Chronic kidney disease: mechanisms of hypoxic glomerulosclerosis and tubulointerstitial fibrosis development and progression
Abstract
The review summarized recent data on the causes of chronic tissue hypoxia that occurs in kidneys in CKD and the mechanisms of development and progression of hypoxic glomerulosclerosis and tubulointerstitial fibrosis. Causes of chronic renal hypoxia are associated with the failure of the oxygen delivery, consumption, and arteriovenous shunting in renal cortical layer. The leading role among them have hypoperfusion of postglomerular capillary network due to the sclerotic glomerular injury and postglomerular capillaries loss, and local oxidative/nitrozative stress development, which increases oxygen consumption by kidney tissue cells. Additional risk factors which contribute to chronic renal hypoxia are anemia and hypoxemia, which are included in the mechanism of nephropathy formation in CKD patients with severe CHF. Nuclear transcription factor HIF-1a is expressed in podocytes and epithelial cells of proximal tubules influenced by chronic tissue hypoxia. This factor initiates intracellular signal pathways leading to epithelial-mesenchymal transformation of these cells into profibrotic phenotype cells and accelerating the processes of glomeruli and tubulointerstitial tissue sclerotic injure of. Elucidation of the causes of chronic renal hypoxia and the mechanisms underlying the development and progression of hypoxic glomerulosclerosis and tubulointerstitial fibrosis will go to development new approaches to CKD renoprotective therapy.
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Review
For citations:
Kuzmin O.B. Chronic kidney disease: mechanisms of hypoxic glomerulosclerosis and tubulointerstitial fibrosis development and progression. Nephrology (Saint-Petersburg). 2015;19(4):6-16. (In Russ.)
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