Outcome and Cost Analysis of Induction Immunosuppression With IL2Mab or ATG in DCD Kidney Transplants

Transplantation - Published Ahead-of-Print Outcome and Cost Analysis of Induction Immunosuppression With IL2Mab or ATG in DCD Kidney Transplants

Background: Kidney transplantation from DCD now represents a significant part of the overall transplant activity in the UK. Outcome of different induction immunosuppression regimes and related cost benefit analysis has been reported by very few studies. This is a single centre study on frequency-matched patients who received a DCD kidney transplant between August 2007 and August 2009. Methods: Data on 45 patients divided in 2 groups were collected prospectively and analyzed retrospectively. Group A (24 patients) received IL2Mab and Group B (21 patients) ATG as induction immunosuppression. Patient and graft survival were similar in both groups. Results: In the ATG-induced group, there was a significant lower rate of DGF, BPAR, and infections requiring readmission. A cost analysis was performed including all immunosuppression-related costs, and it has shown remarkable savings in the ATG-induced group. Conclusion: Considering that the number of DCD kidney transplants is destined to rise in the UK, we believe that ATG is a valid option to continue optimizing outcomes of DCD kidney transplant. In our experience, ATG proved to be safe, effective, and contributed to significant cost savings. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Outcome_and_Cost_Analysis_of_Induction.98285.pdf

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Survival Trends in ESRD Patients Compared With the General Population in the United States

American Journal of Kidney Diseases Survival Trends in ESRD Patients Compared With the General Population in the United States

Background: Health care resources expended on patients with end-stage renal disease (ESRD) have increased extensively, with uncertain changes in outcomes. In this study, we examined survival trends in the United States in patients with ESRD receiving renal replacement therapy with long-term dialysis or transplantation relative to the general population.Study Design: Secondary analysis of records from the US Renal Data System.Setting & Participants: American adults receiving renal replacement therapy in 1977, 1987, 1997, and 2007.Predictor: Year.Outcome: 1-year survival.Measurements: Abridged period life tables were created for each cross-sectional patient group and were compared with general US population life tables to measure relative survival, calculated as differences in average survival between the general US and the ESRD populations.Results: From 1977 to 2007, ESRD patient groups became significantly older (mean age increased from 47 to 58 years) and sicker (ESRD due to diabetes increased from 9.1% to 38.2%; patients with a high death risk increased from 36.8% to 50.7%). Unadjusted age-specific survival improved (for 50-year-olds, average life expectancy increased 8% from 7.3 years in 1977 to 7.9 years in 2007), but age-specific survival increased more extensively in the general US population (from 27.5 years in 1977 to 30.9 years in 2007; 12% improvement). Accounting for this, age-specific relative survival in patients with ESRD decreased (for 50-year-olds, 20.2 life-years lost in 1977 vs 23.0 life-years lost in 2007).Limitations: Our analysis controlled for neither patient comorbid conditions nor initial glomerular filtration rate at the start of renal replacement therapy.Conclusions: Over the past 4 decades, age-specific survival in patients with ESRD has improved, but has not kept pace with that of the general US population. To be complete, future survival studies in patients with ESRD should focus on both temporal changes in survival within this group and changes relative to the general population.


http://www.ajkd.org/article/S0272-6386(13)01227-4/abstract?rss=yes

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Alendronate as an Effective Treatment for Bone Loss and Vascular Calcification in Kidney Transplant Recipients

Journal of Transplantation - XXX Alendronate as an Effective Treatment for Bone Loss and Vascular Calcification in Kidney Transplant Recipients

Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication, with a high risk of fracture, and abdominal aortic calcification (AC) is a known predictor of cardiovascular mortality. In this study of 12 stable kidney recipients, we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC. We randomly divided the subjects into a treatment group with alendronate (group A: 5 subjects) and a control group (group C: 7 subjects). Group A patients received 35 mg/week of alendronate over 24 months, while group C patients were not administered with any bisphosphonates. Two major endpoints were established: (1) the time-dependent change in bone mineral density (BMD) estimated with DEXA and (2) progression of abdominal AC, calculated twice as an index (ACI) using computed tomography data. Over the 2-year study period, group A patients showed significantly increased BMD of 1.86 ± 0.85% ( versus baseline), and almost complete inhibition of ACI progression (38.2 ± 24.2% to 39.6 ± 24.3%), but group C patients showed a decrease in BMD decline with bone loss and progression of ACI (32.8 ± 25.0% to 37.8 ± 29.2%, ). In conclusion, alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification. This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR.


http://www.hindawi.com/journals/jtrans/2014/269613/

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The effect of magnesium supplements on early post-transplantation glucose metabolism: a randomised controlled trial-R1

Transplant International The effect of magnesium supplements on early post-transplantation glucose metabolism: a randomised controlled trial-R1

Abstract

Posttransplantation hypomagnesemia is common and predicts diabetes. Magnesium improves glycemic control in diabetics and insulin sensitivity in insulin resistant subjects.

We aimed to assess the effectiveness of oral magnesium for improving glycemic control and insulin sensitivity at three months posttransplantation.

We conducted a single-centre, open-label, randomised parallel group study. We included adults with serum magnesium < 1.7 mg/dL within two weeks after kidney transplantation. We randomized participants to 450 mg magnesium oxide up to three times daily or no treatment. The primary endpoint was the mean difference in fasting glycemia. Secondary endpoints were the mean difference in AUC of glucose during an oral glucose tolerance test and insulin resistance measured by HOMA-IR. Analyses were on intention-to-treat basis.

In patients randomised to magnesium oxide (N=27) versus no treatment (N=27), fasting glycemia on average was 11.5 mg/dL lower (95% CI 1.7 to 21.3; p=0.02). There was no difference between the two groups neither for two hour AUC where the mean value was 1164mg/dL/min (95%CI -1884 to 4284; p=0.45) lower in the treatment group nor for HOMA-IR.

Magnesium supplements modestly improved fasting glycemia without effect on insulin resistance. Higher baseline glycemia among patients in the control group may have driven the positive outcome.(ClinicalTrials.gov number: NCT01889576).

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Ftri.12287

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Cardiovascular Death in Kidney Recipients Treated With Renin–Angiotensin System Blockers

Transplantation - Most Popular Articles Cardiovascular Death in Kidney Recipients Treated With Renin–Angiotensin System Blockers

BackgroundAngiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are widely prescribed after kidney transplantation, but evidence for an improvement in outcomes is mixed. A recent trial demonstrated a significantly lower incidence of major cardiovascular events in ACEI-treated recipients. MethodsCollaborative Transplant Study data on cardiovascular death during years 2 to 10 after kidney transplantation in patients with a functioning graft were analyzed according to whether ACEI/ARB or other antihypertensive therapy (excluding diuretics) was administered at year 1. ResultsOf 39,251 transplants analyzed, 15,250 (38.9%) received ACEI/ARB and 24,001 (61.1%) received other antihypertensive therapy at year 1 after transplantation. The mean duration of follow-up was 5.8 years. During years 2 to 10 after transplantation, cardiovascular death occurred in 918 patients (cumulative incidence=4.7%) with a functioning graft. The rate of cardiovascular death was similar in patients who received ACEI/ARB therapy or other antihypertensive treatment overall and in subpopulations of patients who were considered by the transplant center to be at an increased cardiovascular risk, had no pretransplant risk factors, were aged 60 years and older, were treated for diabetes at year 1, or had serum creatinine of 130 μmol/L or higher at year 1. Multivariable Cox regression analysis confirmed that treatment with ACEI/ARB did not confer a beneficial effect beyond that conferred by other antihypertensive treatments on the cumulative incidence of cardiovascular death during years 2 to 10 (hazard ratio=1.1, P=0.24). ConclusionsThis large-scale retrospective analysis of prospectively collected data shows that the rate of cardiovascular death in kidney transplant recipients receiving ACEI/ARB or other antihypertensive medications is virtually identical.


http://journals.lww.com/transplantjournal/Fulltext/2014/02150/Cardiovascular_Death_in_Kidney_Recipients_Treated.12.aspx

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Peritoneal dialysis-related peritonitis - PubMed Mobile

http://www.ncbi.nlm.nih.gov/m/pubmed/24336639/


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New Oral Anticoagulants More Effective and Safer Than Warfarin in AFib: Meta-analysis Results

Information sourced from NEJM Journal Watch:

For Atrial Fibrillation, New Oral Anticoagulants Are More Effective and Safer than Warfarin

Meta-analysis results were consistent across a wide range of patients.

Three new oral anticoagulants — the thrombin inhibitor dabigatran (Pradaxa) and the factor Xa inhibitors apixaban (Eliquis) and rivaroxaban (Xarelto) — are approved for preventing stroke and systemic embolism in patients with atrial fibrillation. Edoxaban, a factor Xa inhibitor that is not yet approved by the FDA, is noninferior to warfarin for these indications (NEJM JW Gen Med Nov 19 2013) [PubMed® abstract]. Now, researchers report a meta-analysis of the four major clinical trials in which these newer anticoagulants were compared head to head with warfarin in 72,000 patients (mean age, 72) with atrial fibrillation. Median follow-up was 2 to 4 years.

Compared with warfarin, the newer agents were associated with significantly fewer strokes and systemic embolism events (19% fewer, driven mainly by 51% fewer hemorrhagic strokes). The new anticoagulants and warfarin were similarly effective in preventing ischemic stroke and myocardial infarction. Among those who received the newer agents, intracranial hemorrhage was 52% less common, and all-cause mortality was 10% lower, but gastrointestinal bleeding was 25% more common. The new anticoagulants' effects relative to warfarin were consistent across all major subgroups, including those at different levels of stroke risk (as measured by CHADS₂ score).

COMMENT

The new oral anticoagulants seem to offer clear advantages over warfarin in efficacy, safety, and convenience in patients who have atrial fibrillation, although some adverse effects might emerge with longer-term use.

Bruce Soloway, MD reviewing Ruff CT et al. Lancet 2013 Dec 4.

CITATION(S):

Ruff CT et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet 2013 Dec 4; [e-pub ahead of print]. [PubMed® abstract]

NEJM Journal Watch is produced by NEJM Group, a division of the Massachusetts Medical Society. Copyright ©2014 Massachusetts Medical Society. All rights reserved.

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A Novel Treatment Regimen for BK Viremia

Transplantation - Published Ahead-of-Print A Novel Treatment Regimen for BK Viremia

Background: BK 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. Methods: We 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. Results: There 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%. Conclusions: This 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. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/A_Novel_Treatment_Regimen_for_BK_Viremia.98292.pdf

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Long-Term Follow-Up of a Phase III Clinical Trial Comparing Tacrolimus Extended-Release/MMF, Tacrolimus/MMF, and Cyclosporine/MMF in De Novo Kidney Transplant Recipients

Transplantation - Published Ahead-of-Print Long-Term Follow-Up of a Phase III Clinical Trial Comparing Tacrolimus Extended-Release/MMF, Tacrolimus/MMF, and Cyclosporine/MMF in De Novo Kidney Transplant Recipients

Background: In a phase III, open-label, comparative, noninferiority study, 638 subjects receiving de novo kidney transplants were randomized to one of three treatment arms: tacrolimus extended-release (Astagraf XL) qd, tacrolimus (Prograf) bid, or cyclosporine (CsA) bid. All subjects received basiliximab induction, mycophenolate mofetil, and corticosteroids. Safety and efficacy follow-up data through 4 years are reported. Methods: Evaluations included patient and graft survival, study drug discontinuations, laboratory values including renal function and development of new-onset diabetes after transplantation, concomitant medications, and adverse events. Results: At study termination, 129 Astagraf XL, 113 Prograf, and 79 CsA patients had continued follow-up. Demographic and baseline characteristics were similar in all arms. Four-year Kaplan-Meier estimates of patient survival in the Astagraf XL, Prograf, and CsA groups were 93.2, 91.2, and 91.7%, respectively, while graft survival was 84.7, 82.7, and 83.9%, respectively. At least one serious adverse event was reported in the majority of patients in each group during the study (65.9% Astagraf XL, 69.8% Prograf, and 65.6% CsA). Renal function was not significantly different between Astagraf XL and Prograf. HgbA1c levels were collected every 6 months; the 4-year Kaplan-Meier estimate for incidence of HgbA1c levels >=6.5% was significantly higher for both tacrolimus formulations compared to CsA; 41.1% (Astagraf XL), 33.6% (Prograf), and 21.3% (CsA). Conclusions: In this 4-year follow-up report, patients receiving Astagraf XL and Prograf showed comparable efficacy and safety profiles, with a higher incidence of new-onset diabetes after transplantation but superior renal function compared to patients receiving CsA. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Long_Term_Follow_Up_of_a_Phase_III_Clinical_Trial.98293.pdf

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15-Year Follow-up of a Multicenter, Randomized, Calcineurin Inhibitor Withdrawal Study in Kidney Transplantation

Transplantation - Published Ahead-of-Print 15-Year Follow-up of a Multicenter, Randomized, Calcineurin Inhibitor Withdrawal Study in Kidney Transplantation

Background: Calcineurin inhibitors (CNIs) are essential immunosuppressive drugs after renal transplantation. Because of nephrotoxicity, withdrawal has been a challenge since their introduction. Methods: A randomized multicenter trial included 212 kidney patients transplanted between 1997 and 1999. All patients were initially treated with mycophenolate mofetil (MMF), cyclosporine A (CsA), and prednisone (pred). At 6 months after transplantation, 63 patients were randomized for MMF/pred, 76 for MMF/CsA, and 73 for MMF/CsA/pred. Within 18 months after randomization 23 patients experienced a rejection episode: MMF/pred (27.0%), MMF/CsA (6.8%) and MMF/CsA/pred (1.4%) (P<0.001). Results: During 15 years of follow-up, 73 patients died with a functioning graft, and 43 patients lost their graft. Ninety-six were alive with a functioning graft. Intention-to-treat analysis did not show a significant difference in patient and graft survival. In multivariate analysis, death-censored graft survival was significantly associated with serum creatinine at 6 months after transplantation and maximum PRA but not with the randomization group. CNI withdrawal did not result in a reduced incidence of or death by malignancy or cardiovascular disease. Death-censored graft survival was significantly worse in those patients randomized for CNI withdrawal that had to be reverted to CNI. Independent of randomization group, compared with no rejection, death-censored graft survival was significantly worse in 23 patients with acute rejection after randomization. Conclusion: Fifteen years after conversion to a CNI free regimen, there was no benefit regarding graft and patient survival or regarding prevalence of or death by comorbidities. However, rejection shortly after CNI withdrawal was associated with decreased graft survival. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/15_Year_Follow_up_of_a_Multicenter,_Randomized,.98297.pdf

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More Potent Lipid-Lowering Effect by Rosuvastatin Compared With Fluvastatin in Everolimus-Treated Renal Transplant Recipients

Transplantation - Published Ahead-of-Print More Potent Lipid-Lowering Effect by Rosuvastatin Compared With Fluvastatin in Everolimus-Treated Renal Transplant Recipients

Background: Dyslipidemia is a risk factor for premature cardiovascular morbidity and mortality in renal transplant recipients (RTRs). Pharmacotherapy with mTOR inhibitors aggravates dyslipidemia, thus necessitating lipid-lowering therapy with fluvastatin, pravastatin, or atorvastatin. These agents may not sufficiently lower lipid levels, and therefore, a more potent agent like rosuvastatin maybe needed. Methods: We have aimed to assess the lipid-lowering effect of rosuvastatin as compared with fluvastatin in RTR receiving everolimus. Safety was assessed as the pharmacokinetic (PK) interaction potential of a rosuvastatin/everolimus combination in RTR. A 12-hour everolimus PK investigation was performed in 12 stable RTR receiving everolimus and fluvastatin (80 mg/d). Patients were then switched to rosuvastatin (20 mg/d), and a follow-up 12/24-hour PK investigation of everolimus/rosuvastatin was performed after 1 month. All other drugs were kept unchanged. Results: In RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL cholesterol and total cholesterol by 30.2+/-12.2% (P<0.01) and 18.2+/-9.6% (P<0.01), respectively. Everolimus AUC0-12 was not affected by concomitant rosuvastatin treatment, 80.3+/-21.3 [mu]g*h/L before and 78.5+/-21.9 [mu]g*h/L after, respectively (P=0.61). Mean rosuvastatin AUC0-24 was 157+/-61.7 ng*h/mL, approximately threefold higher than reported in the literature for nontransplants. There were no adverse events, and none of the patients had or developed proteinuria. Conclusion: Rosuvastatin showed a superior lipid-lowering effect compared to fluvastatin in stable RTR receiving everolimus. The combination of everolimus/rosuvastatin seems to be as safe as the everolimus/fluvastatin combination. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/More_Potent_Lipid_Lowering_Effect_by_Rosuvastatin.98298.pdf

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Sterile Leukocyturia Is Associated With Interstitial Fibrosis and Tubular Atrophy in Kidney Allograft Protocol Biopsies

AJT - Early Sterile Leukocyturia Is Associated With Interstitial Fibrosis and Tubular Atrophy in Kidney Allograft Protocol Biopsies

Kidney allograft interstitial fibrosis and tubular atrophy (IF/TA) is associated with a poorer renal function and outcome. In the current clinical practice, an early diagnosis can only be provided by invasive tests. We aimed to investigate the association of sterile leukocyturia with Banff criteria histological findings in kidney allograft protocol biopsies. We studied 348 allograft biopsies from two different European countries performed at 8.5 + 3.5 months after transplantation. In these cases, the presence of sterile leukocyturia (Leuc+, n = 70) or no leukocyturia (Leuc−, n = 278) was analyzed and related to Banff elementary lesions. Only IF/TA was significantly different between Leuc+ and Leuc− groups. IF/TA was present in 85.7% of Leuc+ and 27.7% of Leuc− patients (p < 0.001). IF/TA patients had higher serum creatinine and presence of proteinuria (p < 0.05). Independent predictors of IF/TA were donor age, donor male sex, serum creatinine and Leuc+ (hazard ratio 18.2; 95% confidence interval, 8.1–40.7). The positive predictive value of leukocyturia for predicting IF/TA was 85.7% whereas the negative predictive value was 72.3%. These studies suggest that leukocyturia is a noninvasive and low-cost test to identify IF/TA. An early diagnosis may allow timely interventional measures directed to minimize its impact and improve graft outcome.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.12639

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

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

Background: More 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. Methods: Between 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. Results: The 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. Conclusion: Despite high rates of early rejection, desensitization in living-kidney transplantation results in acceptable 5-year patient and graft survival rates. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Long_Term_Outcomes_of_Kidney_Transplantation.98313.pdf

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

Transplantation - Published Ahead-of-Print Late Antibody-Mediated Rejection in Renal Allografts: Outcome After Conventional and Novel Therapies

Background: Although 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. Methods: Late 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. Results: Overall, 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). Conclusions: A 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. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Late_Antibody_Mediated_Rejection_in_Renal.98314.pdf

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Role of Anti-Vimentin Antibodies in Renal Transplantation

Transplantation - Published Ahead-of-Print Role of Anti-Vimentin Antibodies in Renal Transplantation

Background: The role of non-HLA antibodies in rejection is not clear. We investigate whether antibodies to vimentin are made after renal transplantation and if production is associated with interstitial fibrosis and tubular atrophy (IFTA). Methods: In this retrospective study, sera from 70 recipients of renal allografts (40 controls, 30 IFTA) were studied. The biopsy diagnosis of interstitial fibrosis and tubular atrophy (IFTA) was based on random, cause-indicating biopsies. Sera were collected pretransplant and at 3 monthly intervals up to 5 years posttransplant or diagnosis of IFTA and assayed by ELISA for IgM and IgG anti-vimentin antibodies (AVA) and HLA antibodies. Results: Mean titers of IgM AVA were higher at every year after transplantation compared with pretransplant for both IFTA and controls groups (P<0.001). There was no difference in the mean level of IgM AVA achieved by IFTA and control groups. The mean pretransplant levels of IgG AVA in the IFTA and control group were 18.2+/-11.7 and 11.0+/-8.1, respectively (P=0.001). There was a significant increase between the pretransplant mean levels of IgG AVA and the levels at years 1 to 4 in the IFTA group (years 1-3, P<0.0001, year 4 P=0.003) but not in the controls. There was no significant difference between the numbers of IFTA or control patients achieving a positive value (mean+2SD of pretransplant antibody titers) of IgM AVA (50% versus 37.5%, respectively) or IgG AVA (26.6% versus 12.5%, respectively). There was no association between production of HLA and AVA antibodies. Conclusion: Posttransplant production of IgM AVA is not associated with IFTA. The production of IgG AVA by a minority of IFTA patients suggests that in some individuals, IgG AVA may be involved in the pathology of IFTA. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/Role_of_Anti_Vimentin_Antibodies_in_Renal.98303.pdf

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FRAX Predicts Fracture Risk in Kidney Transplant Recipients

Transplantation - Published Ahead-of-Print FRAX Predicts Fracture Risk in Kidney Transplant Recipients

Background: The World Health Organization Fracture Risk Assessment Tool (FRAX) estimates the 10-year fracture probability. We assessed the prognostic value of FRAX in kidney transplant recipients, as its utility in recipients is unknown. Methods: We considered 458 individuals (mean age 45 years, 64% men) who received a kidney transplant in the province of Manitoba, Canada at the time of their first bone mineral density (BMD) test posttransplant (mean 1.1 years posttransplant; transplant years 1996-2011). FRAX probabilities were calculated from baseline information (age, sex, clinical risk factors, with or without BMD). Recipients were followed a mean of 6.4 years (interquartile range 3.0-10.0 years) after cohort entry for an incident major osteoporotic fracture. Results: In follow-up, 21 (4.6%) recipients experienced a major osteoporotic fracture. The observed 10-year major osteoporotic fracture risk of 6.3% (95% CI, 3.4-9.2%) was concordant with FRAX predictions (5.0% with BMD, 5.6% without BMD). Major osteoporotic fracture scores showed significant fracture prediction (hazard ratio per standard deviation, FRAX without BMD 1.66, 95% CI, 1.10-2.50; FRAX with BMD 1.64, 95% CI, 1.07-2.51). Area under the curve (AUC) for incident major osteoporotic fracture discrimination (AUC: FRAX with BMD 0.62, 95% CI, 0.50-0.74) was similar to the general population. Conclusions: FRAX scores categorized most kidney transplant recipients as a low-risk fracture group, and the low observed fracture rates were consistent with the 10-year fracture predictions. FRAX showed modest fracture prediction and discrimination similar to the general population. Independent validation is needed before clinicians can routinely use FRAX in kidney transplant recipients. (C) 2014 by Lippincott Williams & Wilkins


http://pdfs.journals.lww.com/transplantjournal/9000/00000/FRAX_Predicts_Fracture_Risk_in_Kidney_Transplant.98308.pdf

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Role of BK virus infection in end-stage renal disease patients waiting for kidney transplantation – viral replication dynamics from pre- to post-transplant

Clinical Transplantation Role of BK virus infection in end-stage renal disease patients waiting for kidney transplantation – viral replication dynamics from pre- to post-transplant

Abstract

We report the prevalence of BK virus (BKV) infection before renal transplantation and the dynamics of BKV viremia from pre- to post-transplantation. We assessed 60 kidney transplanted patients from a single cohort in Italy, treated with identical immunosuppressive therapy, for BK viremia at pre-transplantation, 12 h, and three and six months post-transplantation. Polymerase chain reaction showed that the prevalence of plasma BKV replication – considered a marker of infection – was 20% in pre-transplant patients. All pre-transplant-positive patients remained positive post-transplant, whereas the majority of pre-transplant-negative patients remained negative. Viremia dynamics classification revealed three clusters of patients: Cluster A++, pre-transplant-positive patients (20%) who tested positive at least once post-transplant; Cluster B−+, pre-transplant-negative patients (28%) who tested positive at least once post-transplant; and Cluster C– –, pre-transplant-negative patients (52%) who remained negative throughout. These clusters presented significant differences related to the prevalence of substantially positive patients with high plasma viral load (>10³ copies/mL) in cluster A, but not in donors' or grafts' characteristics. We suggest that pre-transplant viral status should be considered as an additional risk factor for post-transplant BKV replication. Therefore, pre-transplant BKV infection screening in kidney transplant patients should be performed for improving planning of personalized immunosuppressant schemes and specific post-transplant surveillance.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12312

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A randomized controlled trial comparing intravesical to extravesical ureteroneocystostomy in living donor kidney transplantation recipients

Kidney International - Issue - nature.com science feeds A randomized controlled trial comparing intravesical to extravesical ureteroneocystostomy in living donor kidney transplantation recipients

A randomized controlled trial comparing intravesical to extravesical ureteroneocystostomy in living donor kidney transplantation recipients

Kidney International 85, 471 (February 2014). doi:10.1038/ki.2013.464

Authors: Inez K B Slagt, Frank J M F Dor, T C Khe Tran, Hendrikus J A N Kimenai, Willem Weimar, Jan N M IJzermans & Türkan Terkivatan

http://feeds.nature.com/~r/ki/rss/current/~3/Fc8OMWnKUhQ/ki.2013.464

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Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation

Kidney International - Issue - nature.com science feeds Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation

Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation

Kidney International 85, 425 (February 2014). doi:10.1038/ki.2013.291

Authors: Satoshi Ashimine, Yoshihiko Watarai, Takayuki Yamamoto, Takahisa Hiramitsu, Makoto Tsujita, Koji Nanmoku, Norihiko Goto, Asami Takeda, Akio Katayama, Kazuharu Uchida & Takaaki Kobayashi

http://feeds.nature.com/~r/ki/rss/current/~3/5eAGy_tiS3g/ki.2013.291

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Cardiovascular Death in Kidney Recipients Treated With Renin–Angiotensin System Blockers

Transplantation - Current Issue Cardiovascular Death in Kidney Recipients Treated With Renin–Angiotensin System Blockers

BackgroundAngiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are widely prescribed after kidney transplantation, but evidence for an improvement in outcomes is mixed. A recent trial demonstrated a significantly lower incidence of major cardiovascular events in ACEI-treated recipients. MethodsCollaborative Transplant Study data on cardiovascular death during years 2 to 10 after kidney transplantation in patients with a functioning graft were analyzed according to whether ACEI/ARB or other antihypertensive therapy (excluding diuretics) was administered at year 1. ResultsOf 39,251 transplants analyzed, 15,250 (38.9%) received ACEI/ARB and 24,001 (61.1%) received other antihypertensive therapy at year 1 after transplantation. The mean duration of follow-up was 5.8 years. During years 2 to 10 after transplantation, cardiovascular death occurred in 918 patients (cumulative incidence=4.7%) with a functioning graft. The rate of cardiovascular death was similar in patients who received ACEI/ARB therapy or other antihypertensive treatment overall and in subpopulations of patients who were considered by the transplant center to be at an increased cardiovascular risk, had no pretransplant risk factors, were aged 60 years and older, were treated for diabetes at year 1, or had serum creatinine of 130 μmol/L or higher at year 1. Multivariable Cox regression analysis confirmed that treatment with ACEI/ARB did not confer a beneficial effect beyond that conferred by other antihypertensive treatments on the cumulative incidence of cardiovascular death during years 2 to 10 (hazard ratio=1.1, P=0.24). ConclusionsThis large-scale retrospective analysis of prospectively collected data shows that the rate of cardiovascular death in kidney transplant recipients receiving ACEI/ARB or other antihypertensive medications is virtually identical.


http://journals.lww.com/transplantjournal/Fulltext/2014/02150/Cardiovascular_Death_in_Kidney_Recipients_Treated.12.aspx

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