TO THE EDITOR
We read with great interest the recent article published in the World Journal of Nephrology by Singh et al[1], which examined the association between vitamin D deficiency at the time of kidney transplantation and the development of post-transplant diabetes mellitus (PTDM). The authors demonstrated that deficient vitamin D levels were significantly associated with an increased risk of PTDM in the post-transplant period. While these findings are clinically relevant, further studies-particularly interventional trials-are required to determine whether vitamin D replacement can modify the risk of PTDM. In this context, we would like to highlight insights from recent observational studies.
PTDM is a common and clinically significant metabolic complication following solid organ transplantation, affecting 10%-40% of recipients[2]. Despite major advances in immunosuppression and transplant care, PTDM continues to impose a substantial burden. It is associated with increased cardiovascular morbidity, higher infection risk, reduced graft survival, and overall poorer long-term outcomes[3].
Preventive strategies have traditionally focused on immunosuppressive modulation and close glycaemic monitoring, whereas modifiable metabolic factors have received comparatively little attention. Vitamin D deficiency is one such factor; despite vitamin D supplementation being a low-cost intervention with a favorable safety profile[4], deficiency is nearly universal in patients with end-stage kidney disease and post-transplant period. Although renal transplantation restores kidney function and 1α-hydroxylation, vitamin D deficiency often persists despite nutritional improvement and normalization of glomerular filtration rate. Therefore, routine assessment and appropriate vitamin D supplementation in post-renal transplant recipients are emphasized[5].
Studies report a high prevalence of vitamin D insufficiency, a problem that often persists or worsens post-transplant due to steroid-induced catabolism, reduced sunlight exposure, sunscreen use to mitigate the elevated risk of skin malignancy associated with chronic immunosuppression, and fluctuations in graft function[6-9]. Beyond its classical effects on bone and mineral metabolism, vitamin D exerts anti-inflammatory, insulin-sensitizing, β-cell-protective, and renin-angiotensin-modulatory actions-mechanisms possibly counteracting the diabetogenic effects of calcineurin inhibitors (CNIs) and glucocorticoids. The doses of vitamin D necessary to achieve a serum 25-hydroxyvitamin D [25(OH)D] concentration of ≥ 30 ng/mL in renal transplant recipients are much higher than those recommended in the general population[4].
Evidence regarding the association between vitamin D status and PTDM has evolved over time[1,4,10-14]. A randomized controlled trial published in 2023 evaluating vitamin D supplementation in renal transplant recipients did not demonstrate improvement in non-skeletal outcomes, including PTDM incidence or glycemic control[4]. However, this study had several limitations, including evaluation of PTDM as part of a composite endpoint, limited power to assess individual outcomes[10], absence of a placebo arm, and the use of low-dose cholecalciferol (400 IU/day) in the control group, which may have attenuated detectable differences between groups[4]. Subsequently, two observational studies published in 2025 reported a significant association between lower serum 25(OH)D levels and an increased risk of PTDM[1,10]. These findings suggest that while supplementation trials have yielded neutral results, vitamin D deficiency itself may still represent an important metabolic risk factor in kidney transplant recipients. Despite this emerging evidence, vitamin D optimization is rarely incorporated into PTDM-prevention protocols. Most transplant programs restrict supplementation to correction of severe deficiency, without structured reassessment or targeted dosing during the high-risk early post-transplant period.
In the context of the global rise in metabolic disease and the persistent challenge of PTDM, vitamin D status warrants renewed attention as a potentially modifiable factor influencing post-transplant glucose homeostasis.
ASSOCIATION OF VITAMIN D DEFICIENCY WITH PTDM
Recent studies[1,10-14] indicate that low baseline or early post-transplant 25(OH)D levels independently predict PTDM. In addition, genetic polymorphisms in the vitamin D receptor-specifically Taq I and Fok I alleles-have been identified as significant risk factors for PTDM in transplant recipients[15]. Renal transplant recipients are more insulin-resistant than the general population due to obesity, central adiposity, corticosteroid exposure, and the metabolic effects of CNIs[16]. The observation that vitamin D deficiency amplifies these diabetogenic influences suggests a synergistic interaction with immunosuppressive therapy[10,11]. The hypothesized mechanisms are summarized in Figure 1.
Figure 1 Hypothesized link between vitamin D deficiency and risk of post-transplant diabetes mellitus.
Vitamin D deficiency may amplify the diabetogenic effects of calcineurin inhibitors and glucocorticoids, contributing to post-transplant diabetes mellitus development. PTDM: Post-transplant diabetes mellitus.
VITAMIN D SUPPLEMENTATION AFTER RENAL TRANSPLANTATION
Despite the high prevalence of vitamin D insufficiency in renal transplant recipients, no universal consensus exists regarding supplementation, and treatment is often suboptimal. In one study[17], high-dose vitamin D3 (100000 IU cholecalciferol every other week for two months, equivalent to 6600 IU/day) effectively corrected vitamin D insufficiency in renal transplant recipients without significant adverse effects and was associated with a significant reduction in PTH levels. To maintain 25(OH)D concentrations between 30-80 ng/mL during the first post-transplant year, monthly dosing of 100000 IU cholecalciferol has been proposed once deficiency has been corrected[18]. These findings highlight the feasibility and safety of vitamin D replacement in transplant recipients, yet such strategies remain underutilized in routine clinical practice.
FUTURE DIRECTIONS
There is a need for well-designed randomized controlled trials to determine whether vitamin D supplementation can reduce the incidence of PTDM, identify optimal dosing strategies, and compare the benefits of pre- vs post-transplant vitamin D optimization. Additionally, mechanistic studies are needed to elucidate the molecular pathways through which vitamin D deficiency interacts with immunosuppressive therapy to impair β-cell function and promote insulin resistance. Together, these research priorities will help clarify the therapeutic potential of vitamin D in improving post-transplant metabolic outcomes.
CONCLUSION
Accumulating evidence indicates that vitamin D deficiency may contribute to the risk of PTDM and other adverse transplant outcomes, highlighting its potential as a modifiable factor. Given its safety, low cost, and ease of implementation, routine vitamin D optimization may be considered as part of post-transplant metabolic management.
