We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (P<0.05) and urine (P<0.001) compared to the stable patients group. Also, in the peripheral blood, miR-142-3p expression was significantly higher in the acute tubular necrosis group compared to the acute rejection group (P<0.05). Urine samples of the acute rejection group presented higher expression compared to the stable patients group (P<0.001) but the difference between acute tubular necrosis and acute rejection groups was not significant in the urinary analyzes (P=0.079). miR-142-3p expression has a distinct pattern of expression in the setting of post-operative acute tubular necrosis after kidney transplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

The aim of the present study was to evaluate messenger RNA expression in kidney allograft recipients. Forty-four kidney transplant recipients were evaluated up to three months after grafting. After transplantation, peripheral blood samples were drawn sequentially for real-time polymerase chain reaction analyses of perforin and TIM-3 genes. Biopsies were obtained to evaluate acute graft dysfunction and interpreted according to the Banff classification. Eight patients presented episodes of acute rejection. Recipients with rejection had significantly higher levels of TIM-3 mRNA transcripts compared to those without rejection (median gene expression 191.2 and 36.9 mRNA relative units, respectively; P<0.0001). Also, perforin gene expression was higher in patients with rejection (median gene expression 362.0 and 52.8 mRNA relative units; P<0.001). Receiver operating characteristic curves showed that the area under the curve (AUC) for the TIM-3 gene was 0.749 (95%CI: 0.670–0.827). Perforin gene mRNA expression provided an AUC of 0.699 (95%CI: 0.599 to 0.799). Overall accuracy of gene expression was 67.9% for the TIM-3 gene and 63.6% for the perforin gene. Combined accuracy was 76.8%. Negative predictive values were 95.3% for the TIM-3 gene, 95.5% for the perforin gene, and 95.4% in the combined analyses. Gene expression was significantly modulated by rejection treatment decreasing 64.1% (TIM-3) and 90.9% (perforin) compared to the median of pre-rejection samples. In conclusion, the longitudinal approach showed that gene profiling evaluation might be useful in ruling out the diagnosis of acute rejection and perhaps evaluating the efficacy of treatment.

No abstract

O transplante renal é atualmente o tratamento de escolha para pacientes com doença renal crônica em estágio terminal. Dentre as complicações decorrentes do transplante, a rejeição aguda é considerada uma das principais, sendo a biópsia o padrão ouro para seu diagnóstico. Por ser um procedimento invasivo e potencialmente deletério, buscam-se novos marcadores para o diagnóstico desse quadro. As ferramentas diagnósticas não invasivas apresentam diversas vantagens, que incluem principalmente a possibilidade de uso frequente e sequencial, facilitando a avaliação do estado imune do receptor. Nesta revisão, apresentam-se os métodos e as vantagens dos mesmos que estão sendo empregados atualmente na pesquisa em transplantes renais, a reação em cadeia da polimerase em tempo real, os micro-arranjos de DNA e mais recentemente os micro-RNAs. Existe a expectativa de que os microarranjos e micro- RNAs venham a desempenhar um papel crucial no transplante de órgãos em assuntos relacionados à identificação de mecanismos moleculares de rejeição aguda, injúria crônica, efeito de toxicidade das drogas imunossupressoras e tolerância. O desenvolvimento de técnicas moleculares capazes de fornecer um painel da atividade imunológica responsável pela agressão ao enxerto de forma não invasiva sugere a possibilidade futura de otimização e individualização do tratamento imunossupressor. Para a realização deste trabalho foi utilizada a busca em bases de dados internacionais (PUBMED, Web of Knowledge) através dos descritores “Transplante de Rim”, “Rejeição de Enxerto” e “Técnicas e Procedimentos Diagnósticos” e foram selecionados apenas estudos de periódicos indexados sendo referidos os estudos de maior importância clínica ou histórica na área.