Early outcomes of kidney transplantation from elderly donors after circulatory death (GEODAS study).

BACKGROUND: Spain has dramatically increased the number of controlled circulatory death donors (cDCD). The initial selection criteria for considering cDCD for kidney transplantation (KT) have been expanded progressively, with practically no limits in donor age during the last years. We aimed to analyze the early clinical outcomes using expanded (> 65 years) cDCD in comparison with standard ones. METHODS: Observational multicenter study including 19 transplant centers in Spain. We performed a systematic inclusion in a central database of every KT from expanded cDCD at each participant unit from January-2012 to January-2017. Surgical procedures and immunosuppressive protocols were based on local practices. Data was analyzed in the central office using logistic and Cox regression or competitive-risk models for multivariate analysis. Median time of follow-up was 18.1 months. RESULTS: 561 KT were performed with kidneys from cDCD, 135 from donors older than 65 years. As expected, recipients from older cDCD were also older (65.8 (SD 8.8) vs 53.7 (SD 11.4) years; p < 0.001) and with higher comorbidity. At 1 year, no differences were found amongst older and younger cDCD KT recipients in terms of serum creatinine (1.6 (SD 0.7) vs 1.5 (SD 0.8) mg/dl; p = 0.29). Non-death censored graft survival was inferior, but death-censored graft survival was not different (95.5 vs 98.2% respectively; p = 0.481). They also presented a trend towards higher delayed graft function (55.4 vs 46.7%; p = 0.09) but a similar rate of primary non-function (3.7 vs 3.1%; p = 0.71), and acute rejection (3.0 vs 6.3%; p = 0.135). In the multivariate analysis, in short follow-up, donor age was not related with worse survival or poor kidney function (eGFR < 30 ml/min). CONCLUSIONS: The use of kidneys from expanded cDCD is increasing for older and comorbid patients. Short-term graft outcomes are similar for expanded and standard cDCD, so they constitute a good-enough source of kidneys to improve the options of KT wait-listed patients.

Trasplante renal con órganos procedentes de donación tras parada circulatoria controlada: resultados del estudio multicéntrico GEODAS-3 / Kidney transplant from controlled donors following circulatory death: Results from the GEODAS-3 multicentre study

Introducción: Varios países eu:ropeos disponen de programas de donación tras parada cardiaca controlada (cDCD). Veintidós centros participan en el grupo GEODAS, cuyos resultados clínicos presentamos desde una perspectiva nefrológica. Métodos: Estudio multicéntrico retrospectivo observacional con inclusión sistemática de todos los trasplantes renales (TR) procedentes de cDCD, siguiendo protocolos locales de extracción e inmunosupresión. Resultados: Se incluyó a 335 donantes tras cDCD (edad media 57,2 años) fallecidos mayoritariamente por eventos cardiovasculares. Se analizan 566 receptores (edad media de 56,5 años; el 91,9% con primer trasplante renal), con una mediana de seguimiento de 1,9 años. La terapia de inducción fue casi universal (timoglobulina 67,4%; simulect 32,8%) con mantenimiento con prednisona-MMF-tacrolimus (91,3%) o combinaciones con mTOR (6,5%). El tiempo medio de isquemia fría (CIT) fue 12,3 h. Hubo un 3,4% de fallo primario del injerto (n = 19), asociado fundamentalmente al tiempo de isquemia fría (solo el CIT ≥ 14 h se asoció a fallo primario del injerto). La función retrasada del injerto (DGF) fue 48,8%. Los factores de riesgo para la DGF fueron: CIT ≥ 14 h OR 1,6, procedencia de hemodiálisis (vs. diálisis peritoneal) OR 2,1 y edad del donante OR 1,01 (por año). Veintiún pacientes fallecieron con injerto funcionante (3,7%), con una supervivencia de paciente e injerto (censurada para muerte) al segundo año del 95% y del 95,1%, respectivamente. El filtrado glomerular estimado al año de seguimiento fue 60,9ml/min. Conclusiones: El CIT es un factor modificable para mejorar la incidencia del fallo primario del injerto en trasplante renal procedente de cDCD. El trasplante renal con cDCD tiene mayor incidencia en la función retrasada del injerto, pero igual supervivencia de paciente e injerto que la referencia histórica para donación en muerte encefálica. Los resultados son satisfactorios para continuar promoviendo este tipo de donación. Conclusiones: El CIT es un factor modificable para mejorar la incidencia del fallo primario del injerto en trasplante renal procedente de cDCD. El trasplante renal con cDCD tiene mayor incidencia en la función retrasada del injerto, pero igual supervivencia de paciente e injerto que la referencia histórica para donación en muerte encefálica. Los resultados son satisfactorios para continuar promoviendo este tipo de donación

Introduction: Many European countries have transplant programmes with controlled donors after cardiac death (cDCD). Twenty-two centres are part of GEODAS group. We analysed clinical results from a nephrological perspective. Methods: Observational, retrospective and multicentre study with systematic inclusion of all kidney transplant recipients from cDCD, following local protocols regarding extraction and immunosuppression. Results: A total of 335 cDCD donors (mean age 57.2 years) whose deaths were mainly due to cardiovascular events were included. Finally, 566 recipients (mean age 56.5 years; 91.9% first kidney transplant) were analysed with a median of follow-up of 1.9 years. Induction therapy was almost universal (thymoglobulin 67.4%; simulect 32.8%) with maintenance with prednisone-MMF-tacrolimus (91.3%) or combinations with mTOR (6.5%). Mean cold ischaemia time (CIT) was 12.3 h. Approximately 3.4% (n = 19) of recipients experienced primary non-function, essentially associated with CIT (only CIT ≥ 14 h was associated with primary non-function). Delayed graft function (DGF) was 48.8%. DGF risk factors were CIT ≥ 14 h OR 1.6, previous haemodialysis (vs. peritoneal dialysis) OR 2.1 and donor age OR 1.01 (per year). Twenty-one patients (3.7%) died with a functioning graft, with a recipient and death-censored graft survival at 2-years of 95% and 95.1%, respectively. The estimated glomerular filtration rate at one year of follow-up was 60.9 ml/min. Conclusions: CIT is a modifiable factor for improving the incidence of primary non-function in kidney transplant arising from cDCD. cDCD kidney transplant recipients have higher delayed graft function rate, but the same patient and graft survival compared to brain-dead donation in historical references. These results are convincing enough to continue fostering this type of donation

Kidney transplant from controlled donors following circulatory death: Results from the GEODAS-3 multicentre study. / Trasplante renal con órganos procedentes de donación tras parada circulatoria controlada: resultados del estudio multicéntrico GEODAS-3.

INTRODUCTION: Many European countries have transplant programmes with controlled donors after cardiac death (cDCD). Twenty-two centres are part of GEODAS group. We analysed clinical results from a nephrological perspective. METHODS: Observational, retrospective and multicentre study with systematic inclusion of all kidney transplant recipients from cDCD, following local protocols regarding extraction and immunosuppression. RESULTS: A total of 335 cDCD donors (mean age 57.2 years) whose deaths were mainly due to cardiovascular events were included. Finally, 566 recipients (mean age 56.5 years; 91.9% first kidney transplant) were analysed with a median of follow-up of 1.9 years. Induction therapy was almost universal (thymoglobulin 67.4%; simulect 32.8%) with maintenance with prednisone-MMF-tacrolimus (91.3%) or combinations with mTOR (6.5%). Mean cold ischaemia time (CIT) was 12.3h. Approximately 3.4% (n=19) of recipients experienced primary non-function, essentially associated with CIT (only CIT ≥ 14 h was associated with primary non-function). Delayed graft function (DGF) was 48.8%. DGF risk factors were CIT ≥ 14 h OR 1.6, previous haemodialysis (vs. peritoneal dialysis) OR 2.1 and donor age OR 1.01 (per year). Twenty-one patients (3.7%) died with a functioning graft, with a recipient and death-censored graft survival at 2-years of 95% and 95.1%, respectively. The estimated glomerular filtration rate at one year of follow-up was 60.9 ml/min. CONCLUSIONS: CIT is a modifiable factor for improving the incidence of primary non-function in kidney transplant arising from cDCD. cDCD kidney transplant recipients have higher delayed graft function rate, but the same patient and graft survival compared to brain-dead donation in historical references. These results are convincing enough to continue fostering this type of donation.

Role of HHV-8 and mTOR pathway in post-transplant Kaposi sarcoma staging.

Kaposi's sarcoma (KS) is one of the most frequent transplant related tumors. Several pathways are involved; however, the impact of the molecular phenotype associated to the tumor stage and the behavior-depending resultant therapy is still unknown. The aim of our study was to analyze the role of HHV-8 and mTOR pathway in tumor stages of skin KS after renal transplantation. Twelve renal transplant recipients with cutaneous KS from five transplant centers (1980-2007) under reduction of immunosuppression or conversion to mTOR inhibitor were included. The expression of HHV-8, PTEN, TGFß, VEGF, phospho-mTOR, and phospho-P70S6K in tumoral tissue was analyzed. KS lesions were classified as patch, plaque, and nodule state. HHV-8 infection was found in all tissue samples. KS lesions showed high activation of VEGF, p-mTOR and p-P70S6K, low PTEN, and null TGFß expression. The only pathway activated in a staging-dependent manner was mTOR with higher p-mTOR and p-P70S6K expression in nodule versus patch stage. KS lesions disappeared after 5.24 months in all converted patients without any recurrence in 14.05 years of mean follow-up. The activation of mTOR pathway according to KS stages supports the rational of the mTOR inhibitor in post-transplant Kaposi.