Antibodies ; immunology ; Graft Rejection ; drug therapy ; immunology ; prevention & control ; Graft Survival ; immunology ; Humans

In the past 50 years, organ transplantation has developed from an improbable laboratory exercise to a major therapeutic success. The surgical problems of organ grafting have, for the most part, been solved. Rejection of grafts is now partially understood and usually controllable by powerful immunosuppressive drugs. A steady improvement in patient outcome, especially following the introduction of cyclosporin as an immunosuppressive agent has resulted in a worldwide shortage of organs for transplantation. This has provoked serious ethical dilemmas in every country. These matters are summarised in the following text.
Biomedical Research ; Cyclosporine ; pharmacology ; Graft Rejection ; drug therapy ; prevention & control ; Humans ; Immunosuppression ; Immunosuppressive Agents ; pharmacology ; Transplants ; ethics

OBJECTIVETo explore the effect of CD40 blockade in suppressing acute rejection of renal graft in rats.

METHODSWith Wistar rats as the donor and male SD rats as the recipients, rat models of acute renal graft rejection was established. The rat models were divided into therapy group and control group, and in the former group, CD40 ligand (CD40L) monoclonal antibody was injected daily for 4 consecutive days starting on the next day following kidney transplantation. On day 5 after the transplantation, the renal graft was harvested for histological examination, and graft rejection was evaluated semiquantitatively.

RESULTSThe mean semiquantitative score of the renal graft was 0.63∓0.52 in the therapy group, significantly lower than that of the control group (3.72∓1.48, P<0.05).

CONCLUSIONCD40L monoclonal antibody can inhibit acute renal graft in rats.

Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; CD40 Antigens ; antagonists & inhibitors ; immunology ; CD40 Ligand ; immunology ; Female ; Graft Rejection ; drug therapy ; prevention & control ; Graft Survival ; drug effects ; Kidney Transplantation ; adverse effects ; Male ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

OBJECTIVETo determine the optimal dose range (therapeutic window) of mycophenolate mofetil (MMF) for preventing acute graft rejection following renal transplantation.

METHODSThe trough concentration of MMF (MPA-C0) at 12 h after oral administration of the drug (two doses daily given at an interval of 12 h) was monitored in 110 renal transplant recipients within a month, in 2-3 months, and over 4 months after the transplantation using EMIT method. The occurrence of acute graft rejection and drug toxicity were observed in all the patients during the one-year follow-up.

RESULTSs The incidence of acute graft rejection after transplantation was 13.64% (15/110) in these patients. Drug toxicity and complications occurred in 32.73% (36/110) of the patients, including 12 cases with reduced white blood cell counts, 10 with MMF cid-associated diarrhea, 10 with infection, 4 with liver function damage. Acute rejection was successfully reversed after methylprednisolone treatment and drug toxicity was managed by corresponding treatment and adjustment of MMF dose. No deaths or graft removal occurred in these patients. The ROC curve showed that a MPA-C0 of 1.40-2.80 mg/L was optimal in preventing acute rejection after the transplantation and reducing adverse drug effects.

CONCLUSIONMonitoring MPA-C0 and individualized MMF dosing help to prevent acute graft rejection, reducing drug toxicity and complications, and improving graft survival rate after renal transplantation.

Graft Rejection ; drug therapy ; prevention & control ; Graft Survival ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Kidney Transplantation ; Methylprednisolone ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Survival Rate ; Time Factors

Aged ; Animals ; Cyclosporine ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Graft Rejection ; drug therapy ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; prevention & control ; Kidney Transplantation ; Phytotherapy

OBJECTIVETo observe and assess the immunosuppressive effect of applying bailing capsule (BLC, a dry powder preparation of Cordyceps sinensis mycelia), after renal transplantation, its influence on other systems of organism, and to explore the possible therapeutic mechanism.

METHODSOne hundred and twenty-one recipients of renal homo-allograft were randomly divided into two groups. The 64 cases in Group A was treated with cyclosporin A (Cs A) + prednisone (pred) + azathioprine (Aza), the 57 in Group B treated with Cs A + pred + BLC. They were followed-up for 1-2 year by checking up blood routine, urine routine, liver and renal function, blood electrolytes, glucose and lipids, and uric acid for 2 times every week in the first month after transplantation, followed by proper re-examination of these items according to various condition.

RESULTSThere was no significant difference between the two groups in aspects of graft survival rate, occurrence of reject reaction, renal function recovery, blood electrolytes and blood glucose levels. However, as compared with Group A, in Group B, levels of urinary erythrocytes and leucocytes, blood alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol, uric acid as well as the incidence of infection were significantly lower, and blood high density lipoprotein, serum total protein, albumin, RBC and WBC count were significantly higher.

CONCLUSIONBLC could effectively prevent the reject response after renal transplantation, protect renal and liver function, stimulate hemopoietic function, improve hypoproteinemia and hyperlipidemia, reduce the infection, etc., therefore, it is an ideal immunosuppressor after organ transplantation.

Adult ; Capsules ; Cordyceps ; Cyclosporine ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Glomerulonephritis ; drug therapy ; surgery ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; Male ; Phytotherapy ; Postoperative Period ; Prednisone ; therapeutic use

PURPOSE: The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. MATERIALS AND METHODS: This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. RESULTS: Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). CONCLUSION: Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.
Adult ; Drug Administration Schedule ; Female ; Graft Rejection/drug therapy/prevention & control ; Humans ; Immunosuppressive Agents/*administration & dosage/adverse effects/therapeutic use ; *Kidney Transplantation ; Male ; Middle Aged ; Safety ; Tacrolimus/*administration & dosage/adverse effects/therapeutic use

This study aimed to investigate the effect of bortezomib in the desensitization and treatment of acute antibody mediated rejection (AAMR) in kidney transplantation. Nine patients who received bortezomib therapy for desensitization (DSZ group, n = 3) or treatment of AAMR (AAMR group, n = 6) were included in this study. In the DSZ group, 2 patients required DSZ owing to positive cross match and 1 owing to ABO mismatch with high baseline anti-ABO antibody titer (1:1,024). Bortezomib was used at 1, 3, 8, and 11 days from the start of the treatment. In the AAMR group, 3 patients showed full recovery of allograft function after bortezomib use and decrease in donor specific anti-HLA antibody (HLA-DSA). However, 3 patients did not respond to bortezomib and experienced allograft failure. In the DSZ group, negative conversion of T-CDC (complement-dependent cytotoxicity) was achieved, and HLA-DSA was decreased to lower than a weak level (median fluorescence intensity [MFI] < 5,000) in 2 patients. In the case of ABO mismatch kidney transplantation, the anti-A/B antibody titer decreased to below the target (< or = 1:16) after bortezomib therapy. Therefore, bortezomib could be an alternative therapeutic option for desensitization and treatment of AAMR that is unresponsive to conventional therapies.
Adult ; Boronic Acids/*therapeutic use ; Desensitization, Immunologic/*methods ; Female ; Graft Rejection/*drug therapy/*prevention & control ; HLA Antigens/immunology ; Humans ; Kidney/surgery ; Kidney Transplantation/*methods ; Male ; Middle Aged ; Pyrazines/*therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the effect of HSGJ on chronic allograft nephropathy (CAN) using standard rat model of CAN.

METHODRenal transplantation was performed with Fisher rats as donors and Lewis rats as recipients. All the recipients were randomly divided into control group and medication groups (high and low dosage of HSGJ, fed every other day). After 16 weeks of treatment, renal function and the histological alteration of CAN were measured. The expression of the TGFbeta1 mRNA in the allograft was evaluated by real-time PCR.

RESULTThe content of 24 h urine protein and the level of serum creatinine in the medication groups were significantly decreased (P < 0.01) as compared with control group, whereas the creatinine clearance was increased (P < 0.01). The degree of glomerular sclerosis and the Banff score of medication groups were lower than the control group respectively (P < 0.01), in consistent with decreased expression of the TGF 1mRNA.

CONCLUSIONHSGJ can prevent the chronic allograft nephropathy and the mechanism may be related with its influence on the expression of the TGFbeta1.

Animals ; Chronic Disease ; Drugs, Chinese Herbal ; therapeutic use ; Glomerulonephritis ; etiology ; immunology ; prevention & control ; Graft Rejection ; drug therapy ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; adverse effects ; Random Allocation ; Rats ; Rats, Inbred F344 ; Rats, Inbred Lew ; Transplantation, Homologous

OBJECTIVETo report preliminary experience of the protocol of combining Campath 1H induction with low-dose monotherapy of tacrolimus and no steroid in two cases of small bowel transplantation.

METHODSCampath 1H 30 mg was infused during the small bowel transplantation, and the patients were given 1 gram of methylprednisolone followed by the Campath 1H and another gram of methylprednisolone before reperfusion. Tacrolimus was infused just after the reperfusion. The tacrolimus was administered from vein first and then from gut tract, the blood tacrolimus level was controlled at 10 to 15 microg/L within the first 3 months after the operation, and reduced to 5 microg/L thereafter.

RESULTSThe two recipients have survived more than 1 year, one received surgical closure of intestinal graft terminal stoma 13 months after the transplantation. One episode of indeterminate to mild acute rejection was verified by pathology through routine ileoscopical biopsy in each cases, and one episode of mild to moderate acute rejection occurred 8 months after the transplantation, and the patients recovered after low dose or bolus steroid therapy. The peripheral lymphocyte counts and monocyte counts decreased greatly after Campath 1H was given, and recovered very slowly thereafter. No sign of infection and graft versus host disease (GVHD) was found, and the grafted intestine achieved excellent function. The total parenteral nutrition was ceased on the day 21 and 14 after the operation, respectively, and the patients lived on oral intake to maintain nutrition status.

CONCLUSIONSIt's showed that the protocol combining Campath 1H induction with low-dose monotherapy of tacrolimus without steroid in small bowel transplantation can control graft rejection effectively without increasing the opportunity of infection, no sign of GVHD is found, and the grafted intestine could achieve excellent function.

Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Drug Therapy, Combination ; Female ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Intestine, Small ; transplantation ; Male ; Tacrolimus ; therapeutic use ; Young Adult