Vitamin D and the Kidney: Two Players, One Console.

Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D's role in different settings, with a special focus on chronic kidney disease and kidney transplant.

Bone Mineral Density Changes in Long-Term Kidney Transplant Recipients: A Real-Life Cohort Study of Native Vitamin D Supplementation.

Vitamin D insufficiency has been associated with reduced bone mineral density (BMD) in kidney transplant patients (KTRs). However, the efficacy of vitamin D supplementation on BMD remains poorly defined, especially for long-term KTRs. We aimed to investigate the effect of native vitamin D supplementation on the BMD of KTRs during a 2-year follow-up. Demographic, clinical, and laboratory data were collected. BMD was evaluated with standard DEXA that was performed at baseline (before vitamin D supplementation) and at the end of study period. BMD was assessed at lumbar vertebral bodies (LV) and right femoral neck (FN) by a single operator. According to WHO criteria, results were expressed as the T-score (standard deviation (SD) relative to young healthy adults) and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as a T-score ≤ -2.5 SD and a T-score < -1 and a > -2.5 SD, respectively. Based on plasma levels, 25-OH-vitamin D (25-OH-D) was supplemented as recommended for the general population. Data from 100 KTRs were analyzed. The mean study period was 27.7 ± 3.4 months. At study inception, 25-OH-D insufficiency and deficiency were recorded in 65 and 35 patients. At the basal DEXA, the percentage of osteopenia and osteoporosis was 43.3% and 18.6% at LV and 54.1% and 12.2% at FN, respectively. At the end of the study, no differences in the Z-score and T-score gains were observed. During linear mixed model analysis, native vitamin D supplementation was found to have a negative nitration with Z-score changes at the right femoral neck in KTRs (p < 0.05). The mean dose of administered cholecalciferol was 13.396 ± 7.537 UI per week; increased 25-OH-D levels were found (p < 0.0001). Either low BMD or 25-OH-vitamin D concentration was observed in long-term KTRs. Prolonged supplementation with 25-OH-D did not modify BMD, Z-score, or T-score.

Denosumab-Induced Hypocalcemia and Hyperparathyroidism in de novo Kidney Transplant Recipients.

INTRODUCTION: Denosumab represents a realistic treatment option to increase bone mineral density in kidney transplant recipients (KTRs). It is still unknown how and at what extent posttransplantation bone disease and graft function influence the effects of denosumab on mineral metabolism indexes. In this study, we analyze risk factors of hypocalcemia and parathyroid hormone (PTH) increase after denosumab administration in eighteen de novo KTRs and its management before and after this treatment. METHODS: We conducted a monocentric, observational, prospective study on de novo KTRs. All KTRs enrolled received a single 60 mg subcutaneous dose of denosumab every 6 months. Before kidney transplantation, no patients were treated with calcio-mimetic. After kidney transplantation and before antiresorptive therapy, no patients were treated with calcio-mimetic drugs and/or vitamin D receptor agonists, while all patients received nutritional vitamin D supplementation (from 1,000 IU to 1,500 IU daily). RESULTS: Hypocalcemia was related to the degree of lumbar osteoporosis (p = 0.047); the increase in the PTH level was correlated to baseline bone turnover markers (bone alkaline phosphatase, serum osteocalcin, and ß-C-terminal telopeptide), the 25 OH status, and eGFR. The introduction of calcitriol, after the PTH increase, in addition to cholecalciferol was necessary to ensure an adequate control of serum calcium and PTH during a follow-up of 15 months. Following the treatment with denosumab, it was observed an improvement of areal bone mineral density both at lumbar and femoral sites with a mean percentual increase of 1.74% and 0.25%, respectively. CONCLUSIONS: Denosumab is an effective treatment for bone disease in KTRs. In our study, the increase in PTH is not a transient event but prolonged throughout the follow-up period and requires continuous supplementation therapy with calcitriol.

Vitamin D Effects on Bone Homeostasis and Cardiovascular System in Patients with Chronic Kidney Disease and Renal Transplant Recipients.

Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease-mineral and bone disorder (CKD-MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.