ACTA ENDOCRINOLOGICA (BUC)

Introduction. Vitamin D [25(OH)D] deficiency is prevalent in chronic kidney disease (CKD), related to bone turnover and potentially involved in arterial calcifications. Objective. To evaluate vitamin D status in nondialysis CKD patients and its relationships with bone turnover markers (BTM) and arterial calcifications. Design. Cross-sectional, prospective, multicentric study. Subjects and methods. One hundred twenty-eight CKD patients (median age 61 years, 58% males, median eGFR 29mL/min) were included. Comorbidities, mineral and bone metabolism parameters were evaluated. Total alkaline phosphatase (T-ALP) was used to assess bone turnover. Atherosclerosis was evaluated by carotid intima-media thickness (CIMT), endothelial calcifications by aortic calcification score (ACS), and arterial stiffness by cardio-ankle vascular index (CAVI). Vitamin D deficiency was defined as 25(OH)D <15 ng/mL. Factors associated with vitamin D, T-ALP and vascular parameters were assessed in multivariate regression models. Results. Prevalence of vitamin D deficiency was 63% and median 25(OH)D was 12.8 ng/mL. Older age, female sex and higher parathormone were predictors of vitamin D deficiency. Increased T-ALP was predicted by higher parathormone, suggesting high turnover bone disease. While age was a determinant of all evaluated vascular parameters, lower 25(OH)D was associated only with endothelial calcifications, which correlated with CAVI, suggesting a direct relation between vitamin D deficiency mediated plaques calcification and arterial stiffness. Conclusion. Vitamin D deficiency was highly prevalent in this non-dialysis CKD cohort and was related to age, sex and parathormone. Vitamin D deficiency was associated with increased calcifications of endothelial plaques, which seemed to increase arterial stiffness.

Secondary hyperparathyroidism, i.e. increased synthesis and secretion of parathyroid hormone and gland hyperplasia, is commonly found in chronic kidney disease. Although it is, at first, an adaptive response to the loss of renal functions in order to maintain the calcium/phosphate homeostasis and normal bone turnover, it is also an important cause of increased morbidity in this clinical setting by leading to renal osteodystrophy and cardiovascular complications. Recent advances in the knowledge on the pathogenesis of parathyroid-related complications in renal failure allowed for new therapeutic approaches. However, many problems remain to be solved in the future. This paper briefly presents the current understanding of pathogenic mechanisms of hyperparathyroidism, bone disease and vascular calcification during chronic kidney disease. In addition, it summarizes the main therapeutic methods available today for controlling secondary hyperparathyroidism and the challenges of practitioners concerning this issue. Finally, the current status of secondary hyperparathyroidism management is analyzed, with emphasis on the Romanian experience.

Background. There are scarce data about prevalence of mineral metabolism (MM) disorders in Romanian predialysis patients, so we assessed their occurrence and relationships in mild to severe chronic kidney disease (CKD). Methods. One hundred fifteen non-dialysis CKD (eGFR 31, 95% CI 29-35mL/min) and 33 matched non-CKD subjects entered this multicentric, cross-sectional study. Serum 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (iPTH), phosphate (PO4), total calcium (tCa) and alkaline phosphatase (AP) were measured, along with demographic and past medical history data. Results. Hypovitaminosis D was equally prevalent in Controls and CKD (91% vs. 96% had 25OHD<30ng/mL). Increasing proportions of hyperparathyroidism (33% - stage 2 to 100% - stage 5; p<0.001) and hyperphosphatemia (2% - stage 3 to 38% - stage 5; p<0.001) were found. Hypocalcemia was more prevalent in stage 5 (25% vs. 6% in stage 4, none in stage 3 and Controls, p<0.001). Mineral metabolism parameters correlated with eGFR. In addition, iPTH was directly associated with PO4, AP, and urinary albumin-tocreatinine ratio (ACR), but inversely with tCa and 25OHD, while negative correlation of 25OHD with age, AP, ACR, and C-reactive protein emerged. In multiple regression, eGFR was the only predictor of iPTH (Beta -0.68, 95%CI -1.35 to -0.90, R2 0.46, p<0.001), whereas age and ACR were the determinants of 25OHD (a model which explained 14% of its variation). Conclusions. Hypovitaminosis D was very common irrespective of CKD presence and severity, and it seems worsened by older age and higher albuminuria. Hyperparathyroidism preceded hyperphosphatemia and hypocalcemia, and it seems mostly dependent on kidney function decline

Context. Benefits of vitamin D therapies in chronic kidney disease (CKD) are debated. Objective. To compare the effects of medium-term native (VitD) and active (VDRA) vitamin D on parameters of mineral metabolism and arterial function in non-dialysis CKD. Design. Open-label, active comparator, randomized study. Subjects and Methods. Forty-eight adult patients, vitamin D naïve, CKD stage 3 to 5 with increased parathyroid hormone (iPTH) were randomized to receive either oral cholecalciferol 1000UI/day (n=24) or paricalcitol 1mcg/day (n=24) for 6 months. Median changes at end of study vs. baseline in serum calcidiol, iPTH, total alkaline phosphatase (ALP), and cardio-ankle vascular index (CAVI) were the efficacy parameters. Results. Higher increase in calcidiol (15.5 [95%CI 13.3; 17.2] vs. 0.4 [95%CI −6.1; 3.7]ng/mL, p<0.001) were found in VitD group. Conversely, the decline of iPTH (−35.2 [95%CI −83; 9] vs. 13.3 [95%CI −8.1; 35]pg/mL, p=0.008) and ALP (−34 [95%CI −58; −11] vs. −10 [95%CI −23; −2] U/L, p=0.02) were greater after paricalcitol. More subjects experienced iPTH decrease in VDRA group (71% vs. 39%, p=0.03). The variation in CAVI and the incidence of hypercalcemia and hyperphosphatemia were similar. Conclusions. It seems that secondary hyperparathyroidism was more efficiently treated by VDRA, whereas cholecalciferol better corrected the calcidiol deficiency in non-dialysis CKD.