Association of Glomerular Filtration Rate Decline With Clinical Outcomes in a Population With Type 2 Diabetes

While historical rate of decline in kidney function is informally used by clinicians to estimate risk of future adverse clinical outcomes especially kidney failure, in people with type 2 diabetes the epidemiology and independent association of historical eGFR slope on risk is not well described.

Determine the association of eGFR slope and risk of clinically important outcomes.

Observational population-based cohort with type 2 diabetes in Alberta.

An Alberta population-based cohort with type 2 diabetes was assembled, characterized, and observed over 1 year (2018) for clinical outcomes of ESKD, first myocardial infarction, first stroke, heart failure, and disease-specific and all-cause hospitalization and mortality. Kidney function was defined using KDIGO criteria using the most recent eGFR and albuminuria measured in the preceding 18 months; annual eGFR slope utilized measurements in the 3 years prior and was parameterized using three methods (percentiles, and linear term with and without missingness indicator). Demographics, laboratory results, medications, and comorbid conditions using validated definitions were described. In addition to descriptive analysis, odds ratios from fully adjusted logistic models regressing outcomes on eGFR slope are reported; the marginal risk of clinical outcomes was also determined.

Among 336 376 participants with type 2 diabetes, the median annual eGFR slope was -0.41 mL/min/1.73 m² (IQR -1.67, 0.62). In fully adjusted models, eGFR slope was independently associated with many adverse clinical outcomes; among those with ≤10th percentile of slope (median -4.71 mL/min/1.73 m²) the OR of kidney failure was 2.22 (95% CI 1.75, 2.82), new stroke 1.23 (1.08, 1.40), heart failure 1.42 (1.27, 1.59), MI 0.98 (0.77, 1.23) all-cause hospitalization 1.31 (1.26, 1.36) and all-cause mortality 1.56 (1.44, 1.68). For every -1 mL/min/1.73 m² in eGFR slope, the OR of outcomes ranged from 1.01 (0.98, 1.05 for new MI) to 1.09 (1.08, 1.10 for all-cause mortality); findings were significant for 10 of the 13 outcomes considered.

Causality cannot be established with this study design.

These findings support consideration of the rate of eGFR decline in risk stratification and may inform clinicians and policymakers to optimize treatment and inform health care system planning.