Renal graft rejection

Recombinant human erythropoietin (epoetin and darbepoetin) provides effective therapy with a very favorable risk-benefit ratio in hemodialysis patients with end-stage chronic renal insufficiency, and in patients with progressive renal insufficiency who are not yet being dialysed (1). It improves cognitive function and the quality of life of patients with chronic uremia (2-5) and is very effective in children with chronic renal graft rejection and anemia (6). It also offers new opportunities for treating anemia in non-uremic patients. In patients with chemotherapy-induced anemia, epoetin increases hemoglobin concentration, reduces transfusion requirements, and improves quality of life (7,8). The response rate to epoetin in patients with multiple myeloma and anemia, which is 55-85% (9), increases when GM-CSF or G-CSF is... 

Georgitis JW, Browning MC, Steiner D, Lorentz WB. Anaphylaxis and desensitization to the murine monoclonal antibody used for renal graft rejection. Ann Allergy 1991 66(4) 343-7. 

Renal transplant pahents with hepatitis C seem to be especially susceptible to injury from IFNa. IFNa triggers renal graft rejection in a substantial number of patients, and is now considered contra-indicated in this setting [58, 59]. 

Stockenhuber, F., Steininger, R., Apperl, A., Muehlbacher, F., Patek, E., Sautner, T., Sertl, K., Graninger, W., Hauser, A. C., and Baicke, P. Soluble interleukin-2 receptor A novel parameter of renal graft rejection. Transplant. Proc. 22, 165-166 (1990). 

Since the identification of PAF in the early 1970 s, the autacoid has steadily emerged as a crucial mediator of diverse pathologies. Indeed, PAF is a potent mediator of anaphylaxis and inflammation and is also implicated in shock, graft rejection, renal disease, ovoimplantation and certain disorders of the central nervous system (CNS) [36,44]. There is also accumulating evidence that PAF is capable of modulating the immune response [45, 46]. 

It is a cyclic polypeptide with 11 amino acids. It selectively inhibits T-lymphocytes proliferation, IL-2 and other cytokine production. It is the most effective drug for prevention and treatment of graft rejection reaction. It is used in cardiac, hepatic, renal, bone marrow transplantation and as second line drug in rheumatoid arthritis, inflammatory bowel disease, dermato-myositis, bronchial asthma and certain other autoimmune diseases. 

Indication Prophylaxis of graft rejection in patients receiving renal and cardiac allogeneic transplantation... 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

Markert UR, Klemm A, Flossmann E, Werner W, Sperschneider H, Funfstuck R. Renal transplantation in early pregnancy with acute graft rejection and development of a hydatidiform mole. Clin Nephrol 1998 49(6) 391-2. 

Ekberg H, Swensson PJ, Simanaitis M, et al, Factor V R506Q mutation (activated protein C resistance) is additional risk factor for early renal graft loss associated with acute vascular rejection, Transplantation 2000 69(8) I 577-1 581. 

M. Moran, et al., Prevention of acute graft rejection by the prostaglandin El analogue misoprostol in renal transplant recipients treated with cyclosporine and prednisone. N. Engl. J. Med. 322 1183-1188, 1990. 

Calcium channel blockers are given to transplant patients for their protective effect against cidosporin-induced nephrotoxicity and to optimize ciclosporin immunosuppression in order to reduce early rejection of renal grafts. Nifedipine has been used to treat cidosporin-induced hypertension, although amlodipine may be just as effective (185). 

Large-scale studies with long periods of follow-up have emphasized the major role of graft arteriopathy (chronic graft rejection) rather than chronic ciclosporin nephrotoxicity as the primary cause of graft failure (111,116,141). Severe ciclosporin nephropathy was the cause of renal transplant failure in less than 1% of patients. 

Influenza infection has been a significant problem in cardiac transplant patients immunization of such patients could therefore be beneficial. However, its use has been limited by concern that stimulation of the immune system might in principle cause an increased risk of cardiac rejection. In the renal transplant experience, influenza infection itself can trigger an immunological response to cause graft rejection, as well as predisposing to other infections. Another concern is whether an immunosuppressed cardiac transplant recipient could seroconvert sufficiently. In a case-control study in 18 cardiac transplant recipients and 18 control patients 6 months or more beyond transplant surgery, there were no differences in the incidence of cardiac rejection or immune responses (28). 

Inolimomab Prevention ot graft rejection Keliximab Rheumatoid arthritis Muromonab Prevention ot acute renal allograft rejection Natalizumab Acute relapse in multiple sclerosis Crohn s disease... 

A 61-year-old Chinese renal transplant recipient, who had taken tacrolimns for 1 year after an episode of rejection had failed to respond to ciclosporin, took rifampicin and 12 days later had an episode of biopsy-proven graft rejection, associated with very low serum tacrolimus concentrations. 

Offermann G, Keller F, Molzahn M. Low cyclosporin A blood levels and acute graft rejection in a renal transplant recipient during rifampin treatment. Am J Nephrol 1985 5(5) 385-7. 

Kreis H, Cisterne JM, Land W, et al. Sirolimus in association with my-cophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 2000 69 1252-1260. 

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