Vitamin D deficiency, inflammation, and albuminuria in chronic kidney disease: complex interactions.
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.


METHODS
A cross-sectional study was carried out.


METHODS
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.
Isakova
Tamara
T
Division of Nephrology and Hypertension, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, USA.
Gutiérrez
Orlando M
OM
Patel
Neha M
NM
Andress
Dennis L
DL
Wolf
Myles
M
Levin
Adeera
A
D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000032:analysis; D000419:Albuminuria / Q000150:complications / Q000453:epidemiology*; D015415:Biomarkers; D002112:Calcifediol / Q000097:blood / Q000172:deficiency*; D002117:Calcitriol / Q000097:blood / Q000172:deficiency*; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000453:epidemiology*; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000453:epidemiology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D012084:Renin-Angiotensin System; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications / Q000453:epidemiology*
D000418:Albumins; D015415:Biomarkers; D015850:Interleukin-6; D014807:Vitamin D; D003404:Creatinine; D002117:Calcitriol; D002112:Calcifediol