title: The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study.
abstract: BACKGROUND
  Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort.
  
  
  METHODS
  We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12. Logistic regression models adjusted for covariates including homocysteine were constructed to test the association between B12 and prevalent albuminuria (UACR ≥17 mg/g [men] and ≥25 mg/g [women]) and reduced kidney function (defined as an eGFR < 60 ml/min/1.73 m(2), RKF). Because of a significant interaction between B12 and homocysteine in the prevalent RKF model (p = 0.005), the model was stratified by the median homocysteine levels. Logistic regression models were constructed to test the association between B12 and incident albuminuria and RKF. The results were replicated in 4445 participants from NHANES 2003-2004.
  
  
  RESULTS
  Baseline B12 levels ranged from 50-1690 pg/ml. Elevated B12 was associated with prevalent albuminuria (OR 1.44 per 1 SD increase, 95% CI 1.10-1.87) and RKF (OR 1.83, 95% CI 1.30-2.60). However after stratifying by median homocysteine levels, this relationship remained only in the higher homocysteine stratum. There was no association between B12 and incident albuminuria (OR 1.17, 95% CI 0.79 - 1.73) or RKF (OR 1.45, 95% CI 0.97 - 1.88). In the NHANES cohort, elevated B12 was associated with RKF after full covariate adjustment (OR 3.06, 95% CI 2.30-4.08). There was no association with albuminuria.
  
  
  CONCLUSIONS
  In participants with high baseline homocysteine levels, increased plasma B12 was associated with RKF.
authors: National Heart, Lung and Blood Institute's Framingham Heart Study and the Center for Population Studies, 73 Mt. Wayte Ave, Suite 2, Framingham, MA, 01702, USA. gearoid.mcmahon@nih.gov.|Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. gearoid.mcmahon@nih.gov.
authors: Gearoid M
authors: GM
authors: McMahon
authors: National Heart, Lung and Blood Institute's Framingham Heart Study and the Center for Population Studies, 73 Mt. Wayte Ave, Suite 2, Framingham, MA, 01702, USA. hwangs2@nhlbi.nih.gov.
authors: Shih-Jen
authors: SJ
authors: Hwang
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. rmtanner316@gmail.com.
authors: Rikki M
authors: RM
authors: Tanner
authors: USDA Human Nutrition Center on Aging, Tufts University, Boston, MA, USA. paul.jacques@tufts.edu.
authors: Paul F
authors: PF
authors: Jacques
authors: USDA Human Nutrition Center on Aging, Tufts University, Boston, MA, USA. jacob.selhub@tufts.edu.
authors: Jacob
authors: J
authors: Selhub
authors: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. pmuntner@uab.edu.
authors: Paul
authors: P
authors: Muntner
authors: National Heart, Lung and Blood Institute's Framingham Heart Study and the Center for Population Studies, 73 Mt. Wayte Ave, Suite 2, Framingham, MA, 01702, USA. foxca@nhlbi.nih.gov.|Renal Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. foxca@nhlbi.nih.gov.|Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. foxca@nhlbi.nih.gov.
authors: Caroline S
authors: CS
authors: Fox
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007677:Kidney Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D011237:Predictive Value of Tests; D011379:Prognosis; D051437:Renal Insufficiency / Q000097:blood* / Q000503:physiopathology; D018570:Risk Assessment; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D014805:Vitamin B 12
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