Original Investigation Serum 25-Hydroxyvitamin D Deficiency and the 5-Year Incidence of CKD Matthew J. Damasiewicz, MD, 1,2 Dianna J. Magliano, PhD, 3 Robin M. Daly, PhD, 4,5 Claudia Gagnon, MD, 5,6 Zhong X. Lu, MD, 2,7 Ken A. Sikaris, MD, 7 Peter R. Ebeling, MD, 5 Steven J. Chadban, PhD, 8,9 Robert C. Atkins, MD, 3 Peter G. Kerr, PhD, 1,2 Jonathan E. Shaw, MD, 3 and Kevan R. Polkinghorne, PhD 1,2 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. Am J Kidney Dis. xx(x):xxx. © 2013 by the National Kidney Foundation, Inc. INDEX WORDS: Vitamin D; albuminuria; chronic kidney disease; glomerular filtration rate; decreased kidney function. V itamin D has a recognized role in human health, and its deficiency has been reported commonly in the general population and chronic kidney disease (CKD) cohorts. 1 Recent research has expanded our understanding of the many effects of vitamin D be- yond its traditional role in regulating bone and min- eral metabolism. 2 CKD affects up to 10%-15% of the adult popula- tion. 3 Proteinuria is an early marker of kidney damage and an important predictor of CKD progression, car- diovascular outcomes, and mortality. 4-6 The decline in kidney function is associated with a reduction in calcitriol levels, and numerous cohort studies have linked calcitriol use with decreased morbidity and mortality in dialysis-dependent and non–dialysis- dependent patients with CKD. 7-10 Experimental data show calcitriol to be a potent inhibitor of the renin- angiotensin system and nuclear factor B (NF-B) pathways, which play important roles in the pathogen- esis of kidney disease. 11,12 The importance of extrare- From the 1 Department of Nephrology, Monash Medical Centre; 2 Department of Medicine, Monash University; 3 Baker IDI Heart and Diabetes Institute; 4 School of Exercise and Nutrition Sciences, Deakin University; 5 NorthWest Academic Centre, University of Melbourne, Western Health, Melbourne, Australia; 6 Centre de recherche du CHUQ, Laval University, Quebec City, Canada; 7 Melbourne Pathology, Melbourne; 8 Department of Nephrology and Transplantation, Royal Prince Alfred Hospital; and 9 Sydney Medical School, University of Sydney, Sydney, Australia. Received July 16, 2012. Accepted in revised form March 6, 2013. Address correspondence to Matthew Damasiewicz, MD, Depart- ment of Nephrology, Monash Medical Centre, 246 Clayton Rd, Clayton 3168, Victoria, Australia. E-mail: matthew.damasiewicz@ monash.edu © 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.03.010 Am J Kidney Dis. 2013;xx(x):xxx 1