Phospholipiduria in 2-bromoethanamine-induced renal papillary necrosis

The possibility that phospholipid excretion in urine might be a marker of r enal papillary necrosis (RPN) induced by 2-bromoethanamine (BEA) was invest igated in male Wistar rats following a single i.p. injection in time course and dose-response experiments. Urinary and serum creatinine as well as ele ctrolytes were also measured in parallel to histological examination of tis sues. A single i.p. injection of BEA caused a characteristic dose-related c hange in urinary phospholipids, notably sphingomyelin (SPM), phosphatidylch oline (PC) and phosphatidylethanolamine (PE) excretion on the first day of treatment. At a lower dose of 30 mg kg(1) BEA, there was no alteration in t he levels of the phospholipids; however, significant increases in the excre tion of SPM, PC and PE at the 90 and 240 mg kg(1) dose level were observed. There was an early increase in the three phospholipids irrespective of whe ther the excretion is expressed in units per hour excretion or units per mi lligram creatinine. The increased excretion of SPM and PC remained over 4 d ays while PE levels returned to normal after day 1. On day 1, urinary flow rate and creatinine were also increased significantly while there was a sig nificant fall in the levels of some electrolytes (Na+, K+, Cl). Parallel hi stological examination also confirmed the presence of RPN at the two higher doses (90, 240 mg kg(1)) of BEA. Other measurements such as blood urea nit rogen and the levels of Ca2+ and Mg2+ in blood were unaffected at all dose levels of BEA. These results demonstrate the potential of specific urinary phospholipids as diagnostic bio-markers for early renal injury associated w ith RPN and may provide an important improvement in the non-invasive approa ch to the therapeutic management of renal diseases, and potentially prevent further degenerative changes.