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      OKT3 therapy in addition to tacrolimus is associated with improved long-term function in patients with steroid refractory renal allograft rejection.

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          The aim of this study was to evaluate long-term allograft salvage rates of patients with steroid refractory allograft rejection after kidney transplantation and to identify factors indicating a successful outcome.

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          Prediction of Creatinine Clearance from Serum Creatinine

          Donald W Cockcroft, Henry Gault (1976)
          A formula has been developed to predict creatinine clearance (C cr ) from serum creatinine (S cr ) in adult males: Ccr = (140 – age) (wt kg)/72 × S cr (mg/100ml) (15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18–92. Values for C cr were predicted by this formula and four other methods and the results compared with the means of two 24-hour C cr’s measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr·s of 0.83; on average, the difference between predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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            Rituximab as treatment for refractory kidney transplant rejection.

            Bryan N Becker, H Sollinger, John D Pirsch … (2004)
            Recent studies have shown that a high density of CD 20+ cells are seen in patients who have steroid-resistant rejection episodes. Rituximab is a high-affinity CD-20 specific antibody that inhibits B-cell proliferation while inducing cellular apoptosis. Thus, it is a rational choice for therapy in transplantation to abrogate B-cell-mediated events. Twenty-seven patients were diagnosed with biopsy-confirmed rejection manifested by thrombotic microangiopathy and/or endothelialitis between 2/99 and 2/02 at our institution. These individuals were treated with a single dose of rituximab, in addition to other therapies, in an effort to reverse their rejection episodes. Twenty-four received additional steroids while 22 of the 27 patients were also treated with plasmapheresis and antithymocyte globulin (ATG). Only three patients experienced graft loss not associated with patient death during the follow-up period (605 +/- 335.3 days). In the 24 successfully treated patients, the serum creatinine at the time of initiating rituximab therapy was 5.6 +/- 1.0 mg/dL and decreased to 0.95 +/- 0.7 mg/dL at discharge. The addition of rituximab may improve outcomes in severe, steroid-resistant or antibody-mediated rejection episodes after kidney transplantation.
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              Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action.

              Jennifer Davis, L Czer, A Quartel … (1998)
              Intravenous gammaglobulin (i.v.IG) contains anti-idiotypic antibodies that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo. In addition, highly HLA-allosensitized patients awaiting transplantation can have HLA alloantibody levels reduced dramatically by i.v.IG infusions, and subsequent transplantation can be accomplished successfully with a crossmatch-negative, histoincompatible organ. In this study, we investigated the possible use of i.v.IG to reduce donor-specific anti-HLA alloantibodies arising after transplantation and its efficacy in treating antibody-mediated allograft rejection (AR) episodes. We present data on 10 patients with severe allograft rejection, four of whom developed AR episodes associated with high levels of donor-specific anti-HLA alloantibodies. Most patients showed rapid improvements in AR episodes, with resolution noted within 2-5 days after i.v.IG infusions in all patients. i.v.IG treatment also rapidly reduced donor-specific anti-HLA alloantibody levels after i.v.IG infusion. All AR episodes were reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients, some with up to 5 years of follow-up. Results of protein G column fractionation studies from two patients suggest that the potential mechanism by which i.v.IG induces in vivo suppression is a sequence of events leading from initial inhibition due to passive transfer of IgG to eventual active induction of an IgM or IgG blocking antibody in the recipient. I.v.IG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to i.v.IG therapy.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Nephron Clin Pract
                Title: Nephron. Clinical practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                ISSN (Print): 1660-2110
                Publication date (Electronic): 2006
                Volume: 103
                Issue: 3
                Affiliations
                [1 ] Department of Nephrology, School of Medicine, University of Duisburg-Essen, Essen, Germany.
                Article
                Publisher Item ID: 92017
                DOI: 10.1159/000092017
                PubMed ID: 16534238
                SO-VID: 3d994ee0-694b-4613-bdeb-7d7f87c21a2d
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