Clinical Features and Implications of Albuminuria Trajectories in Type 2 Diabetes: The Fremantle Diabetes Study Phase 2

Context: The urinary albumin:creatinine ratio (uACR) can exhibit significant temporal changes but few studies have characterized transition patterns between uACR categories in type 2 diabetes. Objective: The study aim was to use group-based trajectory modeling (GBTM) to identify clusters of people with type 2 diabetes and distinct uACR trajectories. Methods: Of 1482 participants in the observational Fremantle Diabetes Study Phase 2, a total of 1145 (77.3%; mean age 65.4 years, 53.3% males) with 2 or more biennial uACR measurements over 6 years were included in GBTM. Independent baseline associates of uACR trajectory group membership were assessed using multinomial regression. Associations between group membership and changes in estimated glomerular filtration rate over 4 years were explored. Results: The optimum GBTM model comprised 6 categories: normoalbuminuria (n = 429, 37.5%), regression (n = 82, 7.2%), progression (n = 71, 6.2%), progression/regression (n = 104, 9.1%), persistent microalbuminuria (n = 401, 35.0%), and persistent macroalbuminuria (n = 58, 5.1%). The latter 5 groups had worse glycemic control than the normoalbuminuria group. The 3 groups starting from/returning to normoalbuminuria had heterogeneous baseline characteristics but a decline in renal function that was similar to the normoalbuminuric group. The persistent microalbuminuria group had adverse baseline cardiometabolic features and longitudinal renal outcomes relative to the normoalbuminuria/other microalbuminuria groups. The persistent macroalbuminuria group had, consistent with its baseline characteristics, the highest mortality (31.0% vs ≤18.5% in the other groups) and most rapid progression of renal dysfunction. Conclusion: GBTM identified distinct uACR trajectory groups with clinical and prognostic implications, and could be used to stratify participants in clinical trials of new therapies for diabetic kidney disease.