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M Hourmant

Publications and source records attributed to M Hourmant.

At least 73 records · Page 4Linked to original sources

[Kidney transplantation after 60 years of age. Survival of patients and functional results].

Between January 1, 1984 and October 1, 1988, 36 cadaveric kidney transplantations were performed in 60 to 66 years' old patients (mean: 62.4 years). Induction immunosuppression consisted of rabbit antithymocyte globulins for 10 days or 33B3.1, an anti RIL2 monoclonal antibody (n = 6), with azathioprine and corticosteroids (less than 1 mg/kg/day). Cyclosporin A (CSA) was given on day 10 in doses of 8 mg/kg/day. Steroids were withdrawn on day 45. Actuarial patient and graft survivals were 66 per cent and 80.5 per cent respectively at 1 and 2 years. Mean +/- SD serum creatinine level was 178 +/- 77 mumol/l at one year. The mean CSA dose adjusted to total blood CSA levels was 4.75 +/- 1.7 mg/kg. Five patients died in the first quarter, 2 of opportunistic infections, 2 of cardiovascular disease and 1 of gastric haemorrhage. The prevalence of rejection episodes during the first 3 months was lower than in the general population (22 per cent vs 27 per cent); all were reversible with bolus injections of corticosteroids. These results indicate that kidney transplantation can successfully be performed in elderly patients with a low rejection rate and an excellent long-term graft survival. However, the mortality was higher than in younger recipients.

Actuarial Analysis↗

Effect of positive crossmatch against donor B lymphocytes in kidney transplantation: a prospective one-center study.

Circulating antibodies reacting with donor lymphocytes, increasingly found in patients awaiting a kidney graft, are a cause of transplantation delays. Some of these antibodies may not be detrimental to the graft, and their recognition could be beneficial for the treatment of immunized patients. In this chapter, we report on a prospective study of 138 cases of kidney transplantation performed against a positive crossmatch (CM) on donor B lymphocytes. In all cases, a negative reaction was required on donor T lymphocytes using recipient pregraft sera. Sera of 36.3% and 43.6% of first and second-graft recipients, respectively, were also reactive on unseparated donor total lymphocytes. First grafts performed against donor B lymphocytes reacted like those with a negative CM in terms of graft survival, rejection incidence, and graft function in the first year. Surprisingly, an uncommonly high rate of success was observed in second grafts performed against a positive donor B-lymphocyte CM as compared to those with a negative B-cell CM (93.5% vs 62.8% graft survival at 2 years; p less than 0.05). In addition, these patients had a decreased rejection incidence and significantly better graft function (p less than 0.05) as compared to those grafted with a negative B-lymphocyte CM. In the 43.6% who also had a positive CM on total donor lymphocytes (negative CM on donor T cells) and would not have been grafted according to common CM policy, actuarial graft survival was 86.7%. Our results within the given procedure show that transplantation against a positive donor B-cell CM is not detrimental to a first graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Azathioprine-cyclosporin A (CyA) double therapy versus CyA alone after the first rejection episode in kidney-transplanted patients under CyA. A randomized study.

A controlled trial was carried out in 78 kidney transplant recipients under cyclosporin A (CyA) monotherapy who had experienced a first rejection episode. Thirty-nine were randomly selected to receive azathioprine (AZA; 2 mg/kg per day) in combination with CyA (group AZA+), while the others continued to receive CyA alone (group AZA-). Four of the patients in the study died; three were in group AZA+ and the cause of their deaths was cardiovascular. Graft survival rates were 97% at 6, 12, and 24 months postrejection in group AZA+ as compared to 97%, 90%, and 81%, respectively, in group AZA- (P less than 0.05 at 12 and 24 months). Significantly more patients were free of rejection with the double therapy than with CyA monotherapy (75% vs 51% at 12 months; P less than 0.05). In spite of the addition of a second immunosuppressive drug, the CyA dosages given and the CyA trough blood levels maintained were similar in the two groups. Serum creatinine was similar in patients with and without AZA. Infectious complications were also similar in both groups. A significant macrocytosis was the only side effect of AZA therapy. On the whole, these data show the benefit of CyA-AZA double therapy in the prevention of rejection recurrence without exposing patients to either increased risk of infection or serious side effects of AZA. Whether this double therapy should be systematically administered to all recipients or only after a first rejection episode is discussed.

Azathioprine↗

Anti-interleukin 2 receptor monoclonal antibody in the treatment of ongoing acute rejection episodes of human kidney graft--a pilot study.

Monoclonal antibodies (MoAbs) against human interleukin 2 receptor (IL-2-R) have been shown to prevent early kidney rejection in animals and humans. We report here the effect of an anti-IL-2-R MoAb (33B3.1) inhibiting IL-2 binding high-affinity sites on activated lymphocytes in 10 declared acute rejection episodes of first cadaveric kidney grafts. Six patients were under cyclosporine treatment only at the time of diagnosis of the rejection. All rejection episodes but one were biopsy-proved cellular rejections. Treatment consisted of intravenous infusions of 33B3.1 at 20 mg/day x 2 days, followed by 10 mg/day for 8 additional days. In case of MoAb ineffectiveness at day 5, anti-IL-2-R MoAb was discontinued and a rescue treatment of corticosteroid boluses (CSb) was given. If not, in all cases corticosteroids (CS) were given (1 mg/kg) at the end of MoAb treatment (day 10) and tapered off thereafter. Two rejection episodes immediately responded to 33B3.1 treatment. During 33B3.1 treatment four other patients had only a stabilization of their blood creatinine concentration, which nevertheless returned to prerejection levels after day 10 when anti-IL-2-R was discontinued and CS administered at 1 mg/kg (no rescue treatment). The four remaining patients had an increase of their blood creatinin levels at day 5 despite 33B3.1 treatment, and their renal function only improved with CSb rescue treatment. One of these patients lost the graft despite rescue treatment, as well as a 9-day course of antithymocyte globulin. Trough levels of MoAb reached a plateau as early as day 2 (approximately 6 micrograms/ml). All patients developed antibodies (IgM and IgG) after day 14. In no instance could unresponsiveness be related to low circulating 33B3.1 trough levels or to early host anti-MoAb immune response (IgM or IgG). We conclude that 33B3.1, known to be effective in preventing early rejection, has only inconsistent and/or incomplete effects on the ongoing rejection process. Our data suggest that once IL-2-dependent clones are expanded in the rejected graft, interference with IL-2/IL-2-R signals does not block the effector mechanisms sustaining acute rejection.

Antibodies, Monoclonal↗

Polyclonal rabbit gamma globulins against a human cytotoxic CD4 T cell clone. II. Use in prevention of rejection in kidney transplantation: a pilot study.

Antiblast globulins (GAB) were prepared by immunization of rabbits with activated T lymphocytes (AT) derived from a rejected kidney allograft. AT consisted of a CD4+ (CD3+, CD2+ TCR alpha+ beta+) clone cytotoxic for HLA DR8-positive targets. The immunizing cells were adapted to industrial growth conditions by repetitive stimulations with an EBV-transformed line from the kidney donor and recombinant IL-2. In the pilot study, GAB (1.0-1.5 mg/kg/day) was given in 12-hr infusions, in association with prednisone (Pred) 1 mg/kg/day and azathioprine (Aza) 2 mg/kg/day, as prophylactic treatment of rejection in 12 kidney-transplanted patients during the first 2 weeks postgrafting. GAB dosage was further adapted according to the level of circulating E-rosette-forming T cells (ERFT). Cyclosporine A (8 mg/kg/day) was given at day 14 as a monotherapy after Pred and Aza were progressively tapered. No patient died, but one kidney was lost from surgical complication. No rejection occurred under GAB treatment; 41% of patients had at least one episode in the first 3 months and 16% from 3 to 9 months. GAB side effects were minor (skin rash: 2, low grade fever: 4) except for one acute serum sickness. Platelet and white blood cell counts were unchanged, but there was a significant decrease in hemoglobin during the 2 weeks of GAB infusions. Few infectious episodes occurred (3 bacterial, 2 viral). GAB monitoring showed a dramatic drop in T11+, T3+, T4+, and T8+ circulating T cells (less than 10% of normal values between days 3 and 14), whereas EFRT cells had a delayed and somewhat lower decrease (less than 10% after day 6 only). Consequently, mean GAB doses had to be raised to 1.3 mg/kg/day at day 4 and 1.6 at days 8 and 14. This pilot study suggests that this new bioreagent should be of major interest in the prophylaxis and treatment of rejection in allograft recipients. A controlled study is in progress.

Animals↗

Economic analysis of an immunosuppressive strategy in renal transplantation.

Recently introduced immunosuppressants, which have been shown to be more effective but apparently more costly than conventional regimens, have renewed interest in the economic evaluation of national policies regarding the management of end-stage renal disease. The present paper addresses these questions, together with the different methods of expressing the costs involved, with reference to a sequential protocol using anti-lymphocyte serum (ALS), followed by cyclosporine from the third post-graft month onwards. The analysis is based on the results of a randomized trial carried out at the University Hospital, Nantes (France), from 1982 to 1984, in which the above protocol was compared to conventional treatment with ALS alone. Despite the considerable cost of long-term cyclosporine treatment, analysis reveals collective financial and social benefits from the reduced rate of graft failure and subsequent return to dialysis.

Antilymphocyte Serum↗

Prophylactic use of a monoclonal antibody (33B3.1) directed against interleukin 2 receptor following human renal transplantation.

33B3.1, a rat IgG2a monoclonal antibody (MAb) directed against interleukin 2 receptor, has been given in association with prednisone and azathioprine to prevent rejection in 30 recipients of a primary cadaveric kidney transplant. The MAb 33B3.1 had been administered intravenously (IV) at 10 mg per day for 2 weeks. Clinical and biological tolerance were excellent. Only one patient had a rejection episode (reversible) during the MAb treatment period. These results were significantly better than those recorded from a historical group of patients that received only prednisone and azathioprine, and were similar to those from patients who received antithymocyte globulin instead of 33B3.1. There was no life threatening infectious episode and all patients are alive. Ninety-seven percent of the patients have a functional graft (follow-up, 30 to 210 days). Enzyme-linked immunosorbent assay (ELISA) of 33B3.1 indicate that circulating trough blood level peaked at day 6 (30 nm). The majority of patients (85%) developed either IgG or IgM antibodies with a maximal response at day 24 for both isotypes. We conclude that this new treatment that targets a functional receptor present on activated lymphocytes only, is well tolerated and highly efficient in preventing early rejection after human renal transplantation.

Animals↗