Phenotypes of diabetic kidney disease and cardiovascular outcomes

To quantify the association between diabetic kidney disease (DKD) phenotypes and cardiovascular disease (CVD) mortality and incident major adverse cardiovascular events (MACE), atrial fibrillation (AF), and peripheral artery disease (PAD).

In this longitudinal analysis of adults with diabetes from NHANES (N = 5035) and the UK Biobank (UKBB, N = 26,968), participants were categorized by estimated glomerular filtration rate (eGFR, ml/min per 1.73m^[2]) and urinary albumin-to-creatinine ratio (UACR, mg/g) into four phenotypes: no DKD (eGFR≥60, UACR<30), albuminuria-only (eGFR≥60, UACR≥30), low eGFR only (eGFR<60, UACR<30), and albuminuria+low eGFR (eGFR<60, UACR≥30). We estimated absolute and relative risk of CVD mortality (both cohorts) and incident non-fatal CVD (UKBB), adjusting for demographics, anthropometric and laboratory values, and medications.

In both cohorts, the albuminuria+low eGFR phenotype was associated with the highest cardiovascular risk versus no DKD (reference). In NHANES, albuminuria-only was more strongly associated with CVD mortality than low eGFR only: albuminuria-only HR 2.56 (95%CI 1.86-3.53), low eGFR only HR 1.92 (1.35-2.73), albuminuria+low eGFR HR 3.16 (2.27-4.41). In UKBB, the low eGFR only phenotype was associated with higher risk of CVD mortality than the albuminuria-only phenotype: albuminuria-only HR 1.88 (1.66-2.13), low eGFR only HR 2.42 (1.99-2.95), albuminuria+low eGFR HR 4.65 (3.78-5.71). In UKBB, the albuminuria+low eGFR phenotype exhibited the strongest association with MACE, AF, and PAD. Similar patterns were observed with absolute risk calculations.

Across two large cohorts, DKD phenotypes conferred distinct cardiovascular risk profiles. Consistent measurement of both eGFR and UACR in clinical practice may facilitate targeted, preventative cardiovascular care in diabetes.