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Outcomes of bisphosphonate and its supplements for bone loss in kidney transplant recipients: a systematic review and network meta-analysis.

ABSTRACT: BACKGROUND:Mineral bone disease constitutes a common complication of post-kidney transplantation, leading to great disability. As there is no consensus on the optimal treatment for post-kidney transplant recipients (KTRs), we aimed to evaluate the efficacy and safety of bisphosphonate and its combined therapies. METHODS:We incorporated relevant trials to perform a network meta-analysis from direct and indirect comparisons. We searched PubMed, Embase and the CENTRAL and the reference lists of relevant articles up to August 1, 2017, for randomized controlled trials. The primary outcome was bone mineral density (BMD) change at the femoral neck and the lumbar spine. RESULTS:From a total of 864 citations, 18 randomized controlled trials with a total of 1200 participants were included. Five different regimens were considered. Bisphosphonate plus calcium revealed a significant gain in percent BMD change than calcium alone at the femoral neck (mean difference (MD), 5.83; 95% credible interval (CrI), 1.61 to 9.27). No significant difference was detected when restricting to absolute terms. At the lumbar spine, bisphosphonate and calcium with or without vitamin D analogs outperformed calcium solely (MD, 0.07; 95% CrI, 0.00 to 0.13; MD, 0.06; 95% CrI, 0.02 to 0.09). Compared to calcium with vitamin D analogs, adding bisphosphonate was associated with marked improvement (MD, 0.03; 95% CrI, 0.00 to 0.05). Considering percent terms, combination of bisphosphonate with calcium and vitamin D analogs showed greater beneficial effects than calcium alone or with either vitamin D analogs or calcitonin (MD, 10.51; 95% CrI, 5.92 to 15.34; MD, 5.48; 95% CrI, 2.57 to 8.42; MD, 6.39; 95% CrI, 0.55 to 12.89). Both bisphosphonate and vitamin D analogs combined with calcium displayed a notable improvement compared to calcium alone (MD, 7.24; 95% CrI, 3.73 to 10.69; MD, 5.02; 95% CrI, 1.20 to 8.84). CONCLUSIONS:Our study suggested that additional use of bisphosphonate was well-tolerated and more favorable in KTRs to improve BMD.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6194739 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Outcomes of bisphosphonate and its supplements for bone loss in kidney transplant recipients: a systematic review and network meta-analysis.

Yang Yan Y Qiu Shi S Deng Linghui L Tang Xi X Li Xinrui X Wei Qiang Q Fu Ping P

BMC nephrology 20181019 1

<h4>Background</h4>Mineral bone disease constitutes a common complication of post-kidney transplantation, leading to great disability. As there is no consensus on the optimal treatment for post-kidney transplant recipients (KTRs), we aimed to evaluate the efficacy and safety of bisphosphonate and its combined therapies.<h4>Methods</h4>We incorporated relevant trials to perform a network meta-analysis from direct and indirect comparisons. We searched PubMed, Embase and the CENTRAL and the referen ...[more]

PMID: 30340537

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Project description:Mineral and bone disorder is one of the severe complications in kidney transplant recipients (KTRs). Previous studies showed that bisphosphonates had favorable effects on bone mineral density (BMD). We sought to compare different bisphosphonate regimens and rank their strategies.We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 01, 2017, for randomized controlled trials (RCTs) comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis (NMA) using Bayesian models and assessed the quality of evidence.A total of 21 RCTs (1332 participants) comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium (mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70). The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate (MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively). In terms of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium (MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively). The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best.Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.

Project description:Background:Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. Objective:To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. Design:Retrospective cohort study. Setting:We used linked health care databases in Alberta, Canada. Patients:We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. Measurements:The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ?0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. Methods:We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). Results:Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (-5.4 vs -1.9 mL/min/1.73 m2, P < .05). Limitations:We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. Conclusion:Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.

Project description:Background and objectivesDespite improvement of short-term graft survival over recent years, long-term graft survival after kidney transplantation has not improved. Studies in the general population suggest the Mediterranean diet benefits kidney function preservation. We investigated whether adherence to the Mediterranean diet is associated with kidney outcomes in kidney transplant recipients.Design, setting, participants, & measurementsWe included 632 adult kidney transplant recipients with a functioning graft for ≥1 year. Dietary intake was inquired using a 177-item validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed using a nine-point Mediterranean Diet Score. Primary end point of the study was graft failure and secondary end points included kidney function decline (doubling of serum creatinine or graft failure) and graft loss (graft failure or death with a functioning graft). Cox regression analyses were used to prospectively study the associations of the Mediterranean Diet Score with study end points.ResultsDuring median follow-up of 5.4 (interquartile range, 4.9-6.0) years, 76 participants developed graft failure, 119 developed kidney function decline, and 181 developed graft loss. The Mediterranean Diet Score was inversely associated with all study end points (graft failure: hazard ratio [HR], 0.68; 95% confidence interval [95% CI], 0.50 to 0.91; kidney function decline: HR, 0.68; 95% CI, 0.55 to 0.85; and graft loss: HR, 0.74; 95% CI, 0.63 to 0.88 per two-point increase in Mediterranean Diet Score) independent of potential confounders. We identified 24-hour urinary protein excretion and time since transplantation to be an effect modifier, with stronger inverse associations between the Mediterranean Diet Score and kidney outcomes observed in participants with higher urinary protein excretion and participants transplanted more recently.ConclusionsAdherence to the Mediterranean diet is associated with better kidney function outcomes in kidney transplant recipients.

Dataset Information

Outcomes of bisphosphonate and its supplements for bone loss in kidney transplant recipients: a systematic review and network meta-analysis.

Publications

Outcomes of bisphosphonate and its supplements for bone loss in kidney transplant recipients: a systematic review and network meta-analysis.

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