Proteinuric and Non-Proteinuric Diabetic Kidney Disease: Different Presentations of the Same Disease?

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease (ESKD) worldwide. This review examines the potential differences in clinical presentation, outcomes, and management between individuals with proteinuric DKD (P-DKD) and non-proteinuric DKD (NP-DKD). Methods: We analyzed articles published globally from 2000 and 2024. Results: Individuals with NP-DKD generally have lower blood pressure levels and a more favorable lipid profile. In contrast, histological studies show that P-DKD is associated with more severe glomerulosclerosis, mesangial expansion, arteriolar hyalinosis, interstitial-fibrosis/tubular atrophy, and immune complex deposits. Additionally, those with P-DKD are more likely to develop diabetic retinopathy and have a higher risk of all-cause mortality and progression to ESKD. Strategies to slow DKD progression, applicable to both NP-DKD and P-DKD, include non-pharmacologic and pharmacologic interventions such as renin-angiotensin system blockers, sodium-glucose co-transporter-2 inhibitors, finerenone, and glucagon-like protein receptor agonists. Conclusions: NP-DKD and P-DKD represent different presentations of the same underlying disease.