Wednesday, August 20, 2014

Clinicopathologic features and outcome of mycophenolate-induced colitis in renal transplant recipients

Clinical Transplantation Clinicopathologic features and outcome of mycophenolate-induced colitis in renal transplant recipients

Abstract

Reports on the clinical course of mycophenolic acid (MPA)-related colitis in kidney transplant recipients are scarce. This study aimed at assessing MPA-related colitis incidence, risk factors, and progression after kidney transplantation. All kidney transplant patients taking MPA who had colonic biopsies for persistent chronic diarrhea, between 2000-2012, at the Kidney Transplantation Unit of Botucatu Medical School Hospital, Brazil, were included. CMV immunohistochemistry was performed in all biopsy specimens. Data on presenting symptoms, medications, immunosuppressive drugs, colonoscopic findings, and follow-up were obtained. Of 580 kidney transplant patients on MPA, 34 underwent colonoscopy. Colonoscopic findings were associated with MPA usage in 16 patients. The most frequent histologic patterns were non-specific colitis (31.3%), IBD-like colitis (25%), normal/near normal (18.8%), graft-vs-host disease-like (18.8%), and ischemia-like colitis (12.5%). All patients had persistent acute diarrhea and weight loss. Six of the 16 MPA-related diarrhea patients (37.5%) showed acute dehydration requiring hospitalization. Diarrhea resolved when MPA was switched to sirolimus (50%), discontinued (18.75%), switched to azathioprine (12.5%), or reduced by 50% (18. 75%). No graft loss occurred. Four patients died during the study period. Late onset MPA was more frequent, and no correlation with MPA dose or formulation was found.

This article is protected by copyright. All rights reserved.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12452

Sent with Reeder



Enviado desde mi iPad

Friday, August 8, 2014

Cardiovascular morbidity and mortality after kidney transplantation

Transplant International Cardiovascular morbidity and mortality after kidney transplantation

Abstract

Kidney transplantation is the optimal treatment for patients with end stage renal disease (ESRD) who would otherwise require dialysis. Patients with ESRD are at dramatically increased cardiovascular (CV) risk compared to the general population. As well as improving quality of life, successful transplantation accords major benefits by reducing cardiovascular risk in these patients. Worldwide, cardiovascular disease remains the leading cause of death with a functioning graft and therefore is a leading cause of graft failure. This review focuses on the mechanisms underpinning excess cardiovascular morbidity and mortality and current evidence for improving cardiovascular risk in kidney transplant recipients. Conventional cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidaemia, and pre-existing ischaemic heart disease are all highly prevalent in this group. In addition, kidney transplant recipients exhibit a number of risk factors associated with pre-existing renal disease. Furthermore, complications specific to transplantation may ensue including reduced graft function, side effects of immunosuppression and post transplantation diabetes mellitus. Strategies to improve cardiovascular outcomes post transplantation may include pharmacological intervention including lipid lowering or antihypertensive therapy, optimisation of graft function, lifestyle intervention and personalising immunosuppression to the individual patients risk profile.

This article is protected by copyright. All rights reserved.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Ftri.12413

Sent with Reeder



Enviado desde mi iPad

Benefits of Rituximab Combined With Intravenous Immunoglobulin for Desensitization in Kidney Transplant Recipients

Transplantation - Current Issue Benefits of Rituximab Combined With Intravenous Immunoglobulin for Desensitization in Kidney Transplant Recipients

imageBackgroundHighly HLA-sensitized (HS) patients have difficulty accessing compatible donors, especially deceased donor (DD) transplants. Desensitization protocols (DES) have evolved, but rigorous evaluation is lacking. Here, we examined the efficacy of rituximab as a DES agent in a placebo-controlled trial. MethodsCandidates were randomized to IVIG+placebo versus IVIG+rituximab. End points included rates of transplantation, antibody-mediated rejection (ABMR), and renal function. Protocol biopsies were performed at 1 year and analysis of patient and graft survival and donor-specific HLA antibodies (DSA) were performed. ResultsInitially, 15 HS DDs were randomized with 13 receiving transplants. However, we discontinued study entry after five serious adverse events were observed. The study was un-blinded and attribution of patients was noted (IVIG+placebo N=7, IVIG+rituximab N=6). No significant differences were seen in DSA levels at transplant. All ABMR episodes occurred in the IVIG+placebo arm and required intense therapy (P=0.06). The two graft losses were in the placebo group. DSA rebound associated with severe ABMR was seen in three patients in the IVIG+placebo group. No rebound was seen in the IVIG+rituximab group. Renal function at 6 and 12 months showed a significant benefit for IVIG+rituximab (P=0.04). ConclusionsBased on limited assessment with acknowledged limitations, both protocols appear effective in achieving levels of DSA allowable for transplantation. However, IVIG+rituximab appeared more effective in preventing DSA rebound and, more importantly, preventing ABMR and development of transplant glomerulopathy.


http://journals.lww.com/transplantjournal/Fulltext/2014/08150/Benefits_of_Rituximab_Combined_With_Intravenous.15.aspx

Sent with Reeder



Enviado desde mi iPad

Diarrhea After Kidney Transplantation: A New Look at a Frequent Symptom.

Transplantation - Published Ahead-of-Print Diarrhea After Kidney Transplantation: A New Look at a Frequent Symptom.

Diarrhea is a frequent but overlooked complication of kidney transplantation. Diarrhea is repeatedly neglected, often considered by patients and clinicians an unavoidable side effect of immunosuppressive regimens. It is, however, associated with a significant impairment in life quality. Severe and chronic posttransplant diarrhea may lead to dehydration, malabsorption, rehospitalization, immunosuppression, noncompliance, and a greater risk of graft loss and death. There is thus a need to optimize and standardize the management of posttransplant diarrhea with consistent diagnostic and therapeutic strategies. A recent study has suggested that the increased sensitivity of molecular tools might help in early pathogen identification and guidance of antimicrobial treatment. Most bacterial and protozoan infections are readily curable with appropriate antimicrobial agents; cryptosporidiosis and C. difficile infections may however be complicated by relapsing courses. In addition, identification of enteric viral genomes in stool has further reduced posttransplant diarrhea of unknown origin. Chronic norovirus-related posttransplant diarrhea, arising from the interplay of the virus and immunosuppressive drugs, has emerged as a new challenge in the field. Prospective and controlled studies are necessary to evaluate the efficacy and safety of innovative anti-norovirus therapeutics, as well as optimal immunosuppressive regimens, to enable viral clearance while preventing rejection and donor-specific antibody formation. This review seeks to provide a basis for the design of future clinical prospective studies. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Diarrhea_After_Kidney_Transplantation___A_New_Look.98094.pdf

Sent with Reeder



Enviado desde mi iPad

I'm sharing "Controlled-dose versus fixed-dose mycophenolate mofetil for kidney transplant recipients: a systematic review and meta-analysis of randomized controlled trials."

I thought you would be interested in this article.

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.
Xianding Wang, Xin Qin, Yong Wang, Zhongli Huang, Xiaohong Li, Quantao Zeng, Hao Zeng, Yiping Lu, Li Wang, Tao Lin

PMID: 23558507

Sent using journal reader: Read by QxMD



Enviado desde mi iPad

Efficacy and safety of conversion from cyclosporine to everolimus in living-donor kidney transplant recipients: an analysis from the ZEUS study

Transplant International Efficacy and safety of conversion from cyclosporine to everolimus in living-donor kidney transplant recipients: an analysis from the ZEUS study

Abstract

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.

This article is protected by copyright. All rights reserved.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Ftri.12411

Sent with Reeder



Enviado desde mi iPad

Wednesday, August 6, 2014

Effect of HCV, HIV and Coinfection in Kidney Transplant Recipients: Mate Kidney Analyses

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.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.12847

Sent with Reeder



Enviado desde mi iPad

Monday, August 4, 2014

Effects of Obesity on Kidney Transplantation Outcomes: A Systematic Review and Meta-Analysis

Transplantation - Most Popular Articles Effects of Obesity on Kidney Transplantation Outcomes: A Systematic Review and Meta-Analysis

imageBackgroundThe 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.


http://journals.lww.com/transplantjournal/Fulltext/2014/07270/Effects_of_Obesity_on_Kidney_Transplantation.10.aspx

Sent with Reeder



Enviado desde mi iPad

Hepatitis C Virus Infection and Kidney Transplantation in 2014: What's New?

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.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.12835

Sent with Reeder



Enviado desde mi iPad

Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

Journal of the American Society of Nephrology current issue Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

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.




http://jasn.asnjournals.org/cgi/content/short/25/8/1825?rss=1

Sent with Reeder



Enviado desde mi iPhone