Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction

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.

Associated clinical and laboratory markers of donor on allograft function after heart transplant

Abstract Introduction: Primary graft dysfunction is a major cause of mortality after heart transplantation. Objective: To evaluate correlations between donor-related clinical/biochemical markers and the occurrence of primary graft dysfunction/clinical outcomes of recipients within 30 days of transplant. Methods: The prospective study involved 43 donor/recipient pairs. Data collected from donors included demographic and echocardiographic information, noradrenaline administration rates and concentrations of soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2), interleukins (IL-6 and IL-10), monocyte chemoattractant protein-1, C-reactive protein and cardiac troponin I. Data collected from recipients included operating, cardiopulmonary bypass, intensive care unit and hospitalization times, inotrope administration and left/right ventricular function through echocardiography. Results: Recipients who developed moderate/severe left ventricular dysfunction had received organs from significantly older donors (P =0.020). Recipients from donors who required moderate/high doses of noradrenaline (>0.23 µg/kg/min) around harvesting time exhibited lower post-transplant ventricular ejection fractions (P =0.002) and required longer CPB times (P =0.039). Significantly higher concentrations of sTNFR1 (P =0.014) and sTNFR2 (P =0.030) in donors were associated with reduced intensive care unit times (≤5 days) in recipients, while higher donor IL-6 (P =0.029) and IL-10 (P =0.037) levels were correlated with reduced hospitalization times (≤25 days) in recipients. Recipients who required moderate/high levels of noradrenaline for weaning off cardiopulmonary bypass were associated with lower donor concentrations of sTNFR2 (P =0.028) and IL-6 (P =0.001). Conclusion: High levels of sTNFR1, sTNFR2, IL-6 and IL-10 in donors were associated with enhanced evolution in recipients. Allografts from older donors, or from those treated with noradrenaline doses >0.23 µg/kg/min, were more frequently affected by primary graft dysfunction within 30 days of surgery.

Cystatin C and inflammatory markers in kidney transplant recipients / Cistatina C e marcadores inflamatórios em receptores de transplante renal

OBJECTIVE: Kidney transplantation is the best option for patients with end-stage renal disease. This study evaluated the profile of cystatin C (CysC), interleukin 2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α) as inflammatory markers in 23 living donor kidney transplant recipients. METHODS: A descriptive, analytical and prospective study was conducted between January 1st, 2007 and June 30th, 2008 on 23 living donor kidney transplant recipients. The biomarkers were evaluated before and 30 and 180 days after transplantation. RESULTS: The mean age of the patients was 34.3 years (± 11.7), females (52 percent) and non-whites (61 percent). Significant difference was found in cystatin C and creatinine before and 30 days after transplantation (p < 0.0001) and before and 180 days after transplantation (p < 0.0001). There was a significant difference in IL-2 between 30 and 180 days post-transplant (p = 0.0418) and in TNF-α between pre-transplant and 30 days post-transplant (p = 0.0001). A negative correlation was observed between cystatin C and TNF-α at pre-transplant and between cystatin C and IL-6 at 180 days post-transplant. Comparison of biopsied and non-biopsied patients showed a significant difference in creatinine and cystatin C at 30 and 180 days post-transplant in biopsied patients. CONCLUSION: Our results showed no significant correlations between CysC, IL-2, IL-6 and TNF-α levels in kidney transplant recipients at short-term follow-up. Moreover, CysC levels were very similar to creatinine levels in contrast to other inflammatory markers studied in biopsied and non-biopsied patients. Further studies are important to evaluate the long-term profile of these markers.

OBJETIVO: O transplante renal é a melhor opção para pacientes renais crônicos em estágio terminal. Este estudo avaliou o perfil da cistatina C (CysC), interleucina 2 (IL-2), IL-6, e fator de necrose tumoral-α (TNF-α) como marcadores inflamatórios em 23 transplantados renais de doador vivo. MÉTODOS: Estudo descritivo, analítico e prospectivo conduzido entre 1o de janeiro (2007) e 30 de junho (2008) em 23 transplantados renais de doador vivo. Os biomarcadores foram avaliados no pré, com 30 e 180 dias do pós-transplante. RESULTADOS: A média de idade foi de 34,3 anos (± 11,7), 52 por cento do sexo feminino e 61 por cento de negros. Foi encontrada diferença significativa na CysC e creatinina antes do transplante e 30 dias após o procedimento (p < 0,0001) e antes do transplante e 180 dias após o procedimento (p < 0,0001). Houve uma diferença significativa na IL-2, entre 30 and 180 dias do pós-transplante (p = 0,0418) e no TNF-α antes do transplante e 30 dias após o procedimento (p = 0,0001). Foi observada uma correlação negativa entre CysC e TNF-α no pré-transplante, e entre CysC e IL-6 com 180 dias do pós-transplante. Em pacientes biopsiados houve uma diferença significante na creatinina e na CysC com 30 e 180 dias do pós-transplante. CONCLUSÃO: Em seguimento a curto prazo, não houve correlação relevante entre os níveis de CysC, IL-2, IL-6 e TNF-α em transplantados renais. Em pacientes biopsiados e não biopsiados, os níveis de CysC foram muito similares aos da creatinina, ao contrário de outros marcadores inflamatórios. Demais estudos são importantes para avaliar o perfil destes marcadores a longo prazo.