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Effect of Bisphosphonates on Bone Health in Adult Renal Transplant Patients: Beyond the First Year Posttransplant-A Systematic Review and Meta-Analysis.

ABSTRACT: Background:Bone mineral density (BMD) decreases postrenal transplantation. Evidence demonstrating the effects of bisphosphonates on BMD and fracture risk beyond 1-year posttransplant is sparse in existing literature, but remains essential to enhance clinical outcomes in this population. Objective:Our study aimed to systematically review and meta-analyze the current literature on the use of any bisphosphonate in the adult renal transplant population beyond the first year of renal transplant to determine its effect on BMD and fracture incidence. Design:We conducted a systematic review and meta-analysis of primary research literature that included full-text, English-language, original randomized clinical trials (RCTs) and observational studies. Setting:Patient data were primarily captured in an outpatient setting across various studies. Patients:Our population of interest was patients older than 18 years who received deceased/living donor kidney transplantation and any bisphosphonate with a follow-up greater than 12 months posttransplantation. Measurements:The primary outcome was change in BMD from baseline. Secondary outcomes were the incidence of fractures and effects of other confounders on bone health. Methods:We included RCTs and observational studies that satisfied our inclusion criteria. Each study was analyzed for risk of bias and data were extrapolated to analyze for overall statistical significance accounting for heterogeneity of studies. Results:Sixteen studies (N = 1762) were analyzed. The follow-up ranged from 12 to 98 months. There was a nonsignificant improvement in BMD with bisphosphonate treatment persisting into the second and third years posttransplant at the lumbar spine. The calculated standardized mean BMD difference was -0.29 (-0.75 to 0.17), P = .22. Only 5 studies reported a total of 43 new fractures. Prednisone (P < .01), low body weight (P < .001), low body mass index (P < .01), and male gender (P < .05) correlated with reduced lumbar and femoral BMD. Limitations:Limitations of this review include the use of BMD as a surrogate outcome, the bias of the included studies, and the incomplete reporting data in numerous analyzed studies. Conclusions:We demonstrate no statistically significant benefit of bisphosphonate treatment on BMD beyond the first year postrenal transplantation. Despite heterogeneity of treatment, a differential nonsignificant improvement in lumbar spine BMD was consistent and may be clinically relevant. Trial Registration:PROSPERO CRD42019125593.

SUBMITTER: Lip A

PROVIDER: S-EPMC6595663 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effect of Bisphosphonates on Bone Health in Adult Renal Transplant Patients: Beyond the First Year Posttransplant-A Systematic Review and Meta-Analysis.

Lip Alyssa A Warias Ashley A Shamseddin M Khaled MK Thomson Benjamin B Wijeratne D Thiwanka DT

Canadian journal of kidney health and disease 20190625

<h4>Background</h4>Bone mineral density (BMD) decreases postrenal transplantation. Evidence demonstrating the effects of bisphosphonates on BMD and fracture risk beyond 1-year posttransplant is sparse in existing literature, but remains essential to enhance clinical outcomes in this population.<h4>Objective</h4>Our study aimed to systematically review and meta-analyze the current literature on the use of any bisphosphonate in the adult renal transplant population beyond the first year of renal t ...[more]

PMID: 31263566

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Project description:Key Points eGFR at 1 year post transplant is an established predictor of graft failure, but the effects of major intercurrent events are not fully known. We assessed the link between 12-month eGFR and long-term graft failure accounting for intercurrent events and competing mortality risks. Acute rejection, cardiovascular events, and infectious events were significant risks; 12-month eGFR remained the dominant driver of graft failure. Visual Abstract Background Estimated glomerular filtration rate (eGFR) at 1 year post transplantation has been shown to be a strong predictor of long-term graft survival. However, intercurrent events (ICEs) may affect the relationship between eGFR and failure risk. Methods The OPTN and USRDS databases on single-organ kidney transplant recipients from 2012 to 2016 were linked. Competing risk regressions estimated adjusted subhazard ratios (SHRs) of 12-month eGFR on long-term graft failure, considering all-cause mortality as the competing risk, for deceased donor (DD) and living donor (LD) recipients. Additional predictors included recipient, donor, and transplant characteristics. ICEs examined were acute rejection, cardiovascular events, and infections. Results Cohorts comprised 25,131 DD recipients and 7471 LD recipients. SHRs for graft failure increased rapidly as 12-month eGFR values decreased from the reference 60 ml/min per 1.73 m2. At an eGFR of 20 ml/min per 1.73 m2, SHRs were 13–15 for DD recipients and 12–13 for LD recipients; at an eGFR of 30 ml/min per 1.73 m2, SHRs were 5.0–5.7 and 5.0–5.5, respectively. Among first-year ICEs, acute rejection was a significant predictor of long-term graft failure in both DD (SHR=1.63, P<0.001) and LD (SHR=1.51, P=0.006) recipients; cardiovascular events were significant in DD (SHR=1.24, P<0.001), whereas non-CMV infections were significant in the LD cohort (SHR=1.32, P=0.03). Adjustment for ICEs did not significantly reduce the association of eGFR with graft failure. Conclusions Twelve-month eGFR is a strong predictor of long-term graft failure after accounting for clinical events occurring from discharge to 1 year. These findings may improve patient management and clinical evaluation of novel interventions.

Project description:AIMS:Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. METHODS AND RESULTS:From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use. CONCLUSIONS:Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.

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.

Dataset Information

Effect of Bisphosphonates on Bone Health in Adult Renal Transplant Patients: Beyond the First Year Posttransplant-A Systematic Review and Meta-Analysis.

Publications

Effect of Bisphosphonates on Bone Health in Adult Renal Transplant Patients: Beyond the First Year Posttransplant-A Systematic Review and Meta-Analysis.

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