Type 2 diabetes mellitus with chronic kidney disease: an updated narrative review of pathophysiology, diagnosis, and contemporary cardio-renal management

Doi: https://doi.org/10.55522/ijti.v4i3.0156

Abstract

Type 2 diabetes mellitus complicated by chronic kidney disease represents a high-risk cardio-renal-metabolic condition associated with progressive kidney function decline, cardiovascular events, heart failure, hospitalization, therapeutic complexity, and premature mortality. Although diabetic kidney disease was traditionally viewed as a microvascular complication mainly driven by chronic hyperglycemia, current evidence indicates that its development and progression result from complex interactions among metabolic, hemodynamic, inflammatory, fibrotic, and cardiovascular mechanisms. Persistent hyperglycemia, insulin resistance, glomerular hyperfiltration, renin–angiotensin–aldosterone system activation, oxidative stress, endothelial dysfunction, podocyte injury, tubular damage, and interstitial fibrosis collectively contribute to albuminuria, reduced estimated glomerular filtration rate, and eventual kidney failure.

Early detection is essential because kidney damage may remain clinically silent for years. Assessment using both estimated glomerular filtration rate and urinary albumin-to-creatinine ratio provides more accurate risk stratification than either parameter alone. As kidney function declines, glycemic assessment and treatment become increasingly complex because anaemia, altered red blood cell turnover, reduced insulin clearance, drug accumulation, comorbidities, and frailty may increase glycemic variability and hypoglycemia risk.

Recent therapeutic advances have shifted management from glucose-centred treatment toward comprehensive cardio-renal-metabolic protection. Sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists provide clinically meaningful benefits beyond glycemic control, including slowing kidney disease progression, reducing albuminuria, lowering heart failure risk, and improving cardiovascular outcomes. This review summarises current understanding of the epidemiology, pathophysiology, diagnosis, risk stratification, and contemporary management of type 2 diabetes complicated by chronic kidney disease, emphasizing early screening, individualized therapy, multidisciplinary care, and long-term organ protection.