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

Abstract

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 .

Keywords: Albuminuria; Diabetic kidney disease; Epidemiology; Glomerular filtration rate; Stroke; Type 2 diabetes.

Conflict of interest statement

Dr Gregg Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Janssen, Medtronic, Merck, and Novartis.

© 2022. The Author(s).

Figures

Fig. 1

Cumulative Incidence of Stroke by CKD stage (A) and CKD risk category (B). CKD was classified according to the KDIGO clinical practice guidelines: (1) no CKD defined as eGFR ≥ 60 and UACR < 30; (2) CKD G1, as eGFR ≥ 90 and UACR ≥ 30; (3) CKD G2, as eGFR between 60 and 89 and UACR ≥ 30; (4) CKD G3, as eGFR between 30 and 59 regardless of UACR. CKD risk categories were defined by eGFR and UACR as follows: (1) low risk, as eGFR ≥ 60 and UACR < 30; (2) moderate risk, as (45 ≤ eGFR < 60 and UACR < 30) or (eGFR ≥ 60 and 30 ≤ UACR ≤ 300); (3) high risk, as (30 ≤ eGFR < 44 and UACR< 30) or (45 ≤ eGFR < 60 and 30 ≤ UACR ≤ 300) or (eGFR ≥ 60 and UACR > 300); (4) very high risk, as (30 ≤ eGFR < 44 and 30 ≤ UACR ≤ 300) or (30 ≤ eGFR < 60 and UACR > 300). CKD indicates chronic kidney disease; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes; UACR, urine albumin-creatinine ratio

Fig. 2

Hazard ratios for incident stroke by age group and CKD stage. Hazard ratios are adjusted for sex, race, treatment arm, duration of diabetes, hemoglobin A1C, cigarette smoking, alcohol intake; body mass index, total-to-HDL cholesterol, systolic BP, use of BP-lowering medications, atrial fibrillation and history of cardiovascular disease, use of antiplatelet agents (including aspirin)/ anticoagulants, diuretics, ACEI/ARB. CKD was classified according to the KDIGO clinical practice guidelines: (1) no CKD defined as eGFR ≥ 60 and UACR < 30; (2) CKD G1, as eGFR ≥ 90 and UACR ≥ 30; (3) CKD G2, as eGFR between 60 and 89 and UACR ≥ 30; (4) CKD G3, as eGFR between 30 and 59 regardless of UACR. ACEI indicates angiotensin-converting enzyme inhibitors; ARB, angiotensin-II receptor blockers; BP, blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein; KDIGO, Kidney Disease: Improving Global Outcomes; UACR, urine albumin-creatinine ratio