Evidence for renal tubular leakage in maleic acid-induced Fanconi syndrome.

Abstract

Micropuncture and microinjection studies were performed in Sprague-Dawley rats 20 h after subcutaneous injection of buffered maleic acid (MA) or buffer alone in experimental and control rats, respectively. Collections were made from earliest and latest accessible portions of proximal tubule (PT). Lissamine green injections and microperfusion of PT demonstrated leakage of lissamine green from late PT sites in MA-treated rats, whereas inulin leakage occurred at a more distal site. Whole kidney GFR was 58% lower in MA-treated rats despite comparable single nephron GFR in PT of both groups. Microinjections of PT with [methoxy-3H]inulin resulted in injected inulin recovery from the contralateral kidney in MA-treated rats of 24.0 +/- 2.0 compared with 4.7 +/- 0.89% in controls, suggesting that tubular leakage of inulin accounted for the lower whole kidney GFR. Net sodium and phosphate transport in early PT was similar in both groups but was decreased in late PT segments in MA-treated rats. Sodium and phosphate excretion in final urine were, however, comparable in both groups. The significantly lower plasma phosphate concentration might account for the blunted phosphaturia in MA-treated rats. These studies demonstrate a segmental effect of MA on 1) tubular leakage to lissamine green from late PT and inulin beyond the late PT, and 2) decreased net sodium and phosphate transport in the PT.