Monday, June 23, 2014

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

Transplantation - Published Ahead-of-Print Effects of Obesity on Kidney Transplantation Outcomes: A Systematic Review and Meta-Analysis.

Background: The 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. Methods: MEDLINE, 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. Results: From 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. Conclusion: In 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. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Effects_of_Obesity_on_Kidney_Transplantation.98165.pdf

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Late Antibody-Mediated Rejection in Renal Allografts: Outcome After Conventional and Novel Therapies

Transplantation - Current Issue Late Antibody-Mediated Rejection in Renal Allografts: Outcome After Conventional and Novel Therapies

imageBackgroundAlthough several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR. MethodsLate AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength. ResultsOverall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv≥2) on index biopsy (OR=50; P=0.06). ConclusionsA major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.


http://journals.lww.com/transplantjournal/Fulltext/2014/06270/Late_Antibody_Mediated_Rejection_in_Renal.9.aspx

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Long-Term Outcomes of Kidney Transplantation Across a Positive Complement-Dependent Cytotoxicity Crossmatch

Transplantation - Current Issue Long-Term Outcomes of Kidney Transplantation Across a Positive Complement-Dependent Cytotoxicity Crossmatch

imageBackgroundMore than 30% of potential kidney transplant recipients have pre-existing anti–human leukocyte antigen antibodies. This subgroup has significantly lower transplant rates and increased mortality. Desensitization has become an important tool to overcome this immunological barrier. However, limited data is available regarding long-term outcomes, in particular for the highest risk group with a positive complement-dependent cytotoxicity crossmatch (CDC XM) before desensitization. MethodsBetween 2002 and 2010, 39 patients underwent living-kidney transplantation across a positive CDC XM against their donors at our center. The desensitization protocol involved pretransplant immunosuppression, plasmapheresis, and low-dose intravenous immunoglobulin±rituximab. Measured outcomes included patient survival, graft survival, renal function, rates of rejection, infection, and malignancy. ResultsThe mean and median follow-up was 5.2 years. Patient survival was 95% at 1 year, 95% at 3 years, and 86% at 5 years. Death-censored graft survival was 94% at 1 year, 88% at 3 years, and 84% at 5 years. Uncensored graft survival was 87% at 1 year, 79% at 3 years, and 72% at 5 years. Twenty-four subjects (61%) developed acute antibody-mediated rejection of the allograft and one patient lost her graft because of hyperacute rejection. Infectious complications included pneumonia (17%), BK nephropathy (10%), and CMV disease (5%). Skin cancer was the most prevalent malignancy in 10% of patients. There were no cases of lymphoproliferative disorder. Mean serum creatinine was 1.7±1 mg/dL in functioning grafts at 5 years after transplantation. ConclusionDespite high rates of early rejection, desensitization in living-kidney transplantation results in acceptable 5-year patient and graft survival rates.


http://journals.lww.com/transplantjournal/Fulltext/2014/06270/Long_Term_Outcomes_of_Kidney_Transplantation.10.aspx

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Optimal Immunosuppression for HIV-Positive Kidney Transplants: Long-Term Randomized Controlled Trials Needed



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A Randomized, Prospective, Parallel Group Study of Laparoscopic Versus Laparoendoscopic Single Site Donor Nephrectomy for Kidney Donation

AJT - Early A Randomized, Prospective, Parallel Group Study of Laparoscopic Versus Laparoendoscopic Single Site Donor Nephrectomy for Kidney Donation

Few prospective, randomized studies have assessed the benefits of laparoendoscopic single site donor nephrectomy (LESS-DN) over laparoscopic donor nephrectomy (LDN). Our center initiated such a trial in January 2011, following subjects randomized to LESS-DN versus LDN from surgery through 5 years postdonation. Subjects complete recovery/satisfaction questionnaires at 2, 6 and 12 months postdonation; transplant recipient outcomes are also recorded. One hundred subjects (49 LESS-DN, 51 LDN) underwent surgery; donor demographics were similar between groups, and included a predominance of female, living-unrelated donors, mean age of 47 years who underwent left donor nephrectomy. Operative parameters (overall time, time to extraction, warm ischemia time, blood loss) were similar between groups. Conversion to hand-assist laparoscopy was required in 3 LESS-DN (6.1%) versus 2 LDN (3.9%; p = 0.67). Questionnaires revealed that 97.2% of LESS-DN versus 79.5% of LDN (p = 0.03) were 100% recovered by 2 months after donation. No significant difference was seen in satisfaction scores between the groups. Recipient outcomes were similar between groups. Our randomized trial comparing LESS donor nephrectomy to LDN confirms that LESS-DN offers a safe alternative to conventional LDN in terms of intra- and post-operative complications. LDN and LESS-DN offer similar recovery and satisfaction after donation.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.12735

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Friday, June 20, 2014

A Randomized, Prospective, Parallel Group Study of Laparoscopic Versus Laparoendoscopic Single Site Donor Nephrectomy for Kidney Donation.

AJT A Randomized, Prospective, Parallel Group Study of Laparoscopic Versus Laparoendoscopic Single Site Donor Nephrectomy for Kidney Donation.

Few prospective, randomized studies have assessed the benefits of laparoendoscopic single site donor nephrectomy (LESS-DN) over laparoscopic donor nephrectomy (LDN). Our center initiated such a trial in January 2011, following subjects randomized to LESS-DN versus LDN from surgery through 5 years postdonation. Subjects complete recovery/satisfaction questionnaires at 2, 6 and 12 months postdonation; transplant recipient outcomes are also recorded. One hundred subjects (49 LESS-DN, 51 LDN) underwent surgery; donor demographics were similar between groups, and included a predominance of female, living-unrelated donors, mean age of 47 years who underwent left donor nephrectomy. Operative parameters (overall time, time to extraction, warm ischemia time, blood loss) were similar between groups. Conversion to hand-assist laparoscopy was required in 3 LESS-DN (6.1%) versus 2 LDN (3.9%; p = 0.67). Questionnaires revealed that 97.2% of LESS-DN versus 79.5% of LDN (p = 0.03) were 100% recovered by 2 months after donation. No significant difference was seen in satisfaction scores between the groups. Recipient outcomes were similar between groups. Our randomized trial comparing LESS donor nephrectomy to LDN confirms that LESS-DN offers a safe alternative to conventional LDN in terms of intra- and post-operative complications. LDN and LESS-DN offer similar recovery and satisfaction after donation.



http://www.unboundmedicine.com/medline/citation/24934732/A_Randomized_Prospective_Parallel_Group_Study_of_Laparoscopic_Versus_Laparoendoscopic_Single_Site_Donor_Nephrectomy_for_Kidney_Donation_

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Wednesday, June 4, 2014

The risk of thromboembolic events in kidney transplant patients

Kidney International - Issue - nature.com science feeds The risk of thromboembolic events in kidney transplant patients

The risk of thromboembolic events in kidney transplant patients

Kidney International 85, 1454 (June 2014). doi:10.1038/ki.2013.536

Authors: Jacobien C Verhave, Vicky Tagalakis, Samy Suissa, François Madore, Marie-Josée Hébert & Héloïse Cardinal




http://feeds.nature.com/~r/ki/rss/current/~3/QjiBNtJw5bs/ki.2013.536

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Phospholipase A2 Receptor Autoantibodies and Clinical Outcome in Patients with Primary Membranous Nephropathy

Journal of the American Society of Nephrology current issue Phospholipase A2 Receptor Autoantibodies and Clinical Outcome in Patients with Primary Membranous Nephropathy

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, with an uncertain clinical outcome. The characterization of the phospholipase A2 receptor (PLA2R) as the major target antigen in primary MN and the detection of circulating autoantibodies in these patients is a major advance in understanding this disease. To test whether PLA2R antibody levels reflect disease activity or clinical outcome, we performed a prospective multicenter study of 133 adult patients with primary MN and detectable serum PLA2R antibodies who had not received immunosuppressive therapy. Patients were followed ≤24 months. PLA2R antibody levels associated with clinical disease activity (proteinuria) in patients with immunosuppressive therapy (n=101) or supportive care (n=32). Within 3 months, immunosuppressive therapy led to a sustained 81% reduction in PLA2R antibody levels paralleled by a 39% reduction in proteinuria. Patients who experienced remission of proteinuria after 12 months had significantly lower PLA2R antibody levels at the time of study inclusion compared with patients with no remission. Patients with high PLA2R antibody levels achieved remission of proteinuria significantly later than patients with low PLA2R antibody levels. PLA2R antibody levels fell over time in patients with spontaneous remission but remained elevated in patients who did not show a reduction in proteinuria. Multivariable Cox regression analysis confirmed PLA2R antibody level as an independent risk factor for not achieving remission of proteinuria. We conclude that a decrease in PLA2R antibody level is associated with a decrease of proteinuria in patients with primary MN.




http://jasn.asnjournals.org/cgi/content/short/25/6/1357?rss=1

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A Novel Treatment Regimen for BK Viremia

Transplantation - Current Issue A Novel Treatment Regimen for BK Viremia

imageBackgroundBK viremia, a prerequisite for BK virus nephropathy (BKVN), affects 5% to 16% of pediatric renal transplant recipients (PRTR). We evaluated the safety and efficacy of a novel approach to treating BK viremia using fluoroquinolones and leflunomide in PRTR. MethodsWe studied 230 PRTR at Mattel Children's Hospital, UCLA, who underwent renal transplantation between January 2003 and October 2010. Nineteen patients were found to have BK viremia. Ciprofloxacin was started when the BK viral load was greater than 625 copies/mL, and patients were switched to leflunomide if BK viral load did not decrease after 2 months of ciprofloxacin therapy. All patients underwent transplant kidney biopsy, and their estimated glomerular filtration rate (eGFR) and BK PCR was measured serially. The side effects of ciprofloxacin and leflunomide were recorded in each patient. ResultsThere was a significant decrease in BK viral load in patients treated with ciprofloxacin and leflunomide (P<0.001) with only a small reduction in immunosuppression. BK viremia was associated with a significantly decreased eGFR (P<0.001), and treatment with ciprofloxacin and leflunomide was associated with improved eGFR (P<0.001). This approach resulted in a BKVN rate of only 1%. ConclusionsThis analysis demonstrates for the first time that, used in a stepwise fashion, ciprofloxacin and leflunomide are effective and safe treatments for BK viremia in PRTR.


http://journals.lww.com/transplantjournal/Fulltext/2014/06150/A_Novel_Treatment_Regimen_for_BK_Viremia.15.aspx

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Monday, June 2, 2014

I'm sharing "Systematic Review and Meta-Analysis on Management of Hemodialysis Catheter-Related Bacteremia."

I thought you would be interested in this article.

Journal of the American Society of Nephrology : JASN 2014 May 22;

Systematic Review and Meta-Analysis on Management of Hemodialysis Catheter-Related Bacteremia.
Saima Aslam, Florin Vaida, Michele Ritter, Ravindra L Mehta

PMID: 24854263

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Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies

Information sourced from BMJ:

BMJ 2014;348:g1903
[Free full-text BMJ article PDF | PubMed® abstract]

Research

Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies

Rajiv Chowdhury, Setor Kunutsor, Anna Vitezova, et al.

Correspondence to: R Chowdhury rajiv.chowdhury@phpc.cam.ac.uk or O H Franco o.franco@erasmusmc.nl

Abstract

Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances.

Design Systematic review and meta-analysis of observational studies and randomised controlled trials.

Data sources Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; [correspondence] with investigators. 

Study selection Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and [cause-specific] mortality outcomes.

Data extraction Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849 412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30 716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics.

Results In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D3 supplementation and 1.04 (0.97 to 1.11) for vitamin D2 supplementation. The effects observed for vitamin D3supplementation remained unchanged when grouped by various characteristics. However, for vitamin D2 supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods.

Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D3 significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D3 and D2 have different effects on mortality risk.

© 2014 BMJ Publishing Group Ltd

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Alberto Reino