Cristina M. Bouissou Soares

Inflamação na doença renal crônica: papel de citocinas

Chronic kidney disease (CKD) is a serious public health problem whose prevalence has increased in the last few years. Its progression is associated with high morbidity and mortality. Several factors are associated with the onset and progression of CKD, such as obesity, hypertension and diabetes mellitus. Beyond these factors, there is evidence of a pathophysiological role for inflammation in CKD. Several cytokines and chemokines have been detected in the plasma and urine of patients at early stages of CKD, and have also been related to CKD complications. The expression of these mediators and renal injury may be influenced by drugs such as angiotensin-converting enzyme inhibitors, statins and antagonists of cytokine receptors. Modulation of the immune-inflammatory response can become a target for CKD treatment. The aim of this study was to review the scientific evidence on the role of inflammation in CKD, especially the effects of cytokines and chemokines.

Predictive factors of progression to chronic kidney disease stage 5 in a predialysis interdisciplinary programme

BACKGROUND The clinical course of chronic kidney disease (CKD) in children is heterogeneous and has not been fully established. The aim of this retrospective cohort study was to identify predictive factors associated with the progression of CKD among the children and adolescents admitted to a Predialysis Interdisciplinary Management Programme (PDIMP). METHODS We analysed the following variables at admission: age, gender, race, blood pressure, primary renal disease, Z-scores for weight and height, CKD stage and degree of proteinuria. Two time-dependent covariates were considered: hypertension and proteinuria. CKD stage 5 was assigned as a dependent variable. Time-fixed and time-dependent Cox regression analyses were applied to evaluate renal survival. RESULTS One hundred and seven patients with CKD stage 2-4 were followed up for a median time of 94 months. Fifty-seven patients (53.3%) progressed to CKD stage 5. After adjustment for time-fixed model, three baseline variables were found to be independent predictors of CKD stage 5: glomerular disease (hazard ratio, HR = 3.0, P = 0.015), CKD stage 4 (HR = 2.6, P = 0.001) and severe proteinuria (HR = 4.1, P = 0.006). After adjustment for the time-dependent model, three variables were found to be independent predictors of CKD stage 5: proteinuria as time-dependent covariate (HR = 1.9, P = 0.041), CKD stage 4 (HR = 2, P = 0.0086) and baseline serum albumin <3.5 g/dl (HR = 2.6, P = 0.0015). CONCLUSIONS Taking into account manageable factors, further prospective controlled studies are necessary to assess intervention measures in order to possibly modify the clinical course of CKD in children.

Anxiety, depression, resilience and quality of life in children and adolescents with pre-dialysis chronic kidney disease

BackgroundChronic kidney disease (CKD) is a risk factor for psychosocial impairment and psychiatric symptoms. Children and adolescents on dialysis frequently have compromised daily life activities and a worse quality of life (QoL) compared with healthy peers. However, few studies have investigated these aspects of CKD in pediatric pre-dialysis CKD patients. Therefore, we have analyzed resilience, QoL and anxiety and depressive symptoms in children and adolescents with pre-dialysis CKD and compared these to the values of healthy controls.MethodsDemographic and clinical data were collected from 28 children and adolescents with pre-dialysis CKD and 28 healthy sex- and age-matched controls. Psychological assessment of the participants was performed using the Wagnild and Young Resilience Scale, Pediatric Quality of Life (QoL) Inventory 4.0 , Child Depression Inventory and Self-report for Childhood Anxiety Related Disorders scales.ResultsOf the 56 children enrolled in our study, the CKD patients were referred to mental health professionals more frequently than the controls. Patients exhibited higher scores for separation anxiety and a higher frequency of clinically significant depressive symptoms. They also had lower overall QoL scores, as well as poorer scores for the psychological, educational and psychosocial subdomains of QoL instruments. There was a negative correlation between anxiety and depressive symptoms and all domains of QoL. Resilience was similar in both groups, but lower in patients with significant depressive symptoms. No significant association was found between clinical or laboratory findings and psychological variables in CKD patients.ConclusionAlthough patients and controls exhibited similar scores of resilience, CKD negatively impacted the QoL of pediatric patients, contributing to a higher frequency of depression and separation anxiety.

A Predictive Model of Progression of CKD to ESRD in a Predialysis Pediatric Interdisciplinary Program

BACKGROUND AND OBJECTIVES The incidence of ESRD in children has increased over the last two decades. Nevertheless, there are still limited data on risk factors related to the emergence of ESRD among patients with CKD. The aim of this study was to develop a model of prediction of ESRD in children and adolescents with CKD (stages 2-4) enrolled in a predialysis interdisciplinary management program. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this retrospective cohort study, 147 patients with CKD admitted from 1990 to 2008 were systematically followed up at a tertiary pediatric nephrology unit for a median of about 4.5 years. The primary outcome was the progression to CKD stage 5. A predictive model was developed using Cox proportional hazards model and evaluated by c statistics. RESULTS The median renal survival was estimated at 98.7 months (95% confidence interval [95% CI], 68.7 to 129.6 months). The probability of reaching CKD stage 5 was estimated as 52% in 10 years. The most accurate model included eGFR, proteinuria at admission, and primary renal disease. Risk score ranged from 0 to 13 points (median, 4 points). The accuracy of the score applied to the sample was high, with c statistics of 0.865 (95% CI, 0.80 to 0.93) and 0.837 (95% CI, 0.76 to 0.91) at follow-up of 2 and 5 years, respectively. By survival analysis, it was estimated that at 10 years after admission, the probability of renal survival was about 63% for patients in the low-risk group and 43% for the medium-risk group; all patients assigned to the high-risk group had CKD stage 5 (P<0.001). CONCLUSION The predictive model of progression of CKD might contribute to early identification of a subgroup of patients at high risk for accelerated renal failure.

Cytokines in chronic kidney disease: potential link of MCP-1 and dyslipidemia in glomerular diseases

BackgroundMany studies have indicated a role for cytokines in chronic kidney disease (CKD). The aim of this study was to evaluate plasma and urinary levels of monocyte chemoattractant protein-1 (MCP-1/CCL2), transforming growth factor-beta1 (TGF-β1), and interleukin-8 (IL-8/CXCL8) in pediatric patients with CKD stages 2–4.MethodsCytokines were measured in 37 healthy controls and in 42 CKD patients by enzyme-linked immunoassay. Patients were divided into groups according to CKD etiology: glomerular disease (group 1, n = 11) and congenital anomalies of the kidney and urinary tract (group 2, n = 31). Urinary cytokine measurements were standardized for creatinine.ResultsPlasma and urinary levels of MCP-1/CCL2 were significantly higher in both CKD groups compared to the control group. Between the two CKD groups, only urinary MCP-1/CCL2 levels were significantly different, with MCP-1/CCL2 levels higher in group 1 patients. Plasma and urinary levels of IL-8/CXCL8 and TGF-β1 were undetectable in the control group but comparable between the two CKD groups. In group 1 patients, urinary MCP-1/CCL2 levels were negatively correlated to serum albumin levels and positively correlated to the levels of total cholesterol and triglycerides. In group 2 patients, urinary levels of IL-8/CXCL8 were negatively correlated with the estimated glomerular filtration rate and positively correlated with body mass index.ConclusionsDifferences in cytokine profiles may be related to CKD etiology and other disease-associated alterations.

Transtornos mentais e qualidade de vida em crianças e adolescentes com doença renal crônica e em seus cuidadores

In the last decades there was a striking improvement in survival of children with chronic kidney disease. As life expectancy has increased in children with CKD, concern has risen about its physical, psychological, and social consequences. The aim of this study was to perform a review of the psychological consequences of CKD in the pediatric population, with the focus on mental disorders and on quality of life. We also reviewed studies regarding emotional and social effects and their possible influences on treatment adhesion. Several studies have shown impairment on quality of life and on mental health of these patients. A better understanding of emotional consequences of CKD in pediatric population possibly can reduce the impact of the renal disease on children. Moreover, a comprehensive approach of children and adolescents with CKD might result in a better clinical control and improve treatment adhesion.

Monitoring of post-vaccination anti-HBs titles vaccine in childrenand adolescents in the pre-dialysis of chronic kidney disease

INTRODUCTION Bacterial or viral diseases are one of the major causes of death in patients with chronic kidney disease (CKD). These patients show a quantitative reduction of levels of antibodies over time. Among the infectious diseases that affect CKD patients, stands out hepatitis B (HB). Immunization and control of antibodies levels against the hepatitis B surface antigen (anti-HBs) are ways to prevent the HB infection in this population. Patients with anti-HBs levels ≥10 IU/ml are considered adequate responders, whereas those with anti-HBs levels ≥ 100 IU/ml are considered excellent responders. OBJECTIVE To analyze the variation of the anti-HBs levels obtained after vaccination against HB in children and adolescents in the pre-dialysis stage of CKD. METHODS A retrospective cohort study on anti-HBs levels of children and adolescents in the pre-dialysis stage of CKD. Correlation between levels of anti-HBs titers and time since the vaccination were estimated. RESULTS From the total of 116 studied patients most of the studied patients were considered excellent responders, obtaining in the three anti-HBs titers percentages of 70.7%, 62.1% and 54.9% respectively. The anti-HBs titer levels showed a negative correlation with the time since vaccination (Kendall Tau-b = -0.16; p = 0.02). CONCLUSION The majority of the studied population was vaccinated by PNI and showed excellent anti-HBs titer levels, even experiencing a progressive reduced response over the time.