Background-Vitamin D is crucial for maintaining musculoskeletal health. Recently, vitamin D insufficiency has been linked to a number of extraskeletal disorders, including diabetes, cancer, and cardiovascular disease. Determinants of circulating 25-hydroxyvitamin D (25-OH D) include sun exposure and dietary intake, but its high heritability suggests that genetic determinants may also play a role.

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney.

Context Diabetes is the leading cause of kidney disease in the developed world. Over time, the prevalence of diabetic kidney disease (DKD) may increase due to the expanding size of the diabetes population or decrease due to the implementation of diabetes therapies. Objective To define temporal changes in DKD prevalence in the United States. Design, Setting, and Participants Cross-sectional analyses of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988–1994 (N = 15 073), NHANES 1999–2004 (N = 13 045), and NHANES 2005–2008 (N=9588). Participants with diabetes were defined by levels of hemoglobin A1c of 6.5% or greater, use of glucose-lowering medications, or both (n = 1431 in NHANES III; n = 1443 in NHANES 1999–2004; n = 1280 in NHANES 2005–2008). Main Outcome Measures Diabetic kidney disease was defined as diabetes with albuminuria (ratio of urine albumin to creatinine >30 mg/g), impaired glomerular filtration rate (<60 mL/min/1.73 m2 estimated using the Chronic Kidney Disease Epidemiology Collaboration formula), or both. Prevalence of albuminuria was adjusted to estimate persistent albuminuria. Results The prevalence of DKD in the US population was 2.2% (95% confidence interval [CI], 1.8%–2.6%) in NHANES III, 2.8% (95% CI, 2.4%–3.1%) in NHANES 1999–2004, and 3.3% (95% CI, 2.8%–3.7%) in NHANES 2005–2008 (P<.001 for trend). The prevalence of DKD increased in direct proportion to the prevalence of diabetes, without a change in the prevalence of DKD among those with diabetes. Among persons with diabetes, use of glucose-lowering medications increased from 56.2% (95% CI, 52.1%–60.4%) in NHANES III to 74.2% (95% CI, 70.4%–78.0%) in NHANES 2005–2008 (P<.001); use of renin-angiotensin-aldosterone system inhibitors increased from 11.2% (95% CI, 9.0%–13.4%) to 40.6% (95% CI, 37.2%–43.9%), respectively (P<.001); the prevalence of impaired glomerular filtration rate increased from 14.9% (95% CI, 12.1%–17.8%) to 17.7% (95% CI, 15.2%–20.2%), respectively (P=.03); and the prevalence of albuminuria decreased from 27.3% (95% CI, 22.0%–32.7%) to 23.7% (95% CI, 19.3%–28.0%), respectively, but this was not statistically significant (P=.07). Conclusions Prevalence of DKD in the United States increased from 1988 to 2008 in proportion to the prevalence of diabetes. Among persons with diabetes, prevalence of DKD was stable despite increased use of glucose-lowering medications and renin-angiotensin-aldosterone system inhibitors.

Type 2 diabetes associates with increased risk of mortality, but how kidney disease contributes to this mortality risk among individuals with type 2 diabetes is not completely understood. Here, we examined 10-year cumulative mortality by diabetes and kidney disease status for 15,046 participants in the Third National Health and Nutrition Examination Survey (NHANES III) by linking baseline data from NHANES III with the National Death Index. Kidney disease, defined as urinary albumin/creatinine ratio $30 mg/g and/ or estimated GFR #60 ml/min per 1.73 m 2 , was present in 9.4% and 42.3% of individuals without and with type 2 diabetes, respectively. Among people without diabetes or kidney disease (reference group), 10-year cumulative all-cause mortality was 7.7% (95% confidence interval [95% CI], 7.0%-8.3%), standardized to population age, sex, and race. Among individuals with diabetes but without kidney disease, standardized mortality was 11.5% (95% CI, 7.9%-15.2%), representing an absolute risk difference with the reference group of 3.9% (95% CI, 0.1%-7.7%), adjusted for demographics, and 3.4% (95% CI, 20.3% to 7.0%) when further adjusted for smoking, BP, and cholesterol. Among individuals with both diabetes and kidney disease, standardized mortality was 31.1% (95% CI, 24.7%-37.5%), representing an absolute risk difference with the reference group of 23.4% (95% CI, 17.0%-29.9%), adjusted for demographics, and 23.4% (95% CI, 17.2%-29.6%) when further adjusted. We observed similar patterns for cardiovascular and noncardiovascular mortality. In conclusion, those with kidney disease predominantly account for the increased mortality observed in type 2 diabetes.