Diabetic nephropathy pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Overview
Thickening of glomerular basement membrane, accumulation of eosinophilic material in the mesangium and intraglomerular hypertension are the major pathophysiologic changes taking place in the nephrons in long standing diabetes mellitus.
Pathophysiology
- The first renal abnormality seen in patients with diabetic nephropathy is hyperfiltration and intraglomerular hypertension.
- Microalbuminuria (serum albumin level:30 - 300 mg/dl) is the earliest abnormality noted in the urine. This change first appears approximately 5 years after diagnosis of diabetes mellitus. Although uncontrolled systemic hypertension, sustained high blood glucose levels and high serum cholesterole levels contribute to faster progression of damage to nephrons and earlier appearance of albumin in urine.
- This microalbuminuria is not detectable on routine protein dipstick.
- As the nephropathy progresses, systemic blood pressure more albumin is filtered across the glomerular membrane and ultimately reaches nephrotic range within the next 5 to 10 years.
- Accumulation of glycosylated proteins also damage the renal tubular epithelium causing type IV renal tubular acidosis, resulting in hyperkalemia.
Gross Pathology
- The kidneys look either normal or increased in size, in contrast to shrunken appearance in chronic renal failure (except amyloidosis and polycystic kidney disease cause chronic renal insufficiency although they result in increased renal dimensions).
Microscopic Pathology
- Earliest microscopic change seen in renal biopsy are thickening of glomerular basement membrane and accumulation of glycosylated proteins and eosinophilic material in the mesangium.
- With progression, the accumulation of extracellular matrix becomes more diffuse and nodular, called Kimmelstein-Wilson lesions.
- The renal arterioles shows thickening secondary to hypertensive arteriosclerosis and hyperlipidemia.
- On immunoflorescent microscopy, the GBM shows deposition of non-immunogenic IgG in a linear pattern.