Absence of Proteinuria Predicts Improvement in Renal Function After Conversion to Sirolimus-based Immunosuppressive Regimens in Lung Transplant Survivors With Chronic Kidney Disease

Abstract

Improvement in renal function has been noted in some lung allograft recipients with chronic kidney disease (CKD) converted from a calcineurin inhibitor (CNI)- to a sirolimus (SRL)-based immunosuppressive regimen. However, not all patients have such a positive response. We sought to investigate independent predictors of a favorable renal response in a cohort of lung transplant recipients. We retrospectively studied 56 lung transplant recipients with CKD, defined as a pre-conversion estimated glomerular filtration rate (eGFR) < or =60 ml/min/1.73 m(2), who had been converted to CNI-sparing regimens using SRL (CNI-free: n = 10; CNI dose reduction + SRL: n = 46). Proteinuria prior to conversion, defined as > or =1(+) on urine dipstick, was determined when available (n = 51). Changes in mean eGFR post-conversion and independent predictors of a favorable renal response, defined as a rise in eGFR > or =20% within 1 month, were investigated. Mean eGFR at conversion was 35 +/- 14 ml/min/1.73 m(2), increasing by 8 +/- 14 ml/min/1.73 m(2) (p < 0.01) by 1 month post-conversion, a trend that remained significant out to 18 months. A total of 43% (n = 24) of patients had a rise in eGFR > or =20%. Forced expiratory volume in 1 second (FEV(1)) remained stable in survivors maintained on SRL and only 1 rejection episode occurred. When controlling for gender, age, pre-conversion eGFR and CNI-free vs CNI-dose reduction, the only variable that remained independently predictive of a favorable renal response was absence of proteinuria, with an odds ratio = 3.3 (95% confidence interval 1.0 to 12.5, p = 0.05). Non-proteinuric lung transplant survivors with CKD are more likely to respond favorably from a renal standpoint after conversion to SRL with CNI-dose reduction or elimination.