Distinct impact of vitamin D insufficiency on calcitriol levels in chronic renal failure and renal transplant patients: a role for FGF23

Mazzaferro, Sandro; Pasquali, Marzia; Pugliese, Francesco; Citterio, Franco; Gargiulo, Antonio R.; Rotondi, Silverio; Tartaglione, Lida; Conte, Carmina; Pirrò, Giuliana; Taggi, Franco

doi:10.5301/jn.5000102

Cited by 19 publications

(11 citation statements)

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“…). The biochemical consequences of low serum 25(OH)D concentrations, namely secondary hyperparathyroidism , suggest that a “laissez‐faire” approach to vitamin D management in RTx patients might not be ideal. In support of this concept, first, associations between worse post‐RTx outcomes and lower initial 25(OH)D concentrations at transplantation have been reported , and second, it should also be noted that in the early post‐RTx period, where most steroid‐related bone density is lost, the use of calcium and vitamin D supplementation is clearly effective as prophylaxis .…”

Section: Discussionmentioning

confidence: 99%

Determinants of vitamin D status in long‐term renal transplant patients

Penny

Frame

Dickinson

et al. 2012

Clinical Transplantation

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In this study, we explored the determinants of vitamin D status in a large cohort of stable, Long-term renal transplant (RTx) patients. Serum 25(OH)D concentrations, and bone biochemistry parameters, were retrospectively analyzed from 266 RTx patients (>10 yr post-engraftment) presenting to clinic over the course of a year. Forty-five percent of the cohort were vitamin D deficient (<37.5 nM), 38% insufficient (37.5 75-nM), and 17% sufficient (>75 nM). Serum 25(OH)D concentrations were higher in patients presenting in summer (p<0.001) and in more active patients (p<0.05). RTx patients with non-melanoma skin cancer (NMSC) (n=45) had higher 25(OH)D concentrations than patients without NMSC (n=221; p<0.05) despite these patients being older, having worse eGFR, transplanted for longer, and less active physically (p<0.05). Lower 25(OH)D concentrations were associated with higher PTH concentrations (p<0.05) which, in the setting of widespread hypovitaminosis, suggests that secondary hyperparathyroidism was common in this cohort. In conclusion, season and activity status are important determinants of vitamin D status. We report, for the first time, that NMSC is associated with higher 25(OH)D, probably through increased UV radiation exposure. Long-term RTx patients may benefit from oral vitamin D supplementation, but this requires a randomized controlled trial to confirm.

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Section: Discussionmentioning

confidence: 99%

Determinants of vitamin D status in long‐term renal transplant patients

Penny

Frame

Dickinson

et al. 2012

Clinical Transplantation

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“…2 ) [25] . Further, FGF23 reductions were repeatedly observed at longer follow-up, approximating normal levels 1-3 years after transplantation [26][27][28] .…”

Section: Epidemiology Of Altered Vitamin D Metabolism In Ktrsmentioning

confidence: 91%

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Cianciolo¹,

Galassi

Capelli³

et al. 2016

Am J Nephrol

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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is common in kidney transplant recipients (KTRs), where secondary hyperparathyroidism (HPTH) and post-transplantation bone disease (PTBD) are potential effectors of both graft and vascular aging. Reduced 25(OH)D levels are highly prevalent in KTRs. Experimental and clinical evidence support the direct involvement of deranged vitamin D metabolism in CKD-MBD among KTRs. This review analyzes the pathophysiology of vitamin D derangement in KTRs and its fall out on patient and graft outcome, highlighting the roles of both nutritional and active vitamin D compounds to treat PTBD, cardiovascular disease (CVD) and graft dysfunction. Fibroblast growth factor-23-parathyroid hormone (PTH)-vitamin D axis, immunosuppressive therapy and previous bone status have been associated with PTBD. Although several studies reported reduced PTH levels in KTRs receiving nutritional vitamin D, its effects on bone mineral density (BMD) remain controversial. Active vitamin D reduced PTH levels and increased BMD after transplantation, but paricalcitol treatment was not accompanied by benefits on osteopenia. Vitamin D is considered protective against CVD due to the widespread pleiotropic effects, but data among KTRs remain scanty. Although vitamin deficiency is associated with lower glomerular filtration rate (GFR) and faster estimated GFR decline and data on the anti-proteinuric effects of vitamin D receptor activation (VDRA) in KTRs sound encouraging, reports on related improvement on graft survival are still lacking. Clinical data support the efficacy of VDRA against HPTH and show promising evidence of VDRA's effect in counteracting post-transplant proteinuria. New insights are mandatory to establish if the improvement of surrogate outcomes will translate into better patient and graft outcome.

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“…Mean repletion-end PTH (109.6 ± 7.5 ng/L) was reduced relative to baseline (144.2 ± 12.0 ng/L), however it still remained significantly elevated. Thus, a repletion-end mean 25(OH)D value of 65.4 nmol/L may still be inadequate and supports a higher therapeutic threshold of 75 mmol/L [26, 27]. Despite this, the significant suppression of the elevated PTH levels following VitD repletion supports the notion that supplementation could be part of an effective therapy to prevent chronic bone density loss.…”

Section: Discussionmentioning

confidence: 99%

Impact of seasonality on the dynamics of native Vitamin D repletion in long-term renal transplant patients

et al. 2017

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Background: Renal transplant recipients (RTRs) are often Vitamin D (VitD) depleted as a result of both chronic kidney disease and mandated sun avoidance behaviours. Repleting VitD may be warranted, but how, and for how long, is unknown, as is the impact of seasonality on the success of repletion. We investigated the impact of seasonality on VitD status following VitD repletion in a large cohort of stable, long-term RTRs. Methods: Serum 25-hydroxyvitamin D [25(OH)D] concentrations and bone biochemistry parameters were analysed from 102 VitD repletion courses in 98 RTRs that had undergone VitD repletion. Repletion was delivered over 6 months with either 240 000 IU colecalciferol if pre-repletion serum VitD was between 20 and 50 nmol/L, or with 360 000 IU if VitD was <20 nmol/L. Twelve months post-repletion 25(OH)D and parathyroid hormone (PTH) were available for 75 patients. Results: At baseline, 25(OH)D was 20.1 ± 1.0 nmol/L, increasing to 65.4 ± 1.8 nmol/L following repletion (+7.55 nmol/L/month, P < 0.0001). Twelve months post-repletion and after no further VitD administration, 25(OH)D fell to 35.4 ± 1.8 nmol/L (14.2 ± 0.7 ng/mL; −2.50 nmol/L/month, P < 0.0001). PTH followed the opposite trend with baseline, repletion-end and post-repletion values being 144.2 ± 12.0, 109.6 ± 7.5 and 129.2 ± 11.4 ng/L, respectively. VitD repletion during the summer was associated with significantly higher at repletion-end 25(OH)D compared with any other time of year [summer 80.9 ± 4.0, autumn 64.1 ± 3.0 (P = 0.002), winter 48.9 ± 3.0 (P <0.001), spring 63.8 ± 2.5 nmol/L (P <0.001)]. There was no hypercalcaemia during repletion and renal transplant function remained stable without any evidence of allograft rejection. Conclusions: VitD repletion can safely and effectively be achieved in the majority of chronic stable RTRs using a 6-month bolus intermediate-dose schedule. Winter repletion is associated with an inadequate response in 25(OH)D; however, all patients experience a post-repletion fall towards deficiency in the absence of maintenance supplementation, irrespective of the season of repletion.

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Distinct impact of vitamin D insufficiency on calcitriol levels in chronic renal failure and renal transplant patients: a role for FGF23

Abstract: A 25D deficit more significantly affects calcitriol concentrations in CRF as compared with TX. Efficiency of vitamin D hydroxylation should be considered when planning vitamin D replacement strategies.

Cited by 19 publications

References 0 publications

Determinants of vitamin D status in long‐term renal transplant patients

Determinants of vitamin D status in long‐term renal transplant patients

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Impact of seasonality on the dynamics of native Vitamin D repletion in long-term renal transplant patients

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