Submitted to: BMC Nephrology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2015
Publication Date: 2/2/2015
Citation: McMahon, G.M., Hwang, S., Tanner, R.M., Jacques, P.F., Selhub, J., Muntner, P., Fox, C.S. 2015. The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study. BMC Nephrology. 16:7. https://doi.org/10.1186/1471-2369-16-7. Interpretive Summary: Variants in the gene encoding cubilin, a type of transport protein, have been associated with vitamin B12 deficiency. Variants in this gene are associated with albuminuria, a condition in which the protein albumin is abnormally high in urine, which is indicative of kidney disease. The association between vitamin B12 and prevalent albuminuria and reduced kidney function in participants from the Framingham Heart Study and National Health and Nutritional Examination Survey (NHANES) 2003-2004 was determined. In the Framingham cohort, elevated vitamin B12 was associated with albuminuria, but this was not seen in NHANES. Elevated vitamin B12 was associated with reduced kidney function in individuals with high baseline homocysteine levels, which is a marker for vitamin B12. The combination of elevated homocysteine along with increased vitamin B12 suggests the possibility of a resistance to the usual effects of B12 in these individuals.
Technical 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. Conclusion: In participants with high baseline homocysteine levels, increased plasma B12 was associated with RKF.