title: Acute cyclosporine-induced nephrotoxicity in renal transplant recipients: the role of the transplanted kidney.
abstract: Cyclosporine A causes an acute reduction in GFR. The interindividual variable reduction in GFR is most likely the result of arteriolar vasoconstriction. Vasoconstriction is attributable either to a local effect of cyclosporine on renal blood vessels (intrinsic mechanism) or to a systemic effect of cyclosporine on circulating and/or neuronal factors (extrinsic mechanism). The aim of the investigation presented here was to establish whether intrinsic or extrinsic mechanisms account for the interindividual differences in the susceptibility to acute cyclosporine-induced nephrotoxicity. For that purpose, this study took advantage of the clinical transplant situation in which two (intrinsically identical) kidneys from a cadaveric donor are transplanted into two (extrinsically) different subjects. The preexisting regular daily cyclosporine doses were raised by 25% for 2 wk and by 50% for another 2 wk in 16 patients with stable renal graft function, representing eight pairs of patients, each of whom had received kidneys from the same donor. In these patients, a mean (+/- SD) maximum cyclosporine-induced increase in serum creatinine concentration of 13 +/- 11% (P < 0.001) and in serum BUN of 27 +/- 33% (P < 0.01), together with a decline in the fractional uric acid excretion of 51 +/- 89% (P < 0.02) were observed. The percentage change in serum creatinine concentrations after increased dosing of cyclosporine paralleled within the subjects receiving their kidneys from the same donor, i.e., when one recipient experienced a large percentage of change after increases of cyclosporine dosing, the corresponding recipient of a kidney from the same donor had a change of the same magnitude. Seven of eight pairs showed a consistent response with respect to a clinically significant increase in serum creatinine concentration of > 15%, with a consistent response purely by chance being < 5%. Thus, the transplanted kidney itself rather than the recipient determines the susceptibility to acute cyclosporine-induced nephrotoxicity.
authors.affiliation: Department of Medicine, University of Berne, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Wissmann
authors.forename: F J
authors.initials: FJ
authors.lastname: Frey
authors.forename: P
authors.initials: P
authors.lastname: Ferrari
authors.forename: D E
authors.initials: DE
authors.lastname: Uehlinger
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine