Amelioration of renal damage by administration of anti-thymocyte globulin to potential donors in a brain death rat model

Brain death (BD), a non-immunological factor of renal injury, triggers an inflammatory process causing pathological signs of cell death in the kidney, such as necrosis and apoptosis. Kidneys from brain dead donors show lower success rates than kidneys from living donors and one strategy to improve transplantation outcome is to precondition the donors. For the first time, anti-rat thymoglobulin (rATG) was administered in an experimental brain death animal model to evaluate if it could ameliorate histopathological damage and improve organ function. Animals were divided into three groups: V (n = 5) ventilated for 2 h; BD (n = 5) brain death and ventilated for 2 h; and BD+rATG (n = 5) brain death, ventilated for 2 h, rATG was administered during brain death (10 mg/kg). We observed lower creatinine levels in treatment groups (means): V, 0·88 ± 0·22 mg/dl; BD, 1·37 ± 0·07 mg/dl; and BD+rATG, 0·64 ± 0·02 mg/dl (BD versus BD+rATG, P < 0·001). In the BD group there appeared to be a marked increase of ATN, whereas ATN was decreased significantly in the rATG group (V, 2·25 ± 0·5 versus BD, 4·75 ± 0·5, P < 0·01; BD+rATG, 2·75 ± 0·5 versus BD 4·75 ± 0·5 P < 0·01). Gene expression was evaluated with reverse transcription–polymerase chain reaction; tumour necrosis factor (TNF)-α, interleukin (IL)-6, C3, CD86 showed no significant difference between groups. Increased IL-10 and decreased CCL2 in BD+rATG compared to BD (both cases P < 0·01). Myeloperoxidase was increased significantly after the brain death setting (V: 32 ± 7·5 versus BD: 129 ± 18). Findings suggest that rATG administered to potential donors may ameliorate renal damage caused by BD. These findings could contribute in the search for specific cytoprotective interventions to improve the quality and viability of transplanted organs.Facultad de Ciencias Médica

Modelo de donante cadavérico con criterio neurológico de muerte en la rata de laboratorio

El modelo experimental de trasplante de órganos y tejidos en la rata, se ha llevado a cabo tradicionalmente con donante vivo. La complejidad de lograr un donante cadavérico en roedores de laboratorio, ha restringido su utilización. Esta situación limita la extrapolación de los resultados a la realidad clínica, donde mayoritariamente se utilizan órganos extraídos de donantes cadavéricos. La necesidad de poseer resultados experimentales, tanto en donante vivo como cadavérico, nos ha llevado a optimizar el modelo de donante de órganos en rata con criterio neurológico de muerte y asistencia respiratoria mecánica.Facultad de Ciencias Médica

Afectación de vías de apoptosis cuando se administra inmunosupresión a los donantes: rol de TNFA, BAX y BCL-2

El trasplante renal en ratas isogénicas es el modelo más ampliamente usado para el estudio de factores de daño no-inmunológicos. TNF∝ es una citokina pro inflamatoria que esta up-regulada en el proceso de injuria por isquemi-reperfusión (IRI) y está involucrada en la vía extrínseca de apoptosis. Bcl-2 y Bax son genes anti y pro apoptóticos involucrados en la vía intrínseca. Nuestro objetivo fue determinar cuáles vías apoptóticas están afectadas por la administración de diferentes drogras inmunosupresoras (sirolimus y FK506) al donanteFacultad de Ciencias Médica

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate´s phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.J.T.S. holds a research contract from the Fundación para la Formación e Investigación de los Profesionales de la Salud de Extremadura (FundeSalud), Instituto de Salud Carlos III. M.F.R. holds a clinical research contract “Juan Rodés” (JR14/00036) from the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III

The Role of Midkine in the Inflammatory Process and Its Correlation with Other Inflammatory Markers in Renal Transplant Recipients

Background: Midkine (MK), which is expressed in the proximal tubular epithelial cells of the kidney, is thought to have a role in the pathophysiology of inflammation-related renal diseases. Both immunological and nonimmunological mechanisms may affect renal functions negatively during the early and late post-transplantation periods. We aimed in our study to evaluate the relationship of MK with clinical findings and inflammatory markers, including high sensitivity C-reactive protein (hs-CRP), interleukin (IL-6) and tumor necrosis factor (TNF-alpha) in the pretransplant and post-transplant period