Absence of proteinuria predicts improvement in renal function after conversion to sirolimus-based immunosuppressive regimens in lung transplant survivors with chronic kidney disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Impaired diurnal blood pressure variation and all-cause mortality.

BACKGROUND: Most healthy people exhibit a decrease in systolic blood pressure (SBP) at night. A drop of <10% from mean daytime values, "non-dipping," is associated with kidney disease and cardiovascular events. We hypothesized that non-dipping would predict all-cause mortality. METHODS: Consecutive patients referred for ambulatory blood pressure (BP) monitoring at the Cleveland Clinic between 1994 and 2004 were included. Mean daytime (6 AM-11 PM) and nighttime (11 PM-6 AM) SBP values were calculated. We examined diurnal BP variation as a continuous variable, ((Mean daytime SBP - Mean nighttime SBP)/(Mean daytime SBP)) x 100%, and also as a categorical variable, defining "non-dipping" as a nocturnal SBP drop of <10%; subjects who exhibited non-dipping were defined as "non-dippers" and the others as "dippers." All-cause mortality was ascertained from the Social Security Death Index. RESULTS: Of the 621 patients included in the study, 261 were dippers and 360 were non-dippers. Non-dippers were older (P < 0.0001), more likely to be non-white (P < 0.05), and had higher rates of smoking, diabetes, hypertension, coronary artery disease, congestive heart failure, and renal insufficiency (P < 0.01 for all). Over a mean follow-up of 6.3 years, 61 patients died, including 10 dippers (3.8%) and 51 non-dippers (14.2%). The unadjusted hazard ratio for death based upon a decrement in the dipping percentage from the 75th to 25th percentile was 2.22 (95% confidence interval 1.64-2.95; P < 0.0001). This was attenuated after adjustment for comorbid conditions, including mean 24-h SBP and renal function: adjusted hazard ratio 1.62 (1.14-2.24; P < 0.005). CONCLUSIONS: Blunted diurnal BP variation is a strong predictor of death, but this may be accounted for, in large part, by its association with other cardiovascular risk factors.