Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients

Doi, Yasufumi; Hamano, Takayuki; Ichimaru, Naotsugu; Tomida, Kodo; Obi, Yoshitsugu; Fujii, Naohiko; Yamaguchi, Satoshi; Oka, Tetsushi; Sakaguchi, Yusuke; Matsui, Isao; Kaimori, Jun-Ya; Abe, Toyofumi; Imamura, Ryoichi; Takahara, Shiro; Tsubakihara, Yoshiharu; Nonomura, Norio; Isaka, Yoshitaka

doi:10.1038/s41598-020-70709-4

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…Only one published study investigated the association between iFGF23 and the overall graft loss in KTRs so far [ 21 ]. In line with our study, the positive association of iFGF23 with poor outcome in the unadjusted analysis was no longer significant after adjusted for risk factors in the multivariate analysis ( P = 0.97), however, this study did not analyze cFGF23.…”

Section: Discussionmentioning

confidence: 99%

C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival

et al. 2021

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Background Increased fibroblast growth factor 23 (FGF23) is a risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease. Limited data exist comparing the association of either c-terminal FGF23 (cFGF23) or intact FGF23 (iFGF23) in kidney transplant recipients (KTRs) with overall (all-cause) graft loss. Methods We conducted a prospective observational cohort study in 562 stable kidney transplant recipients. Patients were followed for graft loss and all-cause mortality for a median follow-up of 48 months. Results During a median follow-up of 48 months, 94 patients had overall graft loss (primary graft loss or death with functioning graft). Both cFGF23 and iFGF23 concentrations were significantly higher in patients with overall graft loss than those without (24.59 [11.43–87.82] versus 10.67 [5.99–22.73] pg/ml; p < 0.0001 and 45.24 [18.63–159.00] versus 29.04 [15.23–60.65] pg/ml; p = 0.002 for cFGF23 and iFGF23, respectively). Time-dependent ROC analysis showed that cFGF23 concentrations had a better discriminatory ability than iFGF23 concentrations in predicting overall (all-cause) graft loss. Cox regression analyses adjusted for risk factors showed that cFGF23 (HR for one unit increase of log transformed cFGF23: 1.35; 95% CI, 1.01–1.79; p = 0.043) but not iFGF23 (HR for one unit increase of log transformed iFGF23: 0.97; 95% CI, 0.75–1.25; p = 0.794) was associated with the overall graft loss. Conclusion Elevated cFGF23 concentrations at baseline are independently associated with an increased risk of overall graft loss. iFGF23 measurements were not independently associated with overall graft loss. The cFGF23 ELISA might detect bioactive FGF23 fragments that are not detected by the iFGF23 ELISA.

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Section: Discussionmentioning

confidence: 99%

C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival

et al. 2021

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“…Hence, cholecalciferol supplementation can be a promising strategy to reduce PTH levels among KTRs without increasing serum calcium levels. Considering the relationship between high PTH levels and worse outcomes, including incident fracture, graft survival, and all‐cause mortality among KTRs, ( 28 , 29 , 30 ) further studies are required to determine whether vitamin D supplementation provides benefits on long‐term outcomes.…”

Section: Discussionmentioning

confidence: 99%

Cholecalciferol Supplementation Attenuates Bone Loss in Incident Kidney Transplant Recipients: A Prespecified Secondary Endpoint Analysis of a Randomized Controlled Trial

Tsujita

Doi

Obi

et al. 2020

Journal of Bone and Mineral Research

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Vitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post‐transplant, we randomized 193 patients to an 11‐month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25‐hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between‐group difference of −15%; 95% confidence interval [CI] −25 to −3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (pint < 0.05). The percent change in lumbar spine (LS) BMD from before KTx to 12 months post‐transplant was −0.2% (95% CI −1.4 to 0.9) in the cholecalciferol group and −1.9% (95% CI −3.0 to −0.8) in the placebo group, with a significant between‐group difference (1.7%; 95% CI 0.1 to 3.3). The beneficial effect of cholecalciferol on LS BMD was prominent in patients with low bone mass pint < 0.05). Changes in serum calcium, phosphate, bone metabolic markers, and BMD at the distal radius were not different between groups. In mediation analyses, change in whole PTH levels explained 39% of treatment effects on BMD change. In conclusion, 4000 IU/d cholecalciferol significantly reduced PTH levels and attenuated LS BMD loss after KTx. This regimen has the potential to eliminate vitamin D deficiency and provides beneficial effects on bone health even under glucocorticoid treatment. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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“…Recently, it has been reported that low levels of 25-OH-VitD might be associated with worse graft outcomes, thus, promoting rejection episodes, possibly through the immunomodulatory mechanism exerted on the immune system (30). In any case, the direct and independent effect of 25-OH-VitD on graft outcome is still a matter of debate (26,(31)(32)(33).…”

Section: Vitamin Dmentioning

confidence: 99%

Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects

et al. 2022

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Renal transplantation (RTx) allows us to obtain the resolution of the uremic status but is not frequently able to solve all the metabolic complications present during end-stage renal disease. Mineral and bone disorders (MBDs) are frequent since the early stages of chronic kidney disease (CKD) and strongly influence the morbidity and mortality of patients with CKD. Some mineral metabolism (MM) alterations can persist in patients with RTx (RTx-p), as well as in the presence of complete renal function recovery. In those patients, anomalies of calcium, phosphorus, parathormone, fibroblast growth factor 23, and vitamin D such as bone and vessels are frequent and related to both pre-RTx and post-RTx specific factors. Many treatments are present for the management of post-RTx MBD. Despite that, the guidelines that can give clear directives in MBD treatment of RTx-p are still missed. For the future, to obtain an ever-greater individualisation of therapy, an increase of the evidence, the specificity of international guidelines, and more uniform management of these anomalies worldwide should be expected. In this review, the major factors related to post-renal transplant MBD (post-RTx-MBD), the main mineral metabolism biochemical anomalies, and the principal treatment for post-RTx MBD will be reported.

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Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients

Cited by 6 publications

References 31 publications

C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival

C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival

Cholecalciferol Supplementation Attenuates Bone Loss in Incident Kidney Transplant Recipients: A Prespecified Secondary Endpoint Analysis of a Randomized Controlled Trial

Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects

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