1. An interesting case of ARF Prof.S.Shivakumar unit R.Anitha, MD PG

2. First Admission on 21/3/03 Mr.Gandhi,36yr old male, with symptoms of chronic cough and expectoration, heamoptysis and fever,was diagnosed to have sputum +ve pulmonary TB.He was started on ATT on 8/3/03.3 weeks later the pt was admitted in the ward with h/o dyspnoea, oliguria, facial puffiness and pedal edema for 10 days.On evaluation of his clinical profile and lab data, he was diagnosed to have renal failure. His inv.reports as follows,

3. Lab reports RFT Bld urea 153 mg/dl Sr creat 21.1 mg/dl Sr electrolytes Na+ 138 mg/dl K+ 3.9 mg/dl Sr uric acid 8 mg/dl Sr phosphate 7.4 mg/dl Urine analysis Alb + Sugar nil Epi cells 2-4 Pus cells 4-6 24 hr urine pr 40 mg/L Urine c/s no growth

4. continued Complete heamogram Hb% 10.6 g% Pcv 32% TC 8600 DC P61 L36 E3 ESR 80/140 Platelets 1 lak cells LFT Total bilirubin 1.0mg/dl SGOT 32 IU/dl SGPT 25 IU/dl Bld glucose 80 mg/dl Total protien 5.6 g% Total cholesterol 200 mg%

5. continued Sr HIV –ve Sr HBsAg –ve VDRL NR ECG WNL CXR bil apical infiltrations s/o PT USG abd bil medical renal disease non specific hepatomegaly

6. Provisional diagnosis Acute Renal Failure ? Drug induced (rifampicin)

7. Treatment given ATT was stopped 60 cycles of PD given After stopping ATT and PD, his RFT values were as follows (2003) Date21/322/328/331/303/409/4 Urea mg/dl153186168988648 Creatinine Mg/dl 21.112.88.04.52.41.5

8. Discharge advise Pt was advised to continue ATT without rifampicin

9. Second Admission on 24/9/06 The pt was readmitted 3yrs later with h/o fever with chills,vomiting, loin pain, oliguria, heamaturia, puffiness of face, pedal edema. His past history revealed that he discontinued ATT after the last admission. Again he developed the symptoms of TB and was found to be sputum +ve and was restarted on ATT(18/09/06).

10. On examination Pt was febrile. Had puffiness of face and pedal edema. His BP was 160/90mmhg. Had basal creps in his lung fields

11. Lab Reports RFT Bld urea 168 mg/dl Sr creat 11.1 mg/dl Sr electrolytes Na+ 138 mg/dl K+ 3.9 mg/dl Sr uric acid 8.3 mg/dl Sr phosphate 6.3 mg/dl Urine analysis Alb ++ Sugar nil Epi cells 1-2 Pus cells 10-12 RBC’s 25-27/hpf Bile salts&pigments nil

12. Continued Complete heamogram Hb% 12.0 g% Pcv 36% TC 7200 DC P54 L43 E3 ESR 28/60 Platelets 1.2 lak cells LFT Total bilirubin 1.0mg/dl SGOT 31 IU/dl SGPT 40 IU/dl Bld glucose 127 mg/dl Total protien 5.6 g% Total cholesterol 256 mg%

13. Continued ECG WNL CXR bil apical infiltrations s/o PT USG abd bil medical renal disease non specific hepatomegaly

14. Diagnosis Acute Renal Failure Rifampicin Induced The occurence of renal failure again ( second time ) definitely proves that Rifampicin is the cause.

15. Treatment given ATT was continued without rifampicin 7 cycles of HD given After stopping rifampicin and HD, his RFT values were as follows (2006) Date26/928/905/1009/1012/1016/10 Urea mg/dl1681051181587828 Creatinine Mg/dl 11.010.79.07.12.01.2

16. Similar cited articles Covic A, Goldsmith DA et al. Rifampicin induced ARF: a series of 60 patients.Nephrol Dial Transplant1983; 13:924-929 Muthukumar T et al.ARF due to rifampicin:a study of 25 patients.Am J Kidney Dis. 2002 oct;40(4):690-6

17. Discussion From the data of TRC chetpet, Of treating more than 8000 pulm & extrapulm pts with rifampicin containing regimen from early 1970’s,3cases of probably rifampicin induced ARF has been reported. A data from nephrology department of MMC states that rifampicin induced ARF constituted 2.5% of all cases of ARF during the study period of 1990-2000. ARF due to rifampicin usually occurs in pts receiving intermittent or interrupted therapy & rarely with continuous therapy.

18. Clinical picture The pt usually presents with gastrointestinal and flu like symptoms and clinical signs of intravascular heamolysis. Post-rifampicin ARF is characteristically ass. with autoimmune heamolysis, thrombocytopenia, DIC, hepatic injury &tubular defects, thus creating a polymorphic picture. Frequent lab findings are anemia, leukocytosis, thrombocytopenia, hypergammaglobulinemia& evidence of hepatic injury.

19. Renal toxicity of rifampicin Acute tubulointerstitial nephritis and/or tubular defects. Isolated or superimposed glomerular injury presenting either with a RPGN or a frank nephrotic syndrome. The presentation is usually oligoanuria. And the urinalysis reveals sterile leukocyturia, protienuria, heamaturia & heamoglobinuria.

20. Immune induced rifampicin toxicity Acc. Of antirifampicin Ab during drug free interval (I Ag - RBC’s & tubular epi) Readministration of drug Intense immune reaction Intravascular heamolysis Immune complex deposition in blood vessels & interstitium heamoglobinuria ATNAIN

21. Diagnosis of post-rifampicin ARF The specific time course of events, in association with a previous normal renal function and absence of other potential causes for ARF, establishes rifampicin as the sole etiology. Routine examination for antirifampicin Ab & renal biopsy are not considered essential for positive diagnosis.

22. Prognosis Clinical course is very favourable with very rare mortality. Prognostic factors: duration of anuric phase& the severity of the immunological abnormalities and inflammatory syndrome(heamolysis, leucocytosis& hypergammaglobulinemia)

23. THANK YOU