Marcelo de Sousa Tavares

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.

Comunicação no ensino médico: estruturação, experiência e desafios em novos currículos médicos

This article relates an experience of a group of teachers of the Integrated Medical Course of the State University of Londrina in teaching communication in the Skills Module. The awareness of the importance of communication skills not only in the doctor-patient relationship but also in the evolution of diseases led to the design of a module with progressive difficulties throughout the first years of the course. The content of the module ranges from observation of patients in the waiting room to discussions on how to transmit information, treatment adherence and management of special groups of patients in different stages of life. The methods used include observation of patients, interviews, group discussions, role-playing, films, round tables, conferences and statements of patients. The evaluation occurs in two parts: formative and cognitive. The training of communication skills is aimed at developing the ability of the student to establish a good doctor-patient relationship, history taking and transmission of information and at promoting treatment adherence.

Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease

INTRODUTION Steroid resistant idiopathic nephrotic syndrome (SRINS) in children is one of the leading causes of progression to chronic kidney disease stage V (CKD V)/end stage renal disease (ESRD). OBJECTIVE The aim of this retrospective study is to evaluate the efficacy of immunosuppressive drugs (IS) and to identify risk factors for progression to ESRD in this population. METHODS Clinical and biochemical variables at presentation, early or late steroid resistance, histological pattern and response to cyclosporine A (CsA) and cyclophosfamide (CP) were reviewed in 136 children with SRINS. The analyzed outcome was the progression to ESRD. Univariate as well as multivariate Cox-regression analysis were performed. RESULTS Median age at onset was 5.54 years (0.67-17.22) and median follow up time was 6.1 years (0.25-30.83). Early steroid-resistance was observed in 114 patients and late resistance in 22. Resistance to CP and CsA was 62.9% and 35% respectively. At last follow-up 57 patients reached ESRD. The renal survival rate was 71.5%, 58.4%, 55.3%, 35.6% and 28.5% at 5, 10, 15, 20 and 25 years respectively. Univariate analysis demonstrated that older age at onset, early steroid-resistance, hematuria, hypertension, focal segmental glomerulosclerosis (FSGS), and resistance to IS were risk factors for ESRD. The Cox proportional-hazards regression identified CsAresistance and FSGS as the only predictors for ESRD. CONCLUSION Our findings showed that CsA-resistance and FSGS were risk factors for ESRD.

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.

Pediatric primary urolithiasis: Symptoms, medical management and prevention strategies.

In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other environmental factors. Although less frequent than adult stone disease, urolithiasis in the pediatric age group is also related to significant morbidity, particularly since stones tend to recur, and, thus, should not be underestimated. Most children with idiopathic stone disease have an underlying metabolic abnormality substantiating the importance of metabolic evaluation already following initial diagnosis of urolithiasis. Identification of the metabolic abnormality allows for more specific prescription of non pharmacological and pharmacological interventions aimed at preventing recurrent stone formation. A better understanding of the causes of kidney stone disease will provide better strategies for stone prevention in children.

Avaliação e manejo da doença cardiovascular em pacientes com doença renal crônica

RESUMO A presente carta ao Editor compara as dificuldades de avaliacao e manejo da doenca cardiovascular em criancas e adolescentes portadores de doenca renal cronica com as mesmas dificuldades encontradas em pacientes adultos. […] Avaliacao e manejo da doenca cardiovascular em pacientes com doenca renal cronica

Bone disease in pediatric idiopathic hypercalciuria

Idiopathic hypercalciuria (IH) is the leading metabolic risk factor for urolithiasis and affects all age groups without gender or race predominance. IH has a high morbidity with or without lithiasis and reduced bone mineral density (BMD), as described previously in pediatric patients as well as in adults. The pathogenesis of IH is complex and not completely understood, given that urinary excretion of calcium is the end result of an interplay between three organs (gut, bone and kidney), which is further orchestrated by hormones, such as 1,25 dihydroxyvitamin D, parathyroid hormone, calcitonin and fosfatonins (i.e., fibroblast growth-factor-23). Usually, a primary defect in one organ induces compensatory mechanisms in the remaining two organs, such as increased absorption of calcium in the gut secondary to a primary renal loss. Thus, IH is a systemic abnormality of calcium homeostasis with changes in cellular transport of this ion in intestines, kidneys and bones. Reduced BMD has been demonstrated in pediatric patients diagnosed with IH. However, the precise mechanisms of bone loss or failure of adequate bone mass gain are still unknown. The largest accumulation of bone mass occurs during childhood and adolescence, peaking at the end of the second decade of life. This accumulation should occur without interference to achieve the peak of optimal bone mass. Any interference may be a risk factor for the reduction of bone mass with increased risk of fractures in adulthood. This review will address the pathogenesis of IH and its consequence in bone mass.

Role of FGF23 in Pediatric Hypercalciuria

Background This study explored the possible role of FGF23 in pediatric hypercalciuria. Methods Plasma FGF23 was measured in 29 controls and 58 children and adolescents with hypercalciuria: 24 before treatment (Pre-Treated) and 34 after 6 months of treatment (Treated). Hypercalciuric patients also measured serum PTH hormone, 25(OH)vitD, phosphate, calcium, creatinine, and 24 h urine calcium, phosphate, and creatinine. Results There were no differences in age, gender, ethnicity, or body mass index either between controls and patients, or between Pre-Treated and Treated patients. Median plasma FGF23 in controls was 72 compared with all patients, 58 RU/mL (p = 0.0019). However, whereas FGF23 in Pre-Treated patients, 73 RU/mL, was not different from controls, in Treated patients it was 50 RU/mL, significantly lower than in both controls (p < 0.0001) and Pre-Treated patients (p = 0.02). In all patients, there was a correlation between FGF23 and urinary calcium (r = 0.325; p = 0.0014). Treated patients had significantly lower urinary calcium (p < 0.0001), higher TP/GFR (p < 0.001), and higher serum phosphate (p = 0.007) versus Pre-Treated patients. Conclusions Pharmacological treatment of hypercalciuric patients resulted in significantly lower urinary calcium excretion, lower serum FGF23, and elevated TP/GFR and serum phosphate concentration, without significant changes in PTH. Further studies are indicated. This trial is registered with Clinical Registration Number RBR 8W27X5.Background This study explored the possible role of FGF23 in pediatric hypercalciuria. Methods Plasma FGF23 was measured in 29 controls and 58 children and adolescents with hypercalciuria: 24 before treatment (Pre-Treated) and 34 after 6 months of treatment (Treated). Hypercalciuric patients also measured serum PTH hormone, 25(OH)vitD, phosphate, calcium, creatinine, and 24 h urine calcium, phosphate, and creatinine. Results There were no differences in age, gender, ethnicity, or body mass index either between controls and patients, or between Pre-Treated and Treated patients. Median plasma FGF23 in controls was 72 compared with all patients, 58 RU/mL (p = 0.0019). However, whereas FGF23 in Pre-Treated patients, 73 RU/mL, was not different from controls, in Treated patients it was 50 RU/mL, significantly lower than in both controls (p < 0.0001) and Pre-Treated patients (p = 0.02). In all patients, there was a correlation between FGF23 and urinary calcium (r = 0.325; p = 0.0014). Treated patients had significantly lower urinary calcium (p < 0.0001), higher TP/GFR (p < 0.001), and higher serum phosphate (p = 0.007) versus Pre-Treated patients. Conclusions Pharmacological treatment of hypercalciuric patients resulted in significantly lower urinary calcium excretion, lower serum FGF23, and elevated TP/GFR and serum phosphate concentration, without significant changes in PTH. Further studies are indicated. This trial is registered with Clinical Registration Number RBR 8W27X5.

Prevalence of risk factors for cardiovascular and kidney disease in Brazilian healthy preschool children

AIM To investigate the prevalence of nutritional parameters of risk for cardiovascular disease (CVD) and kidney diseases in healthy preschool children. METHODS This is an observational cross-sectional study with 60 healthy children, of both genders, aged two to six years old and 56 mothers, in Belo Horizonte, Minas Gerais, Brazil. Preschool children and their families with regular activities at public schools were invited to paticipate in the study. The following characteristics were assessed: Socio-demographic condictions, clinical health, anthropometric, biochemical, lifestyle and data on food consumption. The 56 healthy children were divided into two groups, overweight (C1) and non-overweight (C2), as well as their mothers, respectively, in overweight (M1) and non-overweight (M2). Nutritional status was defined according to results obtained through the Anthro® Software for nutritional analysis. RESULTS Thirty-five children were male, with mean age of 4.44 ± 1.0 years old. Eighty-nine percent of them were eutrophic, 86.7% were sedentary and they had five meals a day. Body mass index (BMI) for age and total cholesterol (TC) was higher on C1 (P = 0.0001) and high density lipoprotein cholesterol (HDL-c) was higher on C2. Mothers were 32.5 ± 7.1 years old, mostly married and employed. Eighty-six percent of them were sedentary and 62.5% were overweight with BMI = 26.38 ± 5.07 kg/m2. Eighteen percent of the overweight mothers had isolated total hypercholesterolemia (TC levels elevated) and 12.5% had low HDL-c levels. The present study showed an association between overweight and obesity during the preschool years and the correspondent mothers’ nutritional status of overweight and obesity (OR = 4.96; 95%CI: 0.558-44.17). There was a positive correlation between the food risk associated with CVD by children and mothers when their consumption was 4 times/wk (P = 0.049; r = 0.516) or daily (P = 0.000008; r = 0.892). CONCLUSION Analyzed children showed high rates of physical inactivity, high serum cholesterol levels and high consumption of food associated with risk for CVD and renal disease. Changes in habits should be encouraged early in kindergarten.

Parathyroid ultrasonography and bone metabolic profile of patients on dialysis with hyperparathyroidism.

AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure. METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics (etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory (calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ(2) test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables. RESULTS Fifty-three patients (66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product (P = 0.03 and P = 0.006, respectively). They also had lower mortality (32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events (27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg(2)/dL(2) [RR 1.48 (1.06, 2.08), P = 0.03], presence of vascular calcification [1.33 (1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25 (1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality. CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure.