title: Vitamin D deficiency--prognostic marker or mortality risk factor in end stage renal disease patients with diabetes mellitus treated with hemodialysis--a prospective multicenter study.
abstract: BACKGROUND
  End stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.
  
  
  METHODS
  Our prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than 12 ng/mL.
  
  
  RESULTS
  Patients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.
  
  
  CONCLUSIONS
  ESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.
authors.affiliation: Department of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Adalbert
authors.initials: A
authors.lastname: Schiller
authors.affiliation: Department of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Florica
authors.initials: F
authors.lastname: Gadalean
authors.affiliation: B Braun Avitum Dialysis Center Timisoara, Timisoara, Romania.
authors.forename: Oana
authors.initials: O
authors.lastname: Schiller
authors.affiliation: Department of Diabetes and Metabolic Diseases, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Romulus
authors.initials: R
authors.lastname: Timar
authors.affiliation: Department of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Flaviu
authors.initials: F
authors.lastname: Bob
authors.affiliation: Department of Diabetes and Metabolic Diseases, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Mircea
authors.initials: M
authors.lastname: Munteanu
authors.affiliation: Department of Obstetrics and Gynecology, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Dana
authors.initials: D
authors.lastname: Stoian
authors.affiliation: Department of Nephrology, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Adelina
authors.initials: A
authors.lastname: Mihaescu
authors.affiliation: Department of Medical Informatics and Biostatistics, 'Victor Babes' University of Medicine and Pharmacy, County Emergency Hospital, Timisoara, Romania.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Timar
mesh_terms: D000328:Adult; D000368:Aged; D003920:Diabetes Mellitus / Q000097:blood* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D006435:Renal Dialysis; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000401:mortality / Q000473:pathology
chemical_list: D014807:Vitamin D