Diabetes With Major Depression Raises Risk for ESRD

Veronica Hackethal, MD

April 11, 2014

The risk of developing end-stage renal disease (ESRD) may be 2 times higher in people with diabetes and major depression, according to results from the Pathways Study, conducted by Margaret K. Yu, MD, from the Health Services Research and Development, Veterans Affairs Puget Sound Health Care System, and the Division of Nephrology, Department of Medicine, and Kidney Research Institute, School of Medicine, and the Department of Epidemiology, School of Public Health, University of Washington, Seattle, and colleagues. The research was published online March 27 in the Clinical Journal of the American Society of Nephrology.

"The current study found that, in this primary care cohort of patients with diabetes, major depressive symptoms were associated with nearly two times the risk of incident ESRD at up to 10 years of follow-up," the authors write. "[T]o our knowledge, this study is the first study to show an association between major depressive symptoms and long-term ESRD risk in this population."

Diabetes is the leading cause of kidney failure, and comorbid depression has been linked to many diabetes complications, including poor glycemic control, medication nonadherence, diabetic nephropathy, and mortality, the authors write. Past studies have suggested a link between depression and progression of chronic kidney disease, although results have been inconsistent.

This study used a prospective, observational cohort design and recruited adults with diabetes from 9 primary care clinics at Group Health (GH), a large health maintenance organization in Washington State. Baseline surveys were mailed in 2001 and 2002, and participants were followed-up until development of ESRD, death, GH disenrollment, or the end of the study (August 15, 2012).

The researchers identified medication data from pharmacy records. They extracted development of ESRD and laboratory and other clinical data from GH databases. The researcher assessed minor and major depressive symptoms using the self-reported Patient Health Questionnaire 9. They assessed diabetes self-care using the self-reported modified Summary of Diabetes Self-Care Activities questionnaire.

The study included 3886 participants, of whom 448 (11.5%) had major depressive symptoms and 327 (8.4%) had minor depressive symptoms. During a median follow-up of 8.8 years, 87 patients (2.2%) developed ESRD. People with major depression had a higher risk for ESRD (hazard ratio, 1.85; 95% confidence interval, 1.02 - 3.33). The researchers found no significant associations between minor depressive symptoms or diabetes self-care parameters and ESRD.

Reliance on self-reported depressive symptoms instead of clinical interview could have overestimated major depression, the authors write. Another weakness of the study was the inability to include data on blood pressure, changes in cardiovascular risk over time, and medication nonadherence. The Summary of Diabetes Self-Care Activities, although a validated questionnaire, may have introduced inaccuracies regarding diabetes self-care. Finally, patients in this study were insured, and the results may not generalize to populations with limited access to care.

"The results from this study lend support to the current American Diabetes Association guidelines, which recommend screening for depression in patients with diabetes and poor self-management," the authors point out.

"This is a large prospective study addressing an important topic. The authors conducted careful statistical analyses adjusting for all major potential confounders, including competing risk of death," Alexander Turchin, MD, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, told Medscape Medical News.

"An important weakness is absence of any information on what's been happening with the patients between the initial survey and the outcome," Dr. Turchin pointed out. "This information could help explain the mechanism of the association between depression and ESRD and provide further evidence for a causal relationship between them. Hemoglobin A1c levels, medication adherence, and blood pressure levels during the follow-up period would have been particularly helpful."

"It is conceivable that treatment for depression could improve patients' adherence to both medications and diet/exercise regimen, thus lowering their blood glucose and blood pressure levels — both known risk factors for ESRD," explained Dr. Turchin. "However, as the authors point out, further research is needed before we can be confident that treatment of depression in patients with diabetes will decrease the risk of kidney failure."

One coauthor has reported being on the board at Eli Lilly and Wyeth and receiving honoraria from Eli Lilly. The other authors have disclosed no relevant financial relationships. Dr. Turchin reports serving on the Advisory Board for Monarch Medical Technologies, as a consultant to GNS Healthcare, and receiving a research grant from Merck.

Clin J Am Soc Nephrol. Published online March 27, 2014. Abstract

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