Phospholipiduria in 2-bromoethanamine-induced renal papillary necrosis

The possibility that phospholipid excretion in urine might be a marker of renal papillary necrosis (RPN) induced by 2-bromoethanamine (BEA) was investigated in male Wistar rats following a single i.p. injection in time course and dose-response experiments. Urinary and serum creatinine as well as electrolytes were also measured in parallel to histological examination of tissues. A single i.p. injection of BEA caused a characteristic dose-related change in urinary phospholipids, notably sphingomyelin (SPM), phosphatidylcholine (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 the levels of the phospholipids; however, significant increases in the excretion 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 whether the excretion is expressed in units per hour excretion or units per milligram creatinine. The increased excretion of SPM and PC remained over 4 days 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 significant fall in the levels of some electrolytes (Na+, K+, Cl). Parallel histological 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 nitrogen 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 with RPN and may provide an important improvement in the non-invasive approach to the therapeutic management of renal diseases, and potentially prevent further degenerative changes.