Overview of pathophysiology, diagnosis, biomarkers, treatment and recent advances in the management of diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is the most common devastating complication of diabetes mellitus and prime etiology of end stage renal disease (ESRD). Age, genetic predisposition, poor glycemic control, uncontrolled blood pressure, dyslipidemia, obesity, smoking are major risk factors. Hyperglycemia is the primary pathogenic factor for activation and maintenance of molecular signaling pathways involving activation of renin-angiotensin-aldosterone system (RAAS), reactive oxygen species (ROS) and inflammatory cytokine production which play a key role in development of Diabetic kidney disease (DKD). Tubuloglomerular feedback (TGF) causes afferent arteriole dilatation, while RAAS activation leads to vasoconstriction of efferent arteriole which aggravates and sustains the glomerular hypertension may further worsen the nephropathy. Diagnosis is based on estimated glomerular filtration rate (eGFR) and albuminuria. Newer biomarkers are being investigated to detect DN in early stages even before Microalbuminuria (MA). Optimal glycemic control , blood pressure control and Renin Angiotensin System (RAS) blockers play a role in delaying the progression however newer therapies may address the unmet needs for prevention of DN.