Author: Leo
Keywords: transplantation kidney | renal interstitial fibrosis | renal
transplantation | perfusion therapy | mycophenolic acid
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| From google images |
Chronic renal allograft nephropathy (CAN) is the most important cause of long-term renal failure, often months after transplantation to several years, the main pathological changes include glomerular sclerosis, renal interstitial fibrosis and tubular atrophy The Other Xu et al. Found that reducing osteopontin (OPN) in vivo can significantly inhibit epithelial cell transdifferentiation of mesenchymal cells, reduce renal interstitial fibrosis, and delay the progress of CAN.
treatment
Renal interstitial fibrosis is one of the main pathological changes of CAN, and it is also a key factor to determine the long-term prognosis of renal transplantation. Decreasing renal interstitial fibrosis is of great significance to improve long-term survival of transplanted kidney. Therefore, the development of inhibition or even reverse the treatment of renal interstitial fibrosis treatment has important clinical significance.
Immunotherapy
Rapamycin (RAPA) RAPA is considered to be a promising immunosuppressive drug, and has been completed in a multi-center clinical study of multiple organ transplants. Compared with the classic neurofilm A inhibitor drugs, RAPA can slow the development of renal interstitial fibrosis, the mechanism is as follows: (1) inhibition of epithelial cells to mesenchymal cell transdifferentiation process; (2) reduce the foot (3) regulation of extracellular matrix deposition, reduction of plasminogen activator inhibitor 1 (VEGF), inhibition of VEGF-mediated podocytes, endothelial cells and mesangial cell proliferation; (3) regulation of extracellular matrix deposition, PAI-1) gene expression, reduce renal interstitial fibrosis and glomerular sclerosis.
As a result, the use of RAPA in immunosuppressive regimens is increasing. In the future, further research on RAPA-induced proteinuria toxicity is needed.
(MMF) MMF is a synthetic prodrug of mycophenolate mofetil (MPA). MPA is a noncompetitive and reversible inhibitor of hypoxanthine nucleotide dehydrogenase (IMPDH), which is a highly specific and highly selective anti-proliferative effect on lymphocytes and becomes a rejection after renal transplantation One of the main drugs.
Recently, Jmng found that MMF can also significantly improve the ischemia-reperfusion injury in the transplanted renal function, reduce the renal interstitial fibrosis. Not only that, other IMPDH inhibitors, such as BMS-566419, can also produce a similar effect of MMF to slow down renal interstitial fibrosis, suggesting that MMF drugs may be a potential drug for the treatment of renal interstitial fibrosis.
New immunosuppressive agents Recent studies have shown that new immunosuppressive agents such as Belatacept.4SC-101 and FR276457 can be used not only in the treatment of autoimmune diseases, but also in the field of organ transplantation; and to confirm that these drugs are slowing the graft Fibrosis has great potential.
LEA29Y (Belatacept) is a T cell co-stimulatory pathway blocker that blocks the binding of CD28 to B7 molecules as a cytotoxic T cell-associated antigen 4 fusion protein (CTLA4-Ig, abatacept) Compared with cyclosporine, Belatacept can increase the expression of Fork-box protein 3, reduce the senescent cells in the transplanted kidney, slow down the renal interstitial fibrosis, and improve the survival rate of the transplanted kidney.
The US Food and Drug Administration approved the use of Belatacept as a prophylactic agent for adult organ transplant rejection in June 2011. Belatacept is expected to be widely used in the treatment of renal allograft rejection and transplanted renal interstitial fibrosis.
4SC-101 is a novel dihydrotidic acid dehydrogenase inhibitor that inhibits the secretion of interleukin-17 in inflammatory bowel disease. It has been reported that 4SC-101 prolongs the survival rate of the transplanted kidney, relieves the acute rejection and delays the process of proteinuria and renal fibrosis. In addition, Kinugasa et al. Found a pan-protein deacetylase inhibitor, the FR276457, which protects the transplanted kidney by inhibiting monocyte chemoattractant protein 1 against the transplanted renal interstitial fibrosis.
(ACEB) / angiotensin II receptor antagonist (ARB) renin-angiotensin system can be activated by elevated transforming growth factor beta (TGF-β) and inflammatory factors; The use of ARB in animal models to selectively block angiotensin receptor can reduce the level of TGF-β, inhibit renal interstitial fibrosis, improve the survival rate of the transplanted kidney.
Recently, the findings were confirmed by clinical randomized controlled trials, and can be better control of postoperative patients with hyperuricemia and hyperkalemia clinical renal transplant recipients after the use of ACEI / ARB drugs, the proposed periodic detection of serum creatinine And potassium, while limiting the intake of potassium, if necessary, oral diuretics.
Physiotherapy
Anesthesia in the field of inert gas widely used - xenon can reduce renal ischemia-reperfusion injury, and reduce renal cell apoptosis and inflammation, inhibition of T lymphocyte infiltration and interstitial fibrosis, slowing the transplantation of renal interstitial fibrosis ; Low-dose laser treatment by inhibiting tubule cell transdifferentiation and inflammation slow down renal interstitial fibrosis. But the clinical need to further confirm the exact role of these methods.
The main mechanism is to promote the production of hepatocyte growth factor and bone morphogenetic protein (7), and to reduce the proliferation of renal tissue, and to promote the proliferation of renal interstitial fibrosis and inflammation. The main mechanism is to promote the production of hepatocyte growth factor and bone morphogenetic protein 7, Outer matrix fibronectin and type Ⅳ collagen content.
The future should be in-depth study of its pharmacokinetics in the human body and the best drug treatment program to further improve the traditional Chinese medicine in organ transplantation in the treatment of the status.
Stem cell therapy
In the field of organ transplantation, the development of mesenchymal stem cells (MSC) is very rapid, mainly due to its in vivo and in vitro to show the immune suppression and its reproductive potential. The human body with multi-directional differentiation of MSC mainly from umbilical cord blood and umbilical cord tissue, placental tissue and bone marrow.
Studies have shown that intravenous infusion of human saddle MSC into the treatment of renal interstitial fibrosis is safe and feasible; and autologous bone marrow MSC perfusion treatment of renal interstitial fibrosis in the human body was also confirmed as safe and feasible.
Although MSC perfusion therapy has not been used clinically, it may provide a new insight into the future treatment of renal interstitial fibrosis. But its potential toxicity, tumor cell contamination risk and ethical issues are urgent to be solved.
Other Xu et al. Found that reducing osteopontin (OPN) in vivo can significantly inhibit epithelial cell transdifferentiation of mesenchymal cells, reduce renal interstitial fibrosis, and delay the progress of CAN.
In addition, it has been found that galectin 3 (Gal-3) can be expressed in a variety of fibrous organs; and Gal-3 on renal tubular protection, can reduce myofibroblast activation, inhibition of type I collagen Synthesis, thereby reducing renal interstitial fibrosis. Thus, suggesting that OPN and Gal-3 may serve as a new target for future treatment of renal interstitial fibrosis.
Summary
Studies on the diagnosis and treatment of renal interstitial fibrosis from different levels of genes, molecules, etc. have made encouraging progress, many of which have entered clinical trials or have been widely used.
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