Cyclosporin 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 from the clearance of creatinine (CCr). Theoretically however, a fall in CCr can be caused by a decrease of GFR, an inhibition of the tubular secretion of creatinine, or the combination of both. CsA has convincingly been shown to decrease GFR, but detailed information on the effects 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 CCr and GFR (using inulin) immediately before and 4 weeks after cessation of CsA therapy in 17 renal transplant patients. In study B, the rise in serum creatinine after administration of cimetidine, which blocks the tubular secretion of creatinine, was compared in renal transplant patients treated with either CsA (in whom secretion might already be inhibited) or azathioprine.


RESULTS
Study A: After cessation of CsA there was an increase of GFR (54+/-15 vs 63+/-16 ml/min/1.73 m2, PCr (71+/-21 vs 82+/-23 ml/min/1.73 m2; PCr and GFR (a measure of the relative contribution of tubular secretion to the clearance of creatinine) did not change significantly (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 CsA and azathioprine treated patients respectively (NS).


CONCLUSIONS
CsA does not substantially inhibit the tubular secretion of creatinine. A rise in serum creatinine after administration of CsA can thus be attributed completely to a fall in GFR.
Hilbrands
L B
LB
Department of Medicine, Division of Nephrology, University Hospital Nijmegen, P.O. Box 7101, NL-6500 HB Nijmegen, The Netherlands.
Wetzels
J F
JF
Hoitsma
A J
AJ
Koene
R A
RA
D000328:Adult; D002927:Cimetidine / Q000494:pharmacology; D003404:Creatinine / Q000378:metabolism*; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D007166:Immunosuppressive Agents; D002927:Cimetidine; D016572:Cyclosporine; D003404:Creatinine