-
Nephrology Dialysis Transplantation 04/2007; 22(3):942-4. · 3.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This prospective study assesses over a period of 6 months, the variations in glomerular filtration rate (GFR) and safety parameters within a cohort of 44 cadaveric renal-transplant (RT) patients presenting with moderate renal insufficiency. They were progressively switched from calcineurin inhibitors (CNIs) based- to sirolimus (SRL) based-therapies aiming SRL troughs at levels approximately 8 ng/ml (range 6-10). All the patients were receiving in addition mycophenolate mofetil. The intent-to-treat (ITT) patient and graft survivals were 100%. Thirty-four patients, i.e. 77.3% completed the study. Overall, there was a significant improvement in the calculated GFR (Nankivell formula) from day 0 to month 6, i.e. from 45.98 (+/-16.3) to 53.07 (+/-12.68) ml/mn (P=0.03). However, renal function improved in only 20 cases (group I), and deteriorated in the others (group II). Groups I and II did not significantly differ with respect to time between transplantation and drug switch, GFR, serum creatinine, and proteinuria at baseline. There was only one case of steroid-sensitive acute rejection. Overall, there was a significant increase in proteinuria from 0 (0-3.15) to 0.57 (0-4.85) g/day (P=0.002). Finally, the conversion was associated with a significant increase in lipids, and a significant decrease in hemoglobin levels.
Transplant International 03/2007; 20(2):128-34. · 2.92 Impact Factor
-
Nephrology Dialysis Transplantation 09/2006; 21(8):2315-7. · 3.40 Impact Factor
-
Maryvonne Hourmant,
Anne Cesbron-Gautier,
Paul I Terasaki,
Kazuo Mizutani,
Anne Moreau,
Aurélie Meurette,
Jacques Dantal,
Magali Giral, Gilles Blancho,
Diego Cantarovich,
Georges Karam,
Gilles Follea,
Jean-Paul Soulillou,
Jean-Denis Bignon
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of the American Society of Nephrology 10/2005; 16(9):2804-12. · 9.66 Impact Factor
-
Flavio Vincenti,
Christian Larsen,
Antoine Durrbach,
Thomas Wekerle,
Björn Nashan, Gilles Blancho,
Philippe Lang,
Josep Grinyo,
Philip F Halloran,
Kim Solez,
David Hagerty,
Elliott Levy,
Wenjiong Zhou,
Kannan Natarajan,
Bernard Charpentier
[show abstract]
[hide abstract]
ABSTRACT: Renal transplantation is the standard of care for patients with end-stage renal disease. Although maintenance immunosuppression with calcineurin inhibitors yields excellent one-year survival, it is associated over the long term with high rates of death and graft loss, owing in part to the adverse renal, cardiovascular, and metabolic effects of these agents. The use of potentially less toxic agents, such as belatacept, a selective blocker of T-cell activation, may improve outcomes.
We randomly assigned renal-transplant recipients to receive an intensive or a less-intensive regimen of belatacept or cyclosporine. All patients received induction therapy with basiliximab, mycophenolate mofetil, and corticosteroids. The primary objective was to demonstrate the noninferiority of belatacept over cyclosporine in the incidence of acute rejection at six months (with an upper bound of the 95 percent confidence interval around the treatment difference of less than 20 percent).
At six months, the incidence of acute rejection was similar among the groups: 7 percent for intensive belatacept, 6 percent for less-intensive belatacept, and 8 percent for cyclosporine. At 12 months, the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was with cyclosporine (66.3, 62.1, and 53.5 ml per minute per 1.73 m2, respectively), and chronic allograft nephropathy was less common with both regimens of belatacept than with cyclosporine (29 percent, 20 percent, and 44 percent, respectively). Lipid levels and blood-pressure values were similar or slightly lower in the belatacept groups, despite the greater use of lipid-lowering and antihypertensive medications in the cyclosporine group.
Belatacept, an investigational selective costimulation blocker, did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation. Belatacept may preserve the glomerular filtration rate and reduce the rate of chronic allograft nephropathy.
New England Journal of Medicine 09/2005; 353(8):770-81. · 53.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
American Journal of Transplantation 07/2005; 5(6):1332-8. · 6.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dendritic cells (DC) represent a tool not only for immune activation, but also potentially for tolerance induction in transplantation. This latter approach is yet to be explored in a pre-clinical primate model. Since no information concerning baboon DC has been available, we characterised the DC of this species derived in vitro from bone marrow (CD34(+)) and peripheral blood (CD14(+)) precursors to determine which would be the most suitable for a tolerance inducing strategy. Baboon DC were differentiated in vitro using protocols similar to those used in humans and their maturation status was assessed and compared according to their phenotype and function. Based on both phenotypic and functional criteria, the CD14-derived baboon DC appeared to be less mature DC, necessitating an additional stimulus in order to become fully mature. The CD34-derived DC on the other hand appeared more mature in nature, without necessarily requiring exposure to overt maturation signals. We suggest therefore that, in the baboon, peripheral blood CD14-derived DC may be more suitable for protocols where tolerance induction is the goal. We now aim to perform further in vitro investigations into the potential tolerance inducing effects of CD14-derived DC alone or in association with other strategies that would be applicable in vivo.
Journal of Immunological Methods 03/2005; 297(1-2):237-52. · 2.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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).
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.
Transplantation 01/2005; 79(1):72-8. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Co-stimulation blockade has already been shown to induce transplantation tolerance in rodents, but until now has failed in large animal models. We therefore sought to investigate whether the addition of rapamycin to a co-stimulation blockade regimen could induce tolerance in baboon recipients of a renal allograft and to characterize the immunological characteristics of rejection.
Two baboons were used for a pharmacological and toxicological analysis and received anti-B7.1 and anti-B7 antibodies every other day for 60 days. Three groups of baboons underwent classical heterotopic renal allotransplantation; the first group received no treatment (control group; n = 2), the second received a combination of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) (B7 group; n = 4), and the third received the anti-B7 antibody treatment as above with an additional treatment of rapamycin (B7-Rapa; n = 4). Graft survival as well as immunological analyses were performed.
Anti-B7 mAb monotherapy prolonged allograft survival in three out of four of the animals, one of whom survived rejection free for 87 days but died from a pulmonary embolism; the fourth animal died without rejection. The addition of rapamycin to the regimen did not prolong survival further; three of the four animals underwent early rejection whereas the fourth survived long term but eventually rejected at day 114. Whereas alloimmunization only occurred in this latter animal, rejection was always characterized by a substantial lymphocyte and monocyte infiltration, associated with a strong pro-inflammatory/cytotoxic mRNA accumulation in the anti-B7-treated animals, but to a lesser extent in the B7-Rapa group. T cells extracted and cloned from a biopsy taken at a stable post-transplant time showed a lower frequency of anti-donor alloreactivity in vitro than those extracted from a rejected tissue. Nevertheless, these non-responding clones failed to show regulatory activity in vitro.
We thus confirm that blocking the CD28/B7 pathway by anti-B7 mAbs could prolong graft survival in baboons, but the addition of rapamycin was insufficient to induce tolerance.
Nephrology Dialysis Transplantation 08/2004; 19(7):1752-60. · 3.40 Impact Factor
-
Séverine Ménoret,
Martine Plat, Gilles Blancho,
Francoise Martinat-Botté,
Pierre Bernard,
Georges Karam,
Laurent Tesson,
Karine Renaudin,
Philippe Guillouet,
Bernard Weill,
Christiane Chéreau,
Louis-Marie Houdebine,
Jean-Paul Soulillou,
Michel Terqui,
Ignacio Anegon
[show abstract]
[hide abstract]
ABSTRACT: New transgenic pigs expressing combinations of regulators of complement activation and other molecules are needed to resist xenograft hyperacute rejection (HAR) and to further analyze and treat xenograft rejection. Double transgenic pigs for human CD55 (hCD55) and human CD59 (hCD59) using the promoter of the human elongation factor 1 alpha gene were generated, and their kidneys were transplanted into nonimmunosuppressed baboons. hCD55 and hCD59 were mainly expressed by the endothelial cells, and these cells showed increased resistance to complement-mediated lysis. Baboons receiving kidneys from hCD55hCD59 pigs survived for 5 and 6 days, and displayed alterations in coagulation. Thrombocytopenia and platelet microthrombi were present within the kidneys. Nontransgenic kidneys showed HAR in less than 2 days. Kidneys from pigs expressing hCD55hCD59 displayed protection against HAR in the absence of immunosuppression. Rejection was associated with coagulopathy leukocyte infiltration and a rebound of anti-alpha Gal antibodies.
Transplantation 06/2004; 77(9):1468-71. · 4.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Purpose of review: The purpose of this paper is to review advances in the field of pig-to-primate xenotransplantation in the past 2 years, which has been dominated by the development of Gal-negative pigs.
Recent findings: In the past 2 years, much effort has been channeled into overcoming one of the major challenges in pig-to-nonhuman primate xenotransplantation: the humoral response. Some success has been achieved using antibody neutralization approaches, whereas inhibition of natural and elicited antiporcine antibodies by targeting B or plasma cells has proven difficult in many cases. Tolerance-inducing approaches in the pig-to-primate combination have given promising results but are severely hampered by the humoral response. The greatest milestone in xenotransplantation in recent years is most certainly the development of knockout pigs for the α-1,3-galactosyltransferase gene and thus negative for the Gal-α-1,3-Gal (Gal) antigen. The results of initial experiments with these donors reported at the recent International Xenotransplantation Association congress suggest that in some cases, coagulation may play a key role in the rejection of such organs but that a tolerance-inducing approach can help to promote rejection-free survival. Some questions remaining in the field of xenotransplantation concern the suitability of nonhuman primates to assess infection by porcine viruses such as porcine endogenous retrovirus and the ethical dilemmas posed by the use of animals as well as the potential health risks for future xenograft recipients and the wider population.
Summary: A new era of preclinical research using Gal-negative donor pigs in nonhuman primates is now beginning, and this will enable the many questions remaining in this field to be addressed.
Current Opinion in Organ Transplantation 05/2004; 9(2):181-185. · 2.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transplantation of a kidney presenting a tumour is an exceptional situation. The authors report a case of programmed renal transplantation after resection of an angiomyolipoma on living donor kidney.
Progrès en Urologie 05/2004; 14(2):205-6. · 0.58 Impact Factor
-
Joanna Ashton-Chess,
Guillaume Meurette,
Georges Karam,
Thomas Petzold,
David Minault,
Jeanne Naulet,
Laurent Tesson,
Martine Plat,
Ignacio Anegon,
Jean-Paul Soulillou, Gilles Blancho
[show abstract]
[hide abstract]
ABSTRACT: Mounting evidence suggests that delayed xenograft rejection (DXR) of discordant xenografts has a strong humoral component. To explore the possibility of targeting this humoral response more efficiently, we performed a preliminary study in baboons immunized against pig blood cells using the immunosuppressor mitoxantrone (Mx). The results from this study showed that, in comparison with cyclophosphamide (CyP), Mx induced a long-lasting depletion of circulating B cells within 6 days of its administration and delayed secondary anti-Gal antibody (Ab) responses to pig blood cell immunizations. Given these results, we next evaluated Mx in an in vivo model of pig to baboon renal xenotransplantation. We performed a series of renal xenotransplantations in baboons using human CD55-CD59 transgenic donor pigs. In the first group of baboons (Mx group; n = 4) Mx was administered 6 days prior to the day of transplantation, the objective being to perform the xenotransplantation in a context where the recipient would have few remaining circulating B cells and thus have an impaired capacity to mount an Ab response to the xenograft. We compared this group to a second group of baboons treated with CyP starting 1 day prior to transplantation (CyP group; n = 2). All baboons receiving Mx or CyP received an additional immunosuppression of cyclosporin A, mycophenolate mofetil and steroids. No hyperacute rejection was observed in either group but all xenografts underwent DXR. Mx did not show superiority to CyP in terms of graft survival with a mean survival time of 8 +/- 2 days compared with 9 days for both CyP-treated baboons. Neither CyP nor Mx decreased serum levels of pre-existing anti-Gal Abs but levels of these Abs decreased dramatically within 1 day of transplantation, likely reflecting their immediate trapping within the xenograft. Interestingly however, in contrast to CyP, Mx inhibited the return of anti-Gal immunoglobulin M (IgM) to the circulation, even at the time of rejection. Nevertheless, strong intragraft deposits of IgM, IgG and the activated complement complex C5b-9 were observed in biopsies at rejection. Furthermore, despite the expected profound depletion of circulating B cells by Mx within 6 days of its administration, biopsies from both groups at rejection displayed a mild B cell infiltrate accompanied by a strong macrophage and intermediate T-cell infiltration, the latter tending to be more abundant in Mx-treated animals. Our data show that in this particular model of pig to baboon xenotransplantation and at the dose used, Mx was not superior to CyP in conferring protection against rejection, despite its capacity to profoundly deplete circulating B cells and to inhibit anti-Gal Ab responses to xenografts. DXR was thus possible without the return of anti-Gal Abs and may have been mediated by the early fixation of pre-existing Abs with secondary complement activation. However, although Mx was not more efficient than CyP in controlling DXR, its capacity to deplete B cells and delay Ab recovery may be beneficial in the context of Gal knockout organ transplantation where the induced Ab response is likely to take precedence over the preformed response.
Xenotransplantation 04/2004; 11(2):112-22. · 2.33 Impact Factor
-
Joanna Ashton-Chess,
Jean-Christian Roussel,
Pierre Bernard,
Nathalie Barreau,
Georges Karam,
Jacques Dantal,
Anne Moreau,
Eric Letessier,
Takaharu Nagasaka,
Cozzi Emanuele,
David Minault,
Jean-Paul Soulillou, Gilles Blancho
[show abstract]
[hide abstract]
ABSTRACT: Delayed xenograft rejection (DXR) remains a major obstacle in discordant xenotransplantation. As strategies of complement inhibition and xenogeneic natural antibody (Ab) removal have been shown to give prolonged xenograft survival, we endeavored to determine whether combining these two strategies would lead to an additive effect in terms of graft survival. The study was initiated with two groups, A and B, where group A received normal kidneys and group B received hCD55 transgenic kidneys. Both groups underwent pre-transplant (day-1) total immunoglobulin (Ig) immunoadsorption (IA) and received an immunosuppression of cyclophosphamide, cyclosporine A, mycophenolate mofetil and corticosteroids. Two subsequent groups (C and D) receiving hCD55 transgenic pig kidneys were then performed with an 'optimized' immunosuppression (Cyclophosphamide starting 1 day earlier) but only group D recipients were immunoadsorbed. Biopsies taken during the post-transplantation period were analyzed for Ab deposition, compliment activation and cellular infiltration. No hyperacute rejection was observed. In the initial immunoadsorbed groups A and B, all baboons underwent DXR, which started surprisingly early (day 5 in most cases. In the subsequent two groups, the immunoadsorbed group D baboons also underwent DXR, again as early as day 5. In contrast, group C baboons did not show any signs of DXR on their day 6 biopsy or at their time of death. Analysis of graft biopsies from the kidneys undergoing rejection or with stable function showed strong deposition of anti-Gal IgM in all cases whereas strong complement C5b-9 deposits were only observed in biopsies at rejection. Cellular infiltration consisted mostly of monocytes/macrophages, was more pronounced in biopsies taken at rejection and was associated with a pro-inflammatory environment involving interleukins 1alpha, 6 and 8. Our findings suggest non-specific Ig (anti-Gal and non-Gal Ig of all isotypes) IA or even incomplete IA in immunosuppressed baboon recipients of transgenic pig kidneys is detrimental to graft survival by being associated with an Ab and compliment driven rejection. We speculate that the IA were insufficient in terms of Ig depletion or frequency inducing an Ab rebound or that this total Ig depletion also removed components facilitating graft survival.
Xenotransplantation 12/2003; 10(6):552-561. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Besides virological and physiological concerns, the success of xenotransplantation (Xt) is still dependent on the prevention of delayed xenograft rejection (DXR). Although multifactorial, DXR is mainly due to xenonatural antibody (Ab) recognizing their xenogenic antigen (Ag) followed by complement activation. Despite the use of intensive treatments capable of inhibiting the humoral response, DXR can still not be avoided and always occurs within weeks following transplantation. Moreover, these latter treatments currently used in Xt could not be used clinically in humans because of their high risk of over-immunosuppressing the patients. Mitoxantrone (Mx) is a drug well known for its antiproliferative properties and is used clinically in oncology and in the treatment of relapsing multiple sclerosis. In models of arthritis in rats, it has been shown to be 10 to 20 times more powerful than cyclophosphamide (CyP) at blocking both inflammatory and B-cell responses. Because of its B-cell inhibitory capacity and considering the implication of the humoral response in xenograft rejection, we have compared Mx with CyP for its ability to block in vivo anti-pig immunization induced via subcutaneous injections of pig red blood cells into baboons. Neither drug was able to inhibit the anti-pig responses following the first and second immunizations, emphasizing the particularity of preformed Ab responses. However, the rise in Ab in the Mx treated animals was significantly delayed as compared with the non-treated as well as the CyP treated animals and was mainly because of a profound depletion of circulating B-cells. Mx displays an interesting antihumoral effect that we now intend to test in a pig kidney to baboon Xt model, with anticipated administration of the drug allowing an early B-cell depletion.
Xenotransplantation 10/2003; 10(5):422-31. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Delayed xenograft rejection (DXR) of pig organs by baboons currently represents the major obstacle to successful xenotransplantation. Although antibodies (Abs) are believed to play a fundamental role in this form of rejection, so far little is known concerning the potential cellular component. Biopsies taken during DXR of human CD55 transgenic pig hearts by non-treated (n = 2), alpha-Gal immunoadsorbed (n = 2), or immunosuppressed (n = 9) baboons were studied. The cellular element was explored by determining not only its phenotype by classical immunohistochemical techniques but also its activity in terms of cytokines, cytolytic enzymes and other mediators using quantitative reverse transcription polymerase chain reaction. All porcine xenografts underwent DXR; within 5 days in non-treated and immunoadsorbed animals but significantly delayed (6 to 29 days) in immunosuppressed animals. Cellular infiltration in non-immunosuppressed grafts consisted predominantly of monocytes/macrophages, CD8 cells and a few CD4 T-cells. The predominant baboon transcripts detectable were the proinflammatory cytokines interleukin1-alpha and tumor necrosis factor-alpha, the lymphokine interferon-gamma and the cytotoxic enzyme granzyme B. However, these cellular components were lacking in the immunosuppressed animals. Despite these differences, strong immunoglobulin M (IgM) and C5b-9 complement deposition was observed in all animals at rejection. Together our findings suggest that although the humoral response plays a predominant role in DXR through IgM Abs and complement activation, there is a clear cellular infiltrate in DXR in this model that is likely to contribute to rejection through a strong pro-inflammatory and cytotoxic environment, necessitating substantial immunosuppression for a prolonged graft survival.
Xenotransplantation 10/2003; 10(5):446-53. · 2.33 Impact Factor
-
Stéphanie Coupel,
Magali Giral-Classe,
Georges Karam,
Jean-François Morcet,
Jacques Dantal,
Diego Cantarovich, Gilles Blancho,
Jean-Denis Bignon,
Pascal Daguin,
Jean-Paul Soulillou,
Maryvonne Hourmant
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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).
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.
Kidney International 08/2003; 64(2):674-80. · 6.61 Impact Factor
-
St|[eacute]|phanie Coupel,
Magali Giral-Classe,
Georges Karam,
Jean-Fran|[ccedil]|ois Morcet,
Jacques Dantal,
Diego Cantarovich, Gilles Blancho,
Jean-Denis Bignon,
Pascal Daguin,
Jean-Paul Soulillou,
Maryvonne Hourmant
[show abstract]
[hide abstract]
ABSTRACT: 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.
Kidney International 07/2003; 64(2):674-680. · 6.61 Impact Factor
-
Magali Giral,
Giovani Pascuariello,
Georges Karam,
Maryvonne Hourmant,
Diego Cantarovich,
Jacques Dantal, Gilles Blancho,
Stephanie Coupel,
Regis Josien,
Pascal Daguin,
Sandra Méchineau,
Jean Paul Soulillou
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
Kidney International 06/2002; 61(5):1880-6. · 6.61 Impact Factor
-
Magali Giral,
Giovani Pascuariello,
Georges Karam,
Maryvonne Hourmant,
Diego Cantarovich,
Jacques Dantal, Gilles Blancho,
Stephanie Coupel,
Regis Josien,
Pascal Daguin,
Sandra M|[eacute]|chineau,
Jean Paul Soulillou
[show abstract]
[hide abstract]
ABSTRACT: 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.
Kidney International 04/2002; 61(5):1880-1886. · 6.61 Impact Factor
