Diabetic Nephropathy

Definition 
Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.

Prevalence 
It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.

Pathophysiology 
• Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. 
• Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar vasodilation. 
• This raises intraglomerular capillary pressure, placing mechanical stress on the filtration barrier. 
• At the same time, non-enzymatic glycation of proteins within the glomerular basement membrane (GBM) and mesangium alters their structure and function. 
• These changes cause the loss of the GBM's negative charge, increased membrane permeability, mesangial matrix expansion, and eventually glomerulosclerosis. 
• The first clinical indicator is microalbuminuria, defined as urinary albumin excretion of 30–300 mg/day. 
• Progression to macroalbuminuria (≥300 mg/day) reflects more extensive glomerular injury. 
• Albuminuria results from structural disruption and impaired charge selectivity of the GBM. 
• Ongoing injury leads to a decreased glomerular filtration rate (GFR), often accompanied by systemic hypertension, which accelerates nephron loss. 
• Without intervention, this process culminates in ESRD.

Clinical Relevance 
• Monitoring albuminuria and estimated GFR is essential for early detection. 
• Optimal glycemic and blood pressure control and renin–angiotensin system blockade can slow disease progression.