25-hydroxyvitamin-d-2 and Renal-Insufficiency--Chronic

Patients with chronic kidney disease (CKD) demonstrate complex mineral metabolism derangements and a high prevalence of vitamin D deficiency. However, the optimal method of 25-hydroxyvitamin D (25(OH)D) repletion is unknown, and trials analysing the comparative efficacy of cholecalciferol and ergocalciferol in this population are lacking. We conducted a randomised clinical trial of cholecalciferol 1250μg (50 000 IU) weekly v. ergocalciferol 1250μg (50 000 IU) weekly for 12 weeks in forty-four non-dialysis-dependent patients with stage 3-5 CKD. The primary outcome was change in total 25(OH)D from baseline to week 12 (immediately after therapy). Secondary analyses included the change in 1,25-dihydroxyvitamin D (1,25(OH)2D), parathyroid hormone (PTH), D2 and D3 sub-fractions of 25(OH)D and 1,25(OH)2D and total 25(OH)D from baseline to week 18 (6 weeks after therapy). Cholecalciferol therapy yielded a greater change in total 25(OH)D (45·0 (sd 16·5) ng/ml) v. ergocalciferol (30·7 (sd 15·3) ng/ml) from baseline to week 12 (P<0·01); this observation partially resulted from a substantial reduction in the 25(OH)D3 sub-fraction with ergocalciferol. However, following cessation of therapy, no statistical difference was observed for total 25(OH)D change from baseline to week 18 between cholecalciferol and ergocalciferol groups (22·4 (sd 12·7) v. 17·6 (sd 8·9) ng/ml, respectively; P=0·17). We observed no significant difference between these therapies with regard to changes in serum PTH or 1,25(OH)2D. Therapy with cholecalciferol, compared with ergocalciferol, is more effective at raising serum 25(OH)D in non-dialysis-dependent CKD patients while active therapy is ongoing. However, levels of 25(OH)D declined substantially in both arms following cessation of therapy, suggesting the need for maintenance therapy to sustain levels.

Topics: 25-Hydroxyvitamin D 2; Academic Medical Centers; Adult; Aged; Calcifediol; Calcitriol; Cholecalciferol; Cohort Studies; Dietary Supplements; Double-Blind Method; Ergocalciferols; Female; Follow-Up Studies; Humans; Kansas; Male; Middle Aged; Outpatient Clinics, Hospital; Parathyroid Hormone; Renal Insufficiency, Chronic; Reproducibility of Results; Vitamin D Deficiency

The association of vitamin D status with high body adiposity is poorly investigated in the chronic kidney disease (CKD) population. The aim of the present study was to describe vitamin D status and to identify body adiposity predictors of vitamin D deficiency, in a nondialyzed CKD population inhabiting a tropical city.. This cross-sectional study included patients with CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min, regularly treated by an interdisciplinary team in an outpatient university clinic, set in a Brazilian city (latitude: 22°54'S; 43°12'W). Adiposity parameters analyzed were body mass index (BMI), total body adiposity (dual-energy x-ray absorptiometry [DXA] and body adiposity index [BAI]), and central body adiposity (DXA-trunk fat and waist-to-height ratio [WHtR]). Laboratory parameters included serum concentrations of 25-hydroxyvitamin D, phosphate, parathyroid hormone, and insulin (insulin resistance [IR evaluation: homeostasis model assessment; HOMA]).. Just under half of the CKD population presented sufficient concentration of 25-hydroxyvitamin D. Total body adiposity, independent of age and eGFR, regardless if evaluated by DXA or BAI, was the predictor of vitamin D deficiency, which in turn was associated with higher serum phosphorus and hyperparathyroidism, but not with IR.

Topics: 25-Hydroxyvitamin D 2; Adiposity; Aged; Body Mass Index; Brazil; Calcifediol; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Models, Biological; Nutritional Status; Obesity; Overweight; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Severity of Illness Index; Tropical Climate; Vitamin D Deficiency; Waist-Height Ratio

This study was designed to evaluate vitamin D status with separate determination of 25-OH D2 and 25-OH D3 and its relationship to vitamin D binding protein (VDBP) in patients with chronic kidney disease (CKD) and long-term haemodialysis patients (HD).. 45 CKD patients, 103 HD patients, and 25 controls (C) were included. Plasma vitamin D concentrations were determined using chromatography and VDBP in serum and urine in CKD using enzyme immunoassay.. Plasma vitamin D levels were lower in CKD (30.16 ± 16.74 ng/mL) and HD (18.85 ± 15.85 ng/mL) versus C (48.72 ± 18.35 ng/mL), P < 0.0001. 25-OH D3 was the dominant form of vitamin D. Serum VDBP was higher in CKD (273.2 ± 93.8 ug/mL) versus C (222 ± 87.6 ug/mL) and HD (213.8 ± 70.9 ug/mL), P = 0.0003. Vitamin D/VDBP ratio was the highest in C and the lowest in HD; however, there was no correlation between vitamin D and VDBP. Urinary concentration of VDBP in CKD (0.25 ± 0.13 ug/mL) correlated with proteinuria (r = 0.43, P = 0.003).. Plasma levels of vitamin D are decreased in CKD patients and especially in HD patients. 25-OH D3 was the major form of vitamin D. Despite urinary losses of VDBP, CKD patients had higher serum VDBP concentrations, indicating compensatory enhanced production. Vitamin D binding protein is not involved in vitamin D deficiency.

Topics: 25-Hydroxyvitamin D 2; Adult; Aged; Calcifediol; Female; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

The effects of vitamin D receptor (VDR) and osteocalcin (OC) expression as well as VDR agonist (VDRA) therapy on circulating endothelial progenitor cells (EPCs) has not been elucidated yet.. We therefore analyzed EPCs in 30 healthy controls and 82 patients undergoing dialysis (no VDRA therapy: 28; oral calcitriol: 30, and intravenous paricalcitol, PCTA: 24). The percentage of EPCs (CD34+/CD133-/KDR+/CD45-) expressing VDR or OC, and VDR and OC expression defined by mean fluorescence intensity (MFI) were analyzed using flow cytometry. The in vitro effect of VDRAs was evaluated in EPCs isolated from each patient group.. The percentage of VDR+ EPCs correlated positively with VDRA therapy and 25(OH)D, and negatively with diabetes, C-reactive protein, hemoglobin and osteopontin. VDR-MFI correlated positively with VDRA therapy, parathyroid hormone (PTH) and 25(OH)D, and negatively with diabetes and osteopontin. The percentage of OC+ EPCs correlated positively with the calcium score, PTH and phosphate, and negatively with 25(OH)D. OC-MFI correlated positively with calcium score, PTH, phosphate and hemoglobin, and negatively with albumin, 25(OH)D and osteopontin. Cell cultures from patients without VDRA therapy had the highest levels of calcium deposition and OC expression, which both significantly decreased following in vitro VDRA administration: in particular extracellular calcium deposition was only reduced by adding PCTA.. Our data suggest that 25(OH)D serum levels and VDRA therapy influence VDR and OC expression on circulating EPCs. Since OC expression may contribute to vascular calcification, we hypothesize a putative protective role of VDRA therapy.

Topics: 25-Hydroxyvitamin D 2; Antigens, CD; C-Reactive Protein; Calcium; Case-Control Studies; Endothelial Cells; Gene Expression Regulation; Humans; Mediator Complex; Osteocalcin; Osteopontin; Parathyroid Hormone; Receptors, Calcitriol; Renal Dialysis; Renal Insufficiency, Chronic; Stem Cells

Vitamin D deficiency is common in patients with chronic kidney disease (CKD). Current guidelines recommend treatment strategies in these patients similar to those for the general population, but the vitamin D nutritional status sufficient to prevent PTH levels from increasing in CKD is unknown. OBJECTIVE, MAIN OUTCOME MEASURE: Our aim was to study the relation between circulating PTH and 25(OH)D levels and to search for a 25(OH)D threshold associated with a significant PTH increase.. In the hospital-referred NephroTest cohort study, we measured 25(OH)D, PTH, and glomerular filtration rate (mGFR) by ⁵¹Cr-EDTA renal clearance in 929 adult patients with nondialysis CKD stages 1 to 5 and no vitamin D supplementation. Patients' mean age was 60.1 ± 14.7 years; 71% were men, and 9% were black. Their median mGFR was 37.8 mL/min/1.73 m².. We found a 25(OH)D threshold of 8 ng/mL with an upper limit of 20 ng/mL (95% confidence interval) by linear piecewise regression modeling of log-PTH for 25(OH)D adjusted for mGFR, age, race, and ionized calcium level. The smoothed curve confirmed that PTH concentration rose steeply when circulating 25(OH)D levels fell to less than 20 ng/mL.. Spontaneous 25(OH)D levels greater than 20 ng/mL seem sufficient to control serum PTH in CKD patients. This result reinforces guidelines to supplement vitamin D only if less than 30 ng/mL.

Topics: 25-Hydroxyvitamin D 2; Aged; Calcifediol; Calcium; Cohort Studies; Female; France; Glomerular Filtration Rate; Humans; Hypercalcemia; Male; Middle Aged; Parathyroid Hormone; Phosphates; Practice Guidelines as Topic; Prevalence; Prospective Studies; Renal Insufficiency, Chronic; Severity of Illness Index; Vitamin D Deficiency