Diabetic kidney disease and risk of incident stroke among adults with type 2 diabetes

Background: Data on the relations between kidney function abnormalities and stroke in type 2 diabetes are limited. We evaluated the associations of kidney function abnormalities and chronic kidney disease (CKD) stages with incident stroke in a large sample of adults with type 2 diabetes. Methods: Participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without history of stroke at baseline were included. Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were assessed at baseline. CKD categories were defined according to the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for stroke in relation to measures of kidney function and CKD categories. Results: A total of 9170 participants (mean age 62.8 [SD: 6.6] years, 38.2% women, 62.9% white) were included. Over a median follow-up of 4.9 years (interquartile range: 4.0–5.7), 156 participants developed a stroke (incidence rate 3.6/1000 person-years [95% CI 3.0–4.2]). After adjusting for relevant confounders, higher UACR and lower eGFR were each associated with increased risk of stroke. Compared to UACR < 30 mg/g, moderate albuminuria and severe albuminuria were associated with increasing hazards for stroke (HR 1.61 [95% CI 1.12–2.32] and 2.29 [95% CI 1.39–3.80], respectively). Compared to eGFR of ≥ 60 mL/min/1.73 m², decreased eGFR (eGFR < 60 mL/min/1.73 m²) was associated with higher risk of stroke (HR 1.50, 95% CI 0.98–2.29). Compared to no CKD, worsening CKD stage was associated with an increasing risk of stroke (HRs of 1.76 [95% CI 1.10–2.83] for CKD G1, 1.77 [95% CI 1.13–2.75] for CKD G2, and 2.03 [95% CI 1.27–3.24] for CKD G3). Conclusions: In a large sample of adults with type 2 diabetes, increasing albuminuria and worsening stages of early CKD were independently associated with higher risk of incident stroke. Trial registration: ClinicalTrials.gov. Identifier: NCT00000620.