de Boer et al analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III) conducted in 1988-1994 and the continuous NHANES (1999-2008) to investigate trends in CKD in people with diabetes. This study found that the prevalence of CKD among people with diabetes has increased over the past two decades and it has done so in proportion to the increasing prevalence of diabetes. This is in contrast to the recent plateau in rates of diabetic end stage renal disease (ESRD).
The authors compared estimates from the 1988-1994, 1999-2004, and 2005-08 survey periods. They defined diabetes as the use of glucose-lowering medications, HbA1c ≥6.5%, or both. To maximize the use of objective criteria, persons who were diagnosed but were treated by only diet or lifestyle modifications would have been classified as nondiabetic if their HbA1c value was<6.5%. Glomerular filtration rate (GFR) was estimated from calibrated serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (2
) and categorized based on the classification system established by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (3
). Kidney disease was defined as an estimated GFR <60 mL/min/1.73 m2
, albuminuria (albumin-to-creatinine ratio >30 mg/g), or both, and kidney disease in a person classified as having diabetes was classified as diabetic kidney disease.
The proportion of the adult population with diabetic kidney disease increased from 2.2% to 3.3% over this 20-year period. The largest increases were observed among persons aged 65 or older (7.1% to 10.7%). Among persons with diabetes, the prevalence of kidney disease remained relatively constant over time at ~35%. Among diabetic adults 65 or older, the prevalence of kidney disease was approximately 50%; this was also constant over the study period. By contrast, the prevalence of albuminuria (with or without low GFR) in persons with diabetes decreased over the study period: from 27.3% in 1988-94 to 24.9% in 1999-2004 to 23.7% in 2005-08. This trend was largely explained by demographic factors, and the temporal differences were not statistically significant after adjustment. By contrast, the prevalence of estimated GFR <60 mL/min/1.73 m2 in persons with diabetes increased over the study period, rising from 14.9% in 1988-94 to 16.7% in 1999-2004 to 17.7% in 2005-08.
Accompanying the observed trends in diabetic kidney disease were significant increases in body mass index and duration of diabetes and significant decreases in mean HbA1c, blood pressure, and serum lipids. As has been shown in other studies (4
), the use of glucose-lowering medications, cholesterol-lowering medications, and renin-angiotensin-aldosterone system (RAAS) inhibitors increased dramatically during this period. The authors show that among persons with diabetes, the proportion taking glucose-lowering medication increased from 56.2% to 74.2%; the proportion taking lipid-lowering medications increased from 8.9% to 50.2%; and the proportion taking RAAS inhibitors increased from 11.2% to 40.6%.
The authors comment that the observed changes in medication use have not translated into a decreased prevalence of diabetic kidney disease. However, trends in obesity and changes in the diagnostic criteria for diabetes are difficult to take fully into account. The decreases in mean HbA1c and increases in average duration of diabetes over time suggest that the case-mix of diabetic adults has changed substantially. The definition of diabetes used in the study does not entirely overcome bias resulting from temporal changes since prescribing practices will reflect both changes in diabetes diagnostic criteria and availability of diabetes drugs over the 20-year period.
Limitations of this study to be considered in the interpretation of the results include the inherent limitations of the cross-sectional (prevalence study) design, which is optimal for estimating prevalence trends, but cannot establish temporality or evaluate the risk of diabetic kidney disease. The lack of information on ESRD—a critical clinical and economic consequence of diabetic kidney disease—is also a weakness. Data from the United States Renal Data System suggest that ESRD incidence rates have reached a plateau in the past decade despite more prevalent comorbid conditions like diabetes (7
). The study is also limited by the availability of only single measurements of albumin and creatinine to characterize CKD. The authors estimate persistence of albuminuria but the subsample of diabetic individuals with repeat albuminuria assessments is small. Serum creatinine-based GFR estimating equations such as the CKD-EPI equation are known to be affected by muscle mass and dietary intake. Decreased muscle mass is associated with certain pathologic changes, including glucose intolerance (8
); thus, the lowered serum creatinine and associated higher estimated GFR may lead to lower estimates of the burden of diabetic kidney disease than might be obtained with another filtration marker. Finally, while this study describes the burden of kidney disease in people with diabetes, it is not clear how much of the burden is due to classic diabetic kidney disease (9
The study benefited from a large sample size, multiple survey periods, and rigorous data collection procedures in NHANES that have remained relatively consistent over time. These data represent some of the most comprehensive data on the prevalence of diabetic kidney disease in the general U.S. population. However, the trends in diabetic kidney disease presented in this study ultimately reflect a complex interplay of changes in diabetes screening, diagnosis, and treatment along with changes in the burden of kidney disease.