Histological study of isoniazid-rifampicin related nephrotoxicity in Wistar rats

Introduction: Nephrotoxicity is a severe adverse effect of antituberculotics with acute renal failure as the most frequent clinical presentation. Associated patohistological feature is tubular necrosis or interstitial nephritis with or without glomerular lesions. The incidence of rifampicin induced kidney damage varies from 1,8% to 16% of all acute renal failures. A well defined clinical, patohistological and patophysiological features of rifampicin nephrotoxicity have not yet been determined and are generally missing. The aim of this study is to perform qualitative histological analysis of Wistar rat kidney after 21 day coadministration of rifampicin and isoniazid. Materials and methods: Twenty one adult male Wistar rats (210-280g) were divided into two groups: Control group (7 rats) and RIF+INH group (14 rats). The control group received 4ml/kg isotonic saline solution while animals in RIF+INH group were coadministered with rifampicin and isoniazid, dissolved in 4ml/kg of isotonic saline in dose of 50mg/kg. Dosing was performed intraperitoneally, daily, during 21 days. After that period animals were euthanized to obtain kidney tissue for histotechnological procedure. Kidney slides were stained with HE and PAS method and analysed using light microscopy. Results: The most important findings of our study were glomerular lesions while renal tubules were generally preserved. Lesions had patchy distribution, renal corpuscles were enlarged with possible mild mesangial hypertrophy. Glomerular capillary tufts showed shrinkage resulting in noticeably dilated Bowman’s space and sporadical lobulation of capillary loops. Conclusion: Intraperitoneal coadministration of rifampicin and isoniazid for 21 days, caused mild to moderate histological changes of kidney tissue in Wistar rats.