2.26
Diabetic nephropathy is a chronic microvascular complication of diabetes driven by prolonged hyperglycemia and associated metabolic and hemodynamic changes within the kidney.
In early stages, hyperglycemia increases tubular reabsorption, triggering renal feedback–mediated afferent arteriolar vasodilation and glomerular hyperfiltration.
The resulting intraglomerular hypertension mechanically injures the filtration barrier.
In parallel, nonenzymatic glycation of basement membrane and mesangial proteins thickens and stiffens the glomerular basement membrane while reducing its negative charge selectivity.
This process reduces the negative charge of the glomerular basement membrane, decreasing repulsion of negatively charged proteins like albumin.
Microalbuminuria initially develops and progresses to macroalbuminuria as injury advances.
Persistent damage expands the mesangial matrix and produces diffuse and nodular glomerulosclerosis, steadily reducing the glomerular filtration rate.
This promotes sodium retention and RAAS activation, leading to hypertension and progressive nephron loss.
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.
Diabetic nephropathy is a chronic microvascular complication of diabetes driven by prolonged hyperglycemia and associated metabolic and hemodynamic changes within the kidney.
In early stages, hyperglycemia increases tubular reabsorption, triggering renal feedback–mediated afferent arteriolar vasodilation and glomerular hyperfiltration.
The resulting intraglomerular hypertension mechanically injures the filtration barrier.
In parallel, nonenzymatic glycation of basement membrane and mesangial proteins thickens and stiffens the glomerular basement membrane while reducing its negative charge selectivity.
This process reduces the negative charge of the glomerular basement membrane, decreasing repulsion of negatively charged proteins like albumin.
Microalbuminuria initially develops and progresses to macroalbuminuria as injury advances.
Persistent damage expands the mesangial matrix and produces diffuse and nodular glomerulosclerosis, steadily reducing the glomerular filtration rate.
This promotes sodium retention and RAAS activation, leading to hypertension and progressive nephron loss.
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