Effects of the prostacyclin analogue iloprost on cyclosporin-induced renal hypoperfusion in stable renal transplant recipients.
BACKGROUND
The synthetic prostacyclin analogues have been proposed to protect against cyclosporin A (CsA) nephrotoxicity. The present study investigated the effect of infusion of the prostacyclin analogue iloprost on the acute CsA-induced renal hypoperfusion and hypofiltration in stable renal-transplant recipients.


METHODS
The study included 10 stable renal-transplant recipients with good graft function (s-creatinine 90-170 micromol/l). Renal function and the acute renal haemodynamic and tubular response to an oral CsA-dose (Sandimmun Neoral, 3 mg.kg-1) were investigated with an infusion of iloprost (1 ng.kg-1.min-1) or placebo on 2 separate days. After an overnight fast, seven 30-min renal clearance periods were performed, two before infusion, three during infusion, and two recovery periods. An additional control clearance study without CsA intake or iloprost/placebo infusion was done in eight of the patients.


RESULTS
CsA ingestion decreased ERPF and GFR significantly with a maximum decline at the end of the clearance study. Iloprost infusion abolished the CsA-induced decrease in ERPF, but had no effect on the CsA-induced decrease in GFR, leading to a significant decline in FF. Renal clearance of lithium (CLi)), used as an index of proximal tulbular outflow, decreased in parallel with GFR after CsA intake, with no additional effects of iloprost. Iloprost infusion decreased blood pressure and increased heart rate.


CONCLUSIONS
Infusion of iloprost causes systemic and renal vasodilation, but has no effect on the CsA-induced decrease in GFR and CLi in stable renal transplant recipients.
Hansen
J M
JM
Department of Clinical Physiology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Christensen
N J
NJ
Fogh-Andersen
N
N
Strandgaard
S
S
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D014665:Vasodilator Agents / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D016572:Cyclosporine; D016285:Iloprost