Tuberculostatic treatment—An unusual case of renal failure

Vilma Bordin1, Fabio Fabbian1, Patrizia Cocco2, Domenico Di Landro1 and Carlo Catalano1

1 Unità Operativa di Nefrologia e Dialisi, 2 Pathology Unit, ULSS 17, Monselice,Italy

Sir,

The incidence of tuberculosis (TB) is increasing worldwide [1,2]. The number of immigrants arriving in Europe from countries outside Europe is increasing and TB is even more frequent among these immigrants. The growth of the number of treated subjects will increase the risk of life-threatening complications of tuberculostatic treatment. Rifampicin, isoniazid and pyrazinamide are potentially hepatotoxic. Isoniazid- related hepatic damage is rare in patients under the age of 20 years but increases with age, and up to 12% of patients receiving isoniazid may have elevated plasma transaminase activities [3]. Renal injury in patients treated for TB is most often due to aminoglycosides or capreomycin [4]. Rifampicin may cause acute tubular necrosis, interstitial nephritis, light-chain proteinuria and rapidly progressive glomerulonephritis [5]. In any case, acute renal failure (ARF) often complicates severe hepatic failure.

Case.

A 26-year-old Chinese man affected by pulmonary TB was started on rifampicin, isoniazid and pyrazinamide. Patient data on admission was not available. At discharge, BUN was 4.4 mmol/l, serum creatinine 80 µmol/l, total bilirubin 6 µmol/l, AST 81 U/l, ALT 133 U/l and CK 25 UI/l.

Two months later, the patient was admitted to our hospital as an emergency. He was pyretic (39.4°C), complained of a cough and vomiting. Relatives reported that he had taken the anti-tubercular treatment discontinuously. Clinical examination revealed a skin rash, mild jaundice and hepatomegaly. BUN was 27 mmol/l, creatinine 128 µmol/l, AST 2580 U/l, ALT 3370 U/L, LDH 2340 U/L, total bilirubin 45 µmol/l, prothrombin time 14%, INR 4, antithrombin III 10% and ammonia 106 µmol/l. White blood cell count showed eosinophilia >20%. Fulminant hepatic failure secondary to tuberculostatic treatment was diagnosed and all medications were discontinued. Over the next few days, he developed oliguria (<200 cc/day), marked hypotension, a haemorrhagic rash and grade 3 encephalopathy. Serum creatinine was 450 µmol/l, the urinary sodium was 16 mEq/l. Unfortunately, no liver was available for transplantation at that time. He was treated with large amounts of plasma expanders, lactulose, neomycin, vitamin K and coagulation factors. Diuresis increased to 2000 cc/day but his general condition remained poor. During the few next days, he developed massive bleeding from the GI tract, again became oliguric and eventually died. The post-mortem examination showed sub-massive necrosis of the liver, large areas of necrosis with caseation in both lungs, the kidneys presented interstitial oedema, small areas of perivascular interstitial infiltrate, whilst glomeruli and vessels were described as normal.

Comment.

At referral, on the basis of the history of discontinuous intake of tuberculostatic drugs, of the skin rash and of the eosinophilia, we thought that the renal failure was due to rifampicin-induced acute tubulointerstitial nephritis. However, presumably this patient presented a pre-renal form of acute renal failure, as shown both by the low urinary sodium, transient increase in daily diuresis with volume expansion and the post-mortem findings.

Hepatotoxicity secondary to chemotherapy of tuberculosis is quite common and probably under-reported [6,7]. It has been suggested that liver function should be tested before drug therapy, and at monthly intervals thereafter [8]. If serum AST rises to more than three times the normal rate or if there is any elevation in serum bilirubin, then isoniazid and rifampicin should be stopped. The reintroduction of such drugs is debatable but the patient's liver function should have returned to normal [8]. ARF is a frequent complication of severe hepatic failure. In 1974, Wilkinson reported 38 cases of ARF in over 48 patients with hepatic failure: among them 16 patients had pre-renal failure and 16 tubular necrosis [9].

References

  1. Grange JM, Zumia A. Paradox of the global emergency of tuberculosis. Lancet 1999; 353: 996[ISI][Medline]
  2. Drobnieski FA. Diagnosing multidrug resistant tuberculosis in Britain. Clinical suspicion should drive rapid diagnosis. Br Med J 1998; 315: 1263–1264
  3. Mandell GL, Petri WA. Antimicrobial agents, drugs for tuberculosis. In: Hardman JG et al. eds, Goodman & Gilman's The Pharmacological Basis of Therapeutics (9th Edn) Section IX, McGraw Hill, New York: 1996; 1155–1167
  4. Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: observation in routine treatment. Tubercle Lung Dis 1996; 77: 37–42[ISI][Medline]
  5. De Vriese An S, Robbrecht DL, Vanholder RC, Vogelaers DP, Lameire NH. Rifampicin-associated acute renal failure: pathophysiologic, immunologic, and clinical features. Am J Kidney Dis 1998; 31: 108–115[ISI][Medline]
  6. Singh J, Garg PK, Tandorn RK. Hepatotoxicity due to antituberculosis therapy. Clinical profile and reintroduction of therapy. J Clin Gastroent 1996; 22: 211–214[ISI][Medline]
  7. Caplin ME, Thompson NP, Hamilton MI, McIntyre N, Burroughs AK. The need for audit: preventable deaths due to hepatotoxicity of anti-tuberculosis chemiotherapy. Gut 1994; 35: F308
  8. Mitchell I, Wendon J, Fitt S, Williams R. Anti-tuberculous therapy and acute liver failure. Lancet 1995; 345: 555–556[ISI][Medline]
  9. Wilkinson SP, Blendis LM, Williams R. Frequency and type of renal and electrolyte disorders in fulminant hepatic failure. Br Med J 1974; 1: 186–189[ISI][Medline]




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