CYCLOSPORINE DOES NOT INHIBIT THE TUBULAR SECRETION OF CREATININE

Background. The immunosuppressive drug cyclosporin is known to impair renal function. The degree of renal dysfunction is usually estimated f rom the clearance of creatinine (C-cr). Theoretically however, a fall in C-cr can be caused by a decrease of GFR, an inhibition of the tubul ar secretion of creatinine, or the combination of both. CsA has convin cingly been shown to decrease GFR, but detailed information on the eff ects of CsA on tubular secretion of creatinine is lacking. Methods. We performed two studies to investigate the influence of CsA on tubular creatinine secretion. In study A we simultaneously measured C-cr and G FR (using inulin) immediately before and 4 weeks after cessation of Cs A therapy in 17 renal transplant patients. In study B, the rise in ser um creatinine after administration of cimetidine, which blocks the tub ular secretion of creatinine, was compared in renal transplant patient s treated with either CsA (in whom secretion might already be inhibite d) or azathioprine. Results. Study A: After cessation of CsA there was an increase of GFR (54 +/- 15 vs 63 + 16 ml/min/1.73 m(2); P<0.01) an d of C-cr (71 +/- 21 vs 82 +/- 23 ml/min/1.73; m(2). P<0.01), but the ratio between C-cr and GFR (a measure of the relative contribution of tubular secretion to the clearance of creatinine) did not change signi ficantly (1.33 +/- 0.21 vs 1.32 +/- 0.30). Study B: In nine couples of patients matched for GFR the relative rises in serum creatinine after administration of cimetidine were 26 +/- 21% and 22 +/- 7% for the Cs A and azathioprine treated patients respectively (NS). Conclusion. CsA does not substantially inhibit the tubular secretion of creatinine. A rise in serum creatinine after administration of CsA can thus be attr ibuted completely to a fall in GFR.