Is typhoid fever associated with an increased risk of acute kidney injury (AKI), particularly in patients with underlying medical conditions, such as young children, older adults, or individuals with impaired renal function?

Typhoid Fever and Acute Kidney Injury

Yes, typhoid fever is definitively associated with acute kidney injury (AKI), though it is an uncommon complication that occurs primarily in patients with specific risk factors, particularly glucose-6-phosphate dehydrogenase (G-6-P.D.) deficiency.

Epidemiology and Risk Factors

Typhoid fever can cause AKI in approximately 15% of hospitalized patients in endemic areas where both typhoid and G-6-P.D. deficiency are common 1. The association is particularly strong in patients with underlying G-6-P.D. deficiency, where the risk of developing both glomerular and tubular renal disease is substantially elevated 2, 1.

Key high-risk populations include:

• Patients with G-6-P.D. deficiency (almost all patients with renal complications in one series were G-6-P.D. deficient) 2
• Young adults and middle-aged patients (most reported cases occur in the 20-40 year age range) 3, 4
• Patients with delayed diagnosis or treatment 3, 4

Mechanisms of Renal Injury

Typhoid-associated AKI occurs through multiple distinct pathophysiologic mechanisms:

Rhabdomyolysis-induced AKI is a well-documented complication where severe muscle breakdown leads to myoglobinuria and acute tubular necrosis, often presenting with markedly elevated creatine phosphokinase levels (>17,000 U/L in severe cases) 3, 4. This mechanism can cause severe metabolic derangements including hyperuricemia, hyperphosphatemia, and hypocalcemia 3.

Glomerular disease manifests as proteinuria (≥1.0 g per 24 hours) with significant hematuria, associated with decreased serum complement (C3) levels during the acute phase 2. This appears to be an immune-mediated process that is transient and resolves with treatment 2.

Acute tubular necrosis can develop independently or in conjunction with rhabdomyolysis, particularly in G-6-P.D. deficient patients who may develop a blackwater fever-like syndrome with hemolysis 1.

Clinical Presentation

Warning signs that should prompt evaluation for AKI in typhoid patients include:

• Blackwater fever syndrome (dark urine, hemolysis) with or without leucocytosis 1
• Severe generalized body aches suggesting rhabdomyolysis 3
• Oliguria or anuria 3, 4
• Severe metabolic acidosis (pH <7.0) 3
• Microscopic or gross hematuria (though isolated hematuria without renal impairment is extremely rare) 5

Diagnostic Workup

Essential laboratory investigations include:

• Serum creatinine, urea, and electrolytes (sodium, potassium, bicarbonate) measured at least every 48 hours or more frequently if clinically unstable 6
• Creatine phosphokinase levels to detect rhabdomyolysis 3, 4
• Urinalysis for hematuria, proteinuria, and myoglobinuria 6, 2
• Serum complement (C3) levels if glomerular disease is suspected 2
• G-6-P.D. enzyme levels in endemic areas 2, 1
• Blood cultures to confirm Salmonella typhi and guide antibiotic therapy 3, 4

Management Approach

Immediate fluid resuscitation is critical, using balanced crystalloid solutions to maintain optimal euvolemia and prevent progression of AKI 6. Volume depletion is a key modifiable risk factor, and aggressive early hydration can prevent oligoanuric renal failure 7, 6.

Antibiotic therapy should be initiated promptly with agents such as ceftriaxone, ciprofloxacin, or imipenem-cilastatin based on local resistance patterns, with doses adjusted for current GFR 6, 3, 4.

Renal replacement therapy (hemodialysis) is indicated for severe AKI with uremia, severe metabolic acidosis (pH <7.0), hyperkalemia, or fluid overload unresponsive to medical management 3, 4.

Nephrotoxin avoidance requires stopping NSAIDs immediately and reviewing all potentially nephrotoxic medications 6.

Prognosis and Recovery

The prognosis for typhoid-associated AKI is generally favorable with appropriate treatment. Most patients regain normal kidney function after resolution of the acute infection 3, 4. However, severe cases may require temporary dialysis support, and some patients may develop persistent complications such as polyneuropathy that improves gradually over time 3.

Critical Pitfall

A common pitfall is failing to consider typhoid fever as an underlying cause of rhabdomyolysis and AKI in patients with appropriate travel history or endemic exposure 3, 4. Clinicians should maintain high suspicion for systemic infections like typhoid when evaluating unexplained AKI, particularly in patients from or traveling to endemic areas (South and Southeast Asia, Central and South America, Africa) 7.