Original Research
Vitamin D Deficiency, Inflammation, and Albuminuria in Chronic Kidney Disease: Complex Interactions

https://doi.org/10.1053/j.jrn.2010.07.002Get rights and content

Objective

Vitamin D may promote cardiovascular health in general population and in chronic kidney disease (CKD) through inhibition of the renin–angiotensin system and anti-inflammatory effects. Although proteinuria is a marker of kidney and cardiovascular disease, few studies have examined vitamin D levels, inflammation, and proteinuria simultaneously in CKD. We evaluated the relationship between calcidiol (25D), calcitriol (1,25D), inflammation, and albuminuria in Study of Early Evaluation of Kidney Disease, a multicenter CKD cohort.

Design

A cross-sectional study was carried out.

Participants

A total of 1,847 participants were studied, of which 387 were randomly selected for inflammatory biomarker assessment.

Predictors and Outcomes

The primary predictors were 25D and 1,25D. The outcome was albuminuria (urine albumin to creatinine ratio [UACR]: >30 mg/g).

Results

Albuminuric patients were more likely to have decreased 25D and 1,25D levels and higher interleukin-6 (IL-6) levels compared with normoalbuminuric patients. The lowest tertiles of 25D and 1,25D were associated with 2 to 3 times increased odds of albuminuria compared with the highest tertiles when adjusted for age, gender, race, systolic blood pressure, and diabetes (OR for 25D: 3.0; 95% CI: 1.3 to 7.0; OR for 1,25D: 2.6; 95% CI: 1.7 to 3.9). In analogous linear regression models, 25D and 1,25D were significantly associated with log UACR (P < .0001, for both). In participants for whom inflammatory markers were measured, demographics-adjusted linear regression models that included IL-6 described attenuation of the relationship between 25D, 1,25D, and UACR.

Conclusions

Low 25D and 1,25D levels are independently associated with albuminuria. IL-6 may be an important intermediary between vitamin D deficiency and albuminuria, or vitamin D deficiency may contribute to inflammation and subsequent albuminuria.

Section snippets

Study Population

The design of Study of Early Evaluation of Kidney Disease has been described in detail previously.18 Study of Early Evaluation of Kidney Disease is a multicenter, community-based, observational cohort study that aimed to evaluate the prevalence of abnormalities in levels of parathyroid hormone (PTH), 25D, 1,25D, calcium, and phosphorus in patients with CKD. More than 70% of subjects were recruited from primary care practices that were equally distributed throughout the United States. Subjects

Description of the Cohort

Characteristics of patients with albuminuria, as defined by UACR >30 mg/g (n = 1,190), compared with UACR ≤30 mg/g (n = 657) are shown in Table 1. Notably, compared with the nonalbuminuric group, patients with albuminuria were more likely to have diabetes, lower eGFR, and decreased 25D and 1,25D levels.

Relationship Between Vitamin D Levels and the Prevalence of Albuminuria

The lowest 25D tertile compared with the highest 25D tertile was associated with the presence of albuminuria in univariate and in all but the 2 final adjusted analyses, the models that included

Discussion

In this cross-sectional study, lower levels of 25D and 1,25D were associated with albuminuria in patients with CKD, with the lowest tertiles of 25D and 1,25D each associated with 2 to 3 times increased odds of albuminuria compared with the highest tertiles. This association for both 25D and 1,25D was independent of age, gender, race, SBP, and diabetes. In the case of 25D, the trend for the observed linear relationship between albuminuria and 25D tertiles persisted with additional adjustment for

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