title: Associations of 25(OH) and 1,25(OH)2 vitamin D with long-term outcomes in stable renal transplant recipients.
abstract: BACKGROUND
  Vitamin D deficiency is common in renal transplant recipients (RTR). The long-term implications of vitamin D deficiency in RTR remain unclear.
  
  
  OBJECTIVE
  We investigated whether 25(OH) or 1,25(OH)2 vitamin D levels are associated with mortality, renal function decline, and graft failure in stable RTR.
  
  
  METHODS
  Observational study with longitudinal design. Followup was 7.0, interquartile range (IQR) 6.2-7.5 years.
  
  
  METHODS
  Single-center outpatient clinic.
  
  
  METHODS
  435 stable RTR (51% men, mean age 52 ± 12 years) were included at a median [IQR] of 6 [3-12] years after kidney transplantation.
  
  
  METHODS
  All-cause mortality, annual change of estimated glomerular filtration rate (eGFR), and graft failure.
  
  
  RESULTS
  Mean 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were 21.6 ± 9.1 ng/ml and 45.2 ± 19.0 pg/ml, respectively. During followup, 99 patients (22.8%) died and 44 patients (10.1%) developed graft failure. In univariable analysis, both 25(OH)D and 1,25(OH)2D were significantly associated with mortality (hazard ratio [HR], 0.64; 95% confidence interval (CI), 0.51-0.81; P < .001 and HR 0.69 [95% CI, 0.55-0.87], P = .002 per SD increase, respectively). The inverse association of 25(OH)D with mortality remained significant after adjustment for potential confounders (HR 0.68 [95% CI, 0.52-0.89], P = .004 per SD increase). The associations of 1,25(OH)2D with mortality and graft failure lost significance after adjustment for renal function. Severe vitamin D deficiency (25[OH]D <12 ng/ml) was independently associated with stronger annual eGFR decline.
  
  
  CONCLUSIONS
  Low 25(OH)D is independently associated with an increased risk of all-cause mortality and 25(OH)D <12 ng/ml with a rapid eGFR decline in stable RTR. The association of low 1,25(OH)2D with mortality or graft failure depends on renal function. These results should encourage randomised controlled trials evaluating the effect of vitamin D supplementation after kidney transplantation.
authors.affiliation: Department of Internal Medicine, Division of Nephrology (C.A.K., I.J.R., M.M.J., G.N., S.J.L.B., M.H.d.B.), University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands; Top Institute Food and Nutrition (I.J.R., M.M.J., S.J.L.B.), 6700 AN Wageningen, The Netherlands; and Department of Laboratory Medicine (A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Keyzer
authors.forename: Ineke J
authors.initials: IJ
authors.lastname: Riphagen
authors.forename: Michel M
authors.initials: MM
authors.lastname: Joosten
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Anna C
authors.initials: AC
authors.lastname: Muller Kobold
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
mesh_terms: D000328:Adult; D000368:Aged; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation / Q000401:mortality*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D066027:Transplant Recipients; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D