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.

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

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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.

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

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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

BackgroundHighly 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

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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

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

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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. Xianding Wang, Xin Qin, Yong Wang, Zhongli Huang, Xiaohong Li, Quantao Zeng, Hao Zeng, Yiping Lu, Li Wang, Tao Lin PMID: 23558507

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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.

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

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