How do Kidneys Progress into Renal Failure?
As renal fibrosis progresses, renal function will decline. Renal fibrosis is a kind of physio pathologic change as well as a progressive process that renal function develops from health to damage, from damage to renal loss. Due to injury, infection, inflammation, blood circulatory disorder, immune reaction and stimulation of other pathogenic factors, renal intrinsic cells will be damaged. As the damage progresses, there will appear deposition and accumulation of abundant collagen which causes renal parenchyma gradually hardens and forms scar, finally renal function will lost completely. The process of fibrosis and hardening of renal intrinsic cells is also the process of renal fibrosis. The unique theory summarized above is called renal fibrosis theory.
The point of treating kidney diseases is to block the process of renal fibrosis and hold back kidneys moving towards Renal Failure. While, how do the kidneys progress into Renal Failure?
1. When various primary or secondary pathologic damages cause local microcirculation dysfunction to damaged kidneys, it will lead to renal tissue—functional units of kidneys ischemia and hypoxia.
2. Endothelial cells on renal blood vessels will be damaged due to ischemia and hypoxia.
3. Once renal capillary endothelial cells are damaged, they will attract inflammatory cells in blood circulation and release pathogenic inflammatory mediators such as IL-1, TNF-αetc, thus starting the process of renal fibrosis. The manifestation of pathological damage is inflammatory reaction of damaged kidneys. At this time, there will appear partial pathological changes to glomerulus, such as mesangial cells proliferation, extracellular matrix (ECM) increased, changes of glomerular basement membrane (GBM). Changes of GBM include filtration holes enlarge or shut up, GBM breaks, charge barrier is damaged and renal permeability strengthens. Therefore, in this stage, there will appear Proteinuria and blood urine, and then glomerulus will gradually progress into renal fibrosis and hardening.
4. Once renal fibrosis has been started, there will continuously generate and release a series of renal toxic factors and growth factors like PDGF and TGF-β.
5. These renal toxic factors can lead to renal functional cells such as mesangial cells, epithelial cells and fibroblast, occur phenotypic transformation.
6. These renal functional cells especially fibroblast, when their phenotype is transformed, will secret and synthesize a series of fibrous collagen proteins like extracellular matrix (ECM) which are not easily to be degraded.
7. The continuous increase of ECM break the dynamic balance mechanism of ECM synthesis and degradation, resulting in ECM synthesis increases while degradation declines. It will finally lead to abundant deposition and accumulation of ECM.
8. Due to abundant deposition and accumulation, the accumulated ECM will replace healthy kidney units, leading continuous glomerulus hardening and tubulointerstitial fibrosis and renal blood vessels fibrosis.
9. The progress of renal fibrosis causes gradual decrease of kidney units. The continuous decline of renal function will finally lead to the formation of scar tissue; all functional kidney units will be destroyed and lost their function. When this state occurs, in clinical kidneys will develop into the end stage of Renal Failure—Uremia.
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