Chronic kidney disease (CKD) is more likely to develop in female diabetics than male diabetics, a recently published study suggests.

Margaret K. Yu, MD, of the VA Puget Sound Health Care System in Seattle, and colleagues studied 1,464 adult patients with diabetes and normal renal function. Over 6,187 patient-years, 924 cases of incident CKD developed, for a total incidence rate of 149.3 cases per 1,000 patient-years. The incidence rate was significantly higher for women than men (154 vs. 144.3 per 1,000 patient-years). Female sex was associated with a 35% increased risk of incident CKD compared with male sex in adjusted analyses that took into account death as a competing risk, demographics, duration of diabetes, baseline estimated glomerular filtration rate (eGFR), CKD risk factors, depressive symptoms, and diabetes self-care, according to a report in Nephrology(2015;20:451-458). The sex differences were consistent across age groups and appeared to be driven mainly by differences in the development of low eGFR rather than microalbuminuria.

“To our knowledge, this is the first study to find that women with diabetes had a greater risk of developing CKD compared with men, after taking into account mortality as a competing risk factor,” Dr. Yu's team wrote.

The researchers defined incident CKD as the first measurement of an eGFR less than 60 mL/min/1.73 m² by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations or sex-specific microalbuminuria (urinary albumin/creatinine ratio) of 25 mg/g or higher for women and 17 mg/g or higher for men. The investigators assessed depressive symptoms using the Patient Health Questionnaire-9, which has been validated in patients with CKD. They assessed diabetes self-care using the modified Summary of Diabetes Self-Care Activities tool, which asks how many days per week a self-care activity was performed.

The investigators pointed out that prospective cohort studies involving patients with diabetes generally have found that men are at higher risk of incident CKD than women, but these studies were not designed to examine sex differences and have limitations. Mortality was not accounted for as a competing event, which is relevant because diabetic men have a shorter life expectancy than women, Dr. Yu and her colleagues explained. Most studies did not use sex-specific microalbuminuria thresholds, which account for sex differences in urine creatinine concentrations. CKD incidence was ascertained by incident albuminuria alone or older methods of estimating GFR—such as the change in the reciprocal serum creatinine, Cockcroft-Gault equation, or the Modification of Diet in Renal Disease study equation—which are less accurate than the CKD-EPI equation in patients without CKD, women, and the elderly, according to Dr. Yu's group. Additionally, no previous study assessed depressive symptoms or diabetes self-care activities, which differ by sex and are associated with increased CKD risk, the authors noted.

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