Glomerulotubular function in long-term renal allograft recipients. A comparison of conventional therapy with cyclosporine

Glomerular and tubular function were assessed, using a lithium clearance technique, in two groups of renal allograft recipients at least one year after transplantation. Group 1 comprised 14 patients receiving low-dose prednisolone and cyclosporine, and group 2, 14 patients receiving low-dose prednisolone and azathioprine. There were no significant differences in creatinine clearances between the two groups, although the clearances of lithium (which is absorbed almost exclusively from the proximal tubule) and sodium were significantly lower in the cyclosporine-treated group. Fractional lithium excretion was also significantly lower in group 1 than in group 2, but there was no significant difference in fractional sodium excretion. The absolute proximal reabsorption of sodium and water did not differ between the groups, although the fractional proximal reabsorption of sodium and water was significantly higher in group 1. In contrast, the distal reabsorption of sodium and of water was significantly lower in the cyclosporine-treated patients than in the azathioprine-treated patients; there were, however, no significant differences in the distal fractional reabsorptions of sodium and water between the two groups. In addition there was no correlation in group 1 between whole-blood cyclosporine levels or time since transplantation and any of the assessed parameters of renal function. These results indicate that tubular concentrating abnormalities in cyclosporine-treated renal allograft recipients are similar to those observed in rodent models of cyclosporine nephrotoxicity. They suggest that the pathogenesis of cyclosporine nephrotoxicity may be similar in renal allograft recipients to that in experimental models.