123: Renal Failure, Acute (Acute Kidney Injury)

The term acute renal failure (ARF) has now been replaced with the term acute kidney injury (AKI), and is now used to encompass mild renal dysfunction to complete anuric kidney failure. In neonates, ARF/AKI is defined as a serum creatinine >1.5 mg/dL (132.6 μmol/L), regardless of age or urine output, with normal maternal renal function. ARF/AKI can be anuric (absence of urinary output by 24–48 hours of age), oliguric (urine output of <1.0 mL/kg), or nonoliguric (>1.0 mL/kg). ARF/AKI can present with normal urinary output (seen in asphyxiated neonates). Normal urine output is ∼1–3 mL/kg/h with almost all infants voiding within 24 hours of birth. See Table 68–1.

In some studies, as many as 24% of neonatal intensive care unit (NICU)-admitted neonates have some degree of renal failure. Prerenal is the most common type in the neonate, which may be identified in up to 85% of cases. Renal incidence is 6–8% and postrenal 3–5%.

The normal newborn kidney has poor concentrating ability (maximum specific gravity 1.025). Renal injury leads to problems with volume overload, hyperkalemia, acidosis, hyperphosphatemia, and hypocalcemia. Postnatally ARF/AKI is traditionally divided into 3 categories:

1. Prerenal failure is due to decreased renal blood flow/perfusion, which leads to a decreased renal function in a normal kidney. Any condition that causes inadequate renal perfusion can cause prerenal ARF/AKI. Common causes include hemorrhage, dehydration, septic shock, congestive heart failure, patent ductus arteriosus (PDA), and necrotizing enterocolitis (NEC). Other causes include respiratory distress syndrome (RDS), hypoxia, congenital heart disease, hypoalbuminemia, perinatal asphyxia, extracorporeal membrane oxygenation/ extracorporeal life support (ECMO/ECLS), and hypotension. Medications in neonates that can decrease renal blood flow include indomethacin, ibuprofen, angiotensin-converting enzyme (ACE) inhibitors, and phenylephrine eye drops. Maternal use of nonsteroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors, or cyclooxygenase (COX)-2 inhibitors can also decrease renal blood flow.

2. Intrinsic renal failure refers to structural damage to the kidneys, which causes renal tubular dysfunction. It includes acute tubular necrosis, congenital anomalies, vascular lesions, and infections/toxins. Acute tubular necrosis (ATN) is the most common cause, and it can be caused by prolonged poor renal perfusion, ischemia or hypoxia, sepsis, cardiac surgery (blood product transfusions), or nephrotoxins (aminoglycosides, NSAIDs, amphotericin B, contrast agents, or acyclovir). Other causes include congenital anomalies (eg, bilateral renal agenesis, polycystic kidney disease, congenital nephrotic syndrome of the Finnish type, renal hypoplasia/dysplasia), vascular lesions (bilateral renal vein/artery thrombosis, cortical necrosis, disseminated intravascular coagulation [DIC]), infections (congenital: syphilis, toxoplasmosis; candidiasis, pyelonephritis), exogenous toxins (uric acid nephropathy, myoglobinuria, hemoglobinuria).

3. Postrenal/obstructive. All of the causes involve obstruction of urinary outflow after the urine has been produced by the kidneys. The most common cause in males is posterior urethral valves. Other causes include urethral strictures, meatal stenosis, bilateral uteropelvic/vesical junction obstruction, neurogenic bladder, large ureteroceles, blocked urinary drainage catheters, megaureter, and prune belly syndrome. Rare causes in neonates include extrinsic tumor compression of the bladder or ureters (sacrococcygeal teratoma) or intrinsic obstruction (nephrolithiasis, bilateral fungal bezoar).

Include dehydration, sepsis, asphyxia, administration of nephrotoxic drugs, prematurity, very low birthweight infants, congenital heart disease undergoing cardiopulmonary bypass, and ECMO/ECLS. Maternal diabetes may increase the risk for renal vein thrombosis and subsequent renal insufficiency.

1. Decreased or absent urine output. Low or absent urine output is usually the presenting problem. Virtually all infants void by 24 hours after birth (see Chapter 68).

2. Family history. History of urinary tract disease in other family members; history of oligohydramnios, which frequently accompanies urinary outflow obstruction or severe renal dysplasia or agenesis; and maternal diabetes should be obtained.

3. Physical examination

   1. Abdominal mass may be due to a distended bladder, polycystic kidneys, hydronephrosis, or tumors

   2. Potter facies is associated with renal agenesis

   3. Meningomyelocele is associated with neurogenic bladder

   4. Pulmonary hypoplasia is due to severe oligohydramnios in utero

   5. Urinary ascites may be seen with posterior urethral valves and severe upper urinary tract obstruction

   6. Prune belly syndrome. Hypoplasia of the abdominal wall musculature, cryptorchidism, and dilated upper urinary tracts

1. Urethral catheterization. Use a 5F or 8F feeding tube to measure volume of retained urine of monitor output (see Chapter 26).

2. Laboratory studies

   1. Blood urea nitrogen (BUN) and creatinine

      1. BUN. 15–20 mg/dL suggests dehydration or renal insufficiency.

      2. Creatinine. Normal serum creatinine values are 0.8–1.0 mg/dL at 1 day, 0.7–0.8 mg/dL at 3 days, and <0.6 mg/dL by 7 days of life. Higher values suggest renal disease except in low birthweight infants, in whom a creatinine level of <1.6 mg/dL is considered normal. (Rule of thumb: If the creatinine doubles, then 50% of the renal function has been lost.)

   2. Urinary indices. (Table 123–1) A spot urine osmolality, serum and spot urine sodium, and serum and urine creatinine are used to calculate the fractional excretion of sodium (FeNa) and the renal failure index (RFI). These indices are of limited value if measured while the effects of diuretics, such as furosemide, are present.

      

   3. Complete blood count (CBC) and platelet count. May reveal thrombocytopenia, which is seen with sepsis or renal vein thrombosis.

   4. Serum potassium. May be increased with renal insufficiency.

   5. Urinalysis. May reveal hematuria (associated with renal vein thrombosis, tumors, or DIC) or pyuria, suggesting urinary tract infection.

   6. Biomarkers

      1. Serum and urinary cystatic C levels. Used to calculate glomerular filtration rate

      2. Plasma and urinary neutrophil gelatinase–associated lipocalin (NGAL) levels.

      3. Serum and urinary interleukin (IL)-18 levels.

      4. Urinary albumin-to-creatinine ratio (ACR).

3. Diagnostic fluid challenge. If the patient does not have clinical volume overload or congestive failure, give a fluid challenge. Administer normal saline or colloid solution, 5–10 mL/kg as an intravenous bolus, and repeat once as needed. If there is no response, give furosemide, 1 mg/kg IV. If there is still no increase in urine output, obstruction above the level of the bladder must be ruled out by ultrasound examination. If there is no evidence of obstruction, and the patient does not respond to these maneuvers, the most likely cause of anuria or oliguria is intrinsic renal failure.

4. Imaging studies

   1. Abdominal ultrasonography. May identify hydronephrosis, dilated ureters, abdominal masses, a distended bladder, or renal vein thrombosis.

   2. Abdominal radiograph studies. May show spina bifida or an absent sacrum, which may be associated with a neurogenic bladder. Displaced bowel loops suggest the presence of a space-occupying mass.

   3. Radionuclide scanning. May be used to assess function of renal parenchymal, but is less accurate in neonates due to immature kidneys.

See also Chapter 68.

1. General management

   1. Replace insensible fluid losses (preterm, 50–70 mL/kg/d; term, 30 mL/kg/d) plus fluid output (urine and gastrointestinal tract).

   2. Keep strict intake and output and frequent weights.

   3. Monitor serum sodium and potassium levels frequently, and replace losses cautiously as needed. Hyperkalemia may be lethal.

   4. Restrict protein to <2 g/kg/d, and ensure adequate nonprotein caloric intake. Breast milk or formulas such as Similac PM 60/40 are frequently used for infants with renal failure.

   5. Hyperphosphatemia and hypocalcemia frequently coexist, and phosphate binders such as aluminum hydroxide, 50–150 mg/kg/d orally, should be used to normalize phosphate. Once phosphate is normalized, calcium (with or without vitamin D supplementation) is usually needed.

   6. For tetany or convulsions, acute intravenous calcium replacement with 10% calcium gluconate, 40 mg/kg, or 10% calcium chloride will increase the serum calcium 1 mg/dL. Monitor ionized calcium.

   7. Metabolic acidosis may require chronic oral bicarbonate supplementation. Blood pressure should be monitored serially because these infants are always at risk for chronic hypertension. Intravenous bicarbonate therapy should be given if the pH is <7.25 or the serum bicarbonate (HCO₃) is <12 mEq.

      HCO₃ deficit = (24 − observed) 0.5 × body weight (kg)

2. Definitive management

   1. Prerenal failure. Treated by providing volume to increase and restore renal perfusion and to treat the underlying cause.

   2. Postrenal failure. Acute management involves bypassing the obstruction with a bladder catheter or by percutaneous nephrostomy drainage, depending on the level of the obstruction. Operative intervention with surgical repair may be indicated to relieve obstruction. Urinary tract infection prophylaxis may be indicated. Consult with pediatric urology.

   3. Intrinsic renal disease. Stop or adjust doses of any nephrotoxic medications if possible. Supportive therapy is indicated (see previous text). Diuretics (furosemide, 1–2 mg/kg/dose) may increase urine output and aid in fluid management, but studies show that it does not improve the course of kidney injury. Low-dose dopamine can increase renal perfusion. (Note: No studies in neonates are reported, but studies in adults have shown it does not improve survival.) Observe for hyponatremia, hyperkalemia, hyperphosphatemia, hypocalcemia, and metabolic acidosis as they can occur frequently in intrinsic renal disease. Follow blood pressure as hypertension can occur (more common in renal artery/venous thrombosis). Renal feeding formulas that have a low renal solute and phosphorus should be considered. Pediatric nephrology should be consulted.

   4. Renal replacement therapy (peritoneal dialysis, hemodialysis, hemofiltration with or without dialysis). This is used if other measures fail. If recovery of renal function is expected or if renal transplantation is considered an option when the child is older, peritoneal dialysis is the treatment most commonly used in the neonate.

The prognosis from ARF/AKI depends on the underlying cause or the extent of damage. If renal disease is caused by toxins or acute tubular necrosis, renal function may recover to some extent with time. Chronic renal failure may ensue as neonates with ARF/AKI are at increased risk. Mortality and morbidity are increased in newborns with multiorgan failure. Factors that increase mortality include hypotension, need for mechanical ventilation, dialysis, use of vasopressors, hemodynamic instability, and multiorgan failure. Follow-up with monitoring of urine, renal function, and blood pressure is necessary.