Kidney transplantation acute rejection

Daclizumab Zenapax (PDL/Roche) Kidney transplant, acute rejection... 

The first clinical apphcation of psoralen and UVA radiation in transplantation was the treatment of kidney allograft acute rejection [168]. This first clinical attempt was performed using PUVA therapy on the donor kidneys previously to its transplantation into the patients. Importantly, fewer rejection episodes were reported in patient receiving treated organs compared with untreated counterparts after 3 months of the transplant. Furthermore, this... 

It is often difficult to differentiate ARF from acute rejection in the kidney transplant recipient, as both conditions may present with similar symptoms and physical examination findings. However, fever and graft tenderness are more likely to occur with rejection while neurotoxicity is more likely to occur with cyclosporine or tacrolimus toxicity. Kidney biopsy is often needed to confirm the diagnosis of rejection.42... 

The induction agents are highly immunosuppressive and, when given prior to some organ transplants (e.g., kidney transplant), allow for significant reductions in acute rejection... 

ORTHOCLONE OKT 3 Muronomab-CD3 Ortho Biotech Reversal of acute kidney transplant rejection, reversal of heart and liver transplant rejection... 

For short-term chnical interventions with the aim of protecting the kidney during acute reperfusion or preventing allograft rejection after transplantation, the prerequisite of parenteral administration does not constitute a serious limitation. 

Simulect/ BasUiximab MAb/IL2Ra acute kidney transplant rejection mouse myeloma 1998 USA... 

OKT-3 was first approved for general medical use in the USA in 1986. Its indication was the treatment of acute kidney transplant rejection (Table 10.4). OKT-3 is produced via ascites grown in mice. The intact antibody is subsequently purified by a combination of ammonium sulphate fractionation and anion exchange chromatography. Despite its therapeutic effectiveness, the product does display some limitations. Its antigenicity in humans (the HAMA response) is one obvious factor which limits its prolonged use. 

Basiliximab is a chimeric mouse-human monoclonal antibody to the IL-2Ra receptor of T cells and daclizumab (Zenapax) is a humanized monoclonal antibody against the same receptor. They prevent binding of interleukin-2 to the CD25 antigen on activated T-lymphocytes thus inhibiting T-lymphocyte proliferation. Like the similar drug basiliximab, daclizumab reduces the incidence and severity of acute rejection in kidney transplantation without increasing the incidence of opportunistic infections. 

Keown, P, and D. Niese, Cyclosporine microemulsion increases drug exposure and reduces acute rejection without incremental toxicity in de novo renal transplantation. International Sandimmun Neoral Study Group. Kidney Int, 1998. 54(3) 938-44. 

Recent data from a kidney pancreas induction study suggests that 2 doses of Daclizumab (2 mg/kg) at day 0 and day 14 is equivalent to 5 doses of 1 mg/kg every 14 days. (Stratta AJ, Alloway RR, Hodge E et al. A multicenter, open-label, comparative trial of two Daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney-pancreas transplant recipients interim analysis. Clin Transplant 2002 l6(l) 60-8.)... 

Simulect (Mab) Acute rejection kidney transplants Recombinant myeloma... 

Daclizumab is used for the prophylaxis of acute rejection in patients receiving kidney transplants. A dose of 1 mg/kg is sufficient to completely block all the IL-2 receptors. It is administered in five doses at a 2-week interval where its elimination half-life is about 20 days. A combination of several other immunosuppressive agents including cyclosporine (or tacrolimus, rapamycin), mycophenolate mofetil and corticosteroids can be used with daclizumab. When it is used in combination with tacrolimus, the doses of tacrolimus are reduced. After tissue transplantation, the addition of daclizumab to the standard immunosuppressive regimen produces reduction in tissue rejection up to 50%. Daclizumab can cause hypersensitivity reactions, but it does not cause cytokine-release syndrome. There is a low incidence of... 

Basiliximab is used for the prophylaxis of acute rejection for patients undergoing kidney transplantation where it is employed in combination with other standard immunosuppressive therapy regimens. After tissue transplantation, its addition to the standard immunosuppressive regimen results in inhibiting tissue rejection up to approximately 30%. Both daclizumab and basiliximab have similar effects on the expression of IL-2a and -(3 chains. 

A 60-year-old white man was admitted for kidney transplantation. Immediately after reperfusion and intravenous methylprednisolone 500 mg, he developed severe bradycardia with hypotension and then cardiac arrest. After resuscitation, his clinical state improved quickly, but on the morning of the first postoperative day directly after the intravenous administration of methylprednisolone 250 mg, he had another episode of severe bradycardia, hypotension, and successful cardiopulmonary resuscitation. A third episode occurred 24 hours later after intravenous methylprednisolone 100 mg, again followed by rapid recovery after resuscitation. Two weeks later, during a bout of acute rejection, he was given intravenous methylprednisolone 500 mg, after which he collapsed and no heartbeat or breathing was detectable after cardiopulmonary resuscitation he was transferred to the intensive care unit, where he died a few hours later. 

Muromonab-CD3 monoclonal antibody Orthoclone OKT3 Acute rejection of heart, liver, and kidney transplants... 

Webster A, Pankhurst T, Rinaldi F, et al. Polyclonal and monoclonal antibodies for treating acute rejection episodes in kidney transplant recipients. Cochrane Database Syst Rev. 2006 CD004756. 

Basiliximab Simulect Treatment of the acute rejection of kidney, heart and liver transplants 1998... 

Daclizumab Zenapax Prophylaxis of acute rejection after allogenic kidney transplantation 1997... 

The first therapeutic antibody approved (Orthoclone OKT-3 or Muromonab CD3, 1986) was indicated not for cancer treatment, but for controlling acute rejection of transplanted organs (kidney, heart, and liver). Nowadays, other clinical indications such as asthma, rheumatoid arthritis, psoriasis, and Crohn s disease are treated with mAbs (see Chapter 17) (Antibody Engineering and Manufacture, 2005 Monoclonal Antibodies and Therapies, 2004 Hot Drugs, 2004 Walsh, 2004). 

Orthoclone Okt3 Muromonab-CD3 Ortho Biotech 6/1991 Reversal of acute kidney transplant rejection NA... 

Qrthoclone OKT3 Monoclonal antibody Acute kidney transplant rejection... 

The effect of ketoconazole in ciclosporin-treated kidney transplant recipients has been the subject of a prospective randomized study (37). In 51 ketoconazole-treated patients and 49 controls there was a similar frequency of acute rejection episodes. However, in the control group, rejection episodes were more recurrent, with a poorer response to treatment. Acute ciclosporin nephrotoxicity was more common in the ketoconazole group, but this was encountered more at induction and rapidly reversed on further reduction of the dose of ciclosporin. Chronic graft dysfunction was significantly less in... 

---