Calcitriol/calcifediol ratio: An indicator of vitamin D hydroxylation efficiency?

Abstract

BackgroundCalcifediol (25D) availability is crucial for calcitriol (1,25D) synthesis, but regulation of vitamin D hydroxylases is majorly responsible for 1,25D synthesis. The net efficiency of vitamin D hydroxylases might be informative. We assume that the ratio between calcitriol and calcifediol (25D/1,25D) serum concentrations could suggest the vitamin D hydroxylation efficiency.MethodsWe evaluated 25D/1,25D in different patient populations: hemodialysis (HD, n = 76), CKD stage 2–5 (n = 111), renal transplant (TX, n = 135), patients with no renal disease (No-CKD, n = 290), and primary hyperparathyroidism (PHP, n = 20).ResultsThe geometric mean of 1,25D/25D (pg/ng) averaged 1.11 (HD), 1.36 (CKD), 1.77 (TX), 2.22 (No-CKD), and 4.11 (PHP), with a progressive increment from HD to PHP (p-value for the trend <0.001). Each clinical condition elicited a significant effect on 25D/1,25D (p < 0.0001) and adjusted multivariate analysis indicated levels of Cas, Ps, PTH, and 25D as predictors of 25D/1,25D. Both in vitamin D deficient and replete subjects (25D< or ≥20 ng/ml) 25D/1,25D associated with each clinical condition (p < 0.0001) and mean values increased progressively from HD to PHP (p-values for the trend <0.0001). Regression analysis between 25D (substrate) and 25D/1,25D (efficiency) revealed an exponential negative correlation in No-CKD (r2Exp = 0.53, p < 0.001) with sharp increments of 25D/1,25D when 25D values are <20 ng/ml. At variance, in CKD (r2lin = 0.19) and in TX (r2lin = 0.32) the regression was linear as if, in case of deficit, some inhibition of the system were operating.Conclusion and General significanceIn conclusion 1,25D/25D can reflect the efficiency of vitamin D hydroxylases more than separate evaluation of 25D and 1,25D and can facilitate the therapeutic choices in different patient populations.

Compromised Activation of Vitamin D After Elective Surgery: A Prospective Pilot Study

“…The lack of PTH response indicates that calcium in conjunction with other factors may blunt the normal PTH response. Calcium is a known regulator of 1‐alpha hydroxylase activity and PTH secretion . Albumin corrected calcium increased significantly after surgery and could theoretically augment the observed 35% decrease in serum 1,25(OH) 2 D 3 .…”

“…Two‐sided ANOVA with Dunnett's test were used to test for differences between time points and adjust for multiple comparisons. The conversion rate (1000 × 1,25(OH) 2 D 3 /25‐OHD) was calculated preoperatively and 3 weeks postoperatively and presented as a function of substrate levels or serum concentrations of putative regulators, and the correlation coefficient was determined.…”

A Case Report of Compound Heterozygous CYP24A1 Mutations Leading to Nephrolithiasis Successfully Treated with Ketoconazole

“…We suggest that it is clinically important to identify patients with this phenotype as testing and treatment options are available which could reduce progression to chronic kidney disease in this population. The population frequency of CYP24A1 mutations is not known and testing is not yet widely available, but utilization of the 25-dihydroxyvitamin D/24,25-dihydroxyvitamin D ratio (after ruling out other causes of hypercalcemia) has been shown to be an effective tool to identify patients who are good candidates for genetic testing [ 3 , 4 , 5 ].…”

Витамин D И Остеоартроз

“…Значно рідше в сироватці крові ви-значають рівень 1,25(OH) 2 D 3 , при цьому використання розрахунку співвідношення 25(ОН)D/1,25(OH) 2 D 3 мо-же відображати ефективність гідроксилювання вітамі-ну D порівняно з окремою оцінкою метаболітів і, на думку авторів, доповнює інформацію для визначення терапевтичного підходу [8]. Проте дослідження в цьо-му напрямку поодинокі.…”