Phylloquinone and Vitamin D Status: Associations with Incident Chronic Kidney Disease in the Framingham Offspring Cohort
ABSTRACT Cardiovascular risk factors are associated with the development of chronic kidney disease (CKD), and CKD and vascular disease are etiologically linked. Evidence suggests deficiencies of vitamins D and K may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. We hypothesized that deficiencies of vitamins D and K may be associated with incident CKD and/or incident albuminuria amongst members of the general population.
We analyzed 1,442 Framingham Heart Study participants (mean age 58 years; 50.5% women), free of CKD (eGFR <60 ml/min/1.73 m(2)), with a mean follow-up of 7.8 years in 2005-2008. Incident albuminuria was defined using sex-specific cut-offs of urine albumin-to-creatinine ratio (≥17 mg/g men and ≥25 mg/g women). Baseline log plasma phylloquinone (vitamin K(1)) and 25(OH)D levels, analyzed as continuous variables and by quartile, were related to risk of incident CKD (n = 108) and incident albuminuria (n = 106) using logistic regression models adjusted for standard risk factors.
Participants in the highest phylloquinone quartile (≥1.78 nmol/l) had an increased risk of CKD (multivariable-adjusted OR Q(4) vs. Q(1) 2.39; p = 0.006) and albuminuria at follow-up (multivariable-adjusted OR Q(4) vs. Q(1) 1.95; p = 0.05), whereas no association was observed with continuous phylloquinone levels for either endpoint. Deficiency of 25(OH)D was not associated with incident CKD or albuminuria in either analysis.
Contrary to our hypothesis, higher plasma phylloquinone levels are associated with an increased risk of incident CKD. Whether plasma phylloquinone is a marker for another unmeasured risk factor requires further study. External validation is necessary given the unexpected nature of these results.
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ABSTRACT: BACKGROUND: Low serum 25-hydroxyvitamin D (25[OH]D) levels have been associated with chronic kidney disease in cross-sectional studies. However, this association has not been studied prospectively in a large general population-based cohort. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 6,180 adults 25 years or older participating in the baseline and 5-year follow-up phases of the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. PREDICTOR: Serum 25(OH)D levels <15 ng/mL were considered deficient. OUTCOMES & MEASUREMENTS: Incident chronic kidney disease was defined as being negative at baseline but positive after 5 years for (1) reduced estimated glomerular filtration rate (eGFR; <60 mL/min/1.72 m(2)) or (2) albuminuria (spot urine albumin-creatinine ratio ≥2.5 mg/mmol [≥22.1 mg/g] for men and ≥3.5 mg/mmol [≥30.9 mg/g] for women). RESULTS: 623 (10.9%) participants were vitamin D deficient, 161 developed incident reduced eGFR, and 222 developed incident albuminuria. In participants with and without vitamin D deficiency, annual age-standardized incidences were 0.92% (95% CI, 0.56%-1.30%) and 0.59% (95% CI, 0.51%-0.68%), respectively, for eGFR <60 mL/min/1.72 m(2) and 1.50% (95% CI, 1.06%-1.95%) and 0.66% (95% CI, 0.56%-0.76%), respectively, for albuminuria. In multivariate regression models, vitamin D deficiency was associated significantly with the 5-year incidence of albuminuria (OR, 1.71; 95% CI, 1.12-2.61; P = 0.01), but not reduced eGFR (OR, 0.93; 95% CI, 0.53-1.66; P = 0.8). LIMITATIONS: The observational nature of the study does not account for unmeasured confounders. Only baseline 25(OH)D level was measured and therefore may not accurately reflect lifetime levels. Differences in baseline characteristics of participants who were included compared with those excluded due to missing data or follow-up may limit the applicability of results to the original AusDiab cohort. CONCLUSIONS: Our prospective cohort study shows that vitamin D deficiency is associated with a higher annual incidence of albuminuria and reduced eGFR and independently predicts the 5-year incidence of albuminuria. These associations warrant further exploration in long-term prospective clinical trials.American Journal of Kidney Diseases 04/2013; 62(1). DOI:10.1053/j.ajkd.2013.03.010 · 5.76 Impact Factor
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ABSTRACT: Vitamin D is associated with cardiovascular disease and renal function but the mechanisms are as yet unexplained. Microalbuminuria is associated with a higher risk of kidney function loss, cardiovascular disease, and mortality. Parathyroid hormone is a predictor of cardiovascular mortality and negatively correlated with glomerular filtration rate. We investigated the association between vitamin D status and 5-year changes in urine albumin creatinine ratio (UACR) and parathyroid hormone (PTH). A random sample of 6,784 individuals aged 30-60 years from a general population participated in the Inter99 study in 1999-2001. Vitamin D (serum-25-hydroxyvitamin D) was measured at baseline by high-performance liquid chromatography. UACR and PTH were measured at baseline and follow-up. Increased UACR was defined as UACR >4.0 mg/g reflecting the upper quartile at baseline. We included 4,330 individuals who participated at 5-year follow-up. In multivariable linear regression analysis, a 10-nmol/l higher baseline level of vitamin D was associated with a 5-year decrease in UACR by 0.92 % (95 % confidence interval, CI 0.13, 1.71). In multivariable logistic regression analysis, the odds ratio of developing increased UACR during follow-up was 0.96 (95 % CI 0.92, 0.98) per 10 nmol/l higher baseline vitamin D level. We found a significant inverse cross-sectional (p < 0.0001) but no prospective association (p = 0.6) between baseline vitamin D status and parathyroid hormone. We found low vitamin D status to be a predictor of long-term development of increased UACR. It remains to be proven whether vitamin D deficiency is a causal and reversible factor in the development of albuminuria.Endocrine 02/2013; 44(2). DOI:10.1007/s12020-013-9887-0 · 3.53 Impact Factor