SUPLEMENTACIÓN CON VITAMINA D NATIVA EN PACIENTES CON ENFERMEDAD RENAL CRÓNICA

Abstract

Background. 25(OH)-vitamin D [25(OH)D] levels are the best indicator of vitamin D stores and its deficiency is very common in patients with chronic kidney disease (CKD). Beyond its calciotropic function as a substrate for synthesis of 1,25(OH)2-vitamin D in the kidney, 25(OH)D deficiency has been linked with higher prevalence of cardiovascular disease, cancer and diabetes mellitus. Moreover, vitamin D supplementation has been associated with better survival in the general population. Nevertheless, the independent predictor value of 25(OH) deficiency in the morbility and mortality of CKD patients needs to be established in prospective studies designed for this population. Similarly, we need controlled trials to confirm that the described relationship between 25(OH)D levels and the occurrence of renal and cardiovascular events is truly causal. Objectives. The aims of this thesis were: (1) To analyze the relationship between vitamin D levels on cardiovascular risk factors, vascular calcification, and survival in patients with CKD ; ( 2) to assess the relationship between vitamin D levels and markers of CKD progression; and (3 ) to analyze the effect of native vitamin D supplementation on bone-related parameters, vascular calcification, and markers for cardiovascular disease and renal progression in CKD patients. Methods. We perform three types of studies : (1) Two cross-sectional studies of 634 and 722 patients with stages 3-5 CKD not on dialysis, respectively, where 25(OH)D levels were correlated with renal progression parameters and cardiovascular risk factors, including proteinuria and vascular calcification; (2) a prospective, 3-year follow-up, observational study of 470 non-dialysis CKD 3-5 patients, which analyzed the ability of vitamin D deficiency to predict death, cardiovascular events and renal progression in this population; and (3) an interventional, controlled trial of 101 patients, that quantified the effect of vitamin D supplementation on markers of renal progression, cardiovascular dysfunction and bone-mineral metabolism in patients with CKD. Results. Vitamin D deficiency was highly prevalent in CKD patients, rising to up to 80% of patients. Low 25(OH)D levels were related to high prevalence of cardiovascular disease (chronic heart failure and peripheral vascular disease) and cardiovascular and renal progression risk factors (ankle-brachial pressure index, diabetes mellitus, diabetic nephropathy and proteinuria). Our data did not demonstrate an association between 25(OH)D levels and vascular calcification. After multivariate analysis, 25(OH)D level < 20 ng/ml was independently associated with worse survival and higher renal progression. Despite the inherent limitations of an observational study, this data supported the potential role of vitamin D supplementation for this population. Vitamin D repletion with daily mild doses of cholecalciferol (600-800 IU/day) was effective to reduce albuminuria in patients with CKD 3-4 stage, with potential cardiovascular and renal long-term benefits for this population that should be tested in future vitamin D supplementation trials. Conclusions / Implications. In non-dialysis CKD patients, vitamin D levels were not only related to cardiovascular and renal progression risk factors, predicting survival and renal progression, but also were demonstrate to be one of the therapeutic targets to reduce albuminuria. These findings could lead to improve the long-term renal and cardiovascular prognosis of this population, whose life expectancy continues to be unacceptable.

Date of Award	25 Jun 2015
Original language	Spanish
Supervisor	Ramón Vicente A. Romero González (Director) & Luis Pallardo Mateu (Director)