Morphological Changes in the Pig Kidney Associated with an Acutely Induced Renal Papillary Necrosis

Abstract

Analgesic abuse leads to the development of renal papillary necrosis (RPN) and may cause upper urothelial carcinoma in man. Animal models offer a potentially important means by which to define the underlying pathogenesis of RPN. Moreover, their use could improve early diagnosis, allowing the identification of which analgesic has the greatest papillotoxic potential and define what factors exacerbate this lesion (1). Many analgesics induce gastro-intestinal toxicity in rats which limits the use of this species for studying analgesic-induced RPN (2). The use of the non-analgesic papillotoxic chemical 2-bromoethanamine (BEA) hydrobromide, has helped define the mechanistic basis of RPN, particularly because this compound targets selectively for the medulla and causes a lesion in rodents within 24–48 hr (1). The BEA-induced RPN in the Wistar rat shows most of the pathological changes described in human analgesic abusers (3). The primary choice of rodents for nephrotoxicity studies reflects their low cost, ready availability, ease of handling and the considerable baseline data on renal function and toxicity. However, the extrapolation of nephrotoxicity data from rodents to man is complicated by the marked renal anatomical and functional differences between the two species. In contrast the human and pig kidney are remarkably similar in terms of physiological and anatomical characteristics (Table I).