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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
What is the optimal level of vitamin D in non-dialysis chronic kidney disease population?
Pablo Molina, José L Górriz, Mariola D Molina, Sandra Beltrán, Belén Vizcaíno, Verónica Escudero, Julia Kanter, Ana I Ávila, Jordi Bover, Elvira Fernández, Javier Nieto, Secundino Cigarrán, Enrique Gruss, Gema Fernández-Juárez, Alberto Martínez-Castelao, Juan F Navarro-González, Ramón Romero, Luis M Pallardó
Pablo Molina, Sandra Beltrán, Belén Vizcaíno, Verónica Escudero, Julia Kanter, Ana I Ávila, José L Górriz, Luis M Pallardó, Department of Nephrology, Dr Peset University Hospital, 46017 Valencia, Spain
José L Górriz, Luis M Pallardó, Department of Medicine, Universitat de València, 46005 Valencia, Spain
Mariola D Molina, Department of Mathematics, Universidad de Alicante, San Vicente del Raspeig, 03690 Alicante, Spain
Jordi Bover, Department of Nephrology, Fundació Puigvert, 080348 Barcelona, Spain
Elvira Fernández, Department of Nephrology, Hospital Universitari de Lleida, IRBlleida (Institut de Reserca Biomèdica de Lleida), 25198 Lleida, Spain
Javier Nieto, Department of Nephrology, Hospital General Universitario de Ciudad Real, 13005 Ciudad Real, Spain
Secundino Cigarrán, Department of Nephrology, Hospital da Costa Burela, 7880 Lugo, Spain
Enrique Gruss, Gema Fernández-Juárez, Department of Nephrology, Hospital Universitario Fundación Alcorcón, 28922 Madrid, Spain
Alberto Martínez-Castelao, Department of Nephrology, Hospital Universitario de Beellvitge, IDIBELL, L’Hospitalet de Llobregat, 08907 Barcelona, Spain
Juan F Navarro-González, Research Unit and Department of Nephrology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
Ramón Romero, Department of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain
Author contributions: Molina P, Górriz JL and Pallardó LM drafted the manuscript, designed the research and supervised the study; Molina P and Molina MD performed statistical analysis; Beltrán S, Vizcaíno B, Escudero V, Kanter J, Ávila AI, Bover J, Fernández E, Nieto J, Cigarrán S, Gruss E, Fernández-Juárez G, Martínez-Castelao A and Navarro-González JF were involved with data collection, and assisted with data analysis; all authors read and approved the final manuscript.
Supported by Abbott and the Spanish Society of Nephrology.
Institutional review board statement: The study was reviewed and approved by the Dr Peset Hospital Research Ethics Committee.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Molina P, Górriz JL and Martínez-Castelao A have received honoraria for giving lectures and for consulting on advisory boards for Abbott. The others authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Pablo Molina, MD, PhD, Department of Nephrology, Dr Peset University Hospital, Avda. Gaspar Aguilar, 90, 46017 Valencia, Spain. molina_pab@gva.es
Telephone: +34-9-61622462 Fax: +34-9-61622462
Received: May 9, 2016
Peer-review started: May 11, 2016
First decision: June 14, 2016
Revised: June 22, 2016
Accepted: August 11, 2016
Article in press: August 13, 2016
Published online: September 6, 2016
AIM
To evaluate thresholds for serum 25(OH)D concentrations in relation to death, kidney progression and hospitalization in non-dialysis chronic kidney disease (CKD) population.
METHODS
Four hundred and seventy non-dialysis 3-5 stage CKD patients participating in OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into 3 groups according to 25(OH)D levels at enrollment (less than 20 ng/mL, between 20 and 29 ng/mL, and at or above 30 ng/mL), considering 25(OH)D between 20 and 29 ng/mL as reference group. Association between 25(OH)D levels and death (primary outcome), and time to first hospitalization and renal progression (secondary outcomes) over a 3-year follow-up, were assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. To identify 25(OH)D levels at highest risk for outcomes, receiver operating characteristic (ROC) curves were performed.
RESULTS
Over 29 ± 12 mo of follow-up, 46 (10%) patients dead, 156 (33%) showed kidney progression, and 126 (27%) were hospitalized. After multivariate adjustment, 25(OH)D < 20 ng/mL was an independent predictor of all-cause mortality (HR = 2.33; 95%CI: 1.10-4.91; P = 0.027) and kidney progression (HR = 2.46; 95%CI: 1.63-3.71; P < 0.001), whereas the group with 25(OH)D at or above 30 ng/mL did not have a different hazard for outcomes from the reference group. Hospitalization outcomes were predicted by 25(OH) levels (HR = 0.98; 95%CI: 0.96-1.00; P = 0.027) in the unadjusted Cox proportional hazards model, but not after multivariate adjusting. ROC curves identified 25(OH)D levels at highest risk for death, kidney progression, and hospitalization, at 17.4 ng/mL [area under the curve (AUC) = 0.60; 95%CI: 0.52-0.69; P = 0.027], 18.6 ng/mL (AUC = 0.65; 95%CI: 0.60-0.71; P < 0.001), and 19.0 ng/mL (AUC = 0.56; 95%CI: 0.50-0.62; P = 0.048), respectively.
CONCLUSION
25(OH)D < 20 ng/mL was an independent predictor of death and progression in patients with stage 3-5 CKD, with no additional benefits when patients reached the levels at or above 30 ng/mL suggested as optimal by CKD guidelines.
Core tip: This study examines the prognosis value of 25(OH)D levels on death, chronic kidney disease (CKD) progression, and hospitalization in a cohort of 3-5 stage CKD subjects not on dialysis. The main findings were the predictor value of vitamin D deficiency (< 20 ng/mL), but not insufficiency (< 30 ng/mL), for the 3-year incidence of death and CKD progression, which remained significant after multivariate adjustments. These results could highlight the need for a revision of the current guidelines, which have defined optimal vitamin D status at ≥ 30 ng/mL based on levels required to suppress parathyroid hormone, as opposed to our study, which evaluates thresholds for serum 25(OH)D concentrations in relation to “hard” endpoints.
