title: Calcitriol/calcifediol ratio: An indicator of vitamin D hydroxylation efficiency?
abstract: BACKGROUND
  Calcifediol (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.
  
  
  METHODS
  We 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).
  
  
  RESULTS
  The 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 (r(2)Exp = 0.53, p < 0.001) with sharp increments of 25D/1,25D when 25D values are <20 ng/ml. At variance, in CKD (r(2)lin = 0.19) and in TX (r(2)lin = 0.32) the regression was linear as if, in case of deficit, some inhibition of the system were operating.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pasquali
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.
authors.forename: Lida
authors.initials: L
authors.lastname: Tartaglione
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.
authors.forename: Silverio
authors.initials: S
authors.lastname: Rotondi
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Muci
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.
authors.forename: Giusi
authors.initials: G
authors.lastname: Mandanici
authors.affiliation: Dept. of Public Health and Infectious Diseases, Sapienza University of Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Farcomeni
authors.affiliation: A.O. Ospedale Mauriziano, Torino, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Marangella
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, Sapienza University of Rome, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Mazzaferro
keywords: Calcifediol; Calcitriol; Chronic renal failure; Renal transplantation; Vitamin D; Vitamin D hydroxylation