Role of Preoperative Donor-Specific Transfusion and Cyclosporine in Haplo-ldentical Living Related Renal Transplant Recipients

Sharma, RK; Rai, Praveer; Kumar, Anant; Kumar, Prem; Gupta, Amit; Kher, Vijay; Agrawal, Soma; Bhandari, M

doi:10.1159/000189494

Cited by 11 publications

(9 citation statements)

References 7 publications

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“…However, Salvatierra et al [2]reported that serum creatinine levels were elevated in the CYA-treated non-DST group, and antihypertensive medication was more frequent in those patients. According to Sharma et al [13], DST did not affect the 1-year graft survival rate when CYA was used for both groups postoperatively. However, 3, 6 and 12 months after transplantation, serum creatinine levels were also higher in the non-DST group despite similar doses of CYA being administered to patients in both groups.…”

Section: Discussionmentioning

confidence: 95%

Long-Term Results of Donor-Specific Blood Transfusion with Cyclosporine in Living Related Kidney Transplantation

Otsuka¹,

Yuzawa²,

Takada³

et al. 2001

Nephron

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Donor-specific blood transfusion (DST) was introduced to achieve better graft survival. However, its benefits are controversial considering the immunosuppression of cyclosporine (CYA) or tacrolimus (Tac), and its long-term effects have not been well discussed. Of the 40 patients who received DST with CYA, 3 (7.5%) became cross-match positive. Of the 37 patients with negative cross-match, 34 patients received a one-haplotype-matched kidney and were compared to patients with one-haplotype-matched kidney transplant without preoperative DST (n = 13). Acute rejection within 3 months after transplant was 29.4% in the DST group, and 15.4% in the non-DST group. All rejection episodes were steroid resistant in the non-DST group. If the graft survival rates were calculated excluding non-immunological graft loss, graft survival rate was 91.0 and 72.8% at 5 and 10 years in the DST group, and 83.3% at 5 and 10 years in the non-DST group, respectively. The two graft survival lines converged 7 years and 7 months after transplantation. No beneficial effect of DST was statistically evident under CYA immunosuppression. In terms of the severity of acute rejection or the onset of chronic rejection, DST induced a small benefit, however, which seemed to disappear within 8 years after transplantation.

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Section: Discussionmentioning

confidence: 95%

Long-Term Results of Donor-Specific Blood Transfusion with Cyclosporine in Living Related Kidney Transplantation

Otsuka¹,

Yuzawa²,

Takada³

et al. 2001

Nephron

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“…A major deficiency of these investigations was the controls considered. Some of the studies had no controls at all [3,9,20,21], others focused either on historical [13,17–19] or on a kind of parallel control group [1,2,4,5,7,8,11,12]. The present investigation appears to be the only one, which considered well‐matched individuals.…”

Section: Discussionmentioning

confidence: 99%

“…The present investigation appears to be the only one, which considered well‐matched individuals. Only in one small study a prospective randomized study design was used [11]. In that study, 15 patients received 250 ml of DST 24 h preoperatively with cyclosporine A coverage and the remaining 15 subjects did not receive a DST [11].…”

Section: Discussionmentioning

confidence: 99%

“…Logistical reasons, the fear of sensitization or transmission of infections like hepatitis and HIV in the early 1980s, have contributed to the disappearance of DST strategies. Nevertheless, several investigations from the last decade suggested a beneficial effect of DST [8–13]. In Bern, we introduced a cyclosporine‐based DST protocol for renal allograft recipients from living‐related/unrelated donation (LRD/LURD) in 1993.…”

Section: Introductionmentioning

confidence: 99%

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Effect of donor-specific transfusions on the outcome of renal allografts in the cyclosporine era

Marti¹,

Henschkowski²,

Laux³

et al. 2006

Transplant Int

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Summary Despite the introduction of new immunosuppressive agents, a steady decline of functioning renal allografts after living donation is observed. Thus nonpharmacological strategies to prevent graft loss have to be reconsidered, including donor‐specific transfusions (DST). We introduced a cyclosporine‐based DST protocol for renal allograft recipients from living‐related/unrelated donation. From 1993 to 2003, 200 ml of whole blood, or the respective mononuclear cells from the potential living donor were administered twice to all of our 61 recipient candidates. The transplanted subjects were compared with three groups of patients without DST from the Collaborative Transplant Study (Heidelberg, Germany) during a 6‐year period. Six patients were sensitized without delay for a subsequent cadaveric kidney. DST patients had less often treatment for rejection and graft survival was superior compared with subjects from the other Swiss transplant centers (n = 513) or from Western Europe (n = 7024). To diminish the probability that superior results reflect patient selection rather than effects of DST, a ‘matched‐pair’ analysis controlling for relevant factors of transplant outcome was performed. Again, this analysis indicated that recipients with DST had better outcome. Thus, our observation suggests that DST improve the outcome of living kidney transplants even when modern immunosuppressive drugs are prescribed.

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“…DST, which consists in injecting donor blood into the recipient before transplantation, is still used in the clinic. Some studies have shown that DST improves graft survival and function (Sharma et al, 1997; Marti et al, 2006). …”

Section: Tolerogenic DC In Animal Modelsmentioning

confidence: 99%

Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials

Moreau¹,

Varey²,

Bériou³

et al. 2012

Front. Immun.

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The use of immunosuppressive (IS) drugs to treat transplant recipients has markedly reduced the incidence of acute rejection and early graft loss. However, such treatments have numerous adverse side effects and fail to prevent chronic allograft dysfunction. In this context, therapies based on the adoptive transfer of regulatory cells are promising strategies to induce indefinite transplant survival. The use of tolerogenic dendritic cells (DC) has shown great potential, as preliminary experiments in rodents have demonstrated that administration of tolerogenic DC prolongs graft survival. Recipient DC, Donor DC, or Donor Ag-pulsed recipient DC have been used in preclinical studies and administration of these cells with suboptimal immunosuppression increases their tolerogenic potential. We have demonstrated that autologous unpulsed tolerogenic DC injected in the presence of suboptimal immunosuppression are able to induce Ag-specific allograft tolerance. We derived similar tolerogenic DC in different animal models (mice and non-human primates) and confirmed their protective abilities in vitro and in vivo. The mechanisms involved in the tolerance induced by autologous tolerogenic DC were also investigated. With the aim of using autologous DC in kidney transplant patients, we have developed and characterized tolerogenic monocyte-derived DC in humans. In this review, we will discuss the preclinical studies and describe our recent results from the generation and characterization of tolerogenic monocyte-derived DC in humans for a clinical application. We will also discuss the limits and difficulties in translating preclinical experiments to theclinic.

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Role of Preoperative Donor-Specific Transfusion and Cyclosporine in Haplo-ldentical Living Related Renal Transplant Recipients

Cited by 11 publications

References 7 publications

Long-Term Results of Donor-Specific Blood Transfusion with Cyclosporine in Living Related Kidney Transplantation

Long-Term Results of Donor-Specific Blood Transfusion with Cyclosporine in Living Related Kidney Transplantation

Effect of donor-specific transfusions on the outcome of renal allografts in the cyclosporine era

Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials

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