961

Abstract

Introduction: Chronic allograft nephropathy is the primary cause of late graft dysfunction in the renal transplant population. The causes are multi-factorial including calcineurin inhibitor nephrotoxicity. Calcineurin inhibitors (CNI), such as tacrolimus and cyclosporine are commonly used in solid organ transplant patients to prevent allograft rejection. They contribute to chronic allograft nephropathy and cause nephrotoxicity in all solid organ transplant populations via afferent arteriolar vasoconstriction. Fenoldopam is a dopamine receptor-1 agonist, which causes vasodilatation in the proximal tubule, and theoretically will directly antagonize the deleterious effects of CNI induced renal failure; with in-vitro data to suggest its efficacy in preventing CNI induced renal failure. Methods: A retrospective chart review was performed on transplant patients, in acute renal failure, admitted to the University of Kentucky medical center from 2004- 2011. Our primary objective was to compare changes in renal function values: serum creatinine (Scr) and urine output (UOP) of patients admitted with acute renal failure due to CNI who received either fenoldopam or no drug. Patient data was collected at baseline (time 0) and then for 4 continuous days upon admission (non-fenoldopam group) or at the point of initiation of fenoldopam (time 1) until day 5, or the end of the infusion. Demographic data were analyzed using either a two sample T-test or Mann-Whitney U test, when appropriate. Repeated measures ANOVA with and without adjustment for covariates for the outcomes of Scr and UOP were performed using SAS version 9.3 by SAS Institute (Cary, NC). Results: A total of 87 patients were analyzed (36 non-fenoldopam; 51 fenoldopam). Differences in demographics were significant for a higher SOFA score in the fenoldopam group, (4.8 ± 2.77 vs 2.97 ± 1.68 p=0.0005) After controlling for confounders, the effect of fenoldopam on urine output (UOP) was not statistically significant (p=0.08771) at any time point throughout the infusion time (days 1-4, or end of infusion, day 5) compared to the non-drug group. The non-drug group saw a statistically significant decrease in Scr over the 4 days (-1.0173 ± 0.2143 p= <0.001). The fenoldopam group saw a decrease in Scr from time 1 (start of infusion) over the 4 time points, however this effect did not reach statistical significance (-0.13 ± 0.2 p=0.5194). Conclusions: Although in-vitro data exist to suggest fenoldopam's efficacy in preventing CNI induced renal failure, fenoldopam was not associated with improvement in renal function parameters in this transplant population. As this is the first reported use of fenoldopam for this indication in humans, there is an opportunity for a randomized trial to determine the utility in CNI induced renal failure.