Serum phosphate optimal timing and range associated with patients survival in haemodialysis: the COSMOS study.

BACKGROUND: Serum phosphate is a key parameter in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). The timing of phosphate measurement is not standardized in the current guidelines. Since the optimal range of these biomarkers may vary depending on the duration of the interdialytic interval, in this analysis of the Current management of secondary hyperparathyroidism: a multicentre observational study (COSMOS), we assessed the influence of a 2- (midweek) or 3-day (post-weekend) dialysis interval for blood withdrawal on serum levels of CKD-MBD biomarkers and their association with mortality risk. METHODS: The COSMOS cohort (6797 patients, CKD Stage 5D) was divided into two groups depending upon midweek or post-weekend blood collection. Univariate and multivariate Cox's models adjusted hazard ratios (HRs) by demographics and comorbidities, treatments and biochemical parameters from a patient/centre database collected at baseline and every 6 months for 3 years. RESULTS: There were no differences in serum calcium or parathyroid hormone levels between midweek and post-weekend patients. However, in post-weekend patients, the mean serum phosphate levels were higher compared with midweek patients (5.5 ± 1.4 versus 5.2 ± 1.4 mg/dL, P < 0.001). Also, the range of serum phosphate with the lowest mortality risk [HR ≤ 1.1; midweek: 3.5-4.9 mg/dL (95% confidence interval, CI: 2.9-5.2 mg/dL); post-weekend: 3.8-5.7 mg/dL (95% CI: 3.0-6.4 mg/dL)] showed significant differences in the upper limit (P = 0.021). CONCLUSION: Midweek and post-weekend serum phosphate levels and their target ranges associated with the lowest mortality risk differ. Thus, clinical guidelines should consider the timing of blood withdrawal when recommending optimal target ranges for serum phosphate and therapeutic strategies for phosphate control.

25(OH)D Concentration in Neonates, Infants, and Toddlers From Poland-Evaluation of Trends During Years 1981-2011.

Introduction: The numerous evidence showing spectrum of vitamin D effects on human health resulted in both updates of vitamin D supplementation guidelines for general population and concerns on potential risk of hypercalcaemia. The aim of this study was to analyse trends in serum 25-hydroxyvitamin D concentration (25(OH)D) change over the 30 years of operation of a single pediatric diagnostic unit. Materials and methods: Calcium-phosphate metabolism markers and 25(OH)D concentrations were analyzed in a group that consisted of newborns and infants commissioned for diagnostics due to suspected calcium-phosphate metabolic disturbances (n = 3,163; mean age 8.0 ± 3.0 months). Results: 25(OH)D < 10 ng/ml was noted in 4.5% of patients (n = 163), 10-20 ng/ml in 14.7% (n = 465), 20-30 ng/ml in 23.9% (n = 756) and 30-50 ng/ml in 35.9% (n = 1,136). The mean 25(OH)D concentration in analyzed group was 37.5 ± 24.5 ng/ml. In patients with 25(OH)D concentration < 10 ng/ml a normal calcaemia (2.25-2.65 mmol/l) was noted in 83.4% cases (n = 136). Eighty one patients had 25(OH)D concentrations above 100 ng/ml with co-existing calcaemia in range of 2.6-4.38 mmol/l (mean Ca = 2.69 mmol/l). Hypocalcaemia (Ca < 2.25 mmol/l) was observed in 0.54%, (n = 17). 13.8% patients revealed calcium levels >2.65 mmol/l (n = 435). In general, the mean calcium-phosphate markers values were within the reference range for age. The highest mean 25(OH)D concentration of 51.8 ng/ml ± 38.8 was noted in years 1981-1999 (n = 305). The lowest mean 25(OH)D value was observed in years 2010-2011 (29.0 ng/ml ± 13.6; n = 412). The trend of decreasing 25(OH)D concentration during analyzed time period was significant (r = -0.29, p < 0.0001). Conclusions: Eighty percentage of children aged 0-36 months had 25(OH)D concentration >20 ng/ml, however, during 3 decades a mean 25(OH)D concentrations trended significantly to decrease. A direct relationship between low 25(OH)D concentration and hypocalcaemia was not observed nor between high 25(OH)D concentration and hypercalcemia.

The hypercalcaemia of CYP24A1 inactivation: new ways to improve diagnosis and treatment.

This case report presents fluoconazole efficacy to reduce hypercalcaemia and increased urinary calcium excretion in a patient with nephrocalcinosis after a long history of recurrent renal stones caused by a loss-of-function mutation of the CYP24A1 gene. The CYP24A1 gene codes for a key enzyme in the vitamin D endocrine system that protects against vitamin D toxicity by degrading the circulating excess of both 1,25-dihydroxyvitamin D, the hormonal form of vitamin D, and its precursor, 25-hydroxyvitamin D. In order to expedite the identification of this rare disorder and improve therapies to avoid its progression to nephrocalcinosis, this editorial updates the current knowledge on the frequency of CYP24A1-inactivating mutations, the features of their early clinical presentation and progression, and the pathophysiology of vitamin D activation in health and in granulomatous disorders that may help improve current treatment.