Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation

Abstract

Objectives: Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function.

Methods: The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients (GFR 44.9 ' 9.9 mL/min/1.73m2 measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ' 0.42 mg/dL) were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d.

Results: At month 12 mean SCr (-0.3 ' 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ' 13.1 mL/min/ 1.73m superset2, p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ' 22 mmHg (p = 0.03).

Conclusions: Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.

Figure 1

SCr levels measured after engraftment, at study inclusion and months 6 and 12 after conversion to MMF therapy. Data are given as box plots, where the limits of the boxes indicate the 25th and 75th percentiles and the lines inside the boxes indicate the 50th (median) percentile. The whiskers indicate the 10th and 90th percentiles.

Figure 2

GFR measured by 99m-Tc-DTPA-Clearance at study inclusion and months 6 and 12 after conversion to MMF therapy. Data are given as box plots, where the limits of the boxes indicate the 25th and 75th percentiles and the lines inside the boxes indicate the 50th (median) percentile. The whiskers indicate the 10th and 90th percentiles.

Figure 3

Systolic and diastolic BP at baseline and 12 months after inclusion into the study. Data are given as box plots, where the limits of the boxes indicate the 25th and 75th percentiles and the lines inside the boxes indicate the 50th (median) percentile. The whiskers indicate the 10th and 90th percentiles.

Figure 4

ALT levels measured at study entry and at months 6 and 12 after conversion to MMF therapy. Data are given as box plots, where the limits of the boxes indicate the 25th and 75th percentiles and the lines inside the boxes indicate the 50th (median) percentile. The whiskers indicate the 10th and 90th percentiles.