Non-Albuminuric Diabetic Kidney Disease: Pathophysiology and Clinical Implications

Diabetic kidney disease traditionally progresses from glomerular hyperfiltration to albuminuria and kidney function loss. However, many individuals with type 2 diabetes mellitus develop reduced kidney function without increased urinary albumin excretion. This non-albuminuric phenotype accounts for approximately 20%–40% of diabetic kidney disease and 39%–55% of cases with reduced kidney function and is increasingly prevalent. Its emergence may reflect changes in disease biology and clinical management, including renin-angiotensin system blockade, improved cardiovascular risk factor control, and population aging. Histological, imaging, and biomarker studies suggest less prominent classic glomerular injury and greater contributions from intrarenal vascular disease, tubulointerstitial injury, and previous acute kidney injury. Kidney outcomes are generally more favorable than in albuminuric diabetic kidney disease, but associations with mortality remain inconsistent and may be influenced by coexisting cardiovascular disease. Treatment evidence is limited because most landmark kidney outcome trials preferentially enrolled patients with albuminuria, leaving uncertainty about optimal management. This review summarizes evidence on the epidemiology, pathophysiology, clinical characteristics, prognosis, and treatment of non-albuminuric diabetic kidney disease, highlighting its heterogeneity and clinical implications.