Diabetes Drugs Fail to Improve Kidney Disease Rates

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.

From press release:

Diabetic kidney disease has become more prevalent in the United States over the past 20 years, despite a substantial increase in the use of medications for the treatment of people with diabetes, according to a study to be published June 22 in JAMA, the Journal of the American Medical Association.

These medications include drugs that lower glucose, blood pressure and lipids.

The widespread application of medications proven to improve health in clinical trials has markedly bettered the control of blood sugar, blood pressure, and cholesterol in the diabetic population in the United States.

Yet diabetic kidney disease continues to rise. This increase was mostly due to the growing number of people with diabetes. But researchers were surprised that diabetic kidney disease increased in direct proportion to the percentage of American adults with diabetes. In other words, there was no apparent progress in preventing kidney disease within the diabetic population.

"Improvements in reaching therapeutic targets in diabetes management have not translated into a decline in diabetic kidney disease," said the lead author of the study, Dr. Ian H. de Boer, assistant professor of medicine in the Division of Nephrology, Kidney Research Institute, and an adjunct assistant professor of epidemiology at the University of Washington (UW) in Seattle.

Diabetic kidney disease is a common complication of diabetes, de Boer explained, and develops in about 40 percent of people with diabetes. Diabetes is the leading cause of chronic kidney disease in the developed world. This type of kidney disease can appear as protein in the urine or impaired functioning of the tubes that filter urine, or both.

Even mild signs of diabetic kidney disease, de Boer noted, are linked with a higher risk of heart disease and death, as well as greater health-care costs

de Boer added that diabetic kidney disease accounts for almost half of the cases of end-stage kidney failure in the United States. Approximately 60 percent of patients with end stage kidney disease die within five years of onset. Medicare spending for the treatment of end stage kidney disease hit $26.8 billion in 2008, based on the latest figures in the U.S. Renal System 2010 Annual Report.

Because the researchers were conservative in estimating diabetic kidney disease, the disorder could be more prevalent than the study figures indicate. The swell in cases of diabetic kidney disease, de Boer said, can't be explained by U.S. demographic changes over the past 20 years in age, gender, race or ethnicity.

One thing that has changed is the clinical manifestation of the disease. Diabetes patients under age 65 are less likely to have protein in their urine than in past years. Earlier studies have shown that tight control of blood sugar levels prevents the appearance of protein in the urine in both type 1 and type 2 diabetes.

However, better diabetes management did not lead to significant improvements in glomerular filtration rate, a test which measures kidney function, de Boer and his research team discovered.

"The results of our research don't suggest that standards of diabetes care for controlling blood sugar levels, high blood pressure, and cholesterol should be changed," de Boer said. "What the findings suggest is that these treatments alone are not doing an effective job of reducing diabetic kidney disease, and researchers need to find additional ways to do that."

The real solution to preventing diabetic kidney disease, de Boer said, is to keep diabetes from occurring in the first place. Diet, exercise, and other lifestyle modifications to prevent or treat obesity are helpful in lowering the risk of type 2 diabetes. Avoiding diabetes frees people from experiencing its many complications, including diabetic kidney disease.

In addition, the study suggests that new interventions are needed to prevent people with diabetes from developing kidney disease. In particular, interventions focused on preventing glomerular filtration rate problems are needed.

In addition to de Boer, other researchers on the study were Tessa C. Rue and Patrick J. Heagerty, both of the Department of Biostatistics, UW School of Public Health; Yoshio N. Hall and Jonathan Himmelfarb, both of the Kidney Research Institute and Division of Nephrology, Department of Medicine, UW School of Medicine, and Noel S. Weiss, Department of Epidemiology, UW School of Public Health.