Effect of cystine dimethylester on renal solute handling and isolated renal tubule transport in the rat: a new model of the Fanconi syndrome.

The effect of cystine dimethylester on the renal handling of phosphate, glucose, alpha-amino nitrogen, amino acids, and protein in vivo and on the uptake of lysine, glycine, taurine, and alpha-methyl glucoside by isolated renal tubules in vitro was studied in adult male rats. Parenteral administration of 400 mumol twice a day for four days of cystine dimethylester led to an increased urine volume, and excretion of phosphate, glucose, alpha-amino nitrogen, and the amino acids glutamine, proline, alanine, 1/2 cystine, ornithine, lysine, histidine, and glycine. Cystine dimethylester treatment did not affect the creatine clearance nor were any renal anatomic abnormalities noted. Intracellular cysteine, but not cystine, was increased in the kidney after the four days of treatment. Pre-incubation of isolated renal tubules with 2 mmol/L cystine dimethylester for ten minutes markedly inhibited the uptake of 0.025 mmol/L lysine, 0.1 mmol/L glycine, 0.01 mmol/L taurine, and 2 mmol/L alpha-methyl glucoside. Incubation with 2 mmol/L cystine dimethylester for ten minutes did not affect the ability of the renal tubule to exclude trypan blue dye, although longer incubation times did lead to significant staining. The intracellular cystine concentration of the renal tubule did rise significantly after incubation with cystine dimethylester, a biochemical correlate of the human disease cystinosis. These studies indicate that cystine dimethylester can induce an experimental form of the Fanconi syndrome both in vivo and in vitro and offers a new model for investigating the mechanisms underlying this enigmatic disorder.