Nine Steps about How ESRF Happens

Several reasons trigger ESRF (End-stage Renal Failure), one of the major culprits is fibrosis. It is a fatal disease and would leave the patients in dangerous situation. However, the disease has some certain steps. By knowing the steps, we can detect the disease in early stage. Nine steps are:

1. Partial microcirculatory disturbance of damaged kidneys results from a variety of pathological damages (primary or secondary damages) incurs ischemia and oxygen deficit of kidney tissues.

2. Ischemia and oxygen deficit impair your vascular endothelial cells in kidneys.

3. Once the endothelial cells in kidney capillary vessels have been damaged, attracting the infiltration of inflammatory cells in blood circulation, in the meantime, morbigenous inflammatory mediators (IL-1 and TNF-α etc.) are released, which triggers the renal fibrosis. The pathological damages are responsible for the inflammation response of damaged kidney.

Local pathological changes of glomerulus would appear for the time being: Mesangial cell proliferation, mesangial matrix increasing.

Changes in glomerular basement membrane: filtered holes enlarge or shut; glomerular basement membrane ruptures; electrostatic barrier damages; permeability of kidneys strengthens.
Consequently, proteinuria and hematuria appear in clinic during this time, glomerulus would gradually progress to fibrosis and hardening afterwards.

4. Once renal fibrosis has been triggered, a series of cell factors and growth factors (PDGF and TGF-β) of renal toxicity are produced and released successively.

5. Those factors with renal toxicity would incur phenotype transdifferentiation of kidney functional cells (mesangial cells, epithelial cells and mechanocyte).

6. Phenotype of mechanocyte especially those in renal interstitium have been transformed, and then a series of uneasy degraded collagen fibrins (extracellular matrix--ECM) have been secreted and synthesized.

7. Owing to the increasing secretion of ECM, dynamic equilibrium mechanism fails to maintain the synthesis and degradation of ECM in kidneys, which is responsible for the reduction of synthesis and decrease of degradation to extracellular matrix in the kidneys, leading to a great amount of extracellular matrix to deposit and gather.

8. Owing to abundant deposition and aggragation of extracellular matrix, collective ECM replace the healthy functional nephrons accordingly, which results in the continuous hardening of glomerulus along with interstitial fibrosis as well as renal vascular fibrosis of renal tubulus.

9. The progressive fibrosis of kidneys causes functional nephrons decreasing, together with the persistent loss of renal function, consequently, fibrosis progresses to cicatrical tissues in the long run. Under this condition, End-stage Renal Failure--end-stage renal failure occurs eventually as functional nephrons are impaired completely and lost their function.