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CHRONIC KIDNEY DISEASE PROGRESSION
Progression of Chronic Kidney Disease
The
rate of progression varies considerably between patients and
diseases, generally being faster in chronic glomerulonephritides
than in tubulointerstitial nephritides.
Mechanisms of Progression
The loss of filtration rate in chronic kidney
disorders is a consequence of progressive
glomerulosclerosis, tubulointerstitial fibrosis, and
vascular sclerosis. Glomerulosclerosis has been
attributed to immunological (glomerulonephritis),
haemodynamic (hypertension), or metabolic (diabetes
mellitus) insults leading to glomerular endothelial
injury. In surviving ('remnant') glomeruli, a
compensatory increase in intraglomerular capillary
pressure (glomerular hypertension) results from a
disproportionate afferent arteriolar vasodilatation
and the loss of autoregulation, exposing them to
systemic hypertension that in turn is associated
with endothelial damage. Injury to the glomerular
endothelium favours platelet adhesion, aggregation,
and the formation of glomerular microthrombi,
allowing the transudation of macromolecules,
including lipids and growth factors, into the
glomerular mesangium. These stimulate mesangial
proliferation and the increased synthesis of
extracellular collagenous matrix.
Tubulointerstitial scarring
There is a correlation between the severity of
tubulointerstitial scarring and GFR. Tubulointerstitial
inflammation and widespread interstitial fibrosis are markers of
a worse outcome in kidney disease: these are characterized by
inadequate healing with excessive collagen deposition and
involve interactions between kidney tubular cells, inflammatory
cells, and resident fibroblasts through the release of cytokines
and growth promoters.
Vascular sclerosis
The extent and severity of kidney vascular changes (arterial and
arteriolar) is also relevant to outcome. Although hyalinosis of
smaller kidney vessels is common in patients of all ages with
chronic kidney disease, severe arteriolar hyalinosis is often
seen in the kidney tissue of patients with chronic nephropathies
in the absence of significant systemic hypertension. Moreover,
the everity of these vascular changes is greater than that seen
in patients with essential hypertension. This arteriolar
hyalinosis further jeopardizes the glomerular and tubular blood
supply, causing ischaemic injury and further scarring.
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