Phenotypic Heterogeneity of Diabetic Kidney Disease and Its Association With Cardiovascular and Renal Outcomes:...

Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is the leading cause of chronic kidney disease (CKD) and progression to end-stage kidney disease (ESKD). DKD exhibits substantial clinical heterogeneity, ranging from the classic proteinuric phenotype to the increasingly recognised nonproteinuric phenotype. However, cardiovascular, kidney and all-cause mortality risks across these phenotypes remain incompletely characterised.

We conducted a retrospective cohort study of 14 367 adults with DKD in the China Renal Data System (CRDS). Major adverse cardiovascular events (MACEs), ESKD and all-cause mortality were ascertained from longitudinal electronic health records. Multi-state models were used to characterise transitions among clinical states and to estimate transition-specific risks across DKD phenotypes.

Over a median follow-up of 2.1 years, 17.1% of participants experienced MACE, while 7.0% and 10.0% progressed to ESKD and experienced all-cause mortality, respectively. High urinary albumin-to-creatinine ratio (UACR)-related phenotypes emerged as persistent risk factors across various disease trajectories. In particular, the phenotype combining low estimated glomerular filtration rate (eGFR) and high UACR had the highest risks of progression to ESKD and of death after MACE.

Our findings show that DKD phenotypes defined by baseline eGFR and UACR were associated with distinct cardiovascular, kidney and mortality risks. Albuminuria remained an important prognostic marker even when eGFR was preserved, whereas the combination of low eGFR and high albuminuria identified the highest risk group. These findings support improved phenotypic risk stratification and may inform future clinical research and individualised risk assessment in DKD.