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Transplantation 2013 Aug 27; 96 (4) : 361-7. Controlled-dose versus fixed-dose mycophenolate mofetil for kidney transplant recipients: a systematic review and meta-analysis of randomized controlled trials. PMID: 23558507 |
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Conversion of living-donor kidney transplant patients from calcineurin inhibitor therapy to an mTOR inhibitor is poorly documented. In the prospective, multicenter ZEUS study, 300 kidney transplant recipients without prior rejection (Banff grade >1) and serum creatinine ≤265μmol/L were randomized to continue cyclosporine or convert to everolimus at 4.5 months post-transplant. In a post hoc analysis of 80 living-donor recipients, adjusted estimated GFR (Nankivell) at month 12 (the primary endpoint) was 74.3 (95%CI [70.7, 77.9]) mL/min/1.73m2 with everolimus versus 63.8 (95%CI [60.0, 67.7]) mL/min/1.73m2) with cyclosporine, a difference of 10.5 mL/min/1.73m2 in favor of everolimus (p<0.001). From randomization to month 12, adjusted estimated GFR increased by a mean of 9.8 (95%CI [6.2, 13.4]) mL/min/1.73m2 with everolimus, versus
-0.7 (95%CI [-4.6, 3.1]) mL/min/1.73m2) (p<0.001) with cyclosporine. There were six biopsy-proven acute rejection episodes in everolimus-treated patients (five Banff grade I) and one episode in cyclosporine-treated patients (Banff grade 1). Overall safety profile was similar between groups. Discontinuation due to adverse events occurred in three everolimus patients (7.1%) and five cyclosporine patients (13.2%) between randomization and month 12. Initiation of everolimus with early elimination of calcineurin therapy is associated with a significant renal benefit at 12 months post-transplant that is observed in both living and deceased-donor recipients.
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AJT - Early Effect of HCV, HIV and Coinfection in Kidney Transplant Recipients: Mate Kidney Analyses
Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV− n = 1700; HIV− n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04–1.47) and patient survival (aHR 1.24, 95% CI 1.06–1.45) compared with HCV−. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48–1.51) and patient survival (aHR 0.80, 95% CI 0.39–1.64) compared with HIV−. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival.
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BackgroundThe effects of obesity on outcomes reported after kidney transplantation have been controversial. The purpose of this systematic review and meta-analysis was to elucidate this issue. MethodsMEDLINE, EMBASE, Cochrane Library, and gray literature were searched up to August 6, 2013. Studies that compared obese and nonobese patients who underwent kidney transplantation and evaluated one of these outcomes—delayed graft function (DGF), acute rejection, graft or patient survival at 1 or 5 years after transplantation, or death by cardiovascular disease (CVD)—were included. Two independent reviewers extracted the data and assessed the quality of the studies. ResultsFrom 1,973 articles retrieved, 21 studies (9,296 patients) were included. Obesity was associated with DGF (relative risk, 1.41; 95% confidence interval, 1.26–1.57; I2=8%; Pheterogeneity=0.36), but not with acute rejection. Graft loss and death were associated with obesity only in the analysis of studies that evaluated patients who received a kidney graft before year 2000. No association of obesity with graft loss and death was found in the analysis of studies that evaluated patients who received a kidney graft after year 2000. Death by CVD was associated with obesity (relative risk, 2.07; 95% confidence interval, 1.17–3.64; I2=0%; Pheterogeneity=0.59); however, most studies included in this analysis evaluated patients who received a kidney graft after year 2000. ConclusionIn conclusion, obese patients have increased risk for DGF. In the past years, obesity was a risk factor for graft loss, death by CVD, and all-cause mortality. However, for the obese transplanted patient today, the graft and patient survival is the same as that of the nonobese patient.Sent with Reeder
AJT - Early Hepatitis C Virus Infection and Kidney Transplantation in 2014: What's New?
Chronic hepatitis C virus (HCV) infection remains an important health problem, which is associated with deleterious consequences in kidney transplant recipients. Besides hepatic complications, several extrahepatic complications contribute to reduced patient and allograft survival in HCV-infected kidney recipients. However, HCV infection should not be considered as a contraindication for kidney transplantation because patient survival is better with transplantation than on dialysis. Treatment of HCV infection is currently interferon-alpha (IFN-α) based, which has been associated with higher renal allograft rejection rates. Therefore, antiviral treatment before transplantation is preferable. As in the nontransplant setting, IFN-free treatment regimens, because of their greater efficacy and reduced toxicity, currently represent promising and attractive therapeutic options after kidney transplantation as well. However, clinical trials will be required to closely evaluate these regimens in kidney recipients. There is also a need for prospective controlled studies to determine the optimal immunosuppressive regimens after transplantation in HCV-infected recipients. Combined kidney and liver transplantation is required in patients with advanced liver cirrhosis. However, in patients with cleared HCV infection and early cirrhosis without portal hypertension, kidney transplantation alone may be considered. There is some agreement about the use of HCV-positive donors in HCV-infected recipients, although data regarding posttransplant survival rates are controversial.
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Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared with placebo. There was a nonsignificant 3% reduction in the incidence of ESRD (1057 [33.9%] cases with simvastatin plus ezetimibe versus 1084 [34.6%] cases with placebo; rate ratio, 0.97; 95% confidence interval [95% CI], 0.89 to 1.05; P=0.41). Similarly, allocation to simvastatin plus ezetimibe had no significant effect on the prespecified tertiary outcomes of ESRD or death (1477 [47.4%] events with treatment versus 1513 [48.3%] events with placebo; rate ratio, 0.97; 95% CI, 0.90 to 1.04; P=0.34) or ESRD or doubling of baseline creatinine (1189 [38.2%] events with treatment versus 1257 [40.2%] events with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD.
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