The Open Transplantation Journal

2009, 3 : 9-13
Published online 2009 April 17. DOI: 10.2174/1874418400903010009
Publisher ID: TOTRANSJ-3-9

c Renal Function Following Heart Transplantation

Pal Falck , Arnt E. Fiane , Odd R. Geiran and Anders Asberg
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box. 1068, Blindern, 0316 Oslo, Norway

ABSTRACT

Background:

The secondary metabolites of cyclosporine A (CsA), AM19, AM1c and AM1c9, have been indicated to be nephrotoxic. The aim of the present pilot study was to investigate the relationship between acute renal failure and CsA metabolite levels, including relevant pharmacokinetic genotypes, following heart transplantation.

Method:

Whole-blood samples were drawn the first posttransplant week in 22 patients (median 54 years, range from 27 to 65). Whole blood concentrations of CsA and its six main metabolites were analyzed with a validated HPLC-MS/MS method, and relevant CYP3A5 and ABCB1 genotypes determined. Renal function was monitored daily during the first posttransplant month and also at months 3, 6 and 12.

Results:

One patient died early posttransplant. Six patients were in need of dialysis directly after transplantation. Nine patients developed sustained impaired renal function, while six had stable renal function. Sustained renal impairment tended to be associated with high levels of toxic metabolites (P=0.08). Six of the patients with possible ABCB1 TTT-haplotype developed renal impairment (P=0.12).

Conclusions:

The present study indicates that toxic CsA metabolites seems to be associated with development of impaired renal function and together with ABCB1 genotyping they might be promising biomarkers for optimalization of immunosuppressive drug treatment in future studies.

Keywords:

Cyclosporine A, heart transplantation, renal impairment, metabolites, nephrotoxicity.