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Maryvonne Hourmant

Publications and source records attributed to Maryvonne Hourmant.

16 recordsLinked to original sources
PubMed2006

Association of kidney transplant failure and antibodies against MICA.

Despite the progress in renal transplantation, acute rejection and graft failure still occur and chronic rejection continues to be the main problem in long-term allograft survival. Although kidney transplant rejection has been linked to anti-HLA antibodies, not all patients with failed kidney transplants have anti-HLA antibodies, indicating that other loci may be involved. Sera of 63 patients who experienced kidney rejection were compared against sera of 82 patients with functioning transplants. Sera were examined for IgG and IgM anti-HLA Class I and II antibodies. They were also tested by cytotoxicity against panels of 26 endothelial cell lines, 8 MHC class I chain-related gene A (MICA) recombinant cell lines, and 28 B lymphoblast cell lines. Among patients whose transplants failed, 65% had anti-HLA antibodies compared with 45% of those with functioning kidneys (p < 0.05). Similarly, among those whose transplants failed, 41% had anti-endothelial cell antibodies in contrast to 22% in functioning patients (p < 0.05). Among patients whose grafts failed, 52% had anti-MICA antibodies versus 21% of those with functioning grafts (p < 0.001). Eleven patients with failed grafts and 32 with functioning grafts were negative for all of the above. However, 6 of the former and 7 of the latter showed positive cytotoxicity against B lymphoblasts (p < 0.05). Taking all antibodies together, 92% of patients with graft failure had antibodies as opposed to 70% of patients with functioning grafts (p < 0.001). We postulate that antibodies against HLA, MICA, endothelial cells, and B lymphoblasts could be independently involved in the slow process of chronic graft failure.

B-Lymphocytes↗
PubMed2005

[Kidney transplantation in aged patients].

The number of elderly patients (> 65 years) on the national waiting list of kidney transplantation and subsequently transplanted has increased 5 times from 1990 to 2004. Transplantation in patients more than 70 years old is not exceptional today. Graft survival is significantly less than in younger patients, but this difference disappears when deaths are censored. Elderly patients generally receive marginal kidneys from aged donors with cardiovascular pathologies or risk factors, which would only reluctantly be transplanted in younger people. Patient survival is significantly better after transplantation than in dialysis and the age of the patient per se should no longer be a contraindication to transplantation. Because of organ shortage and the need for transplanting these aged patients as soon as possible, it appears necessary to find new sources of transplants, harvested from donors with expanded criteria and previously considered inadequate.

Age Factors↗
PubMed2005

Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation.

The involvement of immunologic and nonimmunologic events in long-term kidney allograft failure is difficult to assess. The development of HLA antibodies after transplantation is the witness of ongoing reactivity against the transplant, and several studies have suggested that the presence of HLA antibodies correlates with poor graft survival. However, they have not discriminated between donor-specific (DS) and non-specific (NDS) antibodies. A total of 1229 recipients of a kidney graft, transplanted between 1972 and 2002, who had over a 5-yr period a prospective annual screening for HLA antibodies with a combination of ELISA, complement-dependent cytotoxicity, and flow cytometry tests were investigated; in 543 of them, the screening was complete from transplantation to the fifth year postgrafting. Correlations were established between the presence and the specificity of the antibodies and clinical parameters. A total of 5.5% of the patients had DS, 11.3% had NDS, and 83% had no HLA antibodies after transplantation. NDS antibodies appeared earlier (1 to 5 yr posttransplantation) than DS antibodies (5 to 10 yr). In multivariate analysis, HLA-DR matching, pretransplantation immunization, and acute rejection were significantly associated with the development of both DS and NDS antibodies and also of DS versus NDS antibodies. The presence of either DS or NDS antibodies significantly correlated with lower graft survival, poor transplant function, and proteinuria. Screening of HLA antibodies posttransplantation could be a good tool for the follow-up of patients who receive a kidney transplant and allow immunosuppression to be tailored.

Adult↗
PubMed2005

[The new French rules for the attribution of renal transplants].

The French rules for the attribution of a kidney transplant are regularly evaluated and modified according to scientific progress, evolution of the waiting list and of health policies. Modifications, initiated by the Transplantation Commission of the French-speaking Society of Nephrology, have been introduced in 2004 by the Etablissement français des Greffes and aim at decreasing the number of patients on the waiting list having difficult access to transplantation because of their immunogenetic characteristics (rare ABO or HLA group, HLA immunization). Four points are concerned: 1/ better definition of hyperimmunisation; 2/ introduction of a program based on "acceptable mismatches" as a new priority for hyperimmunized patients; 3/ suppression of the full-match priority to non-immunized patients; 4/ attribution to immunized patients (anti-HLA antibodies=5-80%) who have difficult access to a transplant, of priorities similar to those followed for hyperimmunized patients. This article presents the new rules for the allocation of a kidney transplant and the rationale for the current modifications.

France↗
PubMed2005

Switching from cyclosporine to tacrolimus in patients with chronic transplant dysfunction or cyclosporine-induced adverse events.

BACKGROUND: Progressive renal-function decline caused by chronic allograft nephropathy is the main cause of long-term failure after kidney transplantation. Moreover, chronic cyclosporine (CsA)-induced nephrotoxicity is an important nonimmunologic factor contributing to graft dysfunction and loss, and adverse events may require CsA withdrawal. METHODS: Tacrolimus (Tac) replaced CsA-based immunosuppression in 133 transplant patients (114 kidney, 15 kidney-pancreas, 4 pancreas after kidney) with progressive loss of renal function (71% of patients) or CsA intolerance (29% of patients) not responding to CsA dose-lowering. The primary end-points of this prospective study focusing on renal function were the safety and efficacy of Tac immunosuppression. RESULTS: Tac was generally well tolerated but definitively withdrawn for 23 (17%) patients (21 graft failures, 1 case of diabetes, and 1 case of clinical intolerance). Differential creatinemia (creatinemia-nadir creatinemia after transplantation) decreased significantly from 85.4+/-9.8 to 39.0+/-7.5 mumol/L (P<0.001; mean+/-SEM) after 1 year and 3.6+/-18.1 mumol/L (P<0.01) after 4 years. For patients with CsA intolerance, switch to Tac improved intolerance symptoms in all cases. Blood urea, creatinine clearance, blood total cholesterol, and triglycerides improved significantly, and the percentage of hypertensive patients remained stable with no de novo hypertension. During follow-up, one patient experienced an acute rejection episode (not histologically proven), and four died. Twenty-one (16%) transplants failed, significantly more frequently in patients with advanced renal impairment before Tac (P<0.0001). CONCLUSION: Switching from CsA to Tac can be an alternative strategy in kidney-transplant patients suffering from chronic allograft dysfunction or CsA toxicity. The persistently improved renal function over several months of evaluation suggests that in these patients, Tac might be less nephrotoxic than CsA and could prolong transplant function despite CsA failure.

Adolescent↗
PubMed2005

A single solution for multiple organ procurement and preservation.

Two or three different solutions may be used to preserve thoracic and abdominal organs during a single procurement. The aim of this prospective, multi-center, noncomparative study was to evaluate the safety and efficacy of Celsior (study solution, solution S) as a flushing and cold storage solution for both thoracic and abdominal organs. Between August 1999 and July 2000, 72 consecutive multiple-organ procurements were performed using solution S as the sole solution for flushing out and cold-storing thoracic and abdominal grafts. Two hundred and sixty-four grafts were implanted into 245 recipients (131 kidneys, 9 kidney-pancreases, 69 livers, 34 hearts and 6 heart-lungs). The mean cold ischemia time was 21 h for kidneys (26%>24 h); 11 h 26 min for pancreases, 9 h 16 min for livers (23%>12 h), and 2 h 58 min for hearts and lungs. No cardiac failure or arrhythmia occurred on graft reperfusion. Fourteen percent of kidney recipients had delayed graft function. The mean serum creatinine level at 3 months was 123 +/- 41 micromol/l. All pancreas recipients were insulin-free at 3 months. Primary graft nonfunction occurred in one liver recipient. Complete hepatic artery thrombosis occurred in six liver recipients during the first month; four of these patients had a risk factor for thrombosis. All but three of the heart recipients were in sinus rhythm on day 1, and 65% were extubated on day 1. Inotropic drugs were necessary during the first 72 h in 25% of heart recipients. Twelve-month patient and graft survival rates were, respectively, 100% and 96% (kidney), 100% and 89% (pancreas), 88% and 83% (liver), 77.5% (heart) and 67% (heart-lung). These results suggest that Celsior, a ready-to-use solution, is safe and effective for multiple organ procurement and preservation.

Adolescent↗
PubMed2005

The effect of a first kidney transplant on a subsequent transplant outcome: an experimental and clinical study.

BACKGROUND: Second kidney transplantations have a roughly similar clinical outcome to first transplantations. Nevertheless, the effect of the presence of the first, nonfunctional transplant at the time of the second transplantation may also influence its outcome and has not yet been specifically studied. METHODS: We analyzed the effect of the presence of a first graft on the outcome of a second graft in a rodent allograft model and in a cohort of 240 human second kidney allograft recipients. RESULTS: In rodents, 100 days subsequent to the rejection of the first graft, we observed an increase in blood but not spleen CD4(+)CD25(+) T cells, whereas no differences were observed in transcriptional patterns. Adoptive transfer of day 100 splenocytes did not prolong graft survival. Moreover, the presence of a first rejected graft does not prolong the survival of a second graft performed at a later date. In the human context, a higher incidence of patients with anti-HLA immunization and a higher % of PRA were observed in retransplant recipients with primary allograft nephrectomy. Despite a relatively low statistical power, our data do not suggest significant differences in graft outcome between recipients of second transplants with primary allograft nephrectomy and those without. CONCLUSION: Collectively, the data from both an experimental model and a large cohort of human recipients of a second graft do not suggest a beneficial effect of the presence of a first rejected graft at the time of a second transplantation.

Adolescent↗
PubMed2005

Steroid avoidance versus steroid withdrawal after simultaneous pancreas-kidney transplantation.

Two steroid-sparing immunosuppressive regimens were prospectively compared in recipients of simultaneous pancreas-kidney transplants, one did not include steroids at all and the other included steroids for the first 3 months following transplantation. All patients received rabbit anti-thymocyte globulin, mycophenolate mofetil (MMF) and cyclosporine. Fifty patients were randomised in an open-label, single center and prospective study. The incidence of biopsy-proven acute rejection during the first 12 months after transplantation was the primary endpoint of the study. The incidence of biopsy-proven acute rejection was 4% in both groups. No statistically significant difference in patient (96 and 100%), kidney (96 and 100%) or pancreas (84 and 92%) survival was observed 1 year after transplantation in the steroid avoidance and steroid withdrawal groups, respectively. The total number of adverse events (including severe ones), length of hospitalization and infectious episodes did not differ between groups. Blood glucose and insulin levels, lipid profile and hemoglobin A1C levels did not differ statistically between the two groups. However, the 1-year serum creatinine level was significantly higher in the steroid avoidance group (132 vs. 114 micromol/L; p = 0.02). Steroid avoidance and steroid withdrawal 3 months after transplantation are safe and effective regimens for diabetic patients with pancreas-kidney transplants.

Adolescent↗
PubMed2003

Identification of the antibodies involved in B-cell crossmatch positivity in renal transplantation.

BACKGROUND: The significance of a positive B-cell crossmatch (BCM) in kidney transplantation has always been controversial in the evaluation of its implications on graft survival and specificity of the antibodies involved. METHODS: We have investigated the sera of 62 recipients of a kidney allograft transplanted across a positive BCM (T negative) for the presence of autoantibodies and anti-human leukocyte antigen (HLA) class I and II antibodies, using a combination of lymphocytotoxicity, enzyme-linked immunosorbent assay (ELISA), and flow cytometry tests. The controls were the 930 patients transplanted over the same period of time with a negative T and BCM. RESULTS: Autoantibodies were detected in 16%, and donor specific anti-HLA class II antibodies, mainly DQ, in 23% of the patients. None had antibodies against donor HLA class I. The target of the antibodies was not identified in 61%. Graft survival was comparable in the controls and in the +BCM patients, with nondonor-specific HLA reactivity. Patients with donor-specific anti-HLA class II antibodies had lower early graft survival and a higher incidence of vascular rejection. However, long-term allograft survival was similar to that of the other groups. CONCLUSION: These data suggest that in 77% of the patients, BCM positivity was not related with anti-HLA antibodies, and, in this case, graft survival was similar to that of the -BCM controls. In a minority of patients, anti-HLA class II antibodies were responsible for the +BCM, and their presence was associated with lower early, but not long-term, graft survival. Consequently, a +BCM should not systematically contraindicate kidney transplantation.

Adult↗
PubMed2003

Multivariate analysis of donor risk factors for graft survival in kidney transplantation.

BACKGROUND: The results of the transplantation of marginal donor kidneys remain controversial. This study aimed to investigate the impact of donor risk factors as predictors of kidney-graft outcome. METHODS: Allograft failure risk factors were studied in 7,209 cadaveric kidney-transplant recipients reporting to the Etablissement français des Greffes (EfG) from 1996 to 2000, of which 544 (7.6%) were from donors aged over 60. Both univariate and multivariate analysis were used to assess the effect of donor risk factors and were stratified according to recipient age. RESULTS: Overall graft survival was 91.1% (95% confidence interval [CI] 90.5-91.8) at 1 year, 88.6% (95% CI 87.8-89.4) at 2 years, and 85.6% (95% CI 84.6-86.6) at 3 years posttransplant. Univariate analysis of risk factors showed a significant reduction of graft survival in recipients transplanted with kidneys coming from donors older than 60 years, donors with a history of hypertension, a cerebrovascular cause of death, and a preharvesting serum creatinine greater than 150 micromol/L. Multivariate analysis revealed significantly higher failure rate associated with cerebrovascular cause of death (RR=1.2, P=0.02), history of hypertension (RR=1.2, P=0.04), and elevated serum creatinine (RR=1.3, P=0.03), whereas donor age greater than 60 years was not found as an independent risk factor. CONCLUSIONS: Our results suggest that cerebrovascular cause of death, history of hypertension, and elevated creatinine are significant independent donor risk factors for graft survival, whereas donor age is a statistically significant, but dependent, risk factor. This result is important for the design of allocation and transplantation strategies for kidneys procured in elderly donors.

Adolescent↗
PubMed2003

Non-HLA-type endothelial cell reactive alloantibodies in pre-transplant sera of kidney recipients trigger apoptosis.

The vascular endothelium of transplanted organs represents an important target for allograft-directed immune responses. Although HLA antigens expressed on graft endothelial cells (EC) can become targets of the host immune response, the role of other, non-HLA-encoded EC antigens has been proposed but is still unclear. The aim of this study was to investigate the presence of and to characterize anti-EC antibodies (AECA) in 57 kidney transplant recipients according to their HLA-immunization status. Flow cytometry in pretransplant sera was used to detect AECA reactive with surface antigens on ABO and HLA-typed primary cultures of arterial ECs, stimulated or not with tumor necrosis factor-alpha (TNFalpha) or interferon-gamma (IFNgamma). FACS analysis revealed the presence of AECA in 47% of HLA-sensitized (PRA = 10%: mostly IgG) vs. 16.0% in nonsensitized patients (PRA < 10%) (p < 0.02). No significant correlation was found between the presence of AECA and acute rejection occurrence and graft outcome. Non-HLA reactive AECA are directed against TNFalpha- and IFNgamma-inducible membrane molecule(s), and react with two predominant antigens of approximately 35 kDa and approximately 50 kDa expressed on ECs but not on B cells. Binding of AECA decreases in vitro EC viability by 50-60% by promoting EC apoptosis, as demonstrated by DNA fragmentation assays.

Antibody Specificity↗
PubMed2003

Ten-year survival of second kidney transplants: impact of immunologic factors and renal function at 12 months.

BACKGROUND: The aim of the present study was to assess long-term survival of cadaveric second kidney allografts performed in our center and to determine risk factors predictive of long-term graft outcome. METHODS: Of 1704 kidney transplantations performed between January 1985 and March 1998, 233 were second grafts. The majority of the recipients were sensitized. All patients were treated with the same quadruple immunosuppressive regimen. RESULTS: Kaplan-Meier analysis documented graft survival of 89% at 1 year, 76% at 5 years, and 53% at 10 years. Graft survival was similar for second and primary kidney transplants performed during the same period of time. When long-term second graft survival was examined, only two risk factors were found to be significant: (1) the degree of human leukocyte antigen (HLA) DR mismatch (MM) and (2) the number of acute rejection episodes. Multivariate analysis of several pre- and posttransplant variables also confirmed the importance of HLA MM (DR> A), but also, identified serum creatinine at 12 months as the most significant predictor of graft survival. In addition, the Cox proportional hazards model revealed that only the year of transplantation had an independent significant effect on acute rejection occurrence (RR = 0.591, 95%CI 0.437 to 0.801, P < 0.0007). Indeed, the incidence of acute rejection was found to decrease over time (44% of patients experienced at least one episode of acute rejection before 1990 vs. 17% after 1990). CONCLUSION: Finally, second graft long-term outcome shows an improved evolution according to the time period resulting from a strong decrease in acute rejection incidence and the impact of creatinine at 12 months.

Acute Disease↗
PubMed2002

Acute graft pyelonephritis and long-term kidney allograft outcome.

BACKGROUND: Long-term graft function is the result of multiple parameters, including both immune and non-immune components, which have a beneficial or detrimental potential. Among these, despite its frequency and theoretical interest (expression of "danger signals" in the graft itself), the effects of acute graft pyelonephritis (AGPN) on immediate and long-term outcome have not been studied in a large series. This article reviews a cohort of 1387 consecutive primary renal transplant recipients. METHODS: The objective of the study was to define the risk factor for AGPN, the risk profile for recurrence, and the impact of AGPN on long-term graft survival. According to a higher risk for AGPN in females during their follow-up, statistical analyses (Cox model, and multiple regression analysis) were performed by recipient sex strata. RESULTS: Multivariate analysis showed that CMV infection was the only risk factor for AGPN occurrence. AGPN occurred in 13% of the graft recipients during their follow-up. Taken as a whole, AGPN was not associated with a significantly poor long-term outcome. However, when assessed in more detail, the outcome of this population was found to be more complex and to depend on several factors. Early AGPN (during the first 3 months) was significantly detrimental for graft outcome, independently of acute rejection episodes. Moreover, E. coli involvement in a first episode was linked to an increased AGPN recurrence. CONCLUSION: This analysis did not support the concept that with current immunosuppression, strong "danger signals" such as those derived from bacteria within an allograft, are instrumental in initiating acute or chronic rejection.

Acute Disease↗
PubMed2001

Mycophenolate mofetil does not modify the incidence of cytomegalovirus (CMV) disease after kidney transplantation but prevents CMV-induced chronic graft dysfunction.

Ganciclovir, which is used to treat cytomegalovirus (CMV) infection, has been shown in rodent models to abolish CMV-mediated chronic cellular damage and endothelial cell proliferation; when associated with mycophenolate mofetil (MMF), it has been shown to increase its anti-herpes virus activity. This study tested the hypothesis that kidney graft recipients who received antirejection prophylaxis with MMF and who were treated with ganciclovir for a declared CMV disease could be protected from chronic graft dysfunction. Investigated was the impact of ganciclovir-treated CMV diseases in consecutive first kidney recipients according to their immunosuppressive therapy. The azathioprine (Aza)-treated group (Aza group) included 319 patients. The MMF-treated group (MMF group) included 126 patients. CMV disease was clinically defined and confirmed by virological proof of CMV infection and was treated for at least 14 d with ganciclovir. Despite having the same incidence (21.6% in the Aza group versus 24.6% in the MMF group) and severity, CMV disease was significantly associated with graft loss independent of acute rejection episodes or other factors when tested in a Cox proportional model in the Aza group only (P < 10(-4)). It was shown for the first time that patients whose CMV disease is treated with ganciclovir while they are on MMF therapy are protected from the long-term deleterious consequences of CMV disease on graft survival, independent of acute rejection. It is suggested that the enhanced anti-herpes virus activity of ganciclovir by MMF could contribute to this reported effect, which may represent a significant contribution of MMF efficacy to graft survival.

Acute Disease↗