Fewer cytomegalovirus complications after kidney transplantation by de novo use of mTOR inhibitors in comparison to mycophenolic acid

Transplant Infectious Disease Fewer cytomegalovirus complications after kidney transplantation by de novo use of mTOR inhibitors in comparison to mycophenolic acid

Abstract

Background

Cytomegalovirus (CMV) is a risk factor for patient and graft survival after kidney transplantation.

Methods

We retrospectively analyzed risk factors for CMV infection in 348 patients who received a kidney transplant donated after brain death (n = 232) or by living donation (n = 116) between 2008 and 2013. Of the 348 patients analyzed 91 received a mammalian target of rapamycin inhibitor (mTORi)- based immunosuppressive regimen. A total of 266 patients were treated with standard immunosuppression (Group 1) consisting of basiliximab induction, calcineurin inhibitor (CNI), and either mycophenolic acid (MPA, n = 219) or everolimus (EVE) (n = 47). We also included 82 patients received more intense immunosuppression (Group 2) with lymphocyte depletion, CNI, plus either MPA (n = 38) or EVE (n = 44). Only patients in the high-risk constellation received CMV prophylaxis in Group 1, while all patients in Group 2 received prophylaxis for 6 month.

Results

The overall rate of CMV infections was low with 10.1% in all patients. Despite the different prophylaxis strategies applied, no difference was seen in CMV infections between Group 1 (10.9%) and Group 2 (13.6%). A multivariate analysis revealed that patients on EVE had fewer CMV complications compared with patients on MPA (P = 0.013, odds ratio [OR] 4.8, confidence interval [CI] 1.4–16.5). Donor and recipient age > 65 years was an independent risk factor (P = 0.002, OR 3.2, CI 1.5–6.7) for CMV infections. Patients with CMV infections had significantly worse graft function after 2 years (P = 0.001).

Conclusion

CMV is a significant risk factor for long-term graft outcome. Patients treated with EVE developed fewer CMV complications compared to patients on MPA. The use of mTORi is useful in patients at high risk of developing CMV infections.

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http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Ftid.12494

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Influence of Current and Previous Smoking on Cancer and Mortality After Kidney Transplantation [feedly]

Influence of Current and Previous Smoking on Cancer and Mortality After Kidney Transplantation
http://journals.lww.com/transplantjournal/Fulltext/2016/01000/Influence_of_Current_and_Previous_Smoking_on.34.aspx

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Efficacy and safety of tacrolimus compared with ciclosporin a in renal transplantation: seven-year observational results

Transplant International Efficacy and safety of tacrolimus compared with ciclosporin a in renal transplantation: seven-year observational results

Abstract

Background

The European Tacrolimus vs. Ciclosporin-A Microemulsion (CsA-ME) Renal Transplantation Study demonstrated that tacrolimus decreased acute rejection rates at 6 months.

Methods

Primary endpoints of this investigator-initiated, observational 7-year follow-up study were acute rejection rates, patient and graft survival rates, and a composite endpoint (BPAR, graft loss, patient death). We analyzed data from the original ITT population (n=557; 286 tacrolimus, 271 CsA-ME).

Results

237 tacrolimus and 208 CsA-ME patients provided data. At 7 years, Kaplan-Meier estimated rates of patients free from BPAR were 77.1% in the tacrolimus arm and 59.9% in the CsA-ME arm, graft survival rates amounted to 82.6% and 80.6%, and patient survival rates to 89.9% and 88.1%. Estimated combined endpoint-free survival rates were 60.2% in the tacrolimus arm and 47.0% in the CsA-ME arm (p=<0.0001).

A higher number of patients from the CsA-ME arm crossed over to tacrolimus during 7 year follow-up: 19.7% vs. 7.9% (p=<0.002). More patients in the tacrolimus group stopped steroids and received immunosuppressive monotherapy. Significantly more CsA-ME patients received lipid-lowering medication, experienced cosmetic and cardiovascular adverse events.

Conclusions

Tacrolimus-treated renal transplant recipients had significantly higher combined endpoint-free survival rates mainly driven by lower acute rejection rates despite less immunosuppressive medication at 7 years.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Ftri.12716

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Onset and progression of de novo donor-specific anti-human leukocyte antigen antibodies after BK polyomavirus and preemptive immunosuppression reduction

Transplant Infectious Disease Onset and progression of de novo donor-specific anti-human leukocyte antigen antibodies after BK polyomavirus and preemptive immunosuppression reduction

Abstract

Background

BK polyomavirus (BKPyV) viremia/nephropathy and reduction in immunosuppression following viremia may increase the risk of alloimmune activation and allograft rejection. This study investigates the impact of BKPyV viremia on de novo donor anti-human leukocyte antigen (HLA)-specific antibodies (dnDSA).

Patients and methods

All primary renal transplants at East Carolina University from March 1999 to December 2010, with at least 1 post-transplant BKPyV viral load testing, were analyzed. Patients were negative for anti-HLA antibodies to donor antigens (tested via single antigen beads) at transplantation and at first BKPyV testing.

Results

Nineteen of 174 patients (11%) tested positive for BKPyV viremia. Within 24 months of BKPyV viremia detection, 79% of BKPyV viremic patients developed dnDSA. Only 20% of BKPyV viremia-persistent cases, compared to 86% of BKPyV viremia-resolved cases, developed dnDSA (P = 0.03). Poor allograft survival was evident in BKPyV viremia-persistent patients (60% failure by 2 years post BKPyV diagnosis) and in BKPyV viremia-resolved patients with dnDSA (5-year post BKPyV diagnosis allograft survival of 48%).

Conclusions

Post-transplant BKPyV viremia and preemptive immunosuppression reduction is associated with high rates of dnDSA. When preemptively treating BKPyV viremia, dnDSA should be monitored to prevent allograft consequences.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Ftid.12467

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The incidence and risk factors of deep vein thrombosis after kidney transplantation in Korea: single center experience

Clinical Transplantation The incidence and risk factors of deep vein thrombosis after kidney transplantation in Korea: single center experience

Abstract

Background

The incidence of deep vein thrombosis (DVT) after kidney transplantation (KT) and the risk factors are still unknown in Korean patients. Determining the need for appropriate DVT prophylaxis is difficult when considering the low incidence of DVT in the Asian population. The aim of the present study was to investigate the incidence of DVT occurring 3 months after KT, the DVT occurrence pattern, and risk factors in Korean patients.

Methods

Data from a total of 393 patients who underwent KT from November 2009 to December 2012 were analyzed. Color duplex ultrasonography was used for the diagnosis or screening of DVT in all patients preoperatively and on postoperative day 7, 14, 28 and 90.

Results

The cumulative 3 months incidence of DVT after KT was 4.6%, and there was one symptomatic DVT. Patients with DVT were older than those without DVT at the time of transplantation (52.8 vs. 44.6, P < 0.001). According to univariate and multivariate analysis, older age was identified as a risk factor of DVT at the time of transplantation, whereas history of DVT did not reach statistical significance. There were no deaths related to DVT or pulmonary embolism.

Conclusions

Pharmacological prophylaxis after KT is not necessary because of the low incidence of DVT in Korean patients, and instead, we suggest that long-term mechanical prophylaxis of at least 3 months can be a suitable option. Patients older than 50 years of age have a higher risk of developing DVT, and careful observation is needed in these patients.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12648

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Allograft Nephrectomy versus No-Allograft Nephrectomy for Renal Transplantation: A Meta –Analysis

Clinical Transplantation Allograft Nephrectomy versus No-Allograft Nephrectomy for Renal Transplantation: A Meta –Analysis

Abstract

Objective

To assess the safety and efficacy of allograft nephrectomy vs no-allograft nephrectomy for renal re-transplantation.

Methods: Medline (PubMed), Embase, Ovid, Cochrane, and the Chinese Biomedical Literature databases were searched to identify clinically comparable trials which compared allograft nephrectomy(AN) and no-allograft nephrectomy(no-AN) with renal re-transplantation. RevMan 5.1 software and Stat Manager V4.1 software were used for the meta-analysis.

Results

Eight trials were included involving 1008 patients. Of these, 508 (50.4%) patients underwent AN and 500 (49.6%) had not undergone AN before re-transplantation. The pooled results revealed that the AN group had a longer time interval between graft loss and re-transplantation of 14.40 months (weighted mean difference (WMD) = 11.23; 95% confidence interval (CI): 2.47 to 19.99; P = 0.01). The AN group also had an higher rate of positive PRA (PRA>10%) before re-transplantation (OR: odds ratio =1.62, 95%CI=1.17-2.23, P=0.003). A comparison of serum creatinine (mg/dL) at one year after re-transplantation between the groups showed no significant differences (WMD: −0.25; 95%CI: −0.52–0.03; P = 0.08). There were neither significant differences in one-year graft survival rates (OR: 0.74; 95% CI: 0.31–1.72; P = 0.48) nor one-year patient survival rates (OR: 1.60; 95%CI: 0.57–4.46; P = 0.37) between the groups. Insignificant differences were noted for the rates of acute rejection (OR: 1.30; 95%CI: 0.89 to 1.91; P = 0.17) and postoperative complications (OR: 1.51; 95%CI: 0.24–9.43; P = 0.66) for the groups.

Conclusion

Through our meta-analysis, allograft nephrectomy before re-transplantation seemed well tolerated but conferred no significant benefit. The risk benefit ratio of transplant nephrectomy with re-transplantation must be evaluated in each individual patient.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12654

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A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients

Journal of the American Society of Nephrology current issue A National Study of Outcomes among HIV-Infected Kidney Transplant Recipients

Kidney transplantation is a viable treatment for select patients with HIV and ESRD, but data are lacking regarding long-term outcomes and comparisons with appropriately matched HIV-negative patients. We analyzed data from the Scientific Registry of Transplant Recipients (SRTR; 2002–2011): 510 adult kidney transplant recipients with HIV (median follow-up, 3.8 years) matched 1:10 to HIV-negative controls. Compared with HIV-negative controls, HIV-infected recipients had significantly lower 5-year (75.3% versus 69.2%) and 10-year (54.4% versus 49.8%) post-transplant graft survival (GS) (hazard ratio [HR], 1.37; 95% confidence interval [95% CI], 1.15 to 1.64; P<0.001) that persisted when censoring for death (HR, 1.43; 95% CI, 1.12 to 1.84; P=0.005). However, compared with HIV-negative/hepatitis C virus (HCV)–negative controls, HIV monoinfected recipients had similar 5-year and 10-year GS, whereas HIV/HCV coinfected recipients had worse GS (5-year: 64.0% versus 52.0%, P=0.02; 10-year: 36.2% versus 27.0%, P=0.004 [HR, 1.38; 95% CI, 1.08 to 1.77; P=0.01]). Patient survival (PS) among HIV-infected recipients was 83.5% at 5 years and 51.6% at 10 years and was significantly lower than PS among HIV-negative controls (HR, 1.34; 95% CI, 1.08 to 1.68; P<0.01). However, PS was similar for HIV monoinfected recipients and HIV-negative/HCV-negative controls at both times. HIV/HCV coinfected recipients had worse PS compared with HIV-negative/HCV-infected controls (5-year: 67.0% versus 78.6%, P=0.007; 10-year: 29.3% versus 56.23%, P=0.002 [HR, 1.57; 95% CI, 1.11 to 2.22; P=0.01]). In conclusion, HIV-negative and HIV monoinfected kidney transplant recipients had similar GS and PS, whereas HIV/HCV coinfected recipients had worse outcomes. Although encouraging, these results suggest caution in transplanting coinfected patients.

http://jasn.asnjournals.org/cgi/content/short/26/9/2222?rss=1

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Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study

Journal of the American Society of Nephrology current issue Corticosteroids in IgA Nephropathy: A Retrospective Analysis from the VALIGA Study

Current guidelines suggest treatment with corticosteroids (CS) in IgA nephropathy (IgAN) when proteinuria is persistently ≥1 g/d despite 3–6 months of supportive care and when eGFR is >50 ml/min per 1.73 m². Whether the benefits of this treatment extend to patients with an eGFR≤50 ml/min per 1.73 m², other levels of proteinuria, or different renal pathologic lesions remains unknown. We retrospectively studied 1147 patients with IgAN from the European Validation Study of the Oxford Classification of IgAN (VALIGA) cohort classified according to the Oxford-MEST classification and medication used, with details of duration but not dosing. Overall, 46% of patients received immunosuppression, of which 98% received CS. Treated individuals presented with greater clinical and pathologic risk factors of progression. They also received more antihypertensive medication, and a greater proportion received renin angiotensin system blockade (RASB) compared with individuals without immunosuppressive therapy. Immunosuppression was associated with a significant reduction in proteinuria, a slower rate of renal function decline, and greater renal survival. Using a propensity score, we matched 184 subjects who received CS and RASB to 184 patients with a similar risk profile of progression who received only RASB. Within this group, CS reduced proteinuria and the rate of renal function decline and increased renal survival. These benefits extended to those with an eGFR≤50 ml/min per 1.73 m², and the benefits increased proportionally with the level of proteinuria. Thus, CS reduced the risk of progression regardless of initial eGFR and in direct proportion to the extent of proteinuria in this cohort.

http://jasn.asnjournals.org/cgi/content/short/26/9/2248?rss=1

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Fluorodeoxyglucose F18 Positron Emission Tomography Coupled With Computed Tomography in Suspected Acute Renal Allograft Rejection [feedly]

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Fluorodeoxyglucose F18 Positron Emission Tomography Coupled With Computed Tomography in Suspected Acute Renal Allograft Rejection
// AJT - Early

Management of kidney transplant recipients (KTRs) with suspected acute rejection (AR) ultimately relies on kidney biopsy; however, noninvasive tests predicting nonrejection would help avoid unnecessary biopsy. AR involves recruitment of leukocytes avid for fluorodeoxyglucose F¹⁸ (¹⁸F-FDG), thus ¹⁸F-FDG positron emission tomography (PET) coupled with computed tomography (CT) may noninvasively distinguish nonrejection from AR. From January 2013 to February 2015, we prospectively performed 32 ¹⁸F-FDG PET/CT scans in 31 adult KTRs with suspected AR who underwent transplant biopsy. Biopsies were categorized into four groups: normal (n = 8), borderline (n = 10), AR (n = 8), or other (n = 6, including 3 with polyoma BK nephropathy). Estimated GFR was comparable in all groups. PET/CT was performed 201 ± 18 minutes after administration of 3.2 ± 0.2 MBq/kg of ¹⁸F-FDG, before any immunosuppression change. Mean standard uptake values (SUVs) of both upper and lower renal poles were measured. Mean SUVs reached 1.5 ± 0.2, 1.6 ± 0.3, 2.9 ± 0.8, and 2.2 ± 1.2 for the normal, borderline, AR, and other groups, respectively. One-way analysis of variance demonstrated a significant difference of mean SUVs among groups. A positive correlation between mean SUV and acute composite Banff score was found, with r² = 0.49. The area under the receiver operating characteristic curve was 0.93, with 100% sensitivity and 50% specificity using a mean SUV threshold of 1.6. In conclusion, ¹⁸F-FDG PET/CT may help noninvasively prevent avoidable transplant biopsies in KTRs with suspected AR.

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Randomized Controlled Trial of Mycophenolate Mofetil in Children, Adolescents, and Adults With IgA Nephropathy

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American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation 2015 Jul 21; Randomized Controlled Trial of Mycophenolate Mofetil in Children, Adolescents, and Adults With IgA Nephropathy. Ronald J Hogg, R Curtis Bay, J Charles Jennette, Richard Sibley, Sumit Kumar, Fernando C Fervenza, Gerald Appel, Daniel Cattran, Danny Fischer, R Morrison Hurley, Jorge Cerda, Brad Carter, Beverly Jung, German Hernandez, Debbie Gipson, Robert J Wyatt PMID: 26209543

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Alberto Reino Buelvas

Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial

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American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation 2015 Jul 30; Efficacy of Febuxostat for Slowing the GFR Decline in Patients With CKD and Asymptomatic Hyperuricemia: A 6-Month, Double-Blind, Randomized, Placebo-Controlled Trial. Dipankar Sircar, Soumya Chatterjee, Rajesh Waikhom, Vishal Golay, Arpita Raychaudhury, Suparna Chatterjee, Rajendra Pandey PMID: 26233732

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Alberto Reino Buelvas

Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy

Transplantation - Current Issue Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy

Background: Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction. Methods: We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients. Results: The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results. Conclusions: Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.


http://journals.lww.com/transplantjournal/Fulltext/2015/08000/Clinical_Utility_of_Urinary_Cytology_to_Detect_BK.31.aspx

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Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy

Transplantation - Current Issue Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy

Background: Secretory phospholipase A2 receptor (PLA2R) is the target antigen of the auto-antibodies produced in most (∼70%) patients with primary membranous nephropathy (pMN). The applicability of anti-PLA2R1 antibody monitoring for the prediction of MN recurrence in kidney transplant recipients still is a matter of debate. Methods: We sought to characterize the presence and concentration of anti-PLA2R antibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 21 patients with pMN before and after transplantation to evaluate whether anti-PLA2R concentrations could predict pMN recurrence. Results: The presence of pMN recurrence was significantly correlated with the existence of a positive ELISA assay at graft biopsy or with high level of anti-PLA2R1 activity before transplantation (P = 0.03). In the receiver operating characteristic analysis, anti-PLA2R levels (cut-off of 45 U/mL) during the pretransplantation period accurately predicted pMN recurrence, with a sensitivity of 85.3%, specificity of 85.1%, negative predictive value of 92%, and an area under the curve of 90.8%. This finding supports the hypothesis that anti-PLA2R cause pMN recurrence in humans and indicates the need to prove in an experimental model. Furthermore, 6 of 7 patients with recurrence were carriers of HLA DQA1* 05:01/05 and DQB1* 02:01, confirming these DQ alleles as those associated with higher anti-PLA2R levels. Conclusions: This study is the first to demonstrate pretransplantation circulating anti-PLA2R antibodies in a cohort of renal transplant recipients who prospectively developed recurrent disease. Currently, anti-PLA2R levels measured by ELISA may be a rational tool to establish the risk of MN recurrence in renal allograft recipients.


http://journals.lww.com/transplantjournal/Fulltext/2015/08000/Antiphospholipase_A2_Receptor_Antibody_Levels.30.aspx

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Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies

AJT - Early Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies

Allograft histology 1 year posttransplant is an independent correlate to long-term death-censored graft survival. We assessed prognostic implications of changes in histology first 2 years posttransplant in 938 first kidney recipients, transplanted 1999–2010, followed for 93.4 ± 37.7 months. Compared to implantation biopsies, histology changed posttransplant showing at 1 year that 72.6% of grafts had minor abnormalities (favorable histology), 20.2% unfavorable histology, and 7.2% glomerulonephritis. Compared to favorable, graft survival was reduced in recipients with unfavorable histology (hazards ratio [HR] = 4.79 [3.27–7.00], p < 0.0001) or glomerulonephritis (HR = 5.91 [3.17–11.0], p < 0.0001). Compared to unfavorable, in grafts with favorable histology, failure was most commonly due to death (42% vs. 70%, p < 0.0001) and less commonly due to alloimmune causes (27% vs. 10%, p < 0.0001). In 80% of cases, favorable histology persisted at 2 years. However, de novo 2-year unfavorable histology (15.3%) or glomerulonephritis (4.7%) related to reduced survival. The proportion of favorable grafts increased during this period (odds ratio = 0.920 [0.871–0.972], p = 0.003, per year) related to fewer DGF, rejections, polyoma-associated nephropathy (PVAN), and better function. Graft survival also improved (HR = 0.718 [0.550–0.937], p = 0.015) related to better histology and function. Evolution of graft histologic early posttransplant relate to long-term survival. Avoiding risk factors associated with unfavorable histology relates to improved histology and graft survival.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13423

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Alberto Reino Buelvas

Coronary Events in Obese Hemodialysis Patients Before and After Renal Transplantation [feedly]

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Coronary Events in Obese Hemodialysis Patients Before and After Renal Transplantation
// Clinical Transplantation

Abstract

We examined the impact of obesity (BMI ≥ 30 kg/m², n=357) on prognosis in 1696 hemodialysis (HD) patients before and after renal transplantation (TX). End-points were coronary events, composite CV events, and death.

Obese HD patients were older (55.9 ± 9.2 v 54.2 ± 11), had more diabetes (54% v 40%), dyslipidemia (49% v 30%), altered myocardial scan (38% v 31%), MI (16% v 10%), coronary intervention (11% v 7%), higher total-cholesterol (186 ± 52 v 169 ± 47), and triglycerides (219 ± 167 v 144 ± 91). Obese undergoing TX had more dyslipidemia (46% v 31%), angina (23% v 14%), MI (18% v 5%), increased total-cholesterol (185 ± 56 v 172 ± 48) and triglycerides (237 ± 190 v 149 ± 100). Obesity was independently associated with coronary events (Log-rank=0.008, HR 2.55 %CI 1.27-5.11) and death (Log-rank 0.046, HR 1.52, % CI 1.007 – 2.30) in TX but not in HD.

Obese HD patients had more risk factors and ischemic heart disease but these characteristics did not interfere with prognosis. In TX patients obesity predict coronary events and death.

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Neoplastic and Non-Neoplastic Complications of Solid Organ Transplantation in Patients with Preexisting Monoclonal Gammopathy of Undetermined Significance (MGUS)

Clinical Transplantation Neoplastic and Non-Neoplastic Complications of Solid Organ Transplantation in Patients with Preexisting Monoclonal Gammopathy of Undetermined Significance (MGUS)

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3-7% of the elderly population, with higher prevalence in renal failure patients, and is associated with a 25-fold increased lifetime risk for plasma cell myeloma (PCM), also known as multiple myeloma. Using the California State Inpatient, Emergency Department, and Ambulatory Surgery Databases components of the Healthcare Cost and Utilization Project (HCUP), we sought to determine if patients with MGUS who undergo solid organ allograft (n=22,062) are at increased adjusted relative risk (aRR) for hematological malignancy and other complications. Among solid organ transplant patients, patients with preexisting MGUS had higher aRR of PCM (aRR 19.46; 95%CI 7.05, 53.73; p<0.001), venous thromboembolic events (aRR 1.66; 95%CI 1.15, 2.41; p=0.007), and infection (aRR 1.24; 95%CI 1.06, 1.45; p=0.007). However, when comparing MGUS patients with and without solid organ transplant, there was decreased aRR for PCM with transplant (aRR 0.34; 95%CI 0.13, 0.88; p=0.027), and increased venous thromboembolic events (aRR 2.33; 95%CI 1.58, 3.44; p<0.001) and infectious risks, (aRR 1.44; 95%CI 1.23, 1.70; p<0.001). While MGUS increased the risk of PCM overall following solid organ transplantation, there was lower risk of PCM development compared to MGUS patients who did not receive a transplant. MGUS should not preclude solid organ transplant.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12595

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

You Are What You Eat: Metabolites of Gut Microbiota Provide Novel Insights into Diagnosis and Development of Chronic Kidney Disease

Transplantation - Most Popular Articles You Are What You Eat: Metabolites of Gut Microbiota Provide Novel Insights into Diagnosis and Development of Chronic Kidney Disease

No abstract available


http://journals.lww.com/transplantjournal/Fulltext/2015/07000/You_Are_What_You_Eat___Metabolites_of_Gut.4.aspx

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Atlas of Renal Pathology: Minimal Change Disease

American Journal of Kidney Diseases Atlas of Renal Pathology: Minimal Change Disease

Minimal change disease (MCD) is characterized by nephrotic syndrome. It is the most common cause of nephrotic syndrome in children aged 1 to 7 years and remains a cause of nephrotic syndrome in adults.


http://www.ajkd.org/article/S0272-6386(15)00634-4/abstract?rss=yes

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients

Transplantation - Most Popular Articles Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients

Background: Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR). Methods: Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed. Results: Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211–0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar. Conclusions: Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.


http://journals.lww.com/transplantjournal/Fulltext/2015/07000/Evaluation_of_Low__Versus_High_dose_Valganciclovir.34.aspx

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Alberto Reino Buelvas 

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Recurrent Membranoproliferative Glomerulonephritis Type I After Kidney Transplantation: A 17-Year Single-Center Experience

Transplantation - Current Issue Recurrent Membranoproliferative Glomerulonephritis Type I After Kidney Transplantation: A 17-Year Single-Center Experience

Background: Most previously published studies of patients with membranoproliferative glomerulonephritis type I are small or have short follow-up period. We report the outcome of a fairly large cohort of patients followed up for nearly 10 years. Methods: Retrospective cohort study. Graft survival, recurrence rate and risk factors for recurrence were analyzed for 43 patients transplanted between the years 1995 and 2012. Results: At a mean overall follow-up of 118±61 months (median, 127.8; range, 4.9–217), 12 patients lost their graft (28%). Death-censored actuarial 15-year graft survival rate was 56%. Membranoproliferative glomerulonephritis recurred in eight patients (19%) at a median time of 15.4 months (range, 4.4–70 months). Recurrence led to graft loss in seven patients (88%) within a median of 11.6 months (range, 1.3–54 months) from diagnosis. Median graft survival was 30.5 months for recurrence (range, 7–86). Actuarial 15-year graft survival was 71% for nonrecurrent. The risk for recurrence was higher for patients with human leukocyte antigen (HLA) B49 (odds ratio, 16.9; 95% confidence interval, 1.1–246; P=0.038) and HLA DR4 (odds ratio, 15.9; 95% confidence interval, 1.07–237; P=0.044) alleles. A trend toward increased risk was found with shorter duration of dialysis before transplantation. Four of 16 (25%) living-related versus none of the living-unrelated donors' recipients recurred. The HLA B49, acute tubular necrosis after transplantation, previous transplantations, and Arab origin were all associated with decreased graft and patient survival. Conclusion: Patients without recurrence in the first years should expect an excellent graft survival. Nonrelated living donors should be preferred. The HLA B49 and DR4 alleles may increase the risk for recurrence.


http://journals.lww.com/transplantjournal/Fulltext/2015/06000/Recurrent_Membranoproliferative_Glomerulonephritis.15.aspx

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Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor-Specific Antibody

AJT - Early Rates and Determinants of Progression to Graft Failure in Kidney Allograft Recipients With De Novo Donor-Specific Antibody

Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of −0.65 mL/min/1.73 m²/year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (−2.89 vs. −0.65 mL/min/1.73 m²/year, p < 0.0001) and accelerated post-dnDSA (−3.63 vs. −2.89 mL/min/1.73 m²/year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post-dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell–mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post-dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune-mediated injury, which requires solutions targeting T and B cells.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13347

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Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Journal of the American Society of Nephrology current issue Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8–152.0) to 63.3 (52.0–79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.

http://jasn.asnjournals.org/cgi/content/short/26/5/1205?rss=1

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Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations?

American Journal of Kidney Diseases Metformin Use in Type 2 Diabetes Mellitus With CKD: Is It Time to Liberalize Dosing Recommendations?

Metformin is a very effective drug for type 2 diabetes mellitus (T2DM) with relatively few side effects1 and has other potential benefits, such as lowering of cardiovascular risk2,3 and possible lowering of cancer risk.4 However, there is concern that metformin may increase the risk of lactic acidosis in people with chronic kidney disease (CKD). Considering the number of people with CKD and T2DM,5,6 there are potentially millions of people who are not currently taking metformin who might benefit from this medication.


http://www.ajkd.org/article/S0272-6386(15)00611-3/abstract?rss=yes

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Hypomagnesaemia in kidney transplantation

Transplantation Reviews Hypomagnesaemia in kidney transplantation

In the era of calcineurin inhibitors, hypomagnesaemia is a very common finding in kidney transplant recipients. Especially the first weeks after transplantation it is the rule rather than the exception. Hypomagnesaemia or low magnesium intake have been associated with a higher mortality or more cardiovascular events in the general population, but this association has never been explored in kidney transplant recipients, despite their increased cardiovascular risk. Kidney transplant recipients with pre- or post-transplant hypomagnesaemia seem to have an aberrant glucose metabolism and develop diabetes mellitus more frequently.


http://www.transplantationreviews.com/article/S0955-470X(15)00036-1/abstract?rss=yes

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Alberto Reino Buelvas 

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New-Onset Diabetes After Transplantation: Results From a Double-Blind Early Corticosteroid Withdrawal Trial

AJT - Early New-Onset Diabetes After Transplantation: Results From a Double-Blind Early Corticosteroid Withdrawal Trial

New-onset diabetes after transplantation (NODAT) is an important complication following kidney transplantation. Data from the 5-year early steroid withdrawal double-blind randomized trial were analyzed to determine if steroid avoidance reduced the NODAT risk. Incidence, timing and risk factors for NODAT were evaluated using eight definitions. By American Diabetes Association definition, 36.3% of patients on chronic corticosteroids (CCS) and 35.9% on early corticosteroid withdrawal (CSWD) were diagnosed with NODAT by 5 years. The definition combining fasting blood glucose ≥126 mg/dL on two occasions or treatment identified slightly more cases of NODAT: CCS (39.3%) and CSWD (39.4%). Through 5 years posttransplant, the proportion of NODAT patients requiring treatment were similar (CSWD 22.5% vs. CCS 21.5%); however, insulin therapy was lower with CSWD (3.7% vs. 11.6%; p = 0.049). By multivariate analysis, only age, but not corticosteroid use, was a significant risk factor for NODAT for more than one definition. Numerical, but not statistically significant trends toward lower NODAT rates with CSWD were observed through 5 years for insulin use, HbA1c ≥6.0% and ≥6.5% on two occasions. This prospective, randomized trial of CSWD indicates that CSWD has a limited impact in reducing NODAT when compared to low-dose prednisone (5 mg/day from month 6 to 5 years).

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13247

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{beta}-Blocker Dialyzability and Mortality in Older Patients Receiving Hemodialysis

Journal of the American Society of Nephrology current issue {beta}-Blocker Dialyzability and Mortality in Older Patients Receiving Hemodialysis

Some β-blockers are efficiently removed from the circulation by hemodialysis ("high dialyzability") whereas others are not ("low dialyzability"). This characteristic may influence the effectiveness of the β-blockers among patients receiving long-term hemodialysis. To determine whether new use of a high-dialyzability β-blocker compared with a low-dialyzability β-blocker associates with a higher rate of mortality in patients older than age 66 years receiving long-term hemodialysis, we conducted a propensity-matched population-based retrospective cohort study using the linked healthcare databases of Ontario, Canada. The high-dialyzability group (n=3294) included patients initiating atenolol, acebutolol, or metoprolol. The low-dialyzability group (n=3294) included patients initiating bisoprolol or propranolol. Initiation of a high- versus low-dialyzability β-blocker was associated with a higher risk of death in the following 180 days (relative risk, 1.4; 95% confidence interval, 1.1 to 1.8; P<0.01). Supporting this finding, we repeated the primary analysis in a cohort of patients not receiving hemodialysis and found no significant association between dialyzability and the risk of death (relative risk, 1.0; 95% confidence interval, 0.9 to 1.3; P=0.71). β-Blocker exposure was not randomly allocated in this study, so a causal relationship between dialyzability and mortality cannot be determined. However, our findings should raise awareness of this potentially important drug characteristic and prompt further study.

http://jasn.asnjournals.org/cgi/content/short/26/4/987?rss=1

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Treatment of atherosclerotic renovascular hypertension: review of observational studies and a meta-analysis of randomized clinical trials

Nephrology Dialysis Transplantation - current issue Treatment of atherosclerotic renovascular hypertension: review of observational studies and a meta-analysis of randomized clinical trials

Atherosclerotic renal artery stenosis can cause ischaemic nephropathy and arterial hypertension. We herein review the observational and randomized clinical trials (RCTs) comparing medical and endovascular treatment for control of hypertension and renal function preservation. Using the Population Intervention Comparison Outcome (PICO) strategy, we identified the relevant studies and performed a novel meta-analysis of all RCTs to determine the efficacy and safety of endovascular treatment when compared with medical therapy. The following outcomes were examined: baseline follow-up difference in mean systolic and diastolic blood pressure (BP), serum creatinine, number of drugs at follow-up, incident events (heart failure, stroke, and worsening renal function), mortality, cumulative relative risk of heart failure, stroke, and worsening renal function. Seven studies comprising a total of 2155 patients (1741 available at follow-up) were considered, including the recently reported CORAL Study. Compared with baseline, diastolic BP fell more at follow-up in patients in the endovascular than in the medical treatment arm (standard difference in means –0.21, 95% confidence interval (CI): –0.342 to –0.078, P = 0.002) despite a greater reduction in the mean number of antihypertensive drugs (standard difference in means –0.201, 95% CI: –0.302 to –0.1, P < 0.001). At variance, follow-up changes (from baseline) of systolic BP, serum creatinine, and incident cardiovascular event rates did not differ between treatment arms. Thus, patients with atherosclerotic renal artery stenosis receiving endovascular treatment required less anti-antihypertensive drugs at follow-up than those medically treated. Notwithstanding this, they evidenced a better control of diastolic BP.

http://ndt.oxfordjournals.org/cgi/content/short/30/4/541?rss=1

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Dose-Finding Study of Rivaroxaban in Hemodialysis Patients

American Journal of Kidney Diseases Dose-Finding Study of Rivaroxaban in Hemodialysis Patients

Use of vitamin K antagonists for the prevention of stroke and systemic embolism in dialysis patients with nonvalvular atrial fibrillation is controversial. However, no good alternatives presently are available. The anti−factor Xa antagonist rivaroxaban is contraindicated for lack of pharmacokinetic, pharmacodynamic, and clinical data. This study aims to characterize the pharmacokinetics/pharmacodynamics of rivaroxaban in maintenance hemodialysis patients.


http://www.ajkd.org/article/S0272-6386(15)00490-4/abstract?rss=yes

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Alberto Reino Buelvas 

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Amikacin Prophylaxis and Risk Factors for Surgical Site Infection After Kidney Transplantation

Transplantation - Current Issue Amikacin Prophylaxis and Risk Factors for Surgical Site Infection After Kidney Transplantation

Background: Antibiotic prophylaxis plays a major role in preventing surgical site infections (SSIs). This study aimed to evaluate antibiotic prophylaxis in kidney transplantation and identify risk factors for SSIs. Methods: We evaluated all kidney transplantation recipients from January 2009 and December 2012. We excluded patients who died within the first 72 hr after transplantation, were undergoing simultaneous transplantation of another organ, or were below 12 years of age. The main outcome measure was SSI during the first 60 days after transplantation. Results: A total of 819 kidney transplants recipients were evaluated, 65% of whom received a deceased-donor kidney. The antibiotics used as prophylaxis included cephalosporin, in 576 (70%) cases, and amikacin, in 233 (28%). We identified SSIs in 106 cases (13%), the causative agent being identified in 72 (68%). Among the isolated bacteria, infections caused by extended-spectrum β-lactamase–producing Enterobacteriaceae predominated. Multivariate analysis revealed that the risk factors for post-kidney transplantation SSIs were deceased donor, thin ureters at kidney transplantation, antithymocyte globulin induction therapy, blood transfusion at the transplantation procedure, high body mass index, and diabetes mellitus. The only factor associated with a reduction in the incidence of SSIs was amikacin use as antibiotic prophylaxis. Factors associated with reduced graft survival were: intraoperative blood transfusions, reoperation, human leukocyte antigen mismatch, use of nonstandard immunosuppression therapy, deceased donor, post-kidney transplantation SSIs, and delayed graft function. Conclusion: Amikacin prophylaxis is a useful strategy for preventing SSIs.


http://journals.lww.com/transplantjournal/Fulltext/2015/03000/Amikacin_Prophylaxis_and_Risk_Factors_for_Surgical.14.aspx

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Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients

AJT - Early Noroviruses as a Cause of Diarrhea in Immunocompromised Pediatric Hematopoietic Stem Cell and Solid Organ Transplant Recipients

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1–324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13227

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Alberto Reino Buelvas 

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Limitations of Hemoglobin A1c for the Diagnosis of Posttransplant Diabetes Mellitus

Transplantation - Current Issue Limitations of Hemoglobin A1c for the Diagnosis of Posttransplant Diabetes Mellitus

Background: Posttransplant diabetes mellitus (PTDM) is usually detected 2 to 3 months after transplantation by fasting plasma glucose (fPG) ≥7.0 mmol/L (≥126 mg/dL) and/or 2 hr post-challenge plasma glucose ≥11.1 mmol/L (≥200 mg/dL) during an oral glucose tolerance test (OGTT). Recently, glycosylated hemoglobin (HbA1c) of 6.5% or higher (≥47.5 mmol/mol) has been proposed as an alternative diagnostic criterion (the HbA1c criterion). We aimed to assess the sensitivity of applying the HbA1c criterion alone or in combination with a single measurement of fPG of 7.0 mmol/L or higher (≥126 mg/dL) at 10 weeks after transplantation as screening tests for the diagnosis of PTDM. Methods: From 1999 to 2011, measurements of fPG, HbA1c, and OGTT were performed in 1,619 nondiabetic renal transplant recipients. Results: The HbA1c criterion detected 38.0% of patients with PTDM diagnosed with the standard diagnostic criteria. The specificity was 86.3%. When the HbA1c threshold value was lowered to 6.2% (44.3 mmol/mol), sensitivity increased to 57.8% with a corresponding reduced specificity of 80.4%. A combination of the HbA1c criterion and fPG of 7.0 mmol/L or higher (126 mg/dL) at 10 weeks after transplantation improved diagnostic precision with a sensitivity of 77.7% and a specificity of 96.1%. Conclusion: The proposed diagnostic HbA1c criterion failed to detect most cases of PTDM, and one of four cases of PTDM was detected by OGTT alone. This indicates that the HbA1c threshold value likely needs to be lowered for renal transplant recipients and supports continued use of OGTT as a diagnostic tool for detection of PTDM.


http://journals.lww.com/transplantjournal/Fulltext/2015/03000/Limitations_of_Hemoglobin_A1c_for_the_Diagnosis_of.29.aspx

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Alberto Reino Buelvas 

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Dobutamine Stress Cardiac MRI for Assessment of Coronary Artery Disease Prior to Kidney Transplantation

American Journal of Kidney Diseases Dobutamine Stress Cardiac MRI for Assessment of Coronary Artery Disease Prior to Kidney Transplantation

Cardiovascular disease is the leading cause of death in end-stage kidney disease following successful kidney transplantation.1 The accuracy of noninvasive cardiac stress testing versus coronary angiography in detecting significant coronary artery disease (CAD) prior to kidney transplantation is inadequate.2-4 Dobutamine stress cardiac magnetic resonance (DSCMR) imaging offers highly accurate, prognostically relevant results in detecting inducible myocardial ischemia.5,6 We performed a diagnostic test study to evaluate the utility of DSCMR for identifying significant CAD prior to potential kidney transplantation, using angiography as the reference test.


http://www.ajkd.org/article/S0272-6386(15)00423-0/abstract?rss=yes

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Current Status of Bicarbonate in CKD

Journal of the American Society of Nephrology current issue Current Status of Bicarbonate in CKD

Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been tested very little, especially with respect to standard clinical outcomes. On the basis of fundamental research and small alkali supplementation trials, correcting metabolic acidosis has a strikingly broad array of potential benefits. This review summarizes the published evidence on the association between serum bicarbonate and clinical outcomes. We discuss the role of alkali supplementation in CKD as it relates to retarding kidney disease progression, improving metabolic and musculoskeletal complications.

http://jasn.asnjournals.org/cgi/content/short/26/3/515?rss=1

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Alberto Reino Buelvas 

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Comparison of alemtuzumab versus antithymocyte globulin induction therapy in primary non-sensitized renal transplant patients treated with rapid steroid withdrawal

Clinical Transplantation Comparison of alemtuzumab versus antithymocyte globulin induction therapy in primary non-sensitized renal transplant patients treated with rapid steroid withdrawal

Abstract

Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction therapy in renal transplantation. This retrospective, single-center, cohort study evaluated cumulative incidence of 1-year biopsy-proven acute rejection (BPAR) among 200 consecutive primary non-sensitized kidney transplant recipients who received either alemtuzumab (n=100) or rATG (n=100) induction followed by rapid steroid taper, tacrolimus and mycophenolate mofetil (MMF). Protocol biopsies, plasma and urine BK virus PCR, serum creatinine and iothalamate GFR (iGFR) were obtained at 1, 4 and 12 months from transplantation. The 1-year BPAR rates were similar between the alemtuzumab and rATG groups; however, rejection Banff IA and higher was more common in the alemtuzumab arm (18% vs. 5%, P=0.047). After adjusting for confounding variables, alemtuzumab was still associated with Banff IA and higher rejection (adjusted OR: 3.7, CI: 1.2-10.5, P=0.02). Despite similar rates of BK viremia, more patients in the alemtuzumab arm developed BK nephropathy (16% vs. 3%, P=0.046). 1-year iGFR (53.4 ± 20.2 vs. 71.9 ± 27.2 ml/min/1.73 m², P=0.002) and 3-year graft survival (89.5% vs. 95%, P=0.05) were lower in the alemtuzumab group. In low immunological risk kidney transplant recipients on steroid free immunosuppression, alemtuzumab was associated with more severe rejection and BK nephropathy compared to rATG.

This article is protected by copyright. All rights reserved.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12532

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year

AJT - Early Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year

This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13168

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

AJT Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

• Hellemans R, Hazzan M, Durand D, et al. 
• Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study. [JOURNAL ARTICLE]
• Am J Transplant 2015 Feb 23.

We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.

http://www.unboundmedicine.com/medline/citation/25707875/Daclizumab_Versus_Rabbit_Antithymocyte_Globulin_in_High_Risk_Renal_Transplants:_Five_Year_Follow_up_of_a_Randomized_Study_

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Rotavirus in Organ Transplantation: Drug-Virus-Host Interactions

AJT - Early Rotavirus in Organ Transplantation: Drug-Virus-Host Interactions

Although rotavirus is usually recognized as the most common etiology of diarrhea in young children, it can in fact cause severe diseases in organ transplantation recipients irrespective of pediatric or adult patients. This comprehensive literature analysis revealed 200 cases of rotavirus infection with 8 related deaths in the setting of organ transplantation been recorded. Based on published cohort studies, an average incidence of 3% (187 infections out of 6176 organ recipients) was estimated. Rotavirus infection often causes severe gastroenteritis complications and occasionally contributes to acute cellular rejection in these patients. Immunosuppressive agents, universally used after organ transplantation to prevent organ rejection, conceivably play an important role in such a severe pathogenesis. Interestingly, rotavirus can in turn affect the absorption and metabolism of particular immunosuppressive medications via several distinct mechanisms. Even though rotaviral enteritis is self-limiting in general, infected transplantation patients are usually treated with intensive care, rehydration and replacement of nutrition, as well as applying preventive strategies. This article aims to properly assess the clinical impact of rotavirus infection in the setting of organ transplantation and to disseminate the interactions among the virus, host and immunosuppressive medications.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13135

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Alberto Reino Buelvas 

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Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR.

AJT Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR.

• Loupy A, Viglietti D, Mengel M 
• Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR. [EDITORIAL]
• Am J Transplant 2015 Mar 2.

http://www.unboundmedicine.com/medline/citation/25731892/Complement_Inhibition_in_HLA_Incompatible_Kidney_Transplants:_Persisting_Antibody_Mediated_Injury_Despite_Marked_Decrease_of_Clinical_ABMR_

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Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year.

AJT Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year.

• Cornell LD, Schinstock CA, Gandhi MJ, et al. 
• Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year. [JOURNAL ARTICLE]
• Am J Transplant 2015 Mar 2.

This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

http://www.unboundmedicine.com/medline/citation/25731800/Positive_Crossmatch_Kidney_Transplant_Recipients_Treated_With_Eculizumab:_Outcomes_Beyond_1_Year_

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I'm sharing "A randomized trial of icatibant in ACE-inhibitor-induced angioedema."

New England Journal of Medicine 2015 Jan 29; 372 (5) : 418-25. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. Murat Baş, Jens Greve, Klaus Stelter, Miriam Havel, Ulrich Strassen, Nicole Rotter, Johannes Veit, Beate Schossow, Alexander Hapfelmeier, Victoria Kehl, Georg Kojda, Thomas K Hoffmann PMID: 25629740

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Alberto Reino Buelvas

The Bionic Pancreas: Novel Perspectives on Insulin Replacement Therapies

Transplantation - Most Popular Articles The Bionic Pancreas: Novel Perspectives on Insulin Replacement Therapies

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http://journals.lww.com/transplantjournal/Fulltext/2015/02150/The_Bionic_Pancreas___Novel_Perspectives_on.10.aspx

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Alberto Reino Buelvas 

Médico Internista Nefrólogo