Basic And Clinical Studies On Early Stage Kidney Non-function Following Kidney Transplant

PartⅠPossible mechanisms of the protect effect of PGE1 on expressionof the adhesion molecules and MHC molecules of glomerulus'sendothelial cells and renal transplant.Background: The variability of nerves and body fluids in brain death donors will cause vaso-constract of brain death organs, which reduces bloodstream, then it brings about ischemia/reperfusion injury. Some researches document that expression of adherins and cytokines upregulated in kidneys after reperfusion and expression of E-selection in endothelium up-regulates after oxygen is resupplied, hypoxia will stimulate the up- regulation of P-selection. LO et al reported that the robust expression of ICAM-1 is following hypoxia/ reaeration. Prostaglandin E1 is an endogenous vasodilatation factor, it works under ex vivo condition of low temperature and reduces vasoconstract, and as a result, PGE1 can reduce the injury of ischemia/reperfusion. in the meantime, PGE1 mediates vasodilatation , which benefit the nutrition diffusion to tissue from perfusion solutions and metabolite discharge from tissue, PGE1 can reduce concentration of calcium ion and injury of cells and organelles , PGE1 is lowly produced in the case of hypoxia . When added to low-temperature perfusion and storage solutions, it will better the kidney perfusion by inhibiting coagulation of platelet and dilating blood capillary, it increases the activity of adenylate cyclase and stabilize endothelium and membrane of smooth muscle. Moreover, PGE1 blocks neutrotaxis and inhibits activity oxygen free radicalexcretion of neutrophilic granulocytes. So we try to find the possible mechanisms of the protect effect of PGEl on renal transplant.Object and methods: In vitro, lmmunohistochemistry was applied to detect the expression of the adhesion molecules (ICAM-1, P-Selectin, E-Selectin, MHC-II DR) on the anoxia cultured glomerulus's endothelial cells; In vivo, the donor kidneys were preserved with or without PGEl, post transplantation, the Acute rejection rate(RAR), Delayed graft function rate(RoGF) and early graft dysfunction rate(REGD) were recorded.Results: The expression of the molecules were decrease after cultured with PGEl (0.5703 ±0.0473 Vs 0.6585 ±0.0296; 0.4596 ±0.0517 Vs 0.5297 ±0.0479; 0.2098 ±0.0513 Vs 0.3296 ±0.0847; 0.259 ±0.0463 Vs 0.4933 ±0.0571, p<0.05) ; After perfusion with PGEl, the Rar, Rdgf decreased significantly.Conclusions: PGEl may attenuate the ischemia /reperfusion injury, diminish the acute rejection, and protect renal graft through the following mechanisms: 1.improves the microcirculation of the graft; 2. inhibits the expression of adhesion molecules and MHC molecules.Part Ⅱ.Applying Doppler ultra-sonography screening and Percutaneoustransluminal renal angioplasty and stenting on patients withTransplant renal artery stenosisBackground: Transplant renal artery stenosis is the significant cause of bringing about early transplant failure and death with functionary graft, prevention, early detection and duly treatment will benefit the transplant and survival rate of transplanted recipients, DU is one of methods which screen TRAS non-invasively and it can show the variability of kidney morphology and kinetic bloodstream in kidney arterial stenosis.Data reported that the patients'PSV increased during the period of constract and resistant index decreased, it demonstrated that bloodstream increase at the site of TRAS and perfusion of kidney cortex decreases, demonstration of PSV > 150cm/sec and RI < 0.5 shows that the area of TRAS is approximately 50%(sensitivity90-100%,specificity 87-100%).The researches document that due to the need of determining TRAS diagnosis and subsequent detection of TRAS, the morbidity of TRAS is 2.4%. But it is 12.4% through routine screening, in some cases, it shows no clinic manifestation, TRAS is possible to be detected because of other reasons, some severe complications will come out following operational interventions, the rate of graft loss is 15-20%, the injury rate of ureteris 14%,the rate of reoperation and mortality is 13%, 5% ,respectively. TRAS is effectively treated by kidney artery angioplasty and stent insertion, these interventions are at low risk.This part focused on finding a method to make an early diagnosis and intervention for patients with transplant renal artery stenosis.Objects and methods: Applying Doppler ultrasonography screening and Percutaneous transluminal renal angioplasty on patients with Transplant renal arterystenosis, and the clinical and dynamic parameters were recorded at the baseline of pre-stenting and changes post-stenting.Results: All the 12 patients accept Percutaneous transluminal renal angioplasty and stenting, The procedure was a technical success with no residual stenosis in all patients. The clinical and dynamic indexes improved and transplant kidneys function well.Conclusions: Doppler ultrasonography screening is a reliable, noninvasive, and readily available tool for identifying subjects who may benefit from renal artery stenosis revascularization and for assessing the effectiveness of the procedure; Percutaneous transluminal renal angioplasty and stenting can be a good way to gain good function for the patients with Transplant renal artery stenosis occurred resently.Part ⅢThe effect of the combined regimen of Rapamycin and Cyclosporine on renal transplant recipientsBackground: Acute rejection exerts severely adverse effects to the long-term and short-term survival to kidney transplant , it is one of most important reasons of leading to the transplant dysfunction and graft loss, prevention of acute rejection is critical to reducing early renal graft dysfunction and to increasing the long-term survival rate of kidney transplant. Clinically, monitoring HLA type and immunosuppression will attain the goal of preventing and treating acute rejection, the reduction of early renal graft loss Post-transplantation is dependent on the active and effective prevention and treatment of acute rejection, with the global application of calcineurin , its pronounced kidney toxicity comes gradually out, it displays toxicity , especially when the transplanted kidneys begin to function. Overdosage of cyclosporine will cause the acute tubular necrosis, or failure of kidney function. Any immunosuppressant displays toxicity and side-effect. So we try to seek for the newer and better immunosuppressants to reduce or replace calcineurin for reducing toxicity and side-effects. Combination of immunosupressants is clinically applied to inhibiting and blocking the multiple mechanism of rejection, which will exert the most satisfactory effect of immunosuppression and reduce single dosage. Studies indicate that rapamycin is a potent immunosuppressant and lowly toxic to kidney.This part was designed to observe the effect of the combined regimen of Rapamycin and Cyclosporine on renal transplant recipients.Objects and Methods: The recipients from 2004-01-01 to 2004-08-01 were divided into two groups, group A were given 'CsA+MMF+Pred' regimen, group B were given the 'CsA+RAPA+Pred' regimen, the rate of acute rejection, infection, malignancy and the time of the rejecton onset and renal function were recorded.Results: Group B had a lower acute rejection rate (7.0% VS 20.9%), delayed onset of the rejection(44.3±6.24 VS35.0±5.48d) and earlier renal function(4.8±2.04VS5.9±2.1d).Conclusion: 'CsA+RAPA+Pred' regimen could be a good protocol for better results for renal transplants.