How should a newborn with acute kidney injury, markedly elevated lactate dehydrogenase, and normal bilirubin be managed?

Management of Neonatal Acute Kidney Injury with Elevated LDH and Normal Bilirubin

In a neonate with AKI, markedly elevated LDH, and normal bilirubin, you should immediately investigate for hemolysis as the underlying cause, implement supportive management focused on fluid balance and nephrotoxic medication avoidance, and prepare for potential renal replacement therapy if the infant deteriorates despite conservative measures. 1, 2

Diagnostic Approach: Elevated LDH Points to Hemolysis

The combination of AKI with markedly elevated LDH but normal bilirubin is highly suggestive of hemolysis, particularly in the acute phase before bilirubin accumulates or in cases where bilirubin is being rapidly cleared. 3, 4

Immediately obtain the following laboratory tests:

• Blood type and direct antibody test (Coombs) to identify isoimmune hemolytic disease 5
• Complete blood count with differential and reticulocyte count to assess for anemia and hemolysis 5
• G6PD enzyme activity as G6PD deficiency is a critical cause of hemolytic AKI 5, 6
• Serum creatinine trends recognizing that neonatal creatinine initially reflects maternal levels and a 0.3 mg/dL increase should trigger concern 1
• Peripheral blood smear to look for schistocytes or spherocytes indicating hemolysis 3

Critical Recognition: Neonatal AKI is Often Multifactorial

Neonatal AKI presents unique diagnostic challenges because baseline renal function is immature, GFR is physiologically low at birth, and serum creatinine is an imperfect marker in this population. 1, 2 The most common etiologies in NICU patients are sepsis (77.5% of cases with highest mortality at 30.5%), hypovolemia, hypoxic-ischemic injury, and hemolysis. 3, 7

Monitor urine output closely as oliguria (present in 77.5% of neonatal AKI cases) is a critical diagnostic and prognostic marker. 3

Immediate Management Priorities

1. Address the Underlying Hemolysis

If hemolysis is confirmed:

• Discontinue any potential triggers including medications that may precipitate hemolysis in G6PD deficiency 1
• Avoid phototherapy if congenital porphyria is suspected as this is an absolute contraindication 5
• Consider exchange transfusion if hemolysis is severe with signs of acute bilirubin encephalopathy (lethargy, hypotonia, poor feeding, high-pitched cry) even with normal current bilirubin, as LDH elevation suggests ongoing hemolysis that will lead to hyperbilirubinemia 6

2. Optimize Fluid and Electrolyte Management

Carefully manage fluid balance:

• Monitor daily weights and strict intake/output as fluid overload is associated with worse outcomes in neonatal AKI 8
• Avoid volume depletion which can worsen prerenal AKI, but also avoid excessive fluid administration 7, 8
• Correct electrolyte abnormalities particularly hyperkalemia, which can be life-threatening 7, 8
• Manage acid-base balance as metabolic acidosis commonly accompanies AKI 7

3. Review and Minimize Nephrotoxic Exposures

Implement nephrotoxic medication monitoring:

• Discontinue or adjust aminoglycosides which are the most common nephrotoxic agents in neonates 1, 7
• Avoid NSAIDs (including indomethacin for PDA closure) as they cause reversible renal dysfunction in 40% of premature neonates 7
• Use lipid formulations of amphotericin B rather than conventional formulations if antifungal therapy is needed 1
• Discontinue diuretics temporarily unless needed for volume overload, as they can worsen prerenal azotemia 1

Recent evidence shows that nephrotoxic medication monitoring programs can prevent AKI in high-risk neonates. 4

4. Consider Preventive Pharmacotherapy Based on Etiology

If hypoxic-ischemic encephalopathy is present:

• Administer a single dose of theophylline within the first 60 minutes of life, as multiple trials demonstrate improved fluid control and higher GFR without affecting mortality 1, 4
• This recommendation is specific to severe perinatal asphyxia and should not be used routinely 1

If the infant is premature:

• Consider caffeine therapy as recent evidence shows it may prevent AKI in premature neonates 4

When to Escalate to Renal Replacement Therapy

Prepare for dialysis if:

• Severe oliguria or anuria persists despite conservative management 3, 7
• Life-threatening hyperkalemia develops that is refractory to medical management 7, 8
• Severe metabolic acidosis cannot be corrected 7, 8
• Volume overload causes respiratory compromise 8
• Multiorgan failure develops, as this is associated with significantly higher mortality 7

Peritoneal dialysis has traditionally been the preferred modality for neonates due to vascular access challenges, though continuous renal replacement therapy machines designed specifically for neonates are now available and increasingly used. 4, 7 However, prognosis is poor in oliguric neonates requiring dialysis, with mortality rates of 55.6% in those receiving peritoneal dialysis versus 25.9% in those managed conservatively. 3

Critical Prognostic Factors

Mortality risk is highest with:

• Multiorgan failure (strongest predictor) 7
• Sepsis as the underlying cause (30.5% mortality) 3
• Need for mechanical ventilation and vasopressors 7
• Hemodynamic instability 7
• Requirement for dialysis 3, 7

The overall mortality rate for neonatal AKI is approximately 36.7%, but this varies dramatically based on underlying etiology and severity. 3

Long-Term Follow-Up is Mandatory

All neonates with AKI require lifelong monitoring because:

• Hypoxic-ischemic and nephrotoxic injury can result in decreased nephron number leading to late-onset chronic kidney disease 7
• Substantial nephron loss (as in cortical necrosis) puts infants at risk for renal failure years after apparent recovery 7
• Increased risk of chronic kidney disease and hypertension has been documented in neonates with AKI history 2, 4

Monitor indefinitely:

• Blood pressure at every visit 7
• Urinalysis for proteinuria 7
• Serum creatinine and BUN annually or more frequently if abnormalities develop 7

Common Pitfalls to Avoid

• Do not rely solely on serum creatinine in the first 48-72 hours of life, as it reflects maternal renal function 1
• Do not overlook high-output AKI which is common in neonates and may go unrecognized without creatinine monitoring 1
• Do not assume normal bilirubin excludes hemolysis as LDH rises before bilirubin accumulates 3
• Do not delay investigation of the underlying cause, as neonatal AKI is frequently multifactorial and requires targeted intervention 2, 3
• Do not use low-dose dopamine, fenoldopam, or NAC as they are ineffective for AKI prevention or treatment 1