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Renal failure and haemolysis caused by rifampicin
234
Letters to the Editor
References 1 Harper, J. R. (1982). Anaphylactic reaction to BCG vaccination. Lancet, 1, 403. 2 Tshabalala, R. T. (1983). Anaphylactic reactions to BCG in Swaziland. Lancet, 1, 653. 3 Ungar,J., Muggleton, P. W, Dudley, J. A. R., Griffiths, M. I. (1962).Preparation and propertiesof freeze-dried BCG vaccine of increased stability. British Medical Journal, 2, 1086. 4 Ring, J., Messmer, K. (1977). Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet, 1, 466. 5 Hedin, H., Richter, W., Kraft, D. (1981). Pathomechanism of dextran-induced anaphylactoid reactions in man. International Archives of Allergy and Applied Immunology, 66 (Suppl. 1), 75. 6 Palosuo, T., Milgrom, F. (1981). Appearance of dextrans and anti-dextran antibodies in human sera. International Archives of Allergy and Applied Immunology, 65, 153.
Renal failure and haemolysis caused by rifampicin This is to report a case which resembles the first patient described by Cohn et al in their report of rifampicin-induced renal failure [1]. A 50-year old woman was prescribed 600 mg rifampicin daily for tuberculosis. Three and a half years earlier she had received 9 months chemotherapy including rifampicin, during which she developed leucopenia [2]. The patient had for some years been treated with sodium aurothiomalate and prednisolone (2.5 mg) for rheumatoid arthritis and myalgia. After starting rifampicin her myalgia worsened and the prednisolone dose was increased to 5 mg on the sixth day. On the seventh day laboratory tests including haemoglobin, reticulocyte and white blood cell counts, serum creatinine and aspartate aminotransferase (AST) were all normal. On the seventh day within 1 h of taking rifampicin she developed a 'flu'-syndrome. She did not take the drug the next day, but did so the following morning. Within 1 h she suffered pain in the chest and the flank, chills, thirst, vomiting and diarrhoea. The temperature rose to 39.9 °C. Haemolysis, icterus and renal failure with proteinuria, haematuria and anuria developed. The haemoglobin fell to 7.4 g/I, the serum creatinine rose to 867 pmol/I, bilirubin to 85 Fmol/I and ASTto 225 U/I. The liver function returned to normal 3 days after stopping rifampicin. The anuria-oliguria persisted for 10 days during which seven haemodialyses were performed. The renal function returned to normal in 3 months. A lymphocyte transformation test to rifampicin was negative. Nine cases of haemolytic anaemia and renal failure caused by rifampicin have previously been reported. They occurred during intermittent therapy, when the patient had been irregular in taking daily rifampicin, or when the drug had been resumed after an interval of 3 days to several months [3, 4, 5]. M6hring e t a l [6] have reported a case where the symptoms developed after an interval of 6 weeks. In my case the interval was 31/2 years. The 'flu'-syndrome is extremely rare during daily rifampicin medication [4]. An investigation by Mattson and J~nne [7] with rifampicin rechallenge indicated that it might be caused by mild intravascular haemolysis and is only quantitatively different from more serious reactions, such as massive haemolysis and renal failure. This report seems to confirm that theory. Also myalgia caused by myoglobinaemia and myoglobinuria may be associated with the 'flu'-syndrome [8, 9]. Prednisolone does not seem to prevent haemolysis and renal failure [10]. After such side-effects rifampicin should never by given again [4]. D e p a r t m e n t o f P u l m o n a r y Diseases, North Karelia Central Hospital, SF-80780 Kontioniemi, Finland
A l e x a n d e r H. W. van A s s e n d e l f t
Letters to the Editor
235
References
1 Cohn, J. R., Fye, D. L., Gills, J. M., Frauers, G. C. (1985). Rifampicin induced renal failure. Tubercle, 66, 289. 2 van Assendelft, A. H. W. (1984). Leucopenia caused by two rifampicin preparations. European Journal of Respiratory Diseases, 65, 251. 3 Criel, A., Verwilghen, R. L. (1980). Intravascular haemolysis and renal failure caused by intermittent rifampicin treatment. Blur, 40, 147. 4 Girling, D. J. (1977). Adverse reactions to rifampicin in antituberculosis regimens. Journal of Antimicrobial Chemotherapy, 3, 115. 5 Nessi, R., Bonoldi, G. L., Redaelli, B., di Filippo, G. (1976). Acute renal failure after rifampicin: a case report and survey of the literature. Nephron, 16, 148. 6 M6hring, K., Asbach, H. W., Schubothe, H., Weber, S. (1974). H~molytische Krise mit akutem Nierenversagen unter Rifampicin-Behandlung. Deutsche Medizinisehe Wochenschrift, 99, 1458. 7 Mattson, K., J~nne, J. (1982). Mild intravasal haemolysis associated with flu-syndrome during intermittent rifampicin treatment. European Journal of Respiratory Diseases, 63, 68. 8 Qunibi, W. Y., Godwin, J., Eknoyan, G. (1980). Toxic nephropathy during continuous rifampin therapy. Southern Medical Journal, 73, 791. 9 Bansal, V. K., Bennett, D., Molnar, Z. (1977) Prolonged renal failure after rifampin. American Review of Respiratory Disease, 116, 137. 0 Vathesatogkit, P., Phanichphant, S., Pasukunthapuk, B. (1983) Acute renal failure associated with rifampicin therapy for urethritis. A case report. Journal of the Medical Association of Thailand, 66, 356.
Letters to the Editor
References 1 Harper, J. R. (1982). Anaphylactic reaction to BCG vaccination. Lancet, 1, 403. 2 Tshabalala, R. T. (1983). Anaphylactic reactions to BCG in Swaziland. Lancet, 1, 653. 3 Ungar,J., Muggleton, P. W, Dudley, J. A. R., Griffiths, M. I. (1962).Preparation and propertiesof freeze-dried BCG vaccine of increased stability. British Medical Journal, 2, 1086. 4 Ring, J., Messmer, K. (1977). Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet, 1, 466. 5 Hedin, H., Richter, W., Kraft, D. (1981). Pathomechanism of dextran-induced anaphylactoid reactions in man. International Archives of Allergy and Applied Immunology, 66 (Suppl. 1), 75. 6 Palosuo, T., Milgrom, F. (1981). Appearance of dextrans and anti-dextran antibodies in human sera. International Archives of Allergy and Applied Immunology, 65, 153.
Renal failure and haemolysis caused by rifampicin This is to report a case which resembles the first patient described by Cohn et al in their report of rifampicin-induced renal failure [1]. A 50-year old woman was prescribed 600 mg rifampicin daily for tuberculosis. Three and a half years earlier she had received 9 months chemotherapy including rifampicin, during which she developed leucopenia [2]. The patient had for some years been treated with sodium aurothiomalate and prednisolone (2.5 mg) for rheumatoid arthritis and myalgia. After starting rifampicin her myalgia worsened and the prednisolone dose was increased to 5 mg on the sixth day. On the seventh day laboratory tests including haemoglobin, reticulocyte and white blood cell counts, serum creatinine and aspartate aminotransferase (AST) were all normal. On the seventh day within 1 h of taking rifampicin she developed a 'flu'-syndrome. She did not take the drug the next day, but did so the following morning. Within 1 h she suffered pain in the chest and the flank, chills, thirst, vomiting and diarrhoea. The temperature rose to 39.9 °C. Haemolysis, icterus and renal failure with proteinuria, haematuria and anuria developed. The haemoglobin fell to 7.4 g/I, the serum creatinine rose to 867 pmol/I, bilirubin to 85 Fmol/I and ASTto 225 U/I. The liver function returned to normal 3 days after stopping rifampicin. The anuria-oliguria persisted for 10 days during which seven haemodialyses were performed. The renal function returned to normal in 3 months. A lymphocyte transformation test to rifampicin was negative. Nine cases of haemolytic anaemia and renal failure caused by rifampicin have previously been reported. They occurred during intermittent therapy, when the patient had been irregular in taking daily rifampicin, or when the drug had been resumed after an interval of 3 days to several months [3, 4, 5]. M6hring e t a l [6] have reported a case where the symptoms developed after an interval of 6 weeks. In my case the interval was 31/2 years. The 'flu'-syndrome is extremely rare during daily rifampicin medication [4]. An investigation by Mattson and J~nne [7] with rifampicin rechallenge indicated that it might be caused by mild intravascular haemolysis and is only quantitatively different from more serious reactions, such as massive haemolysis and renal failure. This report seems to confirm that theory. Also myalgia caused by myoglobinaemia and myoglobinuria may be associated with the 'flu'-syndrome [8, 9]. Prednisolone does not seem to prevent haemolysis and renal failure [10]. After such side-effects rifampicin should never by given again [4]. D e p a r t m e n t o f P u l m o n a r y Diseases, North Karelia Central Hospital, SF-80780 Kontioniemi, Finland
A l e x a n d e r H. W. van A s s e n d e l f t
Letters to the Editor
235
References
1 Cohn, J. R., Fye, D. L., Gills, J. M., Frauers, G. C. (1985). Rifampicin induced renal failure. Tubercle, 66, 289. 2 van Assendelft, A. H. W. (1984). Leucopenia caused by two rifampicin preparations. European Journal of Respiratory Diseases, 65, 251. 3 Criel, A., Verwilghen, R. L. (1980). Intravascular haemolysis and renal failure caused by intermittent rifampicin treatment. Blur, 40, 147. 4 Girling, D. J. (1977). Adverse reactions to rifampicin in antituberculosis regimens. Journal of Antimicrobial Chemotherapy, 3, 115. 5 Nessi, R., Bonoldi, G. L., Redaelli, B., di Filippo, G. (1976). Acute renal failure after rifampicin: a case report and survey of the literature. Nephron, 16, 148. 6 M6hring, K., Asbach, H. W., Schubothe, H., Weber, S. (1974). H~molytische Krise mit akutem Nierenversagen unter Rifampicin-Behandlung. Deutsche Medizinisehe Wochenschrift, 99, 1458. 7 Mattson, K., J~nne, J. (1982). Mild intravasal haemolysis associated with flu-syndrome during intermittent rifampicin treatment. European Journal of Respiratory Diseases, 63, 68. 8 Qunibi, W. Y., Godwin, J., Eknoyan, G. (1980). Toxic nephropathy during continuous rifampin therapy. Southern Medical Journal, 73, 791. 9 Bansal, V. K., Bennett, D., Molnar, Z. (1977) Prolonged renal failure after rifampin. American Review of Respiratory Disease, 116, 137. 0 Vathesatogkit, P., Phanichphant, S., Pasukunthapuk, B. (1983) Acute renal failure associated with rifampicin therapy for urethritis. A case report. Journal of the Medical Association of Thailand, 66, 356.