Lrisk Factors for Chronic Rejection in Renal Allograft Recipients

Almond, P. S.; Matas, Arthur J.; Gillingham, Kristen J.; Dünn, David L.; Payne, William D.; Gores, P. F.; Gruessner, R.; Najarían, John S.

doi:10.1097/00007890-199304000-00013

Cited by 632 publications

(241 citation statements)

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“…Increased morbidity and mortality associated with delayed graft function have been noted in clinical studies and represent a relationship between the condition of the engrafted tissue and the subsequent host response. 25,26 In European studies delayed graft function affects as many as 20 to 30% of cadaveric renal transplants. 27 Moreover, the increasing discrepancy between numbers of patients listed for transplantation and potential donors has necessitated the use of so-called suboptimal donors, ie, older than 50 years old and/or organs that have experienced more than 24 hours of cold ischemia.…”

Section: Discussionmentioning

confidence: 99%

Nontransgenic Hyperexpression of a Complement Regulator in Donor Kidney Modulates Transplant Ischemia/Reperfusion Damage, Acute Rejection, and Chronic Nephropathy

Pratt

Jones

Dong

et al. 2003

The American Journal of Pathology

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Complement activation during ischemia and reperfusion contributes to the development of tissue injury with severe negative impact on outcomes in transplantation. To counter the effect of complement, we present a strategy to deliver a novel complement regulator stabilized on cell surfaces within donor organs. The membrane-bound complement regulator is able to inhibit complement activation when the donor organ is revascularized and exposed to host-circulating complement. Application of this construct to donor kidneys protected transplanted tissues from ischemia/reperfusion injury and reduced the deposition of activated complement and histological signs of damage under conditions in which a nontargeted control construct was ineffective. Treatment of donor organs in this way improved graft performance in the short and long term. An analysis of the immune response in allograft recipients showed that reducing graft damage at the time of transplantation through complement regulation also modulated the alloresponse. Additionally, the results of perfusion studies with human kidneys demonstrated the feasibility of targeting endothelial and epithelial surfaces with this construct, to allow investigation in clinical transplantation.

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Section: Discussionmentioning

confidence: 99%

Nontransgenic Hyperexpression of a Complement Regulator in Donor Kidney Modulates Transplant Ischemia/Reperfusion Damage, Acute Rejection, and Chronic Nephropathy

Pratt

Jones

Dong

et al. 2003

The American Journal of Pathology

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“…However, despite recent advances in immunosuppression, acute rejection of the transplanted organ remains a major postoperative problem and is associated with a significantly increased risk for chronic graft rejection and graft loss. [1][2][3][4][5][6] In liver transplant recipients, current immunosuppressive regimens based on cyclosporine (CsA) or tacrolimus are still associated with acute rejection rates of 35% to 55% and 12-month graft and patient survival rates of only 70% to 80% and 80% to 85%, respectively. 7,8 In contrast to renal transplantation, no direct correlation between the occurrence of acute rejection and long-term graft function can be established.…”

mentioning

confidence: 99%

Immunoprophylaxis with basiliximab, a chimeric anti[ndash ]interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients

Calmus

2002

Liver Transplantation

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Acute graft rejection remains a major problem among additional sequelae in liver transplant recipients. Basiliximab, a chimeric monoclonal antibody with high affinity for the CD25 chain of the interleukin-2 receptor, has significantly reduced the incidence of acute rejection episodes in renal transplant recipients. This single-arm, open-label, multicenter study investigated the efficacy and tolerability of basiliximab immunoprophylaxis in adult patients undergoing first elective liver transplantation. One hundred one patients (70 hepatitis C virus [HCV]-negative patients, 31 HCV-positive patients) were administered basiliximab, 20 mg, by intravenous bolus injection the day of transplantation (day 0) and day 4. In addition, all patients were administered triple immunosuppressive therapy with cyclosporine, steroids, and azathioprine. The efficacy of basiliximab was assessed by conventional parameters, and tolerability was assessed by the incidence of adverse events, infections, and laboratory test result abnormalities. At 6 months, the incidence of first acute biopsy-confirmed rejection episodes was 22.8%. Rejections were more frequent in the HCV-positive (29.0%) than HCV-negative subgroup (20.0%; P ‫؍‬ .441). No rejection episode was graded histologically as severe, and no patient required antibody therapy for the management of acute rejection. Ten patients (9.9%) required treatment with tacrolimus for acute rejection episodes. Patient and graft survival rates at 12 months were 90.1% and 88.1%, respectively. Basiliximab caused no injection-site reactions, anaphylaxis, or cytokine release syndrome. Five malignancies were reported at 12 months: of these, three malignancies predated transplantation surgery. Compared with earlier studies, the addition of basiliximab immunoprophylaxis to triple immunosuppressive therapy provides increased efficacy in reducing the incidence of acute rejection episodes, with no clinically significant increase in adverse events. (Liver Transpl 2002;8: 123-131.)

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“…In addition to diminished long-term function and reduced graft survival, AR has also been found to correlate with an increased rate of CR [1,2,7,12,16,171. Our study showed that the risk of CR is much greater in recipients with incompletely reversed AR compared to those with complete reversal.…”

Section: Discussionmentioning

confidence: 99%

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients

Madden¹,

Mulhern²,

Benedetto³

et al. 2000

Transplant Int

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Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5-8 years. Post-transplant sodium iothalamate clearances (IoC1) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20% reduction in IoCl over 2 consecutive years) in IoC1. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after antirejection therapy. The incidence of AR was not significantly different between groups (47 % vs 52 %). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100 YO (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 YO (8/25) of the patients in the decline group had complete reversal ( P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 '30 (14/17) lost their grafts to CR. Overall, only 8 % (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCI. AR is not invariably deleterious to longterm renal graft function if each episode of AR can be completely reversed.

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Lrisk Factors for Chronic Rejection in Renal Allograft Recipients

Cited by 632 publications

References 0 publications

Nontransgenic Hyperexpression of a Complement Regulator in Donor Kidney Modulates Transplant Ischemia/Reperfusion Damage, Acute Rejection, and Chronic Nephropathy

Nontransgenic Hyperexpression of a Complement Regulator in Donor Kidney Modulates Transplant Ischemia/Reperfusion Damage, Acute Rejection, and Chronic Nephropathy

Immunoprophylaxis with basiliximab, a chimeric anti[ndash ]interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients

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