Diabetic nephropathy - early physiological changes (hyperfiltration)
Core concept
- Earliest physiological change in diabetic nephropathy is glomerular hyperfiltration, not the reverse
- Chronic hyperglycaemia -> afferent arteriolar vasodilatation exceeds efferent -> increased glomerular capillary pressure -> increased GFR (often supranormal in early diabetes, a paradox given the eventual outcome is renal failure)
- Sustained intraglomerular hypertension -> mechanical stress on the glomerulus -> mesangial expansion, glomerular basement membrane thickening, podocyte injury -> progressive microalbuminuria -> overt proteinuria -> declining GFR over years
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