En marge d'expériences actuelles visant à développer une méthodologie analytique sur la pharmacocinétique-pharmacodynamique de la N-acétyl-cystéine (NAC) en prévention de la néphropathie liée à l'exposition aux substances de contraste (NESC), une mesure de la clairance des substances de contraste a été mise au point comme marqueur de filtration glomérulaire (FG) étant donné que celles-ci sont totalement éliminées par FG. Ainsi, la mesure de la FG a été déterminée par la clairance de l'iohexol, substance de contraste utilisée en imagerie médicale. L'originalité de ce projet est triple: (1) mesurer la clairance de l'iohexol (Omnipaque) chez des patients recevant également de l'iodixanol (Visipaque), substance de contraste de plus en plus utilisée; (2) explorer la mesure de la clairance d'iodixanol et (3) utiliser la spectrométrie de masse couplée à la chromatographie liquide, qui depuis les dernières années s'est taillée une place de plus en plus importante, pour le dosage de l'iohexol et de l'iodixanol. Le projet actuel s'est déroulé chez 17 sujets avec divers niveaux de fonction rénale devant subir des examens d'imagerie avec des substances de contraste. Une dose-traceur d'iohexol (5 ml) a été co-administrée avec l'iodixanol (environ 95 ml). Des spécimens sanguins ont été obtenus 0, 1, 2, 3, 4, 8 et 24 heures post-imagerie pour mesurer les clairances de l'iohexol et de l'iodixanol. Le comportement des autres marqueurs conventionnels de FG, soit le taux créatinine plasmatique et la clairance de la créatinine, ainsi que la clairance de la cystatine C et la clairance d'iodixanol ont été comparés à la clairance d'iohexol. Par conséquent, un protocole scientifique par HPLC-MSD Tof a été développé afin de séparer et de quantifier les molécules iohexol et iodixanol co-administrées dans le plasma des sujets. Les mesures des taux plasmatiques de ces deux molécules ont permis de déterminer par des calculs pharmacocinétiques que la clairance de l'iohexol discrimine bien la fonction rénale des sujets avec une fonction rénale normale de ceux avec une fonction rénale diminuée. De plus, il a été démontré qu'une seule mesure post-4 heures est suffisante pour diagnostiquer l'état de la fonction rénale d'un patient qui a subi une intervention demandant une exposition aux substances de contraste. Les corrélations entre la clairance de l'iohexol et d'autres marqueurs conventionnels de FG ainsi que celle de l'iodixanol ont illustré que la clairance de la créatinine calculée soit par l'équation MDRD (r = 0,714 et p = 0,001) ou par Cockcroft et Gault (r = 0,518 et p = 0,033) et la clairance de la cystatine C (r = 0,671 et p = 0,003) corrèlaient de manière significative avec l'étalon d'or, soit la clairance de l'iohexol. C'est pourquoi, il pourrait être possible de se fier à la mesure de la clairance de l'iohexol comme meilleur marqueur de FG afin de prévenir, de diagnostiquer et de traiter la NESC. De plus, des expériences scientifiques en recherche fondamentale pourront enfin être menées pour déterminer la relation pharmacodynamique- pharmacocinétique de la N-acétylcystéine dans la prévention de la NESC à l'aide de la mesure de la clairance de l'iohexol comme marqueur fiable de la FG. Enfin, les mécanismes d'action qui interviennent dans la NESC pourront être mieux évalués.

The thesis aimed to investigate cystatin C and creatinine-based estimates of glomerular filtration rate (eGFR), both at admission and during follow-up, on the combined endpoint of cardiovascular death and myocardial infarction in patients with acute coronary syndrome (ACS). We also evaluated two cystatin C assays and assessed genetic determinants of cystatin C concentrations. We used the PLATelet inhibition and Patient Outcomes study, where all types of ACS patients (n=18624) were randomized to ticagrelor or clopidogrel treatment. Multivariable Cox regression models, including clinical variables and biomarkers (troponin and NT-proBNP), and c-statistics were calculated. Cystatin C and the creatinine-based CKD-EPI equation exhibited similar significant prognostic impact on the combined endpoint, with Area Under Curves (AUC) 0.6923 and 0.6941, respectively. Follow-up samples of renal biomarkers did not improve risk prediction. Patients randomized to ticagrelor treatment were associated with a non-sustained larger increase in renal markers at discharge, but neither the change nor the difference between the randomized groups affected cardiovascular risk. Two different cystatin C assays exhibited good correlation 0.86 (95% confidence interval 0.85-0.86), however moderate level of agreement. Risk prediction with a combination of creatinine and cystatin C did not outperform the creatinine-based CKD-EPI equation, AUC: 0.6913 and 0.6924, respectively (n=13050). The genetic polymorphism rs6048952 independently affected the cystatin C concentration with mean levels of 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G, and G/G genotypes, respectively. The genetic polymorphism did not affect outcome overall, however in the non-ST-elevation ACS subgroup a signal that genetic polymorphism may be associated with cardiovascular death was observed (p=0.002). In conclusion: cystatin C or eGFR, irrespective of equation or assay, are important cardiovascular risk factors in ACS patients. Nonetheless, the incremental value of adding any renal variable, to a multivariable risk model, is small. Further research on the impact of cystatin C genetic polymorphism is warranted. / <p>PhD, i medicin.</p>

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by loss of renal function within days to weeks and by glomerular crescents on biopsy. The pathogenesis of this disease is unclear, but circulating factors such as antineutrophil cytoplasmic antibodies (ANCA) are believed to play a major role. In this thesis, we show that deletion of the Von Hippel-Lindau gene (Vhlh) from intrinsic glomerular cells of mice is sufficient to initiate a necrotizing crescentic glomerulonephritis and the clinical features that accompany RPGN. Loss of Vhlh leads to stabilization of hypoxia-inducible factor alpha subunits (HIFαs). Using gene expression profiling, we identified de novo expression of the HIFα target gene Cxcr4. In glomeruli from mice with RPGN, the course of RPGN is markedly improved in mice treated with a blocking antibody to Cxcr4, whereas overexpression of Cxcr4 alone in podocytes of transgenic mice is sufficient to cause glomerular disease. Despite the development of glomerular disease in mice that overexpress Cxcr4, their disease was milder and lacked features of full-blown RPGN. The Vhlh gene encodes VHL protein (pVHL, product of the Von Hippel-Lindau gene) that functions as the substrate recognition component of an E3 ubiquitin ligase. Although HIFα subunits are the best characterized substrates for pVHL, additional non-HIF mediated targets have been identified. To determine the role of HIF stabilization in this RPGN model, we generated double mutants that lack aryl hydrocarbon receptor nuclear translocator gene (Arnt, also called HIF1beta), an obligate dimerization partner for HIFα subunit function. Podocyte-selective deletion of Arnt in Vhlh mutant mice completely rescued the RPGN phenotype and mice survived longer than 8 months of age. Furthermore, stabilization of HIF2α alone led to glomerular disease characterized by crescentic transformation. Collectively, these results indicate an alternative mechanism for the pathogenesis of RPGN and glomerular disease in an animal model and suggest novel molecular pathways for intervention in this disease. In addition, we demonstrate a key role for VHL-HIF-Cxcr4 molecular pathway for the integrity of the glomerular barrier.

Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by loss of renal function within days to weeks and by glomerular crescents on biopsy. The pathogenesis of this disease is unclear, but circulating factors such as antineutrophil cytoplasmic antibodies (ANCA) are believed to play a major role. In this thesis, we show that deletion of the Von Hippel-Lindau gene (Vhlh) from intrinsic glomerular cells of mice is sufficient to initiate a necrotizing crescentic glomerulonephritis and the clinical features that accompany RPGN. Loss of Vhlh leads to stabilization of hypoxia-inducible factor alpha subunits (HIFαs). Using gene expression profiling, we identified de novo expression of the HIFα target gene Cxcr4. In glomeruli from mice with RPGN, the course of RPGN is markedly improved in mice treated with a blocking antibody to Cxcr4, whereas overexpression of Cxcr4 alone in podocytes of transgenic mice is sufficient to cause glomerular disease. Despite the development of glomerular disease in mice that overexpress Cxcr4, their disease was milder and lacked features of full-blown RPGN. The Vhlh gene encodes VHL protein (pVHL, product of the Von Hippel-Lindau gene) that functions as the substrate recognition component of an E3 ubiquitin ligase. Although HIFα subunits are the best characterized substrates for pVHL, additional non-HIF mediated targets have been identified. To determine the role of HIF stabilization in this RPGN model, we generated double mutants that lack aryl hydrocarbon receptor nuclear translocator gene (Arnt, also called HIF1beta), an obligate dimerization partner for HIFα subunit function. Podocyte-selective deletion of Arnt in Vhlh mutant mice completely rescued the RPGN phenotype and mice survived longer than 8 months of age. Furthermore, stabilization of HIF2α alone led to glomerular disease characterized by crescentic transformation. Collectively, these results indicate an alternative mechanism for the pathogenesis of RPGN and glomerular disease in an animal model and suggest novel molecular pathways for intervention in this disease. In addition, we demonstrate a key role for VHL-HIF-Cxcr4 molecular pathway for the integrity of the glomerular barrier.

Publicación a texto completo no autorizada por el autor / Determina la correlación y el grado de concordancia entre la ecuación de CKD-EPI y MDRD con la depuración de creatinina en orina de 24 horas para la estimación de la tasa de filtrado glomerular en pacientes diabéticos tipo 2, mayores de edad que acuden al servicio de Patología Clínica sección Bioquímica depuración de creatinina del HNERM, en el periodo octubre a diciembre 2013. Es un estudio Analítico comparativo, prospectivo observacional. Se obtuvo una muestra de 152 pacientes diabéticos, se aplicó el test de correlación de spearman, se aplicó el coeficiente de correlación de concordancia, y para determinar el bias respecto a la DCC se utilizó la gráfica de Blant altman. Se evaluó las ecuaciones CKD EPI, MDRD 4 con la DCC respectivamente la ecuación CKD EPI tuvo mejor correlación R 0.86, se evaluó el grado de concordancia con el índice Kappa k 0.69 (muy bueno) IC 0.61-0.78, y la ecuación MDRD 4, 0.63, IC 0.56 y 0.71. Se evalúo el bias entre los métodos y se observa en toda la población que la ecuación CKD EPI y MDRD 4 sobrestiman la TFG en relación a la DCC, en -3.1 y -8.1 respectivamente, siendo la ecuación CKD EPI la que tiene menor error sistemático. Se concluye que la ecuación CKD EPI es comparable con la DCC en orina de 24 horas, tiene un mejor desempeño y correlación que la ecuación MDRD 4. / Trabajo académico

Tese (doutorado) - Pontifícia Universidade Católica do Paraná, Curitiba, 2011 / Bibliografia: f.53-60 / Introducao e Objetivos: A doenca renal cronica (DRC) tem sido associada a uma maior mortalidade apos um acidente vascular cerebral (AVC). O envelhecimento aumenta tanto a prevalencia de AVC quanto a de DRC. No entanto acredita-se que a idade avancada pode / Background and objectives: Low estimated glomerular filtration rate (eGFR) is associated to high prevalence of events and mortality due to cardiovascular cause. Ageing is well known as a predictor of death after stroke. Age directly influences eGFR, what

Introdução: O conhecimento da função renal é fundamental para o seguimento dos receptores de transplante renal pediátrico. A habilidade do enxerto em adaptar-se a uma demanda aumentada durante o crescimento parece um fator importante para a função do aloenxerto no longo prazo. O estudo tem por objetivo comparar a função do enxerto renal em receptores pediátricos de acordo com o tipo de doador: adulto ou pediátrico e vivo ou falecido. Metodologia: Examinamos a taxa de filtração glomerular, através da depuração de inulina, em uma coorte pediátrica submetida a transplante renal no período de 2000 a 2010 e a sua associação com as idades do receptor e do doador. Um modelo de classe latente foi utilizado para identificar trajetórias de evolução da função renal pós-transplante. O seguindo passo da análise foi quantificar os efeitos dos fatores de risco na probabilidade de pertencer ao grupo de trajetória de pior evolução. Resultados: Este modelo identificou três trajetórias de função do enxerto renal após o transplante: “baixa e decrescente”, “moderada e estável” e “alta e decrescente”. A probabilidade de pertencer à trajetória de pior resultado (baixa e decrescente) aumentou com o doador falecido comparativamente ao vivo (odds ratio ajustado: 50), com a idade do receptor (odds ratio ajustado: 1,2 por ano de vida do receptor) e com a diferença de idade receptor-doador (odds ratio ajustado: 1,13 por ano adicional). Conclusão: O presente estudo identifica três trajetórias de função do enxerto renal após o transplante renal pediátrico. Os achados sugerem que o doador vivo e o recurso de doadores mais jovens são fatores importantes para a função do enxerto no longo prazo. / Introduction: The knowledge of renal function is crucial for the management of pediatric kidney transplant recipients. The graft ability to adapt to an increasing demand during growth is important factor for long-term allograft function. We aimed to evaluate the long-term progress of glomerular filtration rate in pediatric recipients and the importance of the recipient and donor ages in predicting the risk of poor transplant outcome Methods: We examined the glomerular filtration rate using inulin clearance in a pediatric cohort who underwent kidney transplantation between 2000 and 2010. A longitudinal latent class modeling technique was used to identify renal function trajectories after transplant. The second step of the analysis was the quantification of the effects of the risk factors on the probability of belonging to the poor outcome trajectory group. Results: The study identified three trajectories of renal allograft function after pediatric kidney transplantation: “low and decreasing”, “moderate and stable”, and “high and sharply decreasing” trajectories. The observed probability to belong to the poor outcome group (low and decreasing) increased with deceased versus living donor (adjusted odds ratio: 50), with age recipient (adjusted odds ratio: 1,2 per year of recipient ageing), and with the donor-recipient age difference (adjusted odds ratio: 1,13 per additional year). Conclusion: The present evaluation identified three trajectories of renal allograft function after pediatric kidney transplantation. This results suggests that donor source (living or deceased), age recipient, and age difference between the donor and the recipient are important factors for long-term allograft function.

Made available in DSpace on 2016-07-01T12:30:00Z (GMT). No. of bitstreams: 2 diana_silva_ioc_mest_2015.pdf: 1327366 bytes, checksum: 52c95c7cbdb04fca5bc7a3e03c0b5ffb (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2015 / Made available in DSpace on 2016-07-05T23:52:42Z (GMT). No. of bitstreams: 3 diana_silva_ioc_mest_2015.pdf.txt: 202731 bytes, checksum: 9b39c6a38525112f2bb08a22733cb783 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) diana_silva_ioc_mest_2015.pdf: 1327366 bytes, checksum: 52c95c7cbdb04fca5bc7a3e03c0b5ffb (MD5) Previous issue date: 2015 / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Teresina, PI, Brasil / Introdução. Com a utilização em larga escala da terapia antirretroviral combinada em pacientes com HIV/AIDS, tem se observado um aumento da frequência de doenças crônicas e degenerativas, como a insuficiência renal crônica, nesta população. Algumas drogas utilizadas, como o tenofovir, assim como lesões atribuídas à própria infecção são potencialmente nefrotóxicas. Objetivos. O presente estudo tem como objetivo avaliar a prevalência e os fatores associados às alterações renais em pacientes portadores de HIV/AIDS atendidos em um serviço de referência em Teresina, Piauí. Materiais e Métodos. Foi realizado um estudo do tipo transversal, em pacientes com diagnóstico de HIV/AIDS atendidos no ambulatório do Instituto de Doenças Tropicais Natan Portella. Calculou-se uma amostra aleatória de 109 indivíduos, considerando-se uma frequência esperada de alterações renais de 5%, erro de 4% e nível de confiança de 95%. A coleta de dados se deu de março a julho de 2015. Além de exames de rotina, foram realizados exames mais específicos e sensíveis para avaliar a função renal: microalbuminúria na urina isolada, \03B22-microglobulina na urina e fósforo sérico Resultados. Observou-se que 9,2% dos pacientes apresentaram disfunção renal com TFGe < 60 mL/min/1,73m2 e 28,4% dos pacientes tinham alterações renais, definidas por TFGe < 90 mL/min/1,73m2. A frequência de pacientes com níveis alterados de microalbuminúria na urina isolada foi de 21,1% (23/109). A presença de níveis alterados de fósforo sérico foi observada em 40,4% (44/109) e níveis anormais de \03B22-microglobulina foram observados em 24,8% dos pacientes (27/109). Alteração na concentração de \03B22-microglobulina na urina foi associada ao sexo masculino (31,8%), à idade > 60 anos (58,3%) e ao uso do tenofovir (39,4%). Os pacientes com TFGe < 60 mL/min/1,73m2 e os pacientes hipertensos e diabéticos tinham uma média de tempo maior de uso de TARV. Não observamos correlação entre a contagem de linfócitos TCD4 e a taxa de filtração glomerular. Conclusões. Marcadores como a microalbuminúria na urina isolada e a \03B22-microglobulina na urina tem relevância na identificação precoce de pacientes com disfunção renal incipiente / Abstract: Introduction. With the large-scale use of antiretroviral combination therapy in patients with HIV / AIDS, we have observed an increased frequency of chronic and degenerative diseases such as chronic renal failure in this population. Some drugs used, such as tenofovir, as well as lesions attributed to infection itself, are potentially nephrotoxic. Goals. This study aims to evaluate the prevalence and factors associated with kidney abnormalities in patients with HIV / AIDS treated at a reference service in Teresina, Piauí. Materials and methods. One cross-sectional study was conducted in patients with HIV / AIDS treated at the outpatient clinic of the Institute of Tropical Diseases Natan Portella. We calculated a random sample of 109 subjects, considering an expected frequency of kidney abnormalities of 5%, 4% error and reliability level of 95% .The data collection took place from March to July 2015. In addition to routine tests, more specific and sensitive tests were performed in order to assess the renal function: isolated microalbuminuria in urine, \03B22 microglobulin in urine and serum phosphorus Results. We observed that 9.2% of patients had renal dysfunction with eGFR < 60mL/min/1.73m² and 28.4% of patients had mild, mild to moderate or severe kidney abnormalities defined by eGFR < 90ml/min/1.73m². The frequency of patients with altered levels of microalbuminuria isolated in urine was 21.1% (23/109). The presence of altered levels of serum phosphorus was observed in 40.4% (44/109) and abnormal levels of \03B22-microglobulin were observed in 24.8% of patients (27/109). Changes in the concentration of \03B22-microglobulin in urine was associated with male (31.8%), age> 60 years (58.3%) and the use of tenofovir (39.4%). Patients with eGFR <60 ml/min/1.73m² and hypertensive and diabetic patients had a longer usage of ART. There was no correlation between CD4 lymphocyte count and glomerular filtration rate. Conclusions. Markers as microalbuminuria isolated in urine and \03B22-microglobulin in urine are relevance to the early identification of patients with incipient renal dysfunction. Early diagnosis of renal disease in patients with HIV and identification of risk factors is critical to prevent the progression of kidney damage and to the institution of the appropriate treatment

Introdução: O conhecimento da função renal é fundamental para o seguimento dos receptores de transplante renal pediátrico. A habilidade do enxerto em adaptar-se a uma demanda aumentada durante o crescimento parece um fator importante para a função do aloenxerto no longo prazo. O estudo tem por objetivo comparar a função do enxerto renal em receptores pediátricos de acordo com o tipo de doador: adulto ou pediátrico e vivo ou falecido. Metodologia: Examinamos a taxa de filtração glomerular, através da depuração de inulina, em uma coorte pediátrica submetida a transplante renal no período de 2000 a 2010 e a sua associação com as idades do receptor e do doador. Um modelo de classe latente foi utilizado para identificar trajetórias de evolução da função renal pós-transplante. O seguindo passo da análise foi quantificar os efeitos dos fatores de risco na probabilidade de pertencer ao grupo de trajetória de pior evolução. Resultados: Este modelo identificou três trajetórias de função do enxerto renal após o transplante: “baixa e decrescente”, “moderada e estável” e “alta e decrescente”. A probabilidade de pertencer à trajetória de pior resultado (baixa e decrescente) aumentou com o doador falecido comparativamente ao vivo (odds ratio ajustado: 50), com a idade do receptor (odds ratio ajustado: 1,2 por ano de vida do receptor) e com a diferença de idade receptor-doador (odds ratio ajustado: 1,13 por ano adicional). Conclusão: O presente estudo identifica três trajetórias de função do enxerto renal após o transplante renal pediátrico. Os achados sugerem que o doador vivo e o recurso de doadores mais jovens são fatores importantes para a função do enxerto no longo prazo. / Introduction: The knowledge of renal function is crucial for the management of pediatric kidney transplant recipients. The graft ability to adapt to an increasing demand during growth is important factor for long-term allograft function. We aimed to evaluate the long-term progress of glomerular filtration rate in pediatric recipients and the importance of the recipient and donor ages in predicting the risk of poor transplant outcome Methods: We examined the glomerular filtration rate using inulin clearance in a pediatric cohort who underwent kidney transplantation between 2000 and 2010. A longitudinal latent class modeling technique was used to identify renal function trajectories after transplant. The second step of the analysis was the quantification of the effects of the risk factors on the probability of belonging to the poor outcome trajectory group. Results: The study identified three trajectories of renal allograft function after pediatric kidney transplantation: “low and decreasing”, “moderate and stable”, and “high and sharply decreasing” trajectories. The observed probability to belong to the poor outcome group (low and decreasing) increased with deceased versus living donor (adjusted odds ratio: 50), with age recipient (adjusted odds ratio: 1,2 per year of recipient ageing), and with the donor-recipient age difference (adjusted odds ratio: 1,13 per additional year). Conclusion: The present evaluation identified three trajectories of renal allograft function after pediatric kidney transplantation. This results suggests that donor source (living or deceased), age recipient, and age difference between the donor and the recipient are important factors for long-term allograft function.

Introdução: O conhecimento da função renal é fundamental para o seguimento dos receptores de transplante renal pediátrico. A habilidade do enxerto em adaptar-se a uma demanda aumentada durante o crescimento parece um fator importante para a função do aloenxerto no longo prazo. O estudo tem por objetivo comparar a função do enxerto renal em receptores pediátricos de acordo com o tipo de doador: adulto ou pediátrico e vivo ou falecido. Metodologia: Examinamos a taxa de filtração glomerular, através da depuração de inulina, em uma coorte pediátrica submetida a transplante renal no período de 2000 a 2010 e a sua associação com as idades do receptor e do doador. Um modelo de classe latente foi utilizado para identificar trajetórias de evolução da função renal pós-transplante. O seguindo passo da análise foi quantificar os efeitos dos fatores de risco na probabilidade de pertencer ao grupo de trajetória de pior evolução. Resultados: Este modelo identificou três trajetórias de função do enxerto renal após o transplante: “baixa e decrescente”, “moderada e estável” e “alta e decrescente”. A probabilidade de pertencer à trajetória de pior resultado (baixa e decrescente) aumentou com o doador falecido comparativamente ao vivo (odds ratio ajustado: 50), com a idade do receptor (odds ratio ajustado: 1,2 por ano de vida do receptor) e com a diferença de idade receptor-doador (odds ratio ajustado: 1,13 por ano adicional). Conclusão: O presente estudo identifica três trajetórias de função do enxerto renal após o transplante renal pediátrico. Os achados sugerem que o doador vivo e o recurso de doadores mais jovens são fatores importantes para a função do enxerto no longo prazo. / Introduction: The knowledge of renal function is crucial for the management of pediatric kidney transplant recipients. The graft ability to adapt to an increasing demand during growth is important factor for long-term allograft function. We aimed to evaluate the long-term progress of glomerular filtration rate in pediatric recipients and the importance of the recipient and donor ages in predicting the risk of poor transplant outcome Methods: We examined the glomerular filtration rate using inulin clearance in a pediatric cohort who underwent kidney transplantation between 2000 and 2010. A longitudinal latent class modeling technique was used to identify renal function trajectories after transplant. The second step of the analysis was the quantification of the effects of the risk factors on the probability of belonging to the poor outcome trajectory group. Results: The study identified three trajectories of renal allograft function after pediatric kidney transplantation: “low and decreasing”, “moderate and stable”, and “high and sharply decreasing” trajectories. The observed probability to belong to the poor outcome group (low and decreasing) increased with deceased versus living donor (adjusted odds ratio: 50), with age recipient (adjusted odds ratio: 1,2 per year of recipient ageing), and with the donor-recipient age difference (adjusted odds ratio: 1,13 per additional year). Conclusion: The present evaluation identified three trajectories of renal allograft function after pediatric kidney transplantation. This results suggests that donor source (living or deceased), age recipient, and age difference between the donor and the recipient are important factors for long-term allograft function.