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CONTINUOUS IMPROVEMENT IN MEASURED GLOMERULAR FILTRATION RATE WITH TAPERING CALCINEURIN INHIBITOR AND THE INTRODUCTION OF MYCOPHENOLATE MOFETIL IN LIVER TRANSPLANT RECIPIENTS
CH Dale, PJ Marotta
Multi-organ Transplant Program, London Health Sciences Centre, University of Western Ontario, London, Ontario
BACKGROUND: The incidence of chronic renal failure (CRF) due to calcineurin inhibitor (CNI) nephrotoxicity in liver transplant (LT) recipients is significant. Immunosuppressant regimens that limit renal dysfunction have become a priority and utilization of concomitant therapy such as mycophenolate mofetil (MMF), may prevent renal dysfunction over the long term. Objective measures of renal dysfunction in LT are varied and generally inaccurate. Measured radionucleotide glomerular filtration rate (mGFR), however is quite accurate. Little data exists on the long term impact of CNI reduction on mGFR.
METHODS: LT recipients maintained on CNI monotherapy, with stable liver profile and no recent history of rejection were identified. The CNI dose was tapered sequentially to 25% of the original dose, and MMF was initiated. mGFR was performed at baseline, 6 months and annually. The primary outcome was a change in mGFR from baseline without graft rejection.
RESULTS: 24 LT recipients were identified and began the protocol a mean of 37 months (range 9-102) after LT. Ninety-two percent (22/24) had baseline mGFR confirming stage 2 or worse CRF (< 89 ml/min/1.73m2). The mean baseline mGFR was 59.5 ± 19.5 (range 32-118). The 6 and 12 month mean percent change in mGFR from baseline was +19.2% ± 27.9 (p= 0.007), and +21.2%± 25.5 (p=0.0002). At 6 and 12 months 74% and 75 % of recipients experienced a positive change in mGFR. For patients with stage 3 CRF (n=14; GFR< 60), the mean mGFR at baseline was 47.3 ± 8.1. The 6 and 12 month mean percent change in mGFR from baseline was +17%± 26.5 (p=0.04) and +30.8%± 25.2 (p=0.0006). At 6 and 12 months respectively 77% and 93% experienced no deterioration in mGFR. The mean creatinine improved over 12 months, 114 umol/L vs 104 umol/L (p=<0.0001). Changes in liver profile occurred in 1 patient. Liver biopsy confirmed recurrent disease. The mean dose of MMF was 1812 mg/day, and the average reduction in CNI was 57% for tacrolimus and 65% for cyclosporine.
CONCLUSION: Significant improvement of renal function can be safely accomplished utilizing MMF with reduction of CNI. Those at most risk (stage 3 CRF) had the largest absolute and percent improvement in mGFR. This effect was noted even after many years of CNI monotherapy. The addition of MMF and reduction of CNI at any time after LT should be considered as a means of preserving long term renal function.