Risk of Febuxostat-Associated Myopathy in Patients with CKD

Clinical Journal of the American Society of Nephrology current issue Risk of Febuxostat-Associated Myopathy in Patients with CKD

Background and objectives

Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-associated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain.

Design, setting, participants, & measurements

Our retrospective cohort study included 1332 patients using febuxostat in Taipei Medical University–Wanfang Hospital from February of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries.

Results

The median duration of febuxostat use was 224 days (25th, 75th percentiles: 86, 441.5 days). Of 1332 study participants, 1222 (91.7%) had CKD; the median eGFR was 20.8 ml/min per 1.73 m² (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m²). Forty-one of the participants had febuxostat-associated myopathy (3.2%). All patients with myopathy had CKD, and the incident rate was 0.013 (95% confidence interval, 0.01 to 0.02) events per 100 patient-days in patients with CKD. Of 41 patients with myopathy, 37 had myositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated with myopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95% confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use.

Conclusions

Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat. Regular monitoring of creatine kinase level is suggested for early detection of febuxostat-associated myopathy, particularly in patients with CKD.

http://cjasn.asnjournals.org/cgi/content/short/12/5/744?rss=1

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Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients

 

Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant Recipients

by Colin R. Lenihan, Sumi Sukumaran Nair, Chandan Vangala, Venkat Ramanathan, Maria E. Montez-Rath, Wolfgang C. Winkelmayer

American Journal of Kidney Diseases / 2016-11-17 23:55

Posttransplantation bone disease is a significant problem, with few well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated with hip fracture in the general population and are widely prescribed for kidney transplant recipients.

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Are Octogenarians With End-Stage Renal Disease Candidates for Renal Transplantation?

 

Are Octogenarians With End-Stage Renal Disease Candidates for Renal Transplantation?

by Lønning, Kjersti; Midtvedt, Karsten; Leivestad, Torbjørn; Reisæter, Anna V.; Line, Pål-Dag; Hartmann, Anders; Heldal, Kristian

Transplantation - Most Popular Articles / 2016-11-20 11:07

Background: Elderly patients are the fastest-growing group in need of renal transplantation. This study puts focus on renal transplant recipients in their 80th year or longer at time of engraftment. Is there evidence to support an absolute upper age limit for renal transplantation? Methods: Recipients in their 80th year or longer, transplanted between 1983 and 2015, were included. Data were retrieved from the Norwegian Renal Registry in the end of October 2015. Graft and patient survivals were compared with recipients aged 70 to 79 years at transplantation. Results: Forty-seven patients older than 79 years were transplanted in the defined period. Median age 80.1 years, 81% were men. Median time on dialysis before transplantation was 18.5 months. All patients received an allograft from a deceased donor (median donor age, 61.8 years). In the death-censored graft survival model, there was no statistical difference between the groups. We found improved patient and graft survivals after introduction of mycophenolate mofetil and induction with basiliximab. Patients transplanted before 2000 had increased risk of death compared with those transplanted after 2000 (hazard ratio, 3.2; 95% confidence interval, 1.2-8.7). Median uncensored graft survival for patients transplanted after the year 2000 was 5.0 year (95% confidence interval, 2.4-7.6). Median patient survival was 5.0 years (3.1-6.9) and 5-year patient survival was 55%. Conclusions: Age by itself should not be an absolute contraindication against renal transplantation. An estimated 5-year survival rate of 55% post-engraftment for an 80-year-old patient is in our opinion more than acceptable.

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Renal Tubular Toxicity Associated With Rosuvastatin Therapy

 

Renal Tubular Toxicity Associated With Rosuvastatin Therapy

by Frank L. Ward, Rohan John, Joanne M. Bargman, Rory F. McQuillan

American Journal of Kidney Diseases / 2016-11-14 18:08

Preapproval clinical trials examining the safety and efficacy of rosuvastatin demonstrated an increased incidence of proteinuria, hematuria, rhabdomyolysis, and other acute kidney injury of unknown cause at high doses. The latter cases manifested with urine sediment findings and in some cases, renal histology, indicating renal tubular injury in the absence of rhabdomyolysis. Despite these provocative findings, there have been very few reports in the literature regarding non−rhabdomyolysis-mediated acute kidney injury associated with high-dose rosuvastatin since its widespread introduction more than a decade ago, suggesting that it is either a rare entity or systematically underdiagnosed and under-reported.

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Reduction of extended-release tacrolimus dose in low immunological risk kidney transplant recipients increases risk of rejection and appearance of DSA - a randomized study

 

Reduction of extended-release tacrolimus dose in low immunological risk kidney transplant recipients increases risk of rejection and appearance of DSA - a randomized study

by Philippe Gatault, Nassim Kamar, Matthias Büchler, Charlotte Colosio, Dominique Bertrand, Antoine Durrbach, Laeticia Albano, Joseph Rivalan, Yannick Le Meur, Marie Essig, Nicolas Bouvier, Christophe Legendre, Bruno Moulin, Anne-Elisabeth Heng, Pierre-François Weestel, Johnny Sayegh, Bernard Charpentier, Lionel Rostaing, Eric Thervet, Yvon Lebranchu

American Journal of Transplantation / 2016-11-09 20:25

Abstract

The aim of this study (NCT01744470) was to determine the efficacy and safety of two different doses of extended-release tacrolimus (TacER) in kidney transplant recipients (KTR) between 4 and 12 months post-transplantation. Stable steroid-free KTR were randomized (1:1) after 4 months: Group A 50%-reduction in TacER dose with targeted TacERC0>3μg/L; Group B no change in TacER dose (TacERC0=7-12μg/L). The primary outcome was eGFR at 1 year. Of 300 patients, intent-to-treat analysis included 186 patients (Group A 87, Group B 99). TacERC0 were lower in Group A than in Group B at 6 (4.1±2.7 vs 6.7±3.9μg/L, p<0.0001) and 12 months (5.6±2.0 vs 7.4±2.1μg/L, p<0.0001). eGFR was similar in both groups at 12 months (Group A 56.0±17.5ml/min/1.73m², Group B 56.0±22.1ml/min/1.73m²). More rejection episodes occurred in Group A (Group A 11, Group B 3; p=0.016). At one year, sub-clinical inflammation was more frequent in Group A than in Group B (i>0: 21.4% vs. 8.8%, p=0.047; t>0: 19.6% vs. 8.7%, p=0.076, i+t: 1.14±1.21 vs 0.72±1.01, p=0.038). DSA appeared only in Group A (6 patients vs. 0, p=0.008). TacERC0 should be maintained above 7μg/L during the first year post-transplantation in low immunological risk steroid-free KTR receiving moderate dose of MPA.

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Correlates and Outcomes of Posttransplant Smoking in Solid Organ Transplant Recipients: A Systematic Literature Review and Meta-Analysis

Alberto Carlos Reino Buelvas shared this article with you from Inoreader Message: Background: Despite smoking being an absolute or relative contraindication for transplantation, about 11% to 40% of all patients continue or resume smoking posttransplant. This systematic review with meta-analysis investigated the correlates and outcomes associated with smoking after solid organ transplantation. Methods: We searched PubMed, EMBASE, CINAHL, and PsycINFO from inception until January 2016, using state-of-the art methodology. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed for correlates/outcomes investigated 5 times or more. Results: Seventy-three studies (43 in kidney, 17 in heart, 12 in liver, 1 in lung transplantation) investigated 95 correlates and 24 outcomes, of which 6 correlates and 4 outcomes could be included in the meta-analysis. The odds of smoking posttransplant were 1.33 times higher in men (95% CI, 1.12-1.57). Older indiv iduals were significantly less likely to smoke (OR, 0.48; 95% CI, 0.38-0.62), as were patients with a higher body mass index (OR, 0.68; 95% CI, 0.52-0.89). Hypertension (OR, 1.16; 95% CI, 0.77-1.75), diabetes mellitus (OR, 0.52; 95% CI, 0.15-1.78), and having a history of cardiovascular disease (OR, 0.92; 95% CI, 0.77-1.09) were not significant correlates. Posttransplant smokers had higher odds of newly developed posttransplant cardiovascular disease (OR, 1.41; 95% CI, 1.02-1.95), nonskin malignancies (OR, 2.58; 95% CI, 1.26-5.29), a shorter patient survival time (OR, 0.59; 95% CI, 0.44-0.79), and higher odds of mortality (OR, 1.74; 95% CI, 1.21-2.48). Conclusions: Posttransplant smoking is associated with poor outcomes. Our results might help clinicians to understand which patients are more likely to smoke posttransplant, guide interventional approaches, and provide recommendations for future research. Correlates and Outcomes of Posttransplant Smoking in Solid Organ Transplant Recipients: A Systematic Literature Review and Meta-Analysis Vía Transplantation - Most Popular Articles Background: Despite smoking being an absolute or relative contraindication for transplantation, about 11% to 40% of all patients continue or resume smoking posttransplant. This systematic review with meta-analysis investigated the correlates and outcomes associated with smoking after solid organ transplantation. Methods: We searched PubMed, EMBASE, CINAHL, and PsycINFO from inception until January 2016, using state-of-the art methodology. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed for correlates/outcomes investigated 5 times or more. Results: Seventy-three studies (43 in kidney, 17 in heart, 12 in liver, 1 in lung transplantation) investigated 95 correlates and 24 outcomes, of which 6 correlates and 4 outcomes could be included in the meta-analysis. The odds of smoking posttransplant were 1.33 times higher in men (95% CI, 1.12-1.57). Older individuals were significantly less likely to smoke (OR, 0.48; 95% CI, 0.38-0.62), as were patients with a higher body mass index (OR, 0.68; 95% CI, 0.52-0.89). Hypertension (OR, 1.16; 95% CI, 0.77-1.75), diabetes mellitus (OR, 0.52; 95% CI, 0.15-1.78), and having a history of cardiovascular disease (OR, 0.92; 95% CI, 0.77-1.09) were not significant correlates. Posttransplant smokers had higher odds of newly developed posttransplant cardiovascular disease (OR, 1.41; 95% CI, 1.02-1.95), nonskin malignancies (OR, 2.58; 95% CI, 1.26-5.29), a shorter patient survival time (OR, 0.59; 95% CI, 0.44-0.79), and higher odds of mortality (OR, 1.74; 95% CI, 1.21-2.48). Conclusions: Posttransplant smoking is associated with poor outcomes. Our results might help clinicians to understand which patients are more likely to smoke posttransplant, guide interventional approaches, and provide recommendations for future research. View on the web Inoreader is a light and fast RSS Reader. Follow us on Twitter and Facebook.