What renal complications can occur with anti‑tuberculosis drugs in adult patients receiving standard therapy?

Renal Complications of Anti-Tuberculosis Medications

The most clinically significant renal complication of anti-TB therapy is rifampicin-induced acute interstitial nephritis (AIN), which occurs in approximately 1% of patients and typically presents after re-exposure to the drug, requiring immediate discontinuation and often steroid therapy. 1, 2

Drug-Induced Acute Kidney Injury

Rifampicin-Induced Nephrotoxicity (Most Common)

• Acute interstitial nephritis (AIN) is the predominant mechanism of rifampicin-induced AKI, accounting for the majority of cases in patients receiving standard TB therapy 1, 2
• Typically occurs with re-exposure to rifampicin after previous treatment, with median onset at 45 days (range 21-54 days) after starting therapy 2
• Clinical presentation includes gastrointestinal symptoms in 85% of patients, often with associated hepatitis (53%), but notably without skin rash and with eosinophilia in only a minority 1
• Universal hematuria without significant proteinuria is the characteristic urinary finding; anemia occurs in 90% and thrombocytopenia in 37% of cases 1
• Other rifampicin-induced renal syndromes include crescentic glomerulonephritis, heme pigment-induced acute tubular necrosis, and accelerated hypertension in dialysis patients 3
• Approximately 22% of patients with rifampicin-induced AIN require dialysis, with mortality of 10% primarily related to overwhelming TB infection 1

Rifampicin-Induced Nephrotic Syndrome

• Minimal change disease (MCD) can occur as early as 25 days after starting rifampicin, presenting with nephrotic syndrome and acute renal failure 4
• Requires immediate cessation of rifampicin and often necessitates temporary dialysis plus corticosteroid therapy for complete remission 4
• Renal function and proteinuria should be monitored carefully during the first few months of rifampicin therapy to detect this complication early 4

Isoniazid-Related Renal Effects

• Isoniazid may contribute to minimal change disease when used in combination with rifampicin, though rifampicin is the primary culprit 4
• Can cause pancreatitis and cerebellitis in CKD patients, though these are non-renal complications 3

Pyrazinamide-Induced Complications

• Acute gout secondary to reduced uric acid excretion is a recognized complication in CKD patients receiving pyrazinamide 3
• Metabolites (pyrazinoic acid and 5-hydroxy-pyrazinoic acid) accumulate in renal failure, potentially causing hyperuricemia and hepatotoxicity 5

Aminoglycoside Nephrotoxicity

• Streptomycin, kanamycin, amikacin, and capreomycin carry significant nephrotoxicity risk and should be avoided when possible in patients with pre-existing renal impairment 6
• These agents require dose reduction and serum concentration monitoring if used in CKD patients 7

Management of Drug-Induced AKI

Immediate Actions

• Discontinue rifampicin immediately upon suspicion of AIN; do not rechallenge, as mortality has been reported with rifampicin restart 2
• Consider short-term corticosteroid therapy for pathologically or clinically confirmed AIN (administered in 100% of biopsy-proven cases and 43% of clinical diagnoses) 2
• Levofloxacin may serve as a safer alternative to rifampicin due to its safety profile and potency, though it requires dose adjustment in severe renal impairment 2

Diagnostic Approach

• Maintain high index of suspicion in re-treatment patients, as rifampicin-induced AIN typically occurs with re-exposure 1
• Microhematuria on urine dipstick serves as a useful screening test for early detection 1
• Renal biopsy confirms AIN but is not always necessary when clinical presentation is classic 2

Treatment Continuation

• Restart anti-TB treatment without rifampicin (or without isoniazid if implicated); 80% of patients achieve normalized renal function with this approach 2
• Alternative regimens include 2SHEZ + 10HE (streptomycin, isoniazid, ethambutol, pyrazinamide followed by isoniazid and ethambutol) or fluoroquinolone-based regimens 8

Prevention and Monitoring

Baseline Assessment

• Calculate creatinine clearance using Cockcroft-Gault equation or 24-hour urine collection rather than relying on serum creatinine alone, as low muscle mass can mask severe renal impairment 5
• Screen for microhematuria with urine dipstick at baseline and during early treatment 1

Ongoing Surveillance

• Monitor renal function and proteinuria carefully during the first few months of rifampicin and isoniazid therapy 4
• Duration of oliguria is the main predictor of dialysis requirement; early recognition allows for timely intervention 1
• Consider therapeutic drug monitoring in patients with borderline renal function or uncertain dialysis adequacy 5

Critical Pitfall

Never rechallenge with rifampicin after documented AIN, as two deaths have been reported following rifampicin restart in patients with severe renal failure 2. The renal prognosis is generally good with drug discontinuation, but the disease carries significant morbidity and mortality risks if rifampicin is continued or reintroduced 1.