POST-TRANSPLANT STAGE PROGRESSION IN LIVER TRANSPLANT RECIPIENTS WITH CHRONIC KIDNEY DISEASE (CKD): SINGLE CENTER ANALYSIS WITH 10 YEARS OF FOLLOW-UP

OUTCOMES OF LIVER TRANSPLANTATION I

J.C. Lamattina¹, D.P. Foley¹, J. Mezrich², L.A. Fernandez¹, A. D'alessandro¹, J. Pirsch³, A. Djamali^3
1Department Of Surgery, University of Wisconsin, Madison/WI/UNITED STATES OF AMERICA, ²Surgery, University of Wisconsin, Madison/UNITED STATES OF AMERICA, ³Medicine And Surgery, University of Wisconsin, Madison/UNITED STATES OF AMERICA

Body: Introduction We recently reported the incidence of end-stage renal disease (ESRD) in liver transplant recipients to be 2.6%, 7.5%, and 18% at 5, 10, and 20 years following transplantation despite a calcineurin inhibitor-based maintenance regimen. As outcomes continue to improve, long-term native kidney function becomes more critical to liver recipient survival. The purpose of our study was to analyze risk factors for CKD stage progression in an effort to minimize subsequent ESRD in liver transplant recipients. Methods We performed a retrospective review of 1151 adult, deceased-donor, single-organ primary liver transplantations between 7/17/84 and 12/31/07. Analysis of long-term renal function was performed on 729 patients with available outpatient creatinine values beyond 1 year post-operatively. The primary endpoint in this study was the progression of CKD from one stage to a higher stage (lower GFR). GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. Patients were assigned to a stage of CKD based on the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Initial CKD stage was based on all outpatient creatinine values (≥3) obtained between post-operative months 11 and 14. Stage progression was calculated using all measured outpatient creatinine values obtained during subsequent three month intervals during the study period. Stage progression occurred if the averaged GFR for a given three month block resulted in a higher CKD stage. Kaplan-Meier analysis was used to estimate rates of stage progression. Univariate and multivariate analysis was performed to identify potential risk factors leading to stage progression. The initial immunosuppression of all recipients was a calcineurin-based regimen. Results The overall incidence of stage progression was 28%, 40%, and 53%, at 3, 5, and 10 years. Univariate analysis revealed that stage progression was more likely to occur in patients starting from lower stages (better renal function) at one-year (HR 0.33, CI 0.28-0.38, p<0.0001). Pretransplant diabetes, hypercholesterolemia, and infectious complications during the first year were predictive of subsequent stage progression. Caucasian race and higher physiologic MELD at the time of transplant proved protective. On multivariate analysis, stage of CKD, urinary tract infections, pretransplant diabetes, and hypercholesterolemia were independent risk factors for stage progression. There were no significant differences in the rate of stage progression in patients maintained on cyclosporine versus tacrolimus.

Multivariate Factor	Hazard Ratio	Confidence Interval	p-value
Stage at 1 year	0.28	0.23-0.34	<0.0001
Urinary tract infection	1.39	1.00-1.93	0.048
Pre-transplant diabetes	1.90	1.38-2.63	<0.0001
Hypercholesterolemia	1.46	1.04-2.05	0.028

Conclusions In liver transplant recipients, the stage of CKD at one year is predictive of subsequent stage progression. Risk factors for stage progression are similar to risk factors for ESRD in the general population. Careful long-term monitoring of renal dysfunction and stage progression of CKD may ultimately prove critical to preventing ESRD in liver transplant recipients.

Disclosure: All authors have declared no conflicts of interest.