Renal Failure

Acute renal failure is an abrupt, often temporary loss of renal function after an insult that may or may not be evident at initial evaluation (see Chapter 52 and Chapter 56 ). Oliguria is the rule, polyuria the exception, and anuria uncommon. Urine volume and composition are altered, and fluid, electrolyte, and acid-base disorders are commonly associated. Therapy is directed at maintaining normal metabolic and fluid homeostasis, supporting nutrition, and exhibiting patience. Acute renal failure is caused by prerenal, postrenal (obstructive), or intrinsic renal disorders. Prerenal causes are related to the adequacy of renal blood flow. Reducing systemic cardiac output, or renal blood flow specifically, reduces urine output and ultimately causes azotemia and ischemic renal damage. Measurement of the adequacy of circulating blood volume by CVP and cardiac output and assessment of renal blood flow with Doppler flow studies or nuclear imaging techniques are useful in differentiating prerenal from renal causes of azotemia.^[223]

Postrenal obstruction to urine flow can occur anywhere within the collecting system. Chronic partial obstruction at the level of the bladder neck or the ureterovesical or ureteropelvic junction is a common form of congenital malformation. Posterior urethral valves are often demonstrated in males. All these malformations can cause mechanical obstructive nephropathy and renal injury or renal failure. Signs of obstruction may be subtle and require radiologic, ultrasonic, or endoscopic evaluation. Recurrent urinary tract infections are frequently the clinical manifestation of obstructive lesions.^[224]

Intrinsic renal failure may be due to disorders of the renal glomeruli, tubules, or blood vessels. Glomerular diseases include hemolytic-uremic syndrome (HUS), poststreptococcal glomerulonephritis, Henoch-Schönlein purpura, and other inflammatory and immune complex diseases. Acute tubular injury is most commonly caused by hypoxia and ischemia; other causes are rhabdomyolysis, sepsis, hyperthermia, hemolysis, and myriad nephrotoxins such as mercury, carbon tetrachloride, and ethylene glycol.^[225] Vascular disease, including arterial embolus and venous thrombosis, as well as congenital malformations, can lead to acute renal failure.

Hemolytic-Uremic Syndrome

HUS is one of the most commonly acquired causes of acute renal failure in children. This syndrome is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury. In North America, HUS is most often associated with infection by cytotoxin-producing Escherichia coli O157, but other serotypes and other Shiga-like toxin-producing bacteria have been implicated.^[226]

E. coli O157 is an inhabitant of the intestinal tract of cattle and can contaminate the surface of beef during processing.^[227] The bacterium is killed on cooking, but it survives in uncooked meat or inside undercooked hamburger. Secondary infections can occur as a result of person-to-person spread in daycare centers, institutions, and the military. There also appears to be a familial form of this disease that accounts for a small percentage of the total.^[228]

HUS predominates in children from 6 months to 4 years of age, but it can occur from the neonatal period through adulthood.^[229] It shares many laboratory and clinical features with the adult disease thrombotic thrombocytopenic purpura. In fact, some investigators consider the two disorders to represent a continuum of the same disease. The abnormalities that develop in HUS are believed to be caused by cytotoxins and lipopolysaccharide, a bacterial endotoxin. Toxins damage endothelial cells in the kidney, vasculature, and other organs directly or indirectly by the activation of leukocytes.^[230] Cytokines such as interleukin-1 and tumor necrosis factor, prostaglandin I₂ , thromboxane A₂ , and von Willebrand

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The time from exposure to initial evaluation varies from 3 to 12 days, and symptoms last for about a week. Patients usually have abdominal cramping, bloody diarrhea, tenesmus, and vomiting.^[232] On average, about 10% of children with E. coli O157 bloody diarrhea progress to HUS. Mildly affected patients exhibit anemia, thrombocytopenia, azotemia, decreased urine output, and an uncomplicated course. In severely affected patients, anuria is common, hypertension and seizures may occur, and the duration of illness is protracted. A small number of children will exhibit progressive and permanent renal insufficiency, severe and recurrent hemolysis, thrombocytopenia, and neurologic impairment.

Hematologic abnormalities include hemolysis and thrombocytopenia. The Coombs-negative microangiopathic hemolysis can result in hyperbilirubinemia, and despite reticulocytosis, anemia with hemoglobin concentrations as low as 4 to 5 g/dL can also occur. Thrombocytopenia is caused by platelet destruction and sequestration in the liver and spleen.^[233] The remaining platelets demonstrate impaired aggregation.^[234] Disseminated intravascular coagulation (DIC) is not uncommon. Glomerular capillary endothelial injury is the most consistent renal finding in HUS. Acute renal failure with oliguria or anuria usually lasts less than a week, but it can linger more than 10 weeks.^[235] Glomerular or arterial injury, or both, may predominate, depending on the presence and extent of renal insufficiency (glomerular injury) and hemolysis and hypertension (arterial injury). CNS abnormalities are manifested as decreased levels of consciousness, seizures, irritability, ataxia, hypotonia, hemiparesis, hyperreflexia, and hallucinations. CNS complications may be due to severe hypertension, electrolyte disturbances, microthrombi, or cerebral edema and increased ICP.^[236] Abdominal cramping is common, and vigilance is required to distinguish colitis from intussusception, intestinal stricture or perforation, colonic gangrene, or other surgical emergencies. ^[237] Pancreatitis is common in patients with HUS. CHF may be a result of fluid overload, hypertension, anemia, or myocardial depression secondary to circulating endotoxins.

Treatment is primarily supportive, with meticulous attention paid to volume status, electrolyte and acid-base balance, nutrition, antisepsis, and treatment of hypertension and coagulopathies as required. Enteric isolation is mandatory to prevent secondary spread. Accurate fluid intake and output records and weights and frequent clinical assessment of volume status are the pillars of good management. A central venous catheter can be used for pressure measurements and blood sampling and also as a route for intravenous medications and nutrition. Nephrotoxic drugs should be avoided if possible, or their dose should be modulated and serum levels closely monitored.^[238] Daily fluids should be restricted to replacing insensible losses, urine output, and any ongoing losses. Fluids should be used that reflect the electrolyte content of the losses. Caloric support is essential. Enteral feedings are preferred, but ileus often makes parenteral nutrition necessary. Antidiarrheal medications prolong the duration of colitis, and antibiotics may increase the risk for development of HUS.^{[239] [240]} No specific treatment has been demonstrated to be effective to date. Heparin, fibrinolytic agents, aspirin, dipyridamole, corticosteroids, vitamin E, and furosemide have not proved to affect the outcome of HUS.^[241] Immunoglobulin therapy, plasmapheresis, and infusions of fresh frozen plasma have had mixed results; no therapeutic benefit has been demonstrated.

Dialysis, improved nutrition, and supportive care have decreased the mortality rate from 100% in the original report to less than 10% in the last 30 years. Mortality rates in developing countries and in children who exhibit a genetic predisposition for HUS remain high.

The technique for peritoneal dialysis includes the placement of a soft catheter with multiple holes into the peritoneal cavity through an anterior abdominal wall incision. This procedure is usually performed laparoscopically, but it can be performed in the ICU with the use of local anesthesia. Once placement and patency of the catheter are confirmed, a commercially available dialysate solution is infused into the peritoneal cavity, where it equilibrates with plasma and extracellular fluids by using the parietal and visceral surfaces as semipermeable dialysis membranes. ^[242] The period of fluid instillation (dwell time) for equilibration can be varied, depending on clinical conditions. The composition of the dialysis fluid tends to be similar to that of plasma, with approximately 130 mEq/L of sodium, 100 mEq/L of chloride, 35 mEq/L of acetate or lactate as a buffer, 3.5 mEq/L of calcium, and 1.5 mEq/L of magnesium. The glucose concentration can be varied to be either isosmotic, with 1.5% glucose, or hyperosmotic, with 4.25% glucose. The latter concentration allows for additional intravascular and extracellular fluid to equilibrate with the dialysate fluid so that this fluid, as well as electrolytes, can be removed when the peritoneal cavity is evacuated. Complications occur with peritoneal dialysis. Respiratory compromise from increased abdominal pressure during the dwell time may require intubation and mechanical ventilation in children with preexisting impaired respiratory function. Peritonitis from bacterial or fungal agents as a result of contamination of the dialysis catheter or dialysate can occur in a patient whose host defenses are not normal.^[243] Severe dehydration, including circulatory collapse and metabolic derangements, can occur if peritoneal dialysis is too rapidly or improperly performed. The principles of hemodialysis are essentially the same as those of peritoneal dialysis, but with the blood compartment interfacing with a semipermeable membrane rather than with the peritoneum. Some investigators argue that hemodialysis is more efficient than peritoneal dialysis and is therefore more appropriate in the acute setting.

Hemofiltration or ultrafiltration is an extracorporeal process in which uremic blood is cleansed by a technique based solely on the principle of convective solute transport. During this procedure, an ultrafiltrate of plasma is created by hydrostatic pressure exerted across a highly permeable membrane. Simultaneously, blood volume is replaced by modified lactated Ringer's solution.^[244]

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Outcome

The prognosis in acute renal failure depends on the patient's age, underlying disease, and the extent of the precipitating insult (also see Chapter 23 ). In general, children tend to have a better outcome than adults do; in fact, they usually recover completely from a renal insult of hypoxia or ischemia within a short time, provided that other organ systems are not involved.^[245] In children with chronic renal failure, long-term outpatient peritoneal dialysis or long-term hemodialysis is necessary for survival until a renal transplant can be performed.^[246]