Renal Failure

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Chapter 529 Renal Failure

529.1 Acute Renal Failure

Acute renal failure (ARF), also termed acute renal insufficiency, is a clinical syndrome in which a sudden deterioration in renal function results in the inability of the kidneys to maintain fluid and electrolyte homeostasis. ARF occurs in 2-3% of children admitted to pediatric tertiary care centers and in as many as 8% of infants in neonatal intensive care units. A classification system has been proposed to standardize the definition of acute kidney injury in adults. These criteria of risk, injury, failure, loss, and end-stage renal disease were given the acronym of RIFLE. A modified RIFLE criteria (pRIFLE) has been developed to characterize the pattern of acute kidney injury in critically ill children (Table 529-1). Because RIFLE focuses on glomerular filtration rate (GFR), a modification (Acute Kidney Injury Network, AKIN) categorizes severity by rise in serum creatinine: stage 1 >150%, stage II >200%, stage III >300%.


Risk eCCl decrease by 25% <0.5 mL/kg/hr for 8 hr
Injury eCCl decrease by 50% <0.5 mL/kg/hr for 16 hr
Failure eCCl decrease by 75% or eCCl <35 ml/min/1.73 m2 <0.3 mL/kg/hr for 24 hr or anuric for 12 hr
Loss Persistent failure >4 wk  
End-stage End-stage renal disease (persistent failure >3 mo)  

eCCl, estimated creatinine clearance; pRIFLE, pediatric risk, injury, failure, loss and end-stage renal disease.


ARF has been conventionally classified into 3 categories: prerenal, intrinsic renal, and postrenal (Table 529-2).

Prerenal ARF, also called prerenal azotemia, is characterized by diminished effective circulating arterial volume, which leads to inadequate renal perfusion and a decreased GFR. Evidence of kidney damage is absent. Common causes of prerenal ARF include dehydration, sepsis, hemorrhage, severe hypoalbuminemia, and cardiac failure. If the underlying cause of the renal hypoperfusion is reversed promptly, renal function returns to normal. If hypoperfusion is sustained, intrinsic renal parenchymal damage can develop.

Intrinsic renal ARF includes a variety of disorders characterized by renal parenchymal damage, including sustained hypoperfusion and ischemia. Many forms of glomerulonephritis, including postinfectious glomerulonephritis, lupus nephritis, Henoch-Schönlein purpura nephritis, membranoproliferative glomerulonephritis, and anti-glomerular basement membrane nephritis, can cause ARF. Hemolytic-uremic syndrome (HUS) has been described as the most common cause of intrinsic ARF in the USA (Chapter 512).

Acute tubular necrosis (ATN) occurs most often in critically ill infants and children who have been exposed to nephrotoxic and/or perfusion insults. Sepsis, hypovolemic shock, and increased intra-abdominal pressure (abdominal compartment syndrome) are important causes of ATN. The typical pathologic process of ATN is tubular cell necrosis, although significant histologic changes are not consistently seen in patients with clinical ATN. The mechanisms of injury in ATN can include alterations in intrarenal hemodynamics, tubular obstruction, and passive backleak of the glomerular filtrate across injured tubular cells into the peritubular capillaries.

Tumor lysis syndrome is a specific form of ARF related to spontaneous or chemotherapy-induced cell lysis in patients with lymphoproliferative malignancies. This disorder is primarily caused by obstruction of the tubules by uric acid crystals (Chapters 489 and 490). Acute interstitial nephritis is an increasingly common cause of ARF and is usually a result of a hypersensitivity reaction to a therapeutic agent or various infectious agents (Chapter 526).

Postrenal ARF includes a variety of disorders characterized by obstruction of the urinary tract. In neonates and infants, congenital conditions such as posterior urethral valves and bilateral ureteropelvic junction obstruction account for the majority of cases of ARF. Other conditions such as urolithiasis, tumor (intra-abdominal or within the urinary tract), hemorrhagic cystitis, and neurogenic bladder can cause ARF in older children and adolescents. In a patient with 2 functioning kidneys, obstruction must be bilateral to result in ARF. Relief of the obstruction usually results in recovery of renal function except in patients with associated renal dysplasia or prolonged urinary tract obstruction.

Laboratory Findings

Laboratory abnormalities can include anemia (the anemia is usually dilutional or hemolytic, as in SLE, renal vein thrombosis, HUS); leukopenia (SLE, sepsis); thrombocytopenia (SLE, renal vein thrombosis, sepsis, HUS); hyponatremia (dilutional); metabolic acidosis; elevated serum concentrations of blood urea nitrogen, creatinine, uric acid, potassium, and phosphate (diminished renal function); and hypocalcemia (hyperphosphatemia).

The serum C3 level may be depressed (postinfectious glomerulonephritis, SLE, or membranoproliferative glomerulonephritis), and antibodies may be detected in the serum to streptococcal (poststreptococcal glomerulonephritis), nuclear (SLE), neutrophil cytoplasmic (Wegener granulomatosis, microscopic polyarteritis), or glomerular basement membrane (Goodpasture disease) antigens.

The presence of hematuria, proteinuria, and red blood cell or granular urinary casts suggests intrinsic ARF, in particular glomerular disease. The presence of white blood cells and white blood cell casts, with low-grade hematuria and proteinuria, suggests tubulointerstitial disease. Urinary eosinophils may be present in children with drug-induced tubulointerstitial nephritis.

Urinary indices may be useful in differentiating prerenal ARF from intrinsic ARF (Table 529-3). Patients whose urine shows an elevated specific gravity (>1.020), elevated urine osmolality (UOsm > 500 mOsm/kg), low urine sodium (UNa < 20 mEq/L), and fractional excretion of sodium (FENa) <1% (<2.5% in neonates) most likely have prerenal ARF. Those with a specific gravity of <1.010, low urine osmolality (UOsm < 350 mOsm/kg), high urine sodium (UNa > 40 mEq/L), and FENa > 2% (>10% in neonates) most likely have intrinsic ARF.

Chest radiography may reveal cardiomegaly, pulmonary congestion (fluid overload) or pleural effusions. Renal ultrasonography can reveal hydronephrosis and/or hydroureter, which suggest urinary tract obstruction, or nephromegaly, suggesting intrinsic renal disease. Renal biopsy can ultimately be required to determine the precise cause of ARF in patients who do not have clearly defined prerenal or postrenal ARF.

Though serum creatinine is used to measure kidney function, it is an insensitive and delayed measure of decreased kidney function following acute kidney injury. Other biomarkers under investigation include changes in plasma neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C levels and urinary changes in NGAL, interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1).


Medical Management

In infants and children with urinary tract obstruction, such as in a newborn with suspected posterior ureteral valves, a bladder catheter should be placed immediately to ensure adequate drainage of the urinary tract. The placement of a bladder catheter may also be considered in nonambulatory older children and adolescents to accurately monitor urine output during ARF.

Determination of the volume status is of critical importance when initially evaluating a patient with ARF. If there is no evidence of volume overload or cardiac failure, intravascular volume should be expanded by intravenous administration of isotonic saline, 20 mL/kg over 30 min. In the absence of blood loss or hypoproteinemia, colloid-containing solutions are not required for volume expansion. Severe hypovolemia may require additional fluid boluses (Chapters 53, 54, and 64). Determination of the central venous pressure may be helpful if adequacy of the blood volume is difficult to determine. After volume resuscitation, hypovolemic patients generally void within 2 hr; failure to do so points to intrinsic or postrenal ARF. Hypotension due to sepsis requires vigorous fluid resuscitation followed by a continuous infusion of norepinephrine.

Diuretic therapy should be considered only after the adequacy of the circulating blood volume has been established. Mannitol (0.5 g/kg) and furosemide (2-4 mg/kg) may be administered as a single IV dose. Bumetanide (0.1 mg/kg) may be given as an alternative to furosemide. If urine output is not improved, then a continuous diuretic infusion may be considered. To increase renal cortical blood flow, many clinicians administer dopamine (2-3 µg/kg/min) in conjunction with diuretic therapy, although no controlled data support this practice. There is little evidence that diuretics or dopamine can prevent ARF or hasten recovery. Mannitol may be effective in pigment (myoglobin, hemoglobin)-induced renal failure. Atrial natriuretic peptide may be of value in preventing or treating acute kidney injury; there is little pediatric evidence.

If there is no response to a diuretic challenge, diuretics should be discontinued and fluid restriction is essential. Patients with a relatively normal intravascular volume should initially be limited to 400 mL/m2/24 hr (insensible losses) plus an amount of fluid equal to the urine output for that day. Extrarenal (blood, gastrointestinal [GI] tract) fluid losses should be replaced, milliliter for milliliter, with appropriate fluids. Markedly hypervolemic patients can require further fluid restriction, omitting the replacement of insensible fluid losses, urine output, and extrarenal losses to diminish the expanded intravascular volume. Fluid intake, urine and stool output, body weight, and serum chemistries should be monitored on a daily basis.

In ARF, rapid development of hyperkalemia (serum potassium level >6 mEq/L) can lead to cardiac arrhythmia, cardiac arrest, and death. The earliest electrocardiographic change seen in patients with developing hyperkalemia is the appearance of peaked T waves. This may be followed by widening of the QRS intervals, ST segment depression, ventricular arrhythmias, and cardiac arrest (Chapter 52.4). Procedures to deplete body potassium stores should be initiated when the serum potassium value rises to >6.0 mEq/L. Exogenous sources of potassium (dietary, intravenous fluids, total parenteral nutrition) should be eliminated. Sodium polystyrene sulfonate resin (Kayexalate), 1 g/kg, should be given orally or by retention enema. This resin exchanges sodium for potassium and can take several hours to take effect. A single dose of 1 g/kg can be expected to lower the serum potassium level by about 1 mEq/L. Resin therapy may be repeated every 2 hr, the frequency being limited primarily by the risk of sodium overload.

More-severe elevations in serum potassium (>7 mEq/L), especially if accompanied by electrocardiographic changes, require emergency measures in addition to Kayexalate. The following agents should be administered:

Calcium gluconate counteracts the potassium-induced increase in myocardial irritability but does not lower the serum potassium level. Administration of sodium bicarbonate, insulin, glucose lowers the serum potassium level by shifting potassium from the extracellular to the intracellular compartment. A similar effect has been reported with the acute administration of β-adrenergic agonists in adults, but there are no controlled data in pediatric patients. Because the duration of action of these emergency measures is just a few hours, persistent hyperkalemia should be managed by dialysis.

Mild metabolic acidosis is common in ARF because of retention of hydrogen ions, phosphate, and sulfate, but it rarely requires treatment. If acidosis is severe (arterial pH < 7.15; serum bicarbonate < 8 mEq/L) or contributes to hyperkalemia, treatment is required. The acidosis should be corrected partially by the intravenous route, generally giving enough bicarbonate to raise the arterial pH to 7.20 (which approximates a serum bicarbonate level of 12 mEq/L). The remainder of the correction may be accomplished by oral administration of sodium bicarbonate after normalization of the serum calcium and phosphorus levels. Correction of metabolic acidosis with intravenous bicarbonate can precipitate tetany in patients with renal failure as rapid correction of acidosis reduces the ionized calcium concentration (Chapter 52).

Hypocalcemia is primarily treated by lowering the serum phosphorus level. Calcium should not be given intravenously, except in cases of tetany, to avoid deposition of calcium salts into tissues. Patients should be instructed to follow a low-phosphorus diet, and phosphate binders should be orally administered to bind any ingested phosphate and increase GI phosphate excretion. Common agents include sevelamer (Renagel), calcium carbonate (Tums tablets or Titralac suspension), and calcium acetate (PhosLo). Aluminum-based binders, commonly employed in the past, should be avoided because of the established risk of aluminum toxicity.

Hyponatremia is most commonly a dilutional disturbance that must be corrected by fluid restriction rather than sodium chloride administration. Administration of hypertonic (3%) saline should be limited to patients with symptomatic hyponatremia (seizures, lethargy) or those with a serum sodium level <120 mEq/L. Acute correction of the serum sodium to 125 mEq/L (mmol/L) should be accomplished using the following formula:


ARF patients are predisposed to GI bleeding because of uremic platelet dysfunction, increased stress, and heparin exposure if on hemodialysis or continuous renal replacement therapy. Oral or intravenous H2 blockers such as ranitidine are commonly administered to prevent this complication.

Hypertension can result from hyperreninemia associated with the primary disease process and/or expansion of the extracellular fluid volume and is most common in ARF patients with acute glomerulonephritis or HUS. Salt and water restriction is critical, and diuretic administration may be useful (Chapter 439). Isradipine (0.05-0.15 mg/kg/dose, maximum dose 5 mg qid) may be administered for relatively rapid reduction in blood pressure. Longer-acting agents such as calcium channel blockers (amlodipine, 0.1-0.6 mg/kg/24 hr qd or divided bid) or β-blockers (propranolol, 0.5-8 mg/kg/24 hr divided bid or tid; labetalol, 4-40 mg/kg/24 hr divided bid or tid) may be helpful in maintaining control of blood pressure. Children with severe symptomatic hypertension (hypertensive urgency or emergency) should be treated with continuous infusions of sodium nitroprusside (0.5-10 µg/kg/min), labetalol (0.25-3.0 mg/kg/hr), or esmolol (150-300 µg/kg/min) and converted to intermittently dosed antihypertensives when more stable.

Neurologic symptoms in ARF can include headache, seizures, lethargy, and confusion (encephalopathy). Potential etiologic factors include hyponatremia, hypocalcemia, hypertension, cerebral hemorrhage, cerebral vasculitis, and the uremic state. Diazepam is the most effective agent in controlling seizures, and therapy should be directed toward the precipitating cause.

The anemia of ARF is generally mild (hemoglobin 9-10 g/dL) and primarily results from volume expansion (hemodilution). Children with HUS, SLE, active bleeding, or prolonged ARF can require transfusion of packed red blood cells if their hemoglobin level falls below 7 g/dL. In hypervolemic patients, blood transfusion carries the risk of further volume expansion, which can precipitate hypertension, heart failure, and pulmonary edema. Slow (4-6 hr) transfusion with packed red blood cells (10 mL/kg) diminishes the risk of hypervolemia. The use of fresh washed red blood cells minimizes the risk of hyperkalemia. In the presence of severe hypervolemia or hyperkalemia, blood transfusions are most safely administered during dialysis or ultrafiltration.


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