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M Hourmant

Publications and source records attributed to M Hourmant.

At least 37 records · Page 2Linked to original sources

[Monoclonal antibodies and transplantation].

Several monoclonal antibodies have been evaluated in allograft transplantation, these past years, without being able, to date, to replace polyclonal antibodies. They are classified in four families, each having an individual interest: antibody directed against the CD3/T receptor complex; anti-interleukine II receptor antibodies, specifically blocking activated T lymphocytes; antibodies against adhesion molecules, mainly LFA1 and ICAM1, that, by preventing the reperfusion injury syndrome, should have many clinical applications in the future; antibodies against co-receptor molecules, such as CD4, inducing indefinite allograft tolerance in models of transplantation in rodents, that could be reproducible in human.

Antibodies, Monoclonal↗

Single-center analysis of 468 first cadaveric kidney allografts with a uniform ATG-CsA sequential therapy.

Progress in clinical management and sophistication of immunological treatment of kidney allografts depend upon continuous reassessment of the risk factors related to pre- and post-graft information according to the therapeutical strategies used. We studied predictive factors of long-term graft survival (up to 9 years) and of kidney graft function at one year after surgery in a single-center population of 468 first cadaveric kidney recipients treated with a uniform immunosuppression induction regimen of anti-thymocyte globulin, followed by cyclosporine A. The statistical analysis showed that long-term graft survival was highly correlated with the occurrence of one or more acute cellular rejections and with the timing of these episodes. In addition, this uniformly treated series of patients confirmed the potential importance of gender matching. The magnitude of anti-HLA immunization and delayed graft function were also strongly linked to low graft survival rates. We found no significant influence of HLA matching, with serological HLA typing, on graft loss. The quality of graft function at one year was found to be a strong prognostic factor of long-term graft survival. In addition, the impact of pre- and post-graft parameters were studied in terms of prediction of one-year graft function. A stepwise multivariate analysis showed that graft function at one year was a multivariate phenomenon strongly correlated with a history of acute rejection episodes and with donor and recipient age. However, these 3 factors could account for only 15% of the graft function deterioration, the remaining 85% might be explained in part by chronic cyclosporine toxicity and/or chronic rejection.

Adolescent↗

Late acute failure of well-HLA-matched renal allografts with capillary congestion and arteriolar thrombi.

Seventeen cases of a histologically and clinically unusual renal acute dysfunction in kidney recipients, individualized among a population of 1378, are reported. The basic histological lesion was a huge capillary congestion, associated with capillary and arteriolar thromboses or parenchymal necrosis in most patients, and contrasting with the absence of the classical features of acute cellular rejection, i.e., tubulitis, glomerulitis, edema, and infiltrate. The corresponding clinical history was characterized by its early timing in the course of transplantation (< 3 months), its sudden occurrence in patients usually having good transplant function, leading to end-stage renal failure in a few days, and its resolution under rejection treatment. The occurrence of this syndrome was significantly linked with a good HLA matching: 13 of the 17 recipients were HLA-DR matched (P < 0.0001). The etiology of this syndrome remains unknown. There was no evidence for graft vessel thrombosis. Because of some histological similarities, the usual causes of the hemolytic uremic syndrome, including bacterial and viral infections or cyclosporine arteriolopathy, were discussed. Acute vascular rejection was suspected, but the cross-match was negative on T lymphocytes in all cases and anti-HLA class I and II antibodies were not found to develop at the time of transplant dysfunction, except in 1 patient, in whom the detected anti-DR antibodies were not directed at the kidney donor. Anti-human umbilical vein endothelial cell antibodies, detected in an antibody-dependent cellular cytotoxicity assay, were present in 6 patients (of the 14 tested) at the onset of renal failure, but they were either absent (n = 3) or already present at the time of transplantation (n = 5) in the other 8 patients. Therefore, reliable arguments are lacking to conclude that this acute transplant dysfunction is an acute vascular rejection and its strong association with HLA matching has, as yet, no satisfactory explanation.

Acute Disease↗

Cadaveric renal transplantation after 60 years of age. A single center experience.

We report the outcome of 121 cadaveric renal transplants performed in our institution between September 1985 and April 1992 in 117 patients, aged 60-71 years (mean 63 years) at the time of transplantation. Compared to 640 patients 20-59 years of age transplanted during the same study period, a nonstatistically significant difference was observed in the 5-year actuarial patient (80% and 90%, respectively, in recipients over and under 60 years of age) and transplant (80% and 72%, respectively, in recipients over and under 60 years of age) survival rates. However, elderly patients had significantly lower survival than recipients 20-29 years of age (P < 0.009). Fourteen patients died (all but one with a functioning graft) due to cardiovascular diseases (5%; 42.8% of total deaths), infections (3%; 28.6% of total deaths), and gastrointestinal complications (3%; 28.6% of total deaths). Younger patients showed a similar and nonsignificantly different incidence of cardiovascular- (35%) and infectious-(30%) related deaths. The incidence of acute rejection episodes and cytomegalovirus (CMV) infectious episodes was 27% and 24%, respectively, during the 1st post-transplant year. Ongoing acute rejection and CMV infectious episodes were significantly higher in patients who died than in those still alive (P < 0.002 and P < 0.02, respectively). Cyclosporin maintenance therapy was well tolerated in all patients but one, and 64% of the patients could be maintained without steroids. These data indicate that cadaveric renal transplantation is a safe and effective procedure in the management of chronic renal failure of selected patients 60 years of age or older.

Adolescent↗

Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. I. Results after combined pancreas and kidney transplantation.

A prospective, randomized trial was conducted to evaluate the short-term and long-term effects of induction immunosuppression with the rat IgG 2a monoclonal antibody 33B3.1, directed against the human alpha chain of the interleukin 2-receptor, following primary, cadaveric, combined pancreas and kidney transplantation. Forty patients were randomly assigned to receive 10 mg/day of 33B3.1 (n = 20) or 1.5 mg/kg/day of rabbit antithymocyte globulin (n = 20) for the first 10 postoperative days. Azathioprine, low-dose corticosteroids, and cyclosporine were given in association with either 33B3.1 or ATG. All 40 patients received the entire 10-day bioreagent course and no episode of rejection was observed during this period. Although the incidence of rejection did not significantly differ within the first, second, and third postoperative months (ten 33B3.1 and 6 ATG patients experienced, respectively, 10 and 6 rejection episodes within the first 3 months), the total number of 33B3.1 patients experiencing rejection throughout the follow-up was significantly higher than that of ATG (13 versus 6; P < 0.02). Immunological graft failure accounted for 2 pancreas and 2 kidney losses in the 33B3.1 group versus 1 in the ATG one (P = ns). The total number of infectious episodes was similar in both groups (21 versus 23). Two malignancies were observed in the ATG group (1 responsible for patient's death). One 33B3.1 patient died because of infectious pneumonia and 3 ATG patients died because of 2 cardiovascular diseases and 1 cancer. All patients had functioning grafts at the time of death. The 3-month and 36-month patient, pancreas, and kidney actuarial survival rates were, respectively, 100, 65, and 100%, and 95, 50, and 82% in the 33B3.1 group and 95, 80, and 90%, and 80, 70, and 80% in the ATG one (P = ns). These data suggest that, although a significantly higher rejection episode incidence was observed in patients treated with 33B3.1 monoclonal antibody as compared with ATG, similar long-term results can be obtained following primary cadaveric combined pancreas/kidney transplantation.

Acute Disease↗

Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. II. Results after a second kidney transplantation.

The focus of progress in transplantation immunosuppression is to achieve more specific immunosuppression with monoclonal antibodies. We have already shown that the efficacy of 33B3.1, a rat monoclonal Ig2A directed against the human IL-2 receptor, was similar to that of rabbit antithymocyte globulin in the prevention of acute rejection in first kidney transplants. A similar comparative analysis has been made in 40-sec renal transplants. ATG (1 mg/kg/day) or 33B3.1 (10 mg/day) was administered during the first 10 days postgrafting in association with corticosteroids and azathioprine. Cyclosporine was introduced on day 9 and azathioprine/CsA constituted the patient's maintenance treatment after day 45. Rejection treatment consisted of equine antilymphocyte globulin in both cases and of steroid boluses when patients were under Cyclosporine. One patient in each group died. Graft survival was 90%, 85%, and 79% in the ATG group (n = 20) and 100%, 89%, and 89% in the 33B3.1 group (n = 20) at 3, 12, and 24 months, respectively. Of the ATG group patients, 45% and 40% in the 33B3.1 group had at least one rejection episode, half the episodes in the MoAb cohort occurring under 33B3.1, vs. none in the ATG group. Transplant function was similar in both groups. Viral infections appeared to be more frequent with ATG (60%) than with 33B3.1 (12%), with CMV accounting for half of these in the ATG group, and none in the MoAb group. Tolerance of both agents was good. Of the 33B3.1 recipients, 70% developed anti-33B3.1 antibodies. From these data, we conclude that this anti-IL-2 receptor MoAb seems less effective than rabbit ATG as induction treatment in second kidney transplant patients.

Acute Disease↗

Renal transplantation from cadaver donors over 60 years old.

The influence of donor age on the short- and long-term outcome of cadaveric kidney transplantation was analyzed at our institution. During a 6-year period, 34 and 806 patients underwent kidney transplantation from cadaver donors over or less than age 60, respectively. Graft and patient survivals were compared throughout follow-up and herewith reported. In addition, main medical and surgical complications among recipients of elderly cadaver donors are detailed.

Adult↗

Prospective randomized comparison of University of Wisconsin and UW-modified, lacking hydroxyethyl-starch, cold-storage solutions in kidney transplantation.

University of Wisconsin cold storage solution differs from Euro-Collins by the presence of adenosine, allopurinol, and hydroxyethyl starch, which maintains osmotic pressure. It is now experimentally and clinically well established that the use of UW solution is associated with better liver graft recovery parameters after prolonged cold ischemia time. However, it has been also suggested in animal experiments that HES might not be essential for optimal kidney preservation, at least when cold ischemia time remains within 48 hr. Herein, we present a randomized study comparing UW (n = 44) and a modified UW (UW-mod) (n = 44) solution lacking HES, adenosine, and allopurinol on kidney graft recovery parameters. Forty-one consecutive Euro-Collins flushed kidneys, transplanted immediately before this randomized trial, were used as historical controls. The results indicate that UW-mod was as efficient as UW in preserving the kidney in cold ischemia ranges that did not exceed 48 hr. Both solutions (UW and UW-mod) seemed more effective than Euro-Collins, based on the analysis of several parameters including the number of days until the creatinine was < 300 microM (P < 0.05), the level of the serum creatinine at one month (P < 0.02), and the Cockroft index (P < 0.04). Since UW-mod is three times less expensive than UW, we suggest that the simplified solution could be routinely used to preserve kidneys for transplantation.

Adenosine↗