Cystatin C and inflammatory markers in kidney transplant recipients

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Abstract

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%) and non-whites (61%). 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.

Translated abstract

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% do sexo feminino e 61% 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.

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Inflammation in end-stage renal disease: the hidden enemy.

Peter Stenvinkel (2006)

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this high-risk population, inflammation (interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Indeed, several different inflammatory biomarkers, such as high sensitivity C-reactive protein (hs-CRP), have been shown to independently predict mortality in ESRD patients. As CRP is so strongly associated with vascular disease it has been suggested that this hepatic-derived protein is not only a marker, but also a mediator, of vascular disease. Although in vitro data from studies on endothelial cells, monocytes-macrophages and smooth muscle cells support a direct role for CRP in atherogenesis, data from studies performed in vivo have been controversial. The causes of the highly prevalent state of inflammation in ESRD are multiple, including inflammatory signals associated with the dialysis procedure, decreased renal function, volume overload, comorbidity and intercurrent clinical events. As the prevalence of inflammation varies considerably between continents and races, dietary and/or genetic factors may have an impact on inflammation in ESRD. Elevated CRP in dialysis patients could be evaluated at three different levels: (i) national/regional level; (ii) dialysis unit level; and (iii) individual patient level.

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Cytokines correlate with age in healthy volunteers, dialysis patients and kidney-transplant patients.

Sylvain Galvani, Cindy Canivet, Anne Nègre-Salvayre … (2009)

T-cell functions are currently used as biomarkers for the pharmacodynamic monitoring of immunosuppressive drugs or as disease biomarkers of inflammation/sepsis and organ rejection. In order to evaluate co-factors potentially influencing the expression of the immunological biomarkers, we explored T-cell proliferation, T-cell activation (CD25 and CD71 expressions) and intra-lymphocyte cytokine production (interleukin (IL)-2 and tumor necrosis factor (TNF)-alpha) in healthy volunteers, dialysis patients and stable kidney-transplant patients treated with standard immunosuppressive therapy, i.e. tacrolimus, mycophenolic acid with or without steroids. Age was positively correlated with TNF-alpha expression in all three patient populations, and with IL-2 expression in healthy volunteers and kidney-transplant patients. Further age was correlated with inhibition of lymphocyte proliferation in healthy volunteers and with the T-cell activation marker CD25 in kidney-transplant patients. In healthy volunteers lymphocyte proliferation was higher in woman as compared to men. Other biomarkers of T-cell function were independent of the gender. In the kidney-transplant patient group a significantly lower expression of all biomarkers of T-cell functions compared to healthy volunteers and dialysis patients. In dialysis patients we found significant increased IL-2 expression compared to healthy volunteers, while the other T-cell functions were not significantly different. Further time on dialysis had no effect on the level of biomarker expression. In conclusion we found decreased T-cell functions in kidney-transplant patients compared to healthy volunteers and dialysis patients, increased IL-2 expression in dialysis patients compared to healthy volunteers and in all three populations we found a correlation of age and intra-T-lymphocyte TNF-alpha expression.