Maria Goretti Moreira Guimarães Penido

Idiopathic hypercalciuria: presentation of 471 cases

OBJETIVO: analisar a historia clinica e evolucao de criancas e adolescentes com HI, ressaltando peculiaridades proprias destes pacientes. METODOS: 471 pacientes portadores de HI tem sido acompanhados em regime ambulatorial, sendo submetidos ao protocolo: Rx de abdome, ultra-sonografia de rins e vias urinarias; ionograma, gasometria e bioquimica de sangue; urina de 24 horas para dosagem de calcio e outros eletrolitos e creatinina; urinalise, urocultura e microscopia de contraste de fase; urina de segunda miccao matinal em jejum para dosagem de calcio e creatinina. RESULTADOS: 56% masculinos e 44% femininos; 56% brancos, 37% nao-brancos e 7% sem relato da cor da pele. Ao diagnostico 6% eram lactentes, 15% pre-escolares, 55% escolares e 24% adolescentes. 47% tinha hematuria associada a dor abdominal, 31% hematuria isolada, 14% dor abdominal isolada, e 8% tinham infeccao urinaria, enurese noturna, dor suprapubica ou uretral ou a sindrome miccional com frequencia/urgencia e incontinencia urinaria. A associacao de hipercalciuria com litiase do trato urinario foi positiva em 56% dos pacientes. Em 18,5% houve associacao com hiperuricosuria e em 8,5% com hipocitraturia. 33% dos pacientes tiveram ma evolucao com recorrencia de nefrolitiase, persistencia de hematuria e dor abdominal. CONCLUSOES: a HI deve ser diagnosticada e tratada criteriosamente com o objetivo de reduzir suas consequencias como hematuria, dor abdominal, formacao de calculos urinarios e as possiveis alteracoes osseas. Sinais e sintomas como urgencia e incontinencia urinarias, dor suprapubica e enurese noturna podem ter como causa a hiperexcrecao renal de calcio.

[Urinary excretion of calcium, uric acid and citrate in healthy children and adolescents].

OBJECTIVE To obtain regional reference values for calcium, uric acid and citrate urinary excretion and establish a correlation between those excretions in 24-hour urine sample and single urine sample for their use in clinical practice. METHODS A hundred and twenty-five healthy children and adolescents were randomly chosen and submitted to the following protocol: clinical examination, biochemical analysis of blood, blood cell count, parathormone, 24-hour urine, fasting urine sample and stool test. RESULTS The maximum value of calcium excretion in 24-hour urine was 3.75 mg/kg; in mg/dl of the glomerular filtration rate, it was 0.10; and for the calcium/creatinine (mg/dl) ratio in the fasting urine sample was 0.25. Positive correlation was observed between calcium excretion in the 24-hour urine and the fasting sample (mg/dl and mg/dl of glomerular filtration rate). The maximum values of uric acid excretion in 24-hour urine were 600, 450, and 320 mg and 13, 15 and 18 mg/kg for adolescents, school and preschool children, respectively; in mg/dl of glomerular filtration rate, in the fasting urine sample, it was 0.47. Positive correlation was observed for the uric acid excretion in 24-hour urine and fasting urine samples. The mean values for the citrate excretion in 24-hour urine were 1.6, 1.1 and 0.5 mmol for adolescents, school and preschool children, respectively; for citrate/creatinine ratio, in the fasting urine sample the mean value was 0.3. CONCLUSIONS The calcium and uric acid excretion in 24-hour urine showed correlation with those in the fasting urine sample, which allows their use for metabolic diagnosis, population studies and follow-up of patients with hypercalciuria and hyperuricosuria without voiding control; the citrate/creatinine ratio in the fasting urine sample can be used for controlling patients with hypocitraturia.

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.

Hypophosphatemic rickets due to perturbations in renal tubular function

The common denominator for all types of rickets is hypophosphatemia, leading to inadequate supply of the mineral to the growing bone. Hypophosphatemia can result from insufficient uptake of the mineral from the gut or its disproportionate losses in the kidney, the latter being caused by either tubular abnormalities per se or the effect on the tubule of circulating factors like fibroblast growth factor-23 and parathyroid hormone (PTH). High serum levels of the latter result in most cases from abnormalities in vitamin D metabolism which lead to decreased calcium absorption in the gut and hypocalcemia, triggering PTH secretion. Rickets is a disorder of the growth plate and hence pediatric by definition. However, it is important to recognize that the effect of hypophosphatemia on other parts of the skeleton results in osteomalacia in both children and adults. This review addresses the etiology, pathophysiologic mechanisms, clinical manifestations and treatment of entities associated with hypophosphatemic rickets due to perturbations in renal tubular function.

Pediatric urolithiasis: experience at a tertiary care pediatric hospital

INTRODUCTION Pediatric urolithiasis has become more prevalent in recent decades, with high recurrence rates and considerable morbidity. Most children with idiopathic urolithiasis have an underlying metabolic abnormality and proper research provides therapeutic interventions to reduce the formation of new stones and its complications. OBJECTIVE To identify demographic and clinical characteristics of pediatric urolithiasis, etiology, treatment management, disease recurrence and patient outcomes in a tertiary care pediatric hospital. METHODS A retrospective descriptive study of pediatric patients admitted to the Hospital Infantil Joana de Gusmão in Florianópolis, SC, Brazil, who were diagnosed with urolithiasis, from January 2002 to December 2012. Data were obtained from medical records. Those patients with diagnosis confirmed by imaging and 24hr urine or single sample urine were included. RESULTS We evaluated 106 pediatric patients (65% M). Average age at diagnosis was 8.0 ± 4.2 and 85% of them had positive family history of urolithiasis. Abdominal pain, renal colic and urinary tract infection were the main manifestations. 93.2% had metabolic abnormality and hypercalciuria was the most common. Pharmacological treatment was established in 78% of cases. Potassium citrate and hydrochlorothiazide were used. Surgical treatment was performed in 38% of patients. There was response to treatment in 39% of patients with recurrence of urolithiasis in 34.2% of them. Only 4.7% of patients continued follow-up, 6.6% were referred to other services, 8.5% were discharged and 73.8% lost follow-up. CONCLUSION Pediatric urolithiasis deserves a detailed metabolic evaluation after their initial presentation for treatment, monitoring and prevention of its formation and its complications.

Importância do dismorfismo eritrocitário na investigação da origem da hematúria: revisão da literatura

As hematurias sao achados comuns nos exames de urina de rotina e nem sempre sao sinais de doencas. A presenca de hematuria associada a outras alteracoes urinarias, especialmente a proteinuria, sugere comprometimento do trato urinario e merece investigacao. Na literatura sao inumeros os trabalhos que valorizam a sedimentoscopia urinaria, principalmente a morfologia das hemacias, como indicativo do local do sangramento: se glomerular ou nao-glomerular. Neste artigo, os autores revisam o estudo do dismorfismo eritrocitario, enfatizando a definicao, a fisiopatologia, os metodos, os valores de referencia e as limitacoes apontadas na literatura. As comparacoes com demais marcadores de hemorragia glomerular tambem foram discutidas. No final, os autores relatam como a literatura interpreta e utiliza os resultados da pesquisa do dismorfismo eritrocitario para guiar a propedeutica complementar na investigacao da origem da hematuria.

NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described

Autosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3 months of life. NPHS1 encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease.

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.