of interference, leading to infection or damage. (See Sources of urinary flow obstruction .) Obstructions may be congenital or acquired. Causes include tumors, stones (calculi), trauma, edema, pregnancy, benign prostatic hyperplasia or carcinoma, inflammation of the GI tract, and loss of ureteral peristaltic activity or bladder muscle function.

Consequences of obstruction depend on the location and whether it is unilateral or bilateral, partial or complete, and acute or chronic, as well as the cause. For example, obstruction of a ureter causes hydroureter, or an accumulation of urine within the ureter, which increases retrograde pressure to the renal pelvis and calyces. As urine accumulates in the renal collection system, hydronephrosis results. If the obstruction is complete and acute in nature, increasing pressure transmitted to the proximal tubule inhibits glomerular filtration. If GFR declines to zero, the result is renal failure.

Chronic partial obstruction compresses structures as urine accumulates and the papilla and medulla infarct. The kidneys initially increase in size, but progressive atrophy follows, with eventual loss of renal mass. The underlying tubular damage decreases the kidney's ability to conserve sodium and water and excrete hydrogen ions and potassium; sodium and bicarbonate are wasted. Urine volume is excessive, even though GFR has declined. The result is an increased risk for dehydration and metabolic acidosis.

Tubular obstruction, caused by renal calculi or scarring from repeated infection, can increase interstitial fluid pressure. As fluid accumulates in the nephron, it backs up into Bowman's capsule and space. If the obstruction is unrelieved, nephrons and capillaries collapse, and renal damage is irreversible. The papillae, which are the final site of urine concentration, are particularly affected.

Relief of the obstruction is usually followed by copious diuresis of sodium and water retained during the period of obstruction, and a return to normal GFR. Excessive loss of sodium and water (more than 10 L/day) is uncommon. If GFR doesn't recover quickly, diuresis may not be significant after relief of the obstruction.

Unresolved obstruction can result in infection or even renal failure. Obstructions below the bladder cause urine to accumulate, forming a medium for bacterial growth.

 

AGE ALERT Urinary tract infections are most common in girls aged 7 to 11 years. This is a result of bacteria ascending the urethra.

Cystitis is an infection of the bladder that results in mucosal inflammation and congestion. The detrusor muscle becomes hyperactive, decreasing bladder capacity and leading to reflux into the ureters. This transient reflux can cause acute or chronic pyelonephritis if bacteria ascend to the kidney.

Bilateral obstruction not relieved within 1 week of onset causes acute or chronic renal failure. Chronic renal failure progresses over weeks to months without symptoms until 90% of renal function is lost.

DISORDERS

Renal disorders include acute and chronic renal failure, glomerulonephritis, hypospadias and epispadias, nephrotic syndrome, neurogenic bladder, polycystic kidney, renal agenesis, renal calculi, and vesicoureteral reflux.

Acute renal failure

Acute renal failure, the sudden interruption of renal function, can be caused by obstruction, poor circulation, or underlying kidney disease. Whether prerenal, intrarenal, or postrenal, it usually passes through three distinct phases: oliguric, diuretic, and recovery. About 5% of all hospitalized patients develop acute renal failure. The condition is usually reversible with treatment, but if not treated, it may progress to end-stage renal disease, prerenal azotemia, and death.

Causes

Acute renal failure may be prerenal, intrarenal, or postrenal. Causes of prerenal failure include:

• arrhythmias
• cardiac tamponade
• cardiogenic shock
• heart failure
• myocardial infarction
• burns
• dehydration
• diuretic overuse
• hemorrhage
• hypovolemic shock
• trauma
• antihypertensive drugs
• sepsis
• arterial embolism
• arterial or venous thrombosis
• tumor
• disseminated intravascular coagulation
• eclampsia
• malignant hypertension
• vasculitis.

Causes of intrarenal failure include:

• poorly treated prerenal failure
• nephrotoxins
• obstetric complications
• crush injuries
• myopathy
• transfusion reaction
• acute glomerulonephritis
• acute interstitial nephritis
• acute pyelonephritis
• bilateral renal vein thrombosis
• malignant nephrosclerosis
• papillary necrosis
• polyarteritis nodosa
• renal myeloma
• sickle cell disease
• systemic lupus erythematosus
• vasculitis.

Causes of postrenal failure include:

• bladder obstruction
• ureteral obstruction
• urethral obstruction.

Pathophysiology

The pathophysiology of prerenal, intrarenal, and postrenal failure differ.

Prerenal failure. Prerenal failure ensues when a condition that diminishes blood flow to the kidneys leads to hypoperfusion. Examples include hypovolemia, hypotension, vasoconstriction, or inadequate cardiac output. Azotemia (excess nitrogenous waste products in the blood) develops in 40% to 80% of all cases of acute renal failure.

When renal blood flow is interrupted, so is oxygen delivery. The ensuing hypoxemia and ischemia can rapidly and irreversibly damage the kidney. The tubules are most susceptible to the effects of hypoxemia.

Azotemia is a consequence of renal hypoperfusion. The impaired blood flow results in decreased glomerular filtration rate (GFR) and increased tubular reabsorption of sodium and water. A decrease in GFR causes electrolyte imbalance and metabolic acidosis. Usually, restoring renal blood flow and glomerular filtration reverses azotemia.

Intrarenal failure. Intrarenal failure, also called intrinsic or parenchymal renal failure, results from damage to the filtering structures of the kidneys. Causes of intrarenal failure are classified as nephrotoxic, inflammatory, or ischemic. When the damage is caused by nephrotoxicity or inflammation, the delicate layer under the epithelium (the basement membrane) becomes irreparably damaged, often leading to chronic renal failure. Severe or prolonged lack of blood flow by ischemia may lead to renal damage (ischemic parenchymal injury) and excess nitrogen in the blood (intrinsic renal azotemia).

Acute tubular necrosis, the precursor to intrarenal failure, can result from ischemic damage to renal parenchyma during unrecognized or poorly treated prerenal failure; or from obstetric complications, such as eclampsia, postpartum renal failure, septic abortion, or uterine hemorrhage.

The fluid loss causes hypotension, which leads to ischemia. The ischemic tissue generates toxic oxygen-free radicals, which cause swelling, injury, and necrosis.

Another cause of acute failure is the use of nephrotoxins, including analgesics, anesthetics, heavy metals, radiographic contrast media, organic solvents, and antimicrobials, particularly aminoglycoside antibiotics. These drugs accumulate in the renal cortex, causing renal failure that manifests well after treatment or other toxin exposure. The necrosis caused by nephrotoxins tends to be uniform and limited to the proximal tubules, whereas ischemia necrosis tends to be patchy and distributed along various parts of the nephron.

Postrenal failure. Bilateral obstruction of urine outflow leads to postrenal failure. The cause may be in the bladder, ureters, or urethra.

Bladder obstruction can result from:

• anticholinergic drugs
• autonomic nerve dysfunction
• infection
• tumors.

Ureteral obstructions, which restrict blood flow from kidneys to bladder, can result from:

• blood clots
• calculi
• edema or inflammation
• necrotic renal papillae
• retroperitoneal fibrosis or hemorrhage
• surgery (accidental ligation)
• tumor or uric acid crystals.

Urethral obstruction can be the result of prostatic hyperplasia, tumor, or strictures.

The three types of acute renal failure (prerenal, intrarenal, or postrenal) usually pass through three distinct phases: oliguric, diuretic, and recovery.

Oliguric phase. Oliguria may be the result of one or several factors. Necrosis of the tubules can cause sloughing of cells, cast formations, and ischemic edema. The resulting tubular obstruction causes a retrograde increase in pressure and a decrease in GFR. Renal failure can occur within 24 hours from this effect. Glomerular filtration may remain normal in some cases of renal failure, but tubular reabsorption of filtrate may be accelerated. In this instance, ischemia may increase tubular permeability and cause backleak. Another concept is that intrarenal release of angiotensin II or redistribution of blood flow from the cortex to the medulla may constrict the afferent arterioles, increasing glomerular permeability and decreasing GFR.

Urine output may remain at less than 30 mL/hour or 400 mL/day for a few days to weeks. Before damage occurs, the kidneys respond to decreased blood flow by conserving sodium and water.

Damage impairs the kidney's ability to conserve sodium. Fluid (water) volume excess, azotemia (elevated serum levels of urea, creatinine, and uric acid), and electrolyte imbalance occur. Ischemic or toxic injury leads to the release of mediators and intrarenal vasoconstriction. Medullary hypoxia results in the swelling of tubular and endothelial cells, adherence of neutrophils to capillaries and venules, and inappropriate platelet activation. Increasing ischemia and vasoconstriction further limit perfusion.

Injured cells lose polarity, and the ensuing disruption of tight junctions between the cells promotes backleak of filtrate. Ischemia impairs the function of energy-dependent membrane pumps, and calcium accumulates in the cells. This excess calcium further stimulates vasoconstriction and activates proteases and other enzymes. Untreated prerenal oliguria may lead to acute tubular necrosis.

Diuretic phase. As the kidneys become unable to conserve sodium and water, the diuretic phase, marked by increased urine secretion of more than 400 ml/24 hours, ensues. GFR may be normal or increased, but tubular support mechanisms are abnormal. Excretion of dilute urine causes dehydration and electrolyte imbalances. High blood urea nitrogen (BUN) levels produce osmotic diuresis and consequent deficits of potassium, sodium, and water.

Recovery phase. If the cause of the diuresis is corrected, azotemia gradually disappears and recovery occurs. The diuretic phase may last days or weeks. The recovery phase is a gradual return to normal or near-normal renal function over 3 to 12 months.

 

AGE ALERT Even with treatment, the elderly patient is particularly susceptible to volume overload, precipitating acute pulmonary edema, hypertensive crisis, hyperkalemia, and infection.

Renal failure affects many of the body processes. Metabolic acidosis may be the result of decreased excretion of hydrogen ions. Anemia occurs from erythropoietinemia, glomerular filtration of erythrocytes, or bleeding associated with platelet dysfunction. Sepsis is also common because of decreased white blood cell�mediated immunity. Heart failure can result because of fluid overload and anemia, which cause additional workload to the heart. Anemia also causes tissue hypoxia, which then stimulates increased ventilation and work of breathing. Respiratory compensation for metabolic acidosis has a similar effect on the respiratory system. Abnormalities in quantities or function of anticoagulant proteins, coagulation factor, platelet, or endothelial mediators result in a hypercoagulable state. This results in bleeding or clotting difficulties. Altered mental status and peripheral sensation are believed to be due to effects on the highly sensitive cells of nerves secondary to retained toxins, hypoxia, electrolyte imbalance, and acidosis. The hypermetabolic state induced by this critical illness promotes tissue catabolism.

Signs and symptoms

Signs and symptoms of acute renal failure include:

• oliguria due to decreased GFR
• tachycardia due to hypotension
• hypotension due to hypovolemia
• dry mucous membranes due to stimulation of the sympathetic nervous system
• flat neck veins due to hypovolemia
• lethargy due to altered cerebral perfusion
• cool, clammy skin due to decreased cardiac output and heart failure.

Progressive symptoms include:

• edema related to fluid retention
• confusion due to altered cerebral perfusion and azotemia
• GI symptoms due to altered metabolic status
• crackles on auscultation due to fluid in the lungs
• infection due to altered immune response
• seizures and coma related to alteration in consciousness
• hematuria, petechiae, and ecchymosis related to bleeding abnormalities.

Complications

Complications of acute renal failure may include:

• chronic renal failure
• ischemic parenchymal injury
• intrinsic renal azotemia
• electrolyte imbalance
• metabolic acidosis
• pulmonary edema
• hypertensive crisis
• infection.

Diagnosis

Diagnosis of acute renal failure is based on the following results:

• blood studies showing elevated BUN, serum creatinine, and potassium levels; decreased bicarbonate level, hematocrit, and hemoglobin; and acid pH
• urine studies showing casts, cellular debris, and decreased specific gravity; in glomerular diseases, proteinuria and urine osmolality close to serum osmolality; sodium level less than 20 mEq/L if oliguria results from decreased perfusion, and more than 40 mEq/L if cause is intrarenal
• creatinine clearance test measuring GFR and reflecting the number of remaining functioning nephrons
• electrocardiogram (ECG) showing tall, peaked T waves; widening QRS complex; and disappearing P waves if hyperkalemia is present
• ultrasonography, plain films of the abdomen, kidney-ureter-bladder radiography, excretory urography, renal scan, retrograde pyelography, computed tomographic scans, and nephrotomography.

Treatment

Treatment for acute renal failure includes:

• high-calorie diet that's low in protein, sodium, and potassium to meet metabolic needs
• I.V. therapy to maintain and correct fluid and electrolyte balance
• fluid restriction to minimize edema
• diuretic therapy to treat oliguric phase
• sodium polystyrene sulfonate (Kayexalate) by mouth or enema to reverse hyperkalemia with mild hyperkalemic symptoms (malaise, loss of appetite, muscle weakness)
• hypertonic glucose, insulin, and sodium bicarbonate I.V.― for more severe hyperkalemic symptoms (numbness and tingling and ECG changes)
• hemodialysis to correct electrolyte and fluid imbalances
• peritoneal dialysis to correct electrolyte and fluid imbalances.

Chronic renal failure

Chronic renal failure is usually the end result of gradual tissue destruction and loss of kidney function. It can also result from a rapidly progressing disease of sudden onset that destroys the nephrons and causes irreversible kidney damage.

Few symptoms develop until less than 25% of glomerular filtration remains. The normal parenchyma then deteriorates rapidly, and symptoms worsen as renal function decreases. This syndrome is fatal without treatment, but maintenance on dialysis or a kidney transplant can sustain life.

Causes

Chronic renal failure may be caused by:

• chronic glomerular disease (glomerulonephritis)
• chronic infection (such as chronic pyelonephritis and tuberculosis)
• congenital anomalies (polycystic kidney disease)
• vascular disease (hypertension, nephrosclerosis)
• obstruction (kidney stones)
• collagen disease (lupus erythematosus)
• nephrotoxic agents (long-term aminoglycoside therapy)
• endocrine disease (diabetic neuropathy).

Pathophysiology

Chronic renal failure often progresses through four stages. Reduced renal reserve shows a glomerular filtration rate (GFR) of 35% to 50% of normal; renal insufficiency has a GFR of 20% to 35% of normal; renal failure has a GFR of 20% to 25% of normal; and end-stage renal disease has a GFR less than 20% of normal.

Nephron damage is progressive; damaged nephrons can't function and don't recover. The kidneys can maintain relatively normal function until about 75% of the nephrons are nonfunctional. Surviving nephrons hypertrophy and increase their rate of filtration, reabsorption, and secretion. Compensatory excretion continues as GFR diminishes.

Urine may contain abnormal amounts of protein and red (RBCs) and white blood cells or casts, the major end products of excretion remain essentially normal, and nephron loss becomes significant. As GFR decreases, plasma creatinine levels increase proportionately without regulatory adjustment. As sodium delivery to the nephron increases, less is reabsorbed, and sodium deficits and volume depletion follow. The kidney becomes incapable of concentrating and diluting urine.

If tubular interstitial disease is the cause of chronic renal failure, primary damage to the tubules ― the medullary portion of the nephron ― precedes failure, as do such problems as renal tubular acidosis, salt wasting, and difficulty diluting and concentrating urine. If vascular or glomerular damage is the primary cause, proteinuria, hematuria, and nephrotic syndrome are more prominent.

Changes in acid-base balance affect phosphorus and calcium balance. Renal phosphate excretion and 1,25(OH) ₂ vitamin D ₃ synthesis are diminished. Hypocalcemia results in secondary hypoparathyroidism, diminished GFR, and progressive hyperphosphatemia, hypocalcemia, and dissolution of bone. In early renal insufficiency, acid excretion and phosphate reabsorption increase to maintain normal pH. When GFR decreases by 30% to 40%, progressive metabolic acidosis ensues and tubular secretion of potassium increases. Total-body potassium levels may increase to life-threatening levels requiring dialysis.

In glomerulosclerosis, distortion of filtration slits and erosion of the glomerular epithelial cells lead to increased fluid transport across the glomerular wall. Large proteins traverse the slits but become trapped in glomerular basement membranes, obstructing the glomerular capillaries. Epithelial and endothelial injury cause proteinuria. Mesangial-cell proliferation, increased production of extracellular matrix, and intraglomerular coagulation cause the sclerosis.

Tubulointerstitial injury occurs from toxic or ischemic tubular damage, as with acute tubular necrosis. Debris and calcium deposits obstruct the tubules. The resulting defective tubular transport is associated with interstitial edema, leukocyte infiltration, and tubular necrosis. Vascular injury causes diffuse or focal ischemia of renal parenchyma, associated with thickening, fibrosis, or focal lesions of renal blood vessels. Decreased blood flow then leads to tubular atrophy, interstitial fibrosis, and functional disruption of glomerular filtration, medullary gradients, and concentration.

The structural changes trigger an inflammatory response. Fibrin deposits begin to form around the interstitium. Microaneurysms result from vascular wall damage and increased pressure secondary to obstruction or hypertension. Eventual loss of the nephron triggers compensatory hyperfunction of uninjured nephrons, which initiates a positive-feedback loop of increasing vulnerability.

Eventually, the healthy glomeruli are so overburdened that they become sclerotic, stiff, and necrotic. Toxins accumulate and potentially fatal changes ensue in all major organ systems.

Extrarenal consequences. Physiologic changes affect more than one system, and the presence and severity of manifestations depend on the duration of renal failure and its response to treatment. In some fluid and electrolyte imbalances, the kidneys can't retain salt, and hyponatremia results. Dry mouth, fatigue, nausea, hypotension, loss of skin turgor, and listlessness can progress to somnolence and confusion. Later, as the number of functioning nephrons decreases, so does the capacity to excrete sodium and potassium. Sodium retention leads to fluid overload and edema; the potassium overload leads to muscle irritability and weakness, and life-threatening cardiac arrhythmias.

As the cardiovascular system becomes involved, hypertension occurs, and distant heart sounds may be auscultated if pericardial effusion occurs. Bibasilar crackles and peripheral edema reflect cardiac failure.

Pulmonary changes include reduced macrophage activity and increasing susceptibility to infection. Decreased lung sounds in areas of consolidation reflect the presence of pneumonia. As the pleurae become more involved, the patient may experience pleuritic pain and friction rubs.

The GI mucosa becomes inflamed and ulcerated, and gums may also be ulcerated and bleeding. Stomatitis, uremic fetor (an ammonia smell to the breath), hiccups, peptic ulcer, and pancreatitis in end-stage renal failure are believed to be due to retention of metabolic acids and other metabolic waste products. Malnutrition may be secondary to anorexia, malaise, and reduced dietary intake of protein. The reduced protein intake also affects capillary fragility, and results in decreased immune functioning and poor wound healing.

Normochromic normocytic anemia and platelet disorders with prolonged bleeding time ensue as diminished erythropoietin secretion leads to reduced RBC production in the bone marrow. Uremic toxins associated with chronic renal failure shorten RBC survival time. The patient experiences lethargy and dizziness.

Demineralization of the bone (renal osteodystrophy) manifested by bone pain and pathologic fractures is due to several factors:

• decreased renal activation of vitamin D, decreasing absorption of dietary calcium
• retention of phosphate, increasing urinary loss of calcium
• increased circulation of parathyroid hormone due to decreased urinary excretion.

The skin acquires a grayish-yellow tint as urine pigments (urochromes) accumulate. Inflammatory mediators released by retained toxins in the skin cause pruritus. Uric acid and other substances in the sweat crystallize and accumulate on the skin as uremic frost. High plasma calcium levels are also associated with pruritus.

Restless leg syndrome (abnormal sensation and spontaneous movement of the feet and lower legs), muscle weakness, and decreased deep tendon reflexes are believed to result from the effect of toxins on the nervous system.

Chronic renal failure increases the risk for death from infection. This is related to suppression of cell-mediated immunity and a reduction in the number and function of lymphocytes and phagocytes.

All hormone levels are impaired, in both excretion and activation. Females may be anovulatory, amenorrheic, or unable to carry pregnancy to full term. Males tend to have decreased sperm counts and impotence.

Signs and symptoms

Signs and symptoms of chronic renal failure include:

• hypervolemia due to sodium retention
• hypocalcemia and hyperkalemia due to electrolyte imbalance
• azotemia due to retention of nitrogenous wastes
• metabolic acidosis due to loss of bicarbonate
• bone and muscle pain and fractures caused by calcium-phosphorus imbalance and consequent parathyroid malfunction
• peripheral neuropathy due to accumulation of toxins
• dry mouth, fatigue, and nausea due to hyponatremia
• hypotension due to sodium loss
• altered mental state due to hyponatremia and toxin accumulation
• irregular pulses due to hyperkalemia
• hypertension due to fluid overload
• gum sores and bleeding due to coagulopathies
• yellow-bronze skin due to altered metabolic processes
• dry, scaly skin and severe itching due to uremic frost
• muscle cramps and twitching, including cardiac irritability, due to hyperkalemia
• Kussmaul's respirations due to metabolic acidosis

 

AGE ALERT Growth retardation in children occurs from endocrine abnormalities induced by renal failure. Impaired bone growth and bowlegs in children are also due to rickets.

• infertility, decreased libido, amenorrhea, and impotence due to endocrine disturbances
• GI bleeding, hemorrhage, and bruising due to thrombocytopenia and platelet defects
• pain, burning, and itching in legs and feet associated with peripheral neuropathy
• infection related to decreased macrophage activity.

Complications

Possible complications of chronic renal failure include:

• anemia
• peripheral neuropathy
• cardiopulmonary complications
• GI complications
• sexual dysfunction
• skeletal defects
• paresthesias
• motor nerve dysfunction, such as foot drop and flaccid paralysis
• pathologic fractures.

Diagnosis

Blood study results that help diagnose chronic renal failure include:

• decreased arterial pH and bicarbonate, low hemoglobin and hematocrit
• decreased RBC survival time, mild thrombocytopenia, platelet defects
• elevated blood urea nitrogen, serum creatinine, sodium, and potassium levels
• increased aldosterone secretion related to increased renin production
• hyperglycemia (a sign of impaired carbohydrate metabolism)
• hypertriglyceridemia and low levels of high-density lipoprotein.

Urinalysis results aiding in diagnosis include:

• specific gravity fixed at 1.010
• proteinuria, glycosuria, RBCs, leukocytes, casts, or crystals, depending on the cause.

Other study results used to diagnose chronic renal failure include:

• reduced kidney size on kidney-ureter-bladder radiography, excretory urography, nephrotomography, renal scan, or renal arteriography
• renal biopsy to identify underlying disease
• EEG to identify metabolic encephalopathy.

Treatment

Treatment of chronic renal failure involves:

• low-protein diet, to limit accumulation of end products of protein metabolism that the kidneys can't excrete
• high-protein diet for patients on continuous peritoneal dialysis
• high-calorie diet, to prevent ketoacidosis and tissue atrophy
• sodium and potassium restrictions, to prevent elevated levels
• fluid restrictions, to maintain fluid balance
• loop diuretics, such as furosemide (Lasix), to maintain fluid balance
• digitalis glycosides, such as digoxin, to mobilize fluids causing edema
• calcium carbonate (Caltrate) or calcium acetate (PhosLo), to treat renal osteodystrophy by binding phosphate and supplementing calcium
• transfusions, to treat anemia
• antihypertensives, to control blood pressure and edema
• antiemetics, to relieve nausea and vomiting
• cimetidine (Tagamet) or rantidine (Zantac), to decrease gastric irritation
• methylcellulose or docusate, to prevent constipation
• iron and folate supplements or RBC transfusion for anemia
• synthetic erythropoietin, to stimulate the bone marrow to produce RBCs; supplemental iron, conjugated estrogens, and 1-desamino-8-D-arginine vasopressin (DDAVP), to combat hematologic effects
• antipruritics, such as trimeprazine (Temaril) or diphenhydramine (Benadryl), to relieve itching
• aluminum hydroxide gel (AlaGel), to reduce serum phosphate levels
• supplementary vitamins, particularly B and D, and essential amino acids
• dialysis for hyperkalemia and fluid imbalances
• oral or rectal administration of cation exchange resins, such as sodium polystyrene sulfonate (Kayexalate), and I.V. administration of calcium gluconate, sodium bicarbonate, 50% hypertonic glucose, and regular insulin, to reverse hyperkalemia
• emergency pericardiocentesis or surgery for cardiac tamponade
• intensive dialysis and thoracentesis, to relieve pulmonary edema and pleural effusion
• peritoneal or hemodialysis, to help control end-stage renal disease
• renal transplantation (often the treatment of choice if a donor is available).

Glomerulonephritis

Glomerulonephritis is a bilateral inflammation of the glomeruli, often following a streptococcal infection. Acute glomerulonephritis is also called acute poststreptococcal glomerulonephritis .

CHARACTERISTICS OF GLOMERULAR LESIONS The types of glomerular lesions and their characteristics are: Diffuse lesions: relatively uniform, involve most or all glomeruli (for example, glomerulonephritis) Focal lesions: involve only some glomeruli; others normal Segmental-local: involve only one part of the glomerulus Mesangial: deposits of immunoglobulins in mesangial matrix Membranous: thickening of glomerular capillary wall Proliferative lesions: increased number of glomerular cells Sclerotic lesions: glomerular scarring from previous glomerular injury Crescent lesions: accumulation of proliferating cells in Bowman's space. From Huether, S. Understanding Pathophysiology . St. Louis: Mosby, 1996.

 

AGE ALERT Acute glomerulonephritis is most common in boys aged 3 to 7 years, but it can occur at any age. Up to 95% of children and 70% of adults recover fully; the rest, especially elderly patients, may progress to chronic renal failure within months.

Rapidly progressive glomerulonephritis (RPGN) ― also called subacute, crescentic, or extracapillary glomerulonephritis ― most commonly occurs between the ages of 50 and 60. It may be idiopathic or associated with a proliferative glomerular disease, such as poststreptococcal glomerulonephritis.

 

AGE ALERT Goodpasture's syndrome, a type of rapidly progressive glomerulonephritis, is rare, but occurs most frequently in men aged 20 to 30 years.

Chronic glomerulonephritis is a slowly progressive disease characterized by inflammation, sclerosis, scarring, and, eventually, renal failure. It usually remains undetected until the progressive phase, which is usually irreversible.

Causes

Causes of acute and RPGN include:

• streptococcal infection of the respiratory tract
• impetigo
• immunoglobulin A (IgA) nephropathy (Berger's disease)
• lipoid nephrosis.

Chronic glomerulonephritis is caused by:

• membranoproliferative glomerulonephritis
• membranous glomerulopathy
• focal glomerulosclerosis
• RPGN
• poststreptococcal glomerulonephritis
• systemic lupus erythematosus
• Goodpasture's syndrome
• hemolytic uremic syndrome.

Pathophysiology

In nearly all types of glomerulonephritis, the epithelial or podocyte layer of the glomerular membrane is disturbed. This results in a loss of negative charge. (See Characteristics of glomerular lesions .)

Acute poststreptococcal glomerulonephritis results from the entrapment and collection of antigen-antibody complexes in the glomerular capillary membranes, after infection with a group A beta-hemolytic streptococcus. The antigens, which are endogenous or exogenous, stimulate the formation of antibodies. Circulating antigen-antibody complexes become lodged in the glomerular capillaries. (See Glomerulonephritis .) Glomerular injury occurs when the complexes initiate complement activation and the release of immunologic substances that lyse cells and increase membrane permeability. Antibody damage to basement membranes causes crescent formation. The severity of glomerular damage and renal insufficiency is related to the size, number, location (focal or diffuse), duration of exposure, and type of antigen-antibody complexes.

GLOMERULONEPHRITIS The immune complex depositions that occur in glomerulonephritis are shown. <center>  </center> From Hansen, M. Pathophysiology: Foundations of Disease and Clinical Interventions . Philadelphia: W.B. Saunders Company, 1998.

Antibody or antigen-antibody complexes in the glomerular capillary wall activate biochemical mediators of inflammation ― complement, leukocytes, and fibrin. Activated complement attracts neutrophils and monocytes, which release lysosomal enzymes that damage the glomerular cell walls and cause a proliferation of the extracellular matrix, affecting glomerular blood flow. Those events increase membrane permeability, which causes a loss of negative charge across the glomerular membrane as well as enhanced protein filtration.

Membrane damage leads to platelet aggregation, and platelet degranulation releases substances that increase glomerular permeability. Protein molecules and red blood cells (RBCs) can now pass into the urine, resulting in proteinuria or hematuria. Activation of the coagulation system leads to fibrin deposits in Bowman's space. The result is crescent formation and diminished renal blood flow and glomerular filtration rate (GFR). Glomerular bleeding causes acidic urine, which transforms hemoglobin to methemoglobin and results in brown urine without clots.

The inflammatory response decreases GFR, which causes fluid retention and decreased urine output, extracellular fluid volume expansion, and hypertension. Gross proteinuria is associated with nephrotic syndrome. After 10 to 20 years, renal insufficiency develops and is followed by nephrotic syndrome and end-stage renal failure.

Goodpasture's syndrome is an RPGN in which antibodies are produced against the pulmonary capillaries and glomerular basement membrane. Diffuse intracellular antibody proliferation in Bowman's space leads to a crescent-shaped structure that obliterates the space. The crescent is composed of fibrin and endothelial, mesangial, and phagocytic cells, which compress the glomerular capillaries, diminish blood flow, and cause extensive scarring of the glomeruli. GFR is reduced, and renal failure occurs within weeks or months.

IgA nephropathy, or Berger's disease, is usually idiopathic. Plasma IgA level is elevated, and IgA and inflammatory cells are deposited into Bowman's space. The result is sclerosis and fibrosis of the glomerulus and a reduced GFR.

Lipid nephrosis causes disruption of the capillary filtration membrane and loss of its negative charge. This increased permeability with resultant loss of protein leads to nephrotic syndrome.

Systemic diseases, such as hepatitis B virus, systemic lupus erythematosus, or solid malignant tumors, cause a membranous nephropathy. An inflammatory process causes thickening of the glomerular capillary wall. Increased permeability and proteinuria lead to nephrotic syndrome.

Sometimes the immune complement further damages the glomerular membrane. The damaged and inflamed glomeruli lose the ability to be selectively permeable so that RBCs and proteins filter through as GFR decreases. Uremic poisoning may result. Renal function may deteriorate, especially in adults with sporadic acute poststreptococcal glomerulonephritis, often in the form of glomerulosclerosis accompanied by hypertension. The more severe the disorder, the more likely the occurrence of complications. Hypervolemia leads to hypertension, resulting from either sodium and water retention (caused by the decreased GFR) or inappropriate renin release. The patient develops pulmonary edema and heart failure. (See Averting renal failure in glomerulonephritis .)

Signs and symptoms

Possible signs and symptoms of glomerulonephritis include:

• decreased urination or oliguria due to decreased GFR
• smoky or coffee-colored urine due to hematuria
• shortness of breath due to pulmonary edema
• dyspnea due to pulmonary edema
• orthopnea due to hypervolemia
• periorbital edema due to hypervolemia
• mild to severe hypertension due to sodium or water retention
• bibasilar crackles due to heart failure.

 

AGE ALERT An elderly patient with glomerulonephritis may report vague, nonspecific symptoms such as nausea, malaise, and arthralgia.

Complications

Possible complications of glomerulonephritis are:

• pulmonary edema
• heart failure
• sepsis
• renal failure
• severe hypertension
• cardiac hypertrophy.

Diagnosis

Blood study results that aid in diagnosis include:

• elevated electrolyte, blood urea nitrogen, and creatinine levels
• decreased serum protein level
• decreased hemoglobin in chronic glomerulonephritis
• elevated antistreptolysin-O titers in 80% of patients, elevated streptozyme and anti-DNAase B titers, low serum complement levels indicating recent streptococcal infection.

Urinalysis results that help diagnose glomerulonephritis include:

• RBCs, white blood cells, mixed cell casts, and protein indicating renal failure
• fibrin-degradation products and C3 protein.

 

AGE ALERT Significant proteinuria is not a common finding in an elderly patient.

Other results that help diagnose glomerulonephritis are:

• throat culture showing group A beta-hemolytic streptococcus
• bilateral kidney enlargement on kidney-ureter-bladder X-ray (acute glomerulonephritis)
• symmetric contraction with normal pelves and calyces (chronic glomerulonephritis) as seen on X-ray
• renal biopsy confirming the diagnosis or assessing renal tissue status.

AVERTING RENAL FAILURE IN GLOMERULONEPHRITIS Shown is a flowchart of pathophysiologic occurrences and the treatments that can alter the course of glomerulonephritis. <center>  </center>

Treatment

Treatment involves:

• treating the primary disease to alter immunologic cascade
• antibiotics for 7 to 10 days to treat infections contributing to ongoing antigen-antibody response
• anticoagulants to control fibrin crescent formation in RPGN
• bed rest to reduce metabolic demands
• fluid restrictions to decrease edema
• dietary sodium restriction to prevent fluid retention
• correction of electrolyte imbalances
• loop diuretics such as metolazone (Zaroxolyn) or furosemide (Lasix) to reduce extracellular fluid overload
• vasodilators such as hydralazine (Apresoline) or nifedipine (Procardia) to decrease hypertension
• dialysis or kidney transplantation for chronic glomerulonephritis
• corticosteroids to decrease antibody synthesis and suppress inflammatory response
• plasmapheresis in RPGN to suppress rebound antibody production, possibly combined with corticosteroids and cyclophosphamide (Cytoxan).

Hypospadias and epispadias

Among the most common birth defects, congenital anomalies of the ureter, bladder, and urethra occur in about 5% of all births. The abnormality may be obvious at birth or may go unrecognized until symptoms appear. Hypospadias is a congenital abnormality in which the opening of the urethra is misplaced to the perineal or scrotal region. The defect may be slight or extreme in nature, and it occurs in 1 of 300 live male births.

Epispadias occurs in 1 in 200,000 infant boys and 1 in 400,000 infant girls, and it is expressed in differing degrees. In males, the urethral opening is on the dorsal aspect of the penis. In females, a cleft along the ventral urethral opening extends to the bladder neck.

Causes

Hypospadias and epispadias may be caused by:

• congenital defect
• genetic factors.

Pathophysiology

In hypospadias, the urethral opening is on the ventral surface of the penis. (See Comparing hypospadias and epispadias .) A genetic factor is suspected in less severe cases. It's usually associated with a downward bowing of the penis (chordee), making normal urination with the penis elevated impossible. The ventral prepuce may be absent or defective, and the genitalia may be ambiguous. In the rare case of hypospadias in a female, the urethral opening is in the vagina, and vaginal discharge may be present.

Epispadias occurs more commonly in males than females and often accompanies bladder exstrophy, which is the absence of a portion of the lower abdominal and anterior bladder wall, with a portion of the posterior bladder wall through the deficit. In mild cases, the orifice is on the dorsum of the glans; in severe cases, on the dorsum of the penis. Affected females have a bifid (cleft into two parts) clitoris and a short, wide urethra. Total urinary incontinence occurs when the urethral opening is proximal to the sphincter.

Signs and symptoms

Signs and symptoms of hypospadias and epispadias include:

• displaced urethral opening
• altered voiding patterns due to displaced opening of the urethra
• chordee, or bending of the penis (in hypospadias)
• ejaculatory dysfunction due to displaced penile opening.

Complications

Possible complications are:

• UTI
• urinary obstruction.

COMPARING HYPOSPADIAS AND EPISPADIAS In hypospadias, the urethral opening is on the ventral surface of the penis or within the vagina. <center>  </center> In males with epispadias, a urethral opening occurs on the dorsal surface of the penis; in females, a fissure occurs on the upper wall of the urethra. <center>  </center>

Diagnosis

If sexual identification is questionable, diagnosis is based on:

• buccal smears and karotyping.

Treatment

Treatment may include:

• no treatment (for mild hypospadias in a asymptomatic patient)
• surgery, preferably before the child reaches school age (severe hypospadias)
• surgical repair in several stages, which is almost always necessary (epispadias).

Nephrotic syndrome

Marked proteinuria, hypoalbuminemia, hyperlipidemia, and edema characterize nephrotic syndrome. It results from a defect in the permeability of glomerular vessels. About 75% of the cases result from primary (idiopathic) glomerulonephritis. The prognosis is highly variable, depending on the underlying cause.

 

AGE ALERT Age has no part in the progression or prognosis of nephrotic syndrome. Primary nephrotic syndrome is found predominantly in the preschool child. The incidence peaks at ages 2 and 3 years, and it is rare after the age of 8.

Boys are more frequently affected with primary nephrotic syndrome than girls; the incidence is 3 per 100,000 children per year. Some forms of nephrotic syndrome may eventually progress to end-stage renal failure.

Causes

Causes of nephrotic syndrome include:

• lipid nephrosis (nil lesions)

 

AGE ALERT Lipid nephrosis is the main cause of nephrotic syndrome in children younger than 8 years.

• membranous glomerulonephritis

 

AGE ALERT Membranous glomerulonepritis is the most common lesion in adult idiopathic nephrotic syndrome.

• focal glomerulosclerosis
• membranoproliferative glomerulonephritis
• metabolic diseases, such as diabetes mellitus
• collagen-vascular disorders, such as systemic lupus erythematosus and periarteritis nodosa
• circulatory diseases, such as heart failure, sickle cell anemia, and renal vein thrombosis
• nephrotoxins, such as mercury, gold, and bismuth
• infections, such as tuberculosis and enteritis
• allergic reactions
• pregnancy
• hereditary nephritis
• neoplastic diseases, such as multiple myeloma.

Pathophysiology

In lipid nephrosis, the glomeruli appear normal by light microscopy, and some tubules may contain increased lipid deposits. Membranous glomerulonephritis is characterized by the appearance of immune complexes, seen as dense deposits in the glomerular basement membrane, and by the uniform thickening of the basement membrane. It eventually progresses to renal failure.

Focal glomerulosclerosis can develop spontaneously at any age, can occur after kidney transplantation, or may result from heroin injection. Ten percent of children and up to 20% of adults with nephrotic syndrome develop this condition. Lesions initially affect some of the deeper glomeruli, causing hyaline sclerosis. Involvement of the superficial glomeruli occurs later. These lesions usually cause slowly progressive deterioration in renal function, although remission may occur in children.

Membranoproliferative glomerulonephritis causes slowly progressive lesions in the subendothelial region of the basement membrane. This disorder may follow infection, particularly streptococcal infection, and occurs primarily in children and young adults.

Regardless of the cause, the injured glomerular filtration membrane allows the loss of plasma proteins, especially albumin and immunoglobulin. In addition, metabolic, biochemical, or physiochemical disturbances in the glomerular basement membrane result in the loss of negative charge as well as increased permeability to protein. Hypoalbuminemia results not only from urinary loss, but also from decreased hepatic synthesis of replacement albumin. Increased plasma concentration and low molecular weight accentuate albumin loss. Hypoalbuminemia stimulates the liver to synthesize lipoprotein, with consequent hyperlipidemia, and clotting factors. Decreased dietary intake, as with anorexia, malnutrition, or concomitant disease, further contributes to decreased levels of plasma albumin. Loss of immunoglobulin also increases susceptibility to infections.

Extensive proteinuria (more than 3.5 g/day) and a low serum albumin level, secondary to renal loss, lead to low serum colloid osmotic pressure and edema. The low serum albumin level also leads to hypovolemia and compensatory salt and water retention. Consequent hypertension may precipitate heart failure in compromised patients.

Signs and symptoms

Possible signs and symptoms of nephrotic syndrome include:

• periorbital edema, due to fluid overload
• mild to severe dependent edema of the ankles or sacrum
• orthostatic hypotension, due to fluid imbalance
• ascites, due to fluid imbalance
• swollen external genitalia, due to edema in dependent areas
• respiratory difficulty, due to pleural effusion
• anorexia, due to edema of intestinal mucosa
• pallor and shiny skin with prominent veins
• diarrhea, due to edema of intestinal mucosa
• frothy urine in children
• change in quality of hair, related to protein deficiency
• pneumonia, due to susceptibility of infections.

Complications

Possible complications include:

• malnutrition
• infection
• coagulation disorders
• thromboembolic vascular occlusion (especially in the lungs and legs)
• accelerated atherosclerosis
• hypochromic anemia, due to excessive urinary excretion of transferrin
• acute renal failure.

Diagnosis

Diagnosis is based on:

• consistent heavy proteinuria (24-hour protein more than 3.5 mg/dl)
• urinalysis showing hyaline, granular and waxy fatty casts, and oval fat bodies
• increased serum cholesterol, phospholipid (especially low-density and very low-density lipoproteins), and triglyceride levels, and decreased albumin levels
• renal biopsy for histologic identification of the lesion.

Treatment

Treatment includes:

• correction of underlying cause, if possible
• nutritious diet, including 0.6 g of protein/kg of body weight
• restricted sodium intake, to reduce edema
• diuretics, to diminish edema
• antibiotics, to treat infection
• 8-week course of a corticosteroid, such as prednisone (Deltasone), followed by maintenance therapy or a combination of prednisone and azathioprine (Imuran) or cyclophosphamide (Cytoxan)
• treatment for hyperlipidemia (frequently unsuccessful)
• paracentesis, for acites.

Neurogenic bladder

All types of bladder dysfunction caused by an interruption of normal bladder innervation are referred to as neurogenic bladder. Other names for this disorder include neuromuscular dysfunction of the lower urinary tract, neurologic bladder dysfunction, and neuropathic bladder. Neurogenic bladder can be hyperreflexic (hypertonic, spastic, or automatic) or flaccid (hypotonic, atonic, or autonomous).

Causes

Many factors can interrupt bladder innervation. Cerebral disorders causing neurogenic bladder include:

• cerebrovascular accident
• brain tumor (meningioma and glioma)
• Parkinson's disease
• multiple sclerosis
• dementia
• incontinence associated with aging.

Spinal cord disease or trauma can also cause neurogenic bladder, including:

• spinal stenosis causing cord compression
• arachnoiditis (inflammation of the membrane between the dura and pia mater) causing adhesions between membranes covering the cord
• cervical spondylosis
• spina bifida
• poliomyelitis
• myelopathies from hereditary or nutritional deficiencies
• tabes dorsalis (degeneration of the dorsal columns of the spinal cord)
• disorders of peripheral innervation, including autonomic neuropathies, due to endocrine disturbances such as diabetes mellitus (most common).

Other causes include:

• metabolic disturbances, such as hypothyroidism or uremia
• acute infectious diseases, such as Guillain-Barré syndrome or transverse myelitis (pathologic changes extending across the spinal cord)
• heavy metal toxicity
• chronic alcoholism
• collagen diseases, such as systemic lupus erythematosus
• vascular diseases, such as atherosclerosis
• distant effects of certain cancers, such as primary oat cell carcinoma of the lung
• herpes zoster
• sacral agenesis (absence of a completely formed sacrum).

TYPES OF NEUROGENIC BLADDER   NEURAL LESION TYPE CAUSE     Upper motor Uninhibited Lack of voluntary control in infancy Multiple sclerosis Reflex or automatic Spinal cord transection Cord tumors Multiple sclerosis Lower motor Autonomous Sacral cord trauma Tumors Herniated disk Abdominal surgery with transection of pelvic parasympathetic nerves Motor paralysis Lesions at levels S2, S3, S4 Poliomyelitis Trauma Tumors Sensory paralysis Posterior lumbar nerve roots Diabetes mellitus Tabes dorsalis From Huether, S. Understanding Pathophysiology . St. Louis: Mosby, 1996.

Pathophysiology

An upper motor neuron lesion (at or above T12) causes spastic neurogenic bladder, with spontaneous contractions of detrusor muscles, increased intravesical voiding pressure, bladder wall hypertrophy with trabeculation, and urinary sphincter spasms. The patient may experience small urine volume, incomplete emptying, and loss of voluntary control of voiding. Urinary retention also sets the stage for infection.

A lower motor neuron lesion (at or below S2 to S4) affects the spinal reflex that controls micturition. The result is a flaccid neurogenic bladder with decreased intravesical pressure, and bladder capacity, residual urine retention, and poor detrusor contraction. The bladder may not empty spontaneously. The patient experiences loss of both voluntary and involuntary control of urination. Lower motor neuron lesions lead to overflow incontinence. When sensory neurons are interrupted, the patient can't perceive the need to void.

Interruption of the efferent nerves at the cortical, or upper motor neuron, level results in loss of voluntary control. Higher centers also control micturition, and voiding may be incomplete. Sensory neuron interruption leads to dribbling and overflow incontinence. (See Types of neurogenic bladder .) Altered bladder sensation often makes symptoms difficult to discern.

Retention of urine contributes to renal calculi, as well as infection. Neurogenic bladder can lead to deterioration of renal function if not promptly diagnosed and treated.

Signs and symptoms

Possible signs and symptoms of neurogenic bladder include:

• some degree of incontinence, changes in initiation or interruption of micturition, inability to completely empty the bladder
• frequent urinary tract infections, due to urine retention
• hyperactive autonomic reflexes (autonomic dysreflexia) when the bladder is distended and the lesion is at upper thoracic or cervical level
• severe hypertension, bradycardia, and vasodilation (blotchy skin) above the level of the lesion
• piloerection and profuse sweating above the level of the lesion
• involuntary or frequent scanty urination without a feeling of bladder fullness, due to hyperreflexic neurogenic bladder
• spontaneous spasms (caused by voiding) of the arms and legs, due to hyperreflexic neurogenic bladder
• increased anal sphincter tone, due to hyperreflexic neurogenic bladder
• voiding and spontaneous contractions of the arms and legs, due to tactile stimulation of the abdomen, thighs, or genitalia
• overflow incontinence and diminished anal sphincter tone, due to flaccid neurogenic bladder
• greatly distended bladder without feeling of bladder fullness, due to sensory impairment.

Complications

Complications of neurogenic bladder may include:

• incontinence
• residual urine retention
• urinary tract infection
• calculus formation
• renal failure.

Diagnosis

The following studies may help diagnose neurogenic bladder:

• voiding cystourethrography, to evaluate bladder neck function, vesicoureteral reflux, and incontinence
• urodynamic studies, to evaluate how urine is stored in the bladder, how well the bladder empties urine, and the rate of movement of urine out of the bladder during voiding
• urine flow study (uroflow), to show diminished or impaired urine flow
• cystometry, to evaluate bladder nerve supply, detrusor muscle tone, and intravesical pressures during bladder filling and contraction
• urethral pressure profile, to determine urethral function with respect to length of the urethra and outlet pressure resistance
• sphincter electromyelography, to correlate neuromuscular function of the external sphincter with bladder muscle function during bladder filling and contraction, and to evaluate how well the bladder and urinary sphincter muscles work together
• videourodynamic studies, to correlate visual documentation of bladder function with pressure studies
• retrograde urethrography, to show strictures and diverticula.

Treatment

Treatment includes:

• intermittent self-catheterization, to empty the bladder
• anticholinergics and alpha-adrenergic stimulators for the patient with hyperreflexic neurogenic bladder, until intermittent self-catheterization is performed
• terazosin (Hytrin) and doxazosin (Cardura), to facilitate bladder emptying in neurogenic bladder
• propantheline (Pro-Banthine), methantheline, flavoxate (Urispas), dicyclomine (Bentyl), imipramine (Tofranil), and pseudoephedrine (Sudafed), to facilitate urine storage
• surgery, to correct structural impairment through transurethral resection of the bladder neck, urethral dilation, external sphincterotomy, or urinary diversion procedures
• implantation of an artificial urinary sphincter may be necessary if permanent incontinence follows surgery.

POLYCYSTIC KIDNEY This cross-sectional drawing shows multiple areas of cystic damage. Each indentation depicts a cyst. <center>  </center>

Polycystic kidney disease

Polycystic kidney disease is an inherited disorder characterized by multiple, bilateral, grapelike clusters of fluid-filled cysts that enlarge the kidneys, compressing and eventually replacing functioning renal tissue. (See Polycystic kidney .) The disease affects males and females equally and appears in two distinct forms. Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 1,000 to 1 in 3,000 persons and accounts for about 10% of end-stage renal disease in the United States. The rare infantile form causes stillbirth or early neonatal death. The adult form has an insidious onset but usually becomes obvious between the ages of 30 and 50; rarely, it remains asymptomatic until the patient is in his 70s.

 

AGE ALERT Renal deterioration is more gradual in adults than infants, but in both age groups, the disease progresses relentlessly to fatal uremia.

The prognosis in adults is extremely variable. Progression may be slow, even after symptoms of renal insufficiency appear. Once uremia symptoms develop, polycystic disease usually is fatal within 4 years, unless the patient receives dialysis. Three genetic variants of the autosomal dominant form have been identified (see below).

Causes

Polycystic kidney disease is inherited as:

• autosomal dominant trait (adult type)
• autosomal recessive trait (infantile type).

Pathophysiology

ADPKD occurs as ADPKD-1, mapped to the short arm of chromosome 16 and encoded for a 4,300�amino acid protein; ADPKD-2, mapped to the short arm of chromosome 4 with later onset of symptoms; and a third variety not yet mapped. Autosomal recessive polycystic kidney disease occurs in 1 in 10,000 to 1 in 40,000 live births, and has been localized to chromosome 6.

Grossly enlarged kidneys are caused by multiple spherical cysts, a few millimeters to centimeters in diameter, that contain straw-colored or hemorrhagic fluid. The cysts are distributed evenly throughout the cortex and medulla. Hyperplastic polyps and renal adenomas are common. Renal parenchyma may have varying degrees of tubular atrophy, interstitial fibrosis, and nephrosclerosis. The cysts cause elongation of the pelvis, flattening of the calyces, and indentations in the kidney.

Characteristically, an affected infant shows signs of respiratory distress, heart failure, and, eventually, uremia and renal failure. Accompanying hepatic fibrosis and intrahepatic bile duct abnormalities may cause portal hypertension and bleeding varices.

In most cases, about 10 years after symptoms appear, progressive compression of kidney structures by the enlarging mass causes renal failure.

Cysts also form elsewhere ― such as on the liver, spleen, pancreas, and ovaries. Intracranial aneurysms, colonic diverticula, and mitral valve prolapse also occur.

In the autosomal recessive form, death in the neonatal period is most commonly due to pulmonary hypoplasia.

Signs and symptoms

Signs and symptoms in neonates include:

• pronounced epicanthic folds (vertical fold of skin on either side of the nose); a pointed nose; small chin; and floppy, low-set ears (Potter facies), due to genetic abnormalities
• huge, bilateral, symmetrical masses on the flanks that are tense and can't be transilluminated, due to kidney enlargement
• uremia, due to renal failure.

Signs and symptoms in adults include:

• hypertension, due to activation of the renin-angiotensin system
• lumbar pain, due to enlarging kidney mass
• widening abdominal girth, due to enlarged kidneys
• swollen or tender abdomen caused by the enlarging kidney mass, worsened by exertion and relieved by lying down
• grossly enlarged kidneys on palpation.

Complications

 

AGE ALERT A few infants with this disease survive for 2 years, and then die of hepatic complications or renal, heart, or respiratory failure.

Possible complications in adults include:

• pyelonephritis
• recurrent hematuria
• life-threatening retroperitoneal bleeding from cyst rupture
• proteinuria
• colicky abdominal pain from ureteral passage of clots or calculi
• renal failure.

Diagnosis

Diagnosis is based on the following test results:

• excretory or retrograde urography showing enlarged kidneys, with elongation of the pelvis, flattening of the calyces, and indentations in the kidney caused by cysts
• excretory urography of the neonate showing poor excretion of contrast medium
• ultrasonography, tomography, and radioisotope scans showing kidney enlargement and cysts; tomography, computed tomography, and magnetic resonance imaging showing multiple areas of cystic damage
• urinalysis and creatinine clearance tests showing nonspecific results indicating abnormalities.

Treatment

Treatment includes:

• antibiotics for infections
• adequate hydration to maintain fluid balance
• surgical drainage of cystic abscess or retroperitoneal bleeding
• surgery for intractable pain (uncommon symptom) or analgesics for abdominal pain
• dialysis or kidney transplantation for progressive renal failure
• nephrectomy not recommended (polycystic kidney disease occurs bilaterally, and the infection could recur in the remaining kidney).

Renal agenesis

Renal agenesis is the failure of a kidney to grow or develop. The kidney is usually polycystic and dysplastic. The disease may be unilateral or bilateral, random or hereditary, and occur in isolation or associated with other disorders. Unilateral renal agenesis occurs in 1 in 1,000 live births, and more commonly in males than females.

Bilateral renal agenesis is also called Potter syndrome. It occurs in 1 of every 3,000 live births, and 75% of the cases are in males. Bilateral renal agenesis is not compatible with life, and most affected infants die in utero.

Causes

The causes of renal agenesis are:

• unknown, but suspected to be hereditary.

Pathophysiology

In unilateral renal agenesis, the left kidney is usually absent. The remaining kidney may be completely normal. During the first years of life, this kidney hypertrophies to functionally compensate for the missing kidney. If the kidney has abnormalities of the collecting system, compensation is virtually impossible. Extrarenal congenital abnormalities are common with this type of agenesis.

 

AGE ALERT Infants with Potter syndrome rarely live longer than a few hours.

Signs and symptoms

There are no symptoms of unilateral renal agenesis if the kidney is functioning appropriately. Signs and symptoms of Potter syndrome are due to a congenital defect and include:

• wide-set eyes
• parrot-beak nose
• low-set ears
• receding chin
• pulmonary pathophysiology.

Complications

Renal agenesis may be complicated by:

• renal failure.

Diagnosis

Diagnosis is based on:

• prenatal ultrasound.

Treatment

Treatment includes:

• surgery for structural or functional defects in the remaining kidney.

Renal calculi

Renal calculi, or stones (nephrolithiasis), can form anywhere in the urinary tract, although they most commonly develop on the renal pelves or calyces. They may vary in size and may be solitary or multiple. (See Renal calculi .)

Renal calculi are more common in men than in women and rarely occur in children. Calcium stones generally occur in middle-age men with a familial history of stone formation.

 

CULTURAL DIVERSITY Renal calculi rarely occur in blacks. They are prevalent in certain geographic areas, such as the southeastern United States (called the “stone belt”), possibly because a hot climate promotes dehydration and concentrates calculus-forming substances, or because of regional dietary habits.

Causes

Although the exact cause is unknown, predisposing factors of renal calculi include:

• dehydration
• infection
• changes in urine pH (calcium carbonate stones, high pH; uric acid stones, lower pH)
• obstruction to urine flow leading to stasis in the urinary tract
• immobilization causing bone reabsorption
• metabolic factors
• dietary factors
• renal disease
• gout (a disease of increased uric acid production or decreased excretion).

Pathophysiology

The major types of renal stones are calcium oxalate and calcium phosphate, accounting for 75% to 80% of stones; struvite (magnesium, ammonium, and phosphate), 15%; and uric acid, 7%. Cystine stones are relatively rare, making up 1% of all renal stones.

Calculi form when substances that are normally dissolved in the urine, such as calcium oxalate and calcium phosphate, precipitate. Dehydration may lead to renal calculi as calculus-forming substances concentrate in urine.

RENAL CALCULI Renal calculi vary in size and type. Small calculi may remain in the renal pelvis or pass down the ureter. A staghorn calculus (a cast of the calyceal and pelvic collecting system) may develop from a stone that stays in the kidney.

Stones form around a nucleus or nidus in the appropriate environment. A crystal evolves in the presence of stone-forming substances (calcium oxalate, calcium carbonate, magnesium, ammonium, phosphate, or uric acid) and becomes trapped in the urinary tract, where it attracts other crystals to form a stone. A high urine saturation of these substances encourages crystal formation and results in stone growth.

Stones may be composed of different substances, and the pH of the urine affects the solubility of many stone-forming substances. Formation of calcium oxalate and cystine stones is independent of urine pH.

Stones may occur on the papillae, renal tubules, calyces, renal pelves, ureter, or bladder. Many stones are less than 5 mm in diameter and are usually passed in the urine. Staghorn calculi can continue to grow in the pelvis, extending to the calyces, forming a branching stone, and ultimately resulting in renal failure if not surgically removed.

Calcium stones are the smallest. Most are calcium oxalate or a combination of oxalate and phosphate. Although 80% are idiopathic, they frequently occur with hyperuricosuria (a high level of uric acid in the urine). Prolonged immobilization can lead to bone demineralization, hypercalciuria, and stone formation. In addition, hyperparathyroidism, renal tubular acidosis, and excessive intake of vitamin D or dietary calcium may predispose to renal calculi.

Struvite stones are often precipitated by an infection, particularly with Pseudomonas or Proteus species. These urea-splitting organisms are more common in women. Struvite calculi can destroy renal parenchyma.

Gout results in a high uric acid production, hyperuricosuria, and uric acid stones. Diets high in purine (such as meat, fish, and poultry) elevate levels of uric acid in the body. Regional enteritis and ulcerative colitis can precipitate the formation of uric acid stones. These diseases often result in fluid loss and loss of bicarbonate, leading to metabolic acidosis. Acidic urine enhances the formation of uric acid stones.

Cystinuria is a rare hereditary disorder in which a metabolic error causes decreased tubular reabsorption of cystine. This causes an increased amount of cystine in the urine. Because cystine is a relatively insoluble substance, its presence contributes to stone formation.

Infected, scarred tissue may be an ideal site for calculus development. In addition, infected calculi (usually magnesium ammonium phosphate or staghorn calculi) may develop if bacteria serve as the nucleus in calculus formation.

Urinary stasis allows calculus constituents to collect and adhere and also encourages infection, which compounds the obstruction.

Calculi may either enter the ureter or remain in the renal pelvis, where they damage or destroy renal parenchyma and may cause pressure necrosis.

In ureters, calculi cause obstruction with resulting hydronephrosis and tend to recur. Intractable pain and serious bleeding also can result from calculi and the damage they cause. Large, rough calculi occlude the opening to the ureteropelvic junction and increase the frequency and force of peristaltic contractions, causing hematuria from trauma. The patient usually reports pain travelling from the costovertebral angle to the flank and then to the suprapubic region and external genitalia (classic renal colic pain). Pain intensity fluctuates and may be excruciating at its peak. The patient with calculi in the renal pelvis and calyces may report a constant dull pain. He may also report back pain if calculi are causing obstruction within a kidney and severe abdominal pain from calculi traveling down a ureter. Infection can develop in static urine or after trauma as the stone abrades surfaces. If the stone lodges and blocks urine, hydronephrosis can occur.

Signs and symptoms

Possible signs and symptoms of renal calculi include:

• severe pain resulting from obstruction
• nausea and vomiting
• fever and chills from infection
• hematuria when calculi abrade a ureter
• abdominal distention
• anuria from bilateral obstruction, or obstruction of a patient's only kidney.

Complications

Complications include:

• damage or destruction of renal parenchyma
• pressure necrosis
• obstruction by the stone
• hydronephrosis
• bleeding
• pain
• infection.

Diagnosis

The following tests may be used to diagnose renal calculi:

• kidney-ureter-bladder (KUB) radiography, to show most renal calculi
• excretory urography, to help confirm the diagnosis and determine the size and location of calculi
• kidney ultrasonography, to detect obstructive changes, such as unilateral or bilateral hydronephrosis and radiolucent calculi not seen on KUB radiography
• urine culture showing pyuria, a sign of urinary tract infection
• 24-hour urine collection, for calcium oxalate, phosphorus, and uric acid excretion levels
• calculus analysis, for mineral content
• serial blood calcium and phosphorus levels diagnose hyperparathyroidism and increased calcium, relative to normal serum protein
• blood protein levels, to determine the level of free calcium unbound to protein.

Treatment

Treatment may include:

• increasing fluid intake to more than 3 L/day to promote hydration
• antimicrobial agents to treat infection, varying with the cultured organism
• analgesics such as meperidine (Demerol) or morphine for pain
• diuretics to prevent urinary stasis and further calculus formation; thiazides to decrease calcium excretion into the urine
• methenamine mandelate to suppress calculus formation when infection is present
• low-calcium diet to prevent recurrence
• oxalate-binding cholestyramine for absorptive hypercalciuria
• parathyroidectomy for hyperparathyroidism
• allopurinol (Zyloprim) for uric acid calculi
• daily small doses of ascorbic acid to acidify urine
• cystoscope with manipulation of the calculus to remove renal calculi too large for natural passage
• percutaneous ultrasonic lithotripsy and extracorporeal shock wave lithotripsy or laser therapy to shatter the calculus into fragments for removal by suction or natural passage
• surgical removal of cystine calculi or large stones or placement of urinary diversion around the stone to relieve obstruction.

Vesicoureteral reflux

In vesicoureteral reflux, urine flows from the bladder back into the ureters and eventually into the renal pelvis or the parenchyma. When the bladder empties only part of the stored urine, urinary tract infection may result. This disorder is most common during infancy in boys and during early childhood (ages 3 to 7) in girls. Primary vesicoureteral reflux that results from congenital anomalies is more common in females.

 

CULTURAL DIVERSITY There is a much lower incidence of vesicoureteral reflux in blacks. Indeed, it's extremely rare.

Up to 25% of asymptomatic siblings of children with diagnosed primary vesicoureteral reflux also have the disorder. Secondary vesicoureteral reflux occurs in adults.

Causes

Primary vesicoureteral reflux is caused by congenital anomalies of the ureters or bladder, including:

• short or absent intravesical ureters
• ureteral ectopia lateralis (ureter that opens more laterally in the bladder wall)
• ureteral duplication
• ureterocele
• gaping or golf-hole ureteral orifice.

Secondary vesicoureteral reflux is due to damage by:

• bladder outlet obstruction
• iatrogenic injury
• trauma
• inadequate detrusor muscle buttress in the bladder
• cystitis, repeated infections
• neurogenic bladder

Pathophysiology

Incompetence of the ureterovesical junction and shortening of intravesical ureteral musculature allow backflow of urine into the ureters when the bladder contracts during voiding. Congenital paraureteral bladder diverticulum, acquired diverticulum (from outlet obstruction), flaccid neurogenic bladder, and high intravesical pressure may cause inadequate detrusor muscle contraction in the bladder from outlet obstruction or an unknown cause.

Vesicoureteral reflux also may result from cystitis; inflammation of the intravesical ureter causes edema and intramural ureter fixation. This usually leads to reflux in people with congenital ureteral or bladder anomalies or other predisposing conditions. Recurrent urinary tract infections can lead to acute or chronic pyelonephritis and renal damage due to renal scarring, hypertension, or calculi.

Signs and symptoms

Signs and symptoms of vesicoureteral reflux include:

• urinary frequency and urgency due to urinary tract infection
• burning on urination
• hematuria
• foul-smelling urine
• high fever and chills due to urinary tract infection
• flank pain
• painful urination
• vomiting
• malaise
• palpation showing a hard, thickened bladder if posterior urethral valves are causing an obstruction in males.

 

AGE ALERT Infants with vesicoureteral reflux may have dark, concentrated urine due to retention. In children, fever, nonspecific abdominal pain, and diarrhea may be the only clinical effects. In children younger than 5 years, repeated urinary tract infections are suggestive of reflux.

Complications

Possible complications include:

• recurrent urinary tract infections
• pyelonephritis
• anemia
• hypertension
• renal obstruction
• renal failure.

Diagnosis

The following test results help diagnose vesicoureteral reflux:

• clean-catch urinalysis showing bacterial count more than 100,000/ml, sometimes without pyuria; microscopic examination showing red and white blood cells and increased urine pH (active infection); specific gravity less than 1.010 due to inability to concentrate urine
• elevated serum creatinine (more than 1.2 mg/dl) and blood urea nitrogen (more than 18 mg/dl) levels due to advanced renal dysfunction
• voiding cystourethrography to identify and determine the degree of reflux and show when reflux occurs
• catheterization of the bladder after the patient voids to determine the amount of residual urine
• I.V. pyelogram to diagnose vesicoureteral reflux by visualization
• excretory urography to show a dilated lower ureter, a ureter visible for its entire length, hydronephrosis, calyceal distortion, and renal scarring
• cystoscopy (may confirm diagnosis)
• radioisotope scanning and renal ultrasonography to detect reflux and screen the upper urinary tract for damage secondary to infection and other renal abnormalities.

Treatment

Treatment of vesicoureteral reflux includes:

• antibiotics to treat reflux secondary to infection or related to neurogenic bladder and, in children, a short intravesical ureter (disappears spontaneously with growth)
• long-term prophylactic antibiotic therapy for recurrent infection
• vesicoureteral reimplantation to treat recurrent infection despite prophylactic antibiotic therapy
• transurethral sphincterotomy to relieve obstructed outlet
• bladder augmentation to decrease intravesical pressure.