Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial.

Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE (VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 [13.7] years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 [0.60-1.48]; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 [0.07-0.86], P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).

[A rare cause of anemia in a chronic dialyzed patient]. / Une cause rare d'anémie chez une patiente hémodialysée chronique.

We reported the case of a female in chronic dialysis since 3 years who developed a normocytic a regenerative anemia with no evident etiology. A bone marrow smear revealed a copper deficiency, a rare cause of anemia in general and dialyzed populations. Copper supplementation improved anemia with a decrease in transfusions rate and erythropoietin dosage. This case suggests that a copper deficiency has to be considered when a myelodysplastic syndrome is associated with neurologic symptoms and granulocytes precursors vacuolization identified in bone marrow smear. A blood titration of trace elements should be considered in front of a refractory anemia with no evident etiology.

Pretransplant serum vitamin D levels and risk of cancer after renal transplantation.

BACKGROUND: Serum levels of 25-OH-D3 inversely correlate with the incidence of various types of cancers in the general population. Because risk factors and incidence of cancer in renal transplant recipients (RTRs) are different from the general population, this study was designed to determine whether pretransplant 25-OH-D3 levels could be predictive of cancer risk in RTRs. METHODS: Pretransplant 25-OH-D3 levels were reviewed in 363 consecutive RTRs. The impact of 25-OH-D3 levels on the development of cancer was then analyzed with respect to other known risk factors. RESULTS: One hundred twenty-four patients (34.2%) showed vitamin D deficiency, 185 (51%) vitamin D insufficiency, and 54 (14.8%) with normal vitamin D levels. Thirty-two cancers (8.8%) occurred in 32 patients. A higher incidence of cancer was observed in patients with vitamin D deficiency (13.7% vs. 7% for patients with vitamin D insufficiency [P=0.068] and 3.7% for those with normal vitamin D levels [P=0.007]). 25-OH-D3 levels were lower in patients who developed cancer after transplantation (13.7+/-6 vs. 18.3+/-17.8 ng/mL, P=0.022). Age (hazard ratio, 1.06; 95% confidence interval, 1.02-1.11, for each 1 year increase; P=0.009) and low 25-OH-D3 levels (hazard ratio, 1.12; 95% confidence interval, 1.04-1.23, for every 1 ng/mL decrease; P=0.021) were independent risk factors for development of cancer. CONCLUSION: Pretransplant level of 25-OH-D3 is an important determinant for subsequent development of cancer after transplantation. Future studies should examine whether 25-OH-D3 supplementation can effectively decrease the incidence of cancer in RTRs.

Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.

BACKGROUND: In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose, i.v. folinic acid combined with high-dose i.v. pyridoxine was highly effective in correcting plasma total homocysteine (tHcy) concentrations in haemodialysis patients. To confirm these findings, we conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid. METHODS: In a 6-month prospective, randomized, controlled trial, 60 chronic haemodialysis patients, matched for age, gender, dialysis duration, and average screening pre-treatment-fasting tHcy levels, were given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60 patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral vitamin B12. RESULTS: Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3, respectively, P=NS). Mean percentage reduction at 6 months was also similar in the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively, P=NS). CONCLUSIONS: These findings show that the tHcy-lowering effects of high-dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable, suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism. Furthermore, they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients.