Optimization of immunosuppression by switching from azathioprine to enteric-coated mycophenolate sodium in stable kidney transplant patients.

The aim of our retrospective, observational, single center study was to analyze renal function changes among stable kidney transplant patients treated with a calcineurin inhibitor (CNI) + azathioprine (AZA), in whom immunosuppression was optimized by a switch from AZA to enteric-coated mycophenolate sodium (EC-MPS) with a view to protecting long-term renal function. Between April 2005 and June 2008, 36 renal transplant patients on previous treatment with a CNI and AZA for a period of 86.94 +/- 66.9 months were switched to EC-MPS. After the change, there were no cases of acute rejection episodes. Six patients (16.6%) developed gastrointestinal secondary effects and 5 had to discontinue EC-MPS treatment: 4 due to severe diarrhea 1 due to thrombocytopenia. Among the remaining patients, it was possible to gradually increase the EC-MPS dose (starting at 376 +/- 122 mg/d vs current at 533.5 +/- 210 mg/d; P < .002), maintaining through levels at 2.1 +/- 1.9 ng/mL. Although 11 patients (30.5%) displayed chronic allograft nephropathy upon the preconversion biopsy, at a follow-up of 29.2 +/- 9.4 months they showed significantly improved renal function (Modification of Diet in Renal Disease [MDRD4] at change 49.5 +/- 19.8 mL/min/1.73 m(2) vs current MDRD4 55.6 +/- 23.4 mL/min/1.73 m(2); P = .02), with no increase in proteinuria (proteinuria at change 0.4 +/- 0.4 g/d vs current proteinuria 0.4 +/- 0.5 g/d; P = NS). This improvement was evident without changes in CNI levels: cyclosporine at change 133.1 +/- 30.2 ng/mL vs current 122 +/- 28 ng/mL (P = NS) and tacrolimus at change 7.7 +/- 2.2 ng/mL vs current 8.2 +/- 2.4 ng/mL (P = NS). In conclusion, conversion from AZA to EC-MPA to optimize immunosuppression seemed to be safe, with no complications in 85% of cases, as well as effective, achieving improved long-term renal function protection. These results suggested a greater protective immunological effect by switching from AZA to EC-MPA.

[Experience with kidney transplantation with children as donors]. / Experiencia en trasplante renal con donantes infantiles.

OBJECTIVE: To analyze the results achieved with transplantation of children kidneys to adult recipients. METHODS: The results achieved with transplantation of children cadaver kidneys (< 15 years) from 1989 to 1994 over a follow-up period of at least 36 months were reviewed. Patients (n = 43) were stratified into group A (13 grafts from donors < or = 6 years), group B (30 grafts from donors > 6 years) and group C (control group), which comprised 73 patients who received grafts from donors of an ideal age during the same time period. All three groups were similar for variables considered to influence the results of transplantation, except for the higher incidence of hypotension in group B. RESULTS: The number of episodes of rejection was three-fold higher in group A than in the control group (p = 0.019). A higher incidence of surgical complications, principally vascular complications (arterial thrombosis, renal rotation), was found in group A versus the control group (p = 0.039). When the grafts transplanted en bloc from donors under 12 months were excluded from the analysis, the incidence of vascular or urological surgical complications in group A was not found to be higher than that of the control group. No difference was found for mean length of stay, renal function (creatininemia), graft or patient survival for the three groups. CONCLUSIONS: Grafts from donors more than 6 years old showed a similar behavior as those from donors of an ideal age. Furthermore, single kidneys from donors aged more than 12 months can be transplanted with excellent results. It is necessary to have a larger series to confirm and explain the high incidence of acute rejection in grafts from donors less than 6 years old.

Los injertos renales de donantes cadáver mayores de 60 años deben ser considerados subóptimos / Cadaver kidney grafts from donors over 60 should be considered suboptimal

Ante la escasez de órganos para trasplante una posible solución es la utilización de injertos procedentes de donantes añosos (mayores de 50 años). Revisamos nuestra experiencia en el periodo entre 1989-1994, para obtener un seguimiento mínimo de 36 meses. Para ello, comparamos tres grupos: donantes entre 50-60 años (N = 32), donantes mayores de 60 años (N = 25) y un control de edades "ideales" (N = 73). Los resultados han puesto de manifiesto que los donantes mayores de 60 años presentan, con respecto al control, una mayor incidencia de NTA (p = 0,032), una creatininemia significativamente mayor en todos los intervalos considerados y una supervivencia del injerto inferior en un 14 por ciento y un 40 por ciento a los 12 y 36 meses respectivamente (p = 0,0009). Los motivos de estas diferencias cabe atribuirlos a factores intrínsecos relacionados con los cambios que la edad y condiciones patológicas ejercen sobre estos órganos, ya que no se ha detectado una mayor incidencia de complicaciones inmunológicas o quirúrgica (AU)

[HLA compatibility and antigenic re-exposure. Impact on the clinical course of cadaver kidney transplantation]. / Compatibilidad HLA y reexposición antigénica. Influencia en la evolución del retrasplante renal de cadáver.

OBJECTIVES: A number of prediction factors on the outcome of cadaver renal transplants have been recognized, particularly the influence of recipient response to the first graft. However, the influence of HLA compatibility and of repeated recipient and donor antigen mismatches remain a controversy. The importance of the foregoing on the survival of the second renal graft is analyzed in this study. METHODS: The clinical records of 80 patients who had undergone a second cadaver renal transplantation from 1985 to 1995 at the Hospital 12 de Octubre (Madrid, Spain) were reviewed. Data on the recipient, donor and graft characteristics and outcome of the first and second transplants were collected for multivariate analysis of graft survival using the Cox regression method. The importance of the overall HLA compatibility and of each HLA locus, and the effect of antigenic re-exposure on the survival of the second renal graft were analyzed. RESULTS: The multivariate analysis showed a significant increase of the survival of the second graft when there were at least three compatible antigens between donor and recipient (p = 0.02). Compatibility of the HLA-A and DR loci appeared to improve the outcome, although the differences were not statistically significant. However, a significant improvement in the survival of the second cadaver renal allograft was found for repeated HLA mismatches between the recipient and donors (p = 0.006). CONCLUSIONS: Our data corroborate the benefits of assigning renal grafts according to the degree of HLA compatibility also for the second renal transplant. Furthermore, our data show that re-exposure to previous mismatched antigens need not be hazardous for the second renal transplant in the cyclosporine era.

[Cadaver kidney grafts from donors over 60 years of age should be considered as suboptimal]. / Los injertos renales de donantes cadáver mayores de 60 años deben ser considerados subóptimos.

Considering the scarcity of organs for transplantation, one possible solution is the use of grafts from aged donors (over 50 years). We have reviewed our experience in the case of kidney transplantation considering the period from 1989-1994 in order to attain a minimum follow-up of 36 months. We compare three groups: donors aged between 50-60 years (n = 32), donors aged over 60 years (n = 25) and a control group formed by donors of "ideal" ages. The results show that kidneys from donors over 60 years evidence, as compared to the control group, a higher incidence of acute tubular necrosis (p = 0.032), significantly higher blood creatinine levels in all the intervals considered, and a graft survival which is 14% less at 12 months and 40% less at 36 months (p = 0.0009). These differences are most probably to be attributed to the changes caused in these organs by advancing age and by previous pathological situations, as we have not detected a higher incidence of immunologic or surgical complications.

[Impact of transplantectomy of the first graft on the clinical course of cadaver renal retransplantation]. / Influencia de la trasplantectomía del primer injerto en la evolución del retrasplante renal de cadáver.

PURPOSE: At the present time a number of prediction factors on the outcome of second cadaver renal transplants are known, in particular the influence of recipient response to the first graft. However, we do not know if retaining or removing the non-functioning organ has any repercussion on subsequent transplants. This is the object of the present study. MATERIAL AND METHODS: A retrospective study was carried out on the clinical records of 80 patients who had undergone a second cadaver renal transplant under CyA between 1985-1995 at Hospital 12 de Octubre. Data on the characteristics and outcome of the first and second transplants were collected, plus those concerning the recipient and donor. These variables were used to construct a multivariant analysis model of graft survival. The nephrectomy of the non-functioning graft was only carried out when absolutely necessary (n = 58). RESULTS: The multivariant analysis showed that the nephrectomy of the non functioning graft did not modify the risk of recipient sensitization or the probability of developing acute or chronic rejection of the second graft. However, it reduced the risk of losing this second graft at medium or long term significantly (p = 0.009). CONCLUSIONS: These data constitute the first solid argument in favor of elective nephrectomy in candidates for a second cadaver renal transplant. Nevertheless, a more thorough study should be carried out of the immunological mechanism involved before recommending this as a general procedure.