Nefropatia por imunoglobulina A pós-transplante renal: perfil anatomoclínico, fatores prognósticos e tratamento
Data
2015-05-04
Autores
Cabral, Diogo Buarque Cordeiro 
Orientadores
Kirsztajn, Gianna Mastroianni
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivos: Descrever a nefropatia por IgA pós-transplante renal quanto ao diagnóstico, prognóstico e tratamento. Secundariamente, avaliar fatores prognósticos para remissão e perda do enxerto. Metodologia: Coorte retrospectiva que incluiu pacientes submetidos a transplante renal em centro único entre janeiro de 1998 e julho de 2012 com diagnóstico de nefropatia por IgA. Para avaliação de fatores de risco, foram selecionados aqueles que, ao diagnóstico apresentavam relação proteína/creatinina na urina maior ou igual a 1,0 g/g e/ou disfunção do enxerto, com seguimento mínimo de 6 meses. Resultados: Foram identificados 56 pacientes, a maioria homens (68%), brancos (65%), receptores de rim de doador vivo (84%) e idade de 34,5 ± 9,9 anos. O diagnóstico ocorreu 52,2 ± 34,0 meses após o transplante e 25,4 ± 27,7 meses após detecção de proteinuria > 0,3 g/g. No diagnóstico, havia hematúria dismórfica em 95% e disfunção do enxerto em 75% dos casos. A proteinúria foi de 3,1 ± 2,2 g/g e albumina 3,5 ± 0,7 mg/dL. Utilizando a classificação de Oxford, a proliferação mesangial (91%) e a esclerose segmentar (77%) foram as lesões histológicas mais comuns e apenas 18,2% apresentavam fibrose intersticial e atrofia tubular em mais de 25% do fragmento. A renoproteção com Inibidores da enzima conversora de angiotensinogênio em angiotensina ou bloqueadores do receptor de angiotensina foi comum (86%) e em 80% dos casos houve mudanças na imunossupressão com a intenção de tratar. O aumento da dose de prednisona (83%) foi a mais comum, com doses e duração variadas. Pulso de metilprednisolona foi associada em 64%, conversões para ciclofosfamida em 17% e sais de micofenolato em 19%. A perda do enxerto ocorreu em 30%, sendo 88% dessas atribuídas à glomerulonefrite. Houve remissão parcial e completa em 49% e 17%, respectivamente. A remissão parcial ocorreu em 20% dos que perderam o enxerto contra 63% daqueles com rim funcionante ao final de 42,5 ± 33,3 meses (p=0,01). Na análise multivariada, a presença de disfunção do enxerto diminuiu as chances de remissão parcial (HR=0,34, 0,15-0,78, IC 95%) e os fatores associados a perda do enxerto pela nefropatia por IgA foram: doador falecido (HR 28,04, IC 95% 4,41-178,39, p<0,01), idade do doador (HR 1,09, IC 95% 1,04-1,16, p<0,01,) e o percentual de queda da TFG no diagnóstico (HR 1,13, IC 95% 1,06-1,20, p<0,01). Nenhum tratamento foi associado a melhor desfecho renal, contudo os pacientes que perderam o enxerto apresentava pior taxa de filtração glomerular no diagnóstico, indicativo de doença mais grave. Conclusões: A nefropatia por IgA pós-transplante se apresenta com proteinúria e disfunção do enxerto. As lesões histológicas não determinaram prognóstico renal na amostra estudada. Remissão parcial foi associada a menor risco de perda do enxerto, enquanto doadores falecidos, mais velhos e o grau de disfunção do enxerto no diagnóstico conferiram pior prognóstico renal. O tratamento imunossupressor foi baseado principalmente em aumento da dose de prednisona, mas são necessários estudos prospectivos e controlados para melhor avaliação do tratamento a ser instituído.
Introduction: Recurrence of glomerulonephritis is the third cause of graft loss in 10 years. IgA nephropathy is one of the most common glomerulopathies after transplantation, but many aspects are still poorly defined. Objectives: To describe IgA nephropathy after kidney transplantation regarding the diagnosis, prognosis and treatment. Secondly, evaluate factors for its remission and graft loss. Methods: Retrospective cohort including patients transplanted between 1998 and 2012 diagnosed with IgA nephropathy in the graft. In order to assess risk factors, we selected those with clinically relevant disease (protein-creatinine ratio in urine higher or equal to 1.0 g/g and/or graft dysfunction) and a minimum of six months follow-up. Results: We identified 56 patients, most men (68%), white (65%), living donor recipients (84%) and with age of 34.5 ± 9.9 years. The diagnosis occurred in 52.2 ± 34.0 months after transplant, when dysmorphic hematuria was found in 95% and graft dysfunction in 75% of cases. Proteinuria was 3.1 ± 2.2 g/g serum albumin 3.5 ± 0.7 mg/dL. Using the Oxford classification, the mesangial proliferation (91%) and segmental sclerosis (77%) were the most common injuries and only 18.2% had interstitial fibrosis and tubular atrophy in more than 25% of the fragment. The renoprotection with antiproteinuric medications was common (86%). In 80% of the cases there were changes in immunosuppression with the intention to treat. The increase in prednisone dose (83%) was the most common, with varying doses and duration. Methylprednisolone pulse therapy was associated in 64%, conversion to cyclophosphamide in 17% and to mycophenolate salts in 19%. Graft loss occurred in 30% of cases and 88% of those attributed to IgA nephropathy. There was partial and complete remission in 49% and 17%, respectively. Partial remission occurred in 20% of those who lost the graft versus 63% of those with functioning kidney at the end of 42.5 ± 33.3 months (p = 0.01). In multivariate analysis, factors associated with graft loss by IgA nephropathy were: deceased donor (HR 28.04, 95% CI 4.41-178.39, p <0.01), donor age (HR 1.09, 95% CI 1.04-1.16, p <0.01) and the percentage of fall in glomerular filtration rate at diagnosis (HR 1.13, 95% CI 1.06-1.20, p <0.01 ) and this was also associated with a lower chance of remission of glomerulonephritis (HR = 0.97, 95% CI 0.94 to 0.99, p = 0.009). No treatment was associated with better renal outcome, but patients who have lost the graft presented with worse allograft function, indicative of more severe disease. Conclusion: IgA nephropathy after transplantation presented with hematuria, proteinuria and graft dysfunction. The histological lesions were not predictors of renal outcome in this population. Remission, even if partial, has been associated with reduced risk of graft loss, while deceased and older donors, as well as the degree of graft dysfunction at diagnosis result in worse prognosis. The immunosuppressive treatment was mainly based on the increase in steroid dose and we were unable to evaluate its benefit. Regarding the treatment, prospective and controlled studies are needed to define the best management.
Introduction: Recurrence of glomerulonephritis is the third cause of graft loss in 10 years. IgA nephropathy is one of the most common glomerulopathies after transplantation, but many aspects are still poorly defined. Objectives: To describe IgA nephropathy after kidney transplantation regarding the diagnosis, prognosis and treatment. Secondly, evaluate factors for its remission and graft loss. Methods: Retrospective cohort including patients transplanted between 1998 and 2012 diagnosed with IgA nephropathy in the graft. In order to assess risk factors, we selected those with clinically relevant disease (protein-creatinine ratio in urine higher or equal to 1.0 g/g and/or graft dysfunction) and a minimum of six months follow-up. Results: We identified 56 patients, most men (68%), white (65%), living donor recipients (84%) and with age of 34.5 ± 9.9 years. The diagnosis occurred in 52.2 ± 34.0 months after transplant, when dysmorphic hematuria was found in 95% and graft dysfunction in 75% of cases. Proteinuria was 3.1 ± 2.2 g/g serum albumin 3.5 ± 0.7 mg/dL. Using the Oxford classification, the mesangial proliferation (91%) and segmental sclerosis (77%) were the most common injuries and only 18.2% had interstitial fibrosis and tubular atrophy in more than 25% of the fragment. The renoprotection with antiproteinuric medications was common (86%). In 80% of the cases there were changes in immunosuppression with the intention to treat. The increase in prednisone dose (83%) was the most common, with varying doses and duration. Methylprednisolone pulse therapy was associated in 64%, conversion to cyclophosphamide in 17% and to mycophenolate salts in 19%. Graft loss occurred in 30% of cases and 88% of those attributed to IgA nephropathy. There was partial and complete remission in 49% and 17%, respectively. Partial remission occurred in 20% of those who lost the graft versus 63% of those with functioning kidney at the end of 42.5 ± 33.3 months (p = 0.01). In multivariate analysis, factors associated with graft loss by IgA nephropathy were: deceased donor (HR 28.04, 95% CI 4.41-178.39, p <0.01), donor age (HR 1.09, 95% CI 1.04-1.16, p <0.01) and the percentage of fall in glomerular filtration rate at diagnosis (HR 1.13, 95% CI 1.06-1.20, p <0.01 ) and this was also associated with a lower chance of remission of glomerulonephritis (HR = 0.97, 95% CI 0.94 to 0.99, p = 0.009). No treatment was associated with better renal outcome, but patients who have lost the graft presented with worse allograft function, indicative of more severe disease. Conclusion: IgA nephropathy after transplantation presented with hematuria, proteinuria and graft dysfunction. The histological lesions were not predictors of renal outcome in this population. Remission, even if partial, has been associated with reduced risk of graft loss, while deceased and older donors, as well as the degree of graft dysfunction at diagnosis result in worse prognosis. The immunosuppressive treatment was mainly based on the increase in steroid dose and we were unable to evaluate its benefit. Regarding the treatment, prospective and controlled studies are needed to define the best management.
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Citação
CABRAL, Diogo Buarque Cordeiro. Nefropatia por imunoglobulina A pós-transplante renal: perfil anatomoclínico, fatores prognósticos e tratamento. 2016. 65 f. Dissertação (Mestrado em Nefrologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2016.