João Tomás de Abreu Carvalhaes

Oral vitamin intake in children receiving long-term dialysis

OBJECTIVE To evaluate dietary and oral supplement vitamin intake in children submitted to dialysis (peritoneal dialysis and hemodialysis). DESIGN Prospective clinical trial in a 12-month follow-up period. SETTING Children with end-stage renal disease (ESRD) who attended the pediatric nephrology clinic of Universidade Federal de São Paulo-Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, Brazil. PATIENTS Thirty children (18 girls, 23 in peritoneal dialysis, 7 in hemodialysis) with age 9.3 +/- 7.4 years. INTERVENTION METHODOLOGY: Six successive assessments of both anthropometric indexes and 3-day dietary diaries in children receiving a daily dose of oral water-soluble vitamin supplement. MAIN OUTCOME MEASURES Anthropometric indexes (weight/age [W/A], height/age [H/A], midarm muscle area/age [MAMA/A], and fat area/age [FA/A]) and dietary adequacy-% recommended dietary allowance (RDA) (computerized nutritional analysis from 3-day dietary intake diary). RESULTS Anthropometric indexes analysis showed that 53% of children were <-2.0 standard deviation score (SDS) of W/A, 63% were <-2.0 SDS of H/A, and 43.3% were <-1.65 SDS of MAMA/A, suggesting growth deficit and low muscle wasted. Total caloric intake was lower than 100% of RDA in 90% of children. Dietary intake of water-soluble vitamins was <100% of RDA in the majority of children, as follows: vitamin C (24/30), B1 (28/30), B2 (22/30), B3 (27/30), B6 (26/30), B12 (1/30), pantothenic acid (24/30), and folic acid (9/30). The combined dietary and vitamin supplement intake resulted in excessive oral intake for almost all the vitamins. CONCLUSION Dietary intake of water-soluble vitamins is lower than the RDA in the majority of children with ESRD; supplementation is necessary to reach the RDA. The use of the available vitamin supplement resulted in vitamin intakes that exceeded the RDA for almost all of the vitamins. However, we do not know if these intakes exceeded the childrens requirements, nor whether they had any clinically significant harmful effects.

Prediction of steroid responsiveness in the idiopathic nephrotic syndrome using urinary retinol-binding protein and beta-2-microglobulin

OBJECTIVES To determine the prevalence of early proximal tubular dysfunction, measured by urinary excretion of retinol-binding protein (RBP) and beta-2-microglobulin (B2M), in patients with the idiopathic nephrotic syndrome and to investigate the value of these tests in predicting steroid responsiveness. DESIGN Before-after trial with 8-week treatment period. SETTING Tertiary referral center. PATIENTS Sequential sample of 37 patients with the idiopathic nephrotic syndrome caused by minimal change disease, focal segmental glomerulosclerosis, or mesangial proliferative glomerulonephritis. INTERVENTION All patients were treated with prednisone as one dose of 1 to 1.5 mg/kg body weight per day for 8 weeks. MEASUREMENTS Urinary RBP was measured by an immunoenzymometric assay and B2M, by an enzyme-linked immunosorbent assay. Remission of the nephrotic syndrome after steroid treatment was the main outcome variable. RESULTS Elevated levels of urinary RBP and B2M before treatment were detected in 65% and 75% of the patients, respectively. Median urinary RBP and B2M, before treatment, were significantly higher in the steroid-unresponsive group than in the responsive group (P less than 0.01). In the steroid-responsive group, urinary RBP and B2M levels decreased significantly after remission (P less than 0.01). In the steroid-unresponsive group, the likelihood ratios for urinary RBP greater than 4000 micrograms/g creatinine and for B2M greater than 3000 micrograms/g creatinine were 3.8 and 3.0, respectively. The probability was 100% that values of RBP of less than 1300 micrograms/g creatinine and B2M of less than 130 micrograms/g creatinine were from steroid-responsive patients. Multivariate analysis confirmed that higher urinary levels of RBP and B2M were associated with a lower likelihood of steroid responsiveness, independent of age and histologic diagnosis. CONCLUSIONS Proximal tubular dysfunction is frequent in patients with the idiopathic nephrotic syndrome. Pretreatment urinary RBP and B2M levels may be helpful in identifying nephrotic patients who are more likely to be responsive to steroids.

Bone mineral density and bone histomorphometry in children on long-term dialysis.

Bone mineral density (BMD) at the lumbar vertebrae (L1–L4) was assessed by dual-energy X-ray absorptiometry (DXA) in 20 children with chronic kidney disease (CKD) on dialysis, and its results were compared with bone biopsy and biochemical parameters. Biopsy specimens provided evidence of hyperparathyroid bone disease in eight cases (40%), and low bone turnover in 12 (60%). For BMD, expressed as Z-scores relative to normal, median Z-scores were −1.05 (range −2.36 to 1.06) for hyperparathyroid patients and −1.05 (range −4.40 to −0.03) for low bone turnover patients, with no statistical differences between groups (P = 0.512). In relation to BMD, of the whole sample, five (25%) had a Z-score under −2.0. When it was corrected for height, BMD was in the normal range. Additionally, there were no significant differences in single samples of serum calcium, alkaline phosphatase, phosphorus and intact parathyroid hormone (PTH) between groups with high or low bone turnover. Assessment of nutritional status, through height/age, showed that ten patients had Z-scores below −2.0 (median −2.12, range −7.13 to 0.73). In conclusion, renal osteodystrophy (ROD) seems to have a high prevalence among CKD pediatric patients, although only approximately a quarter of them developed changes in BMD. In children with CKD, measurements of bone mineral density may not be used for classification of various forms of ROD.

Plasma levels of acylated and total ghrelin in pediatric patients with chronic kidney disease

This cross-sectional study set out to compare total and acyl ghrelin levels in children with mild chronic kidney disease (CKD) undergoing conservative treatment (n = 19) with children with end-stage renal disease (ESRD) undergoing hemodialysis (n = 24), and with healthy controls (n = 20). The relationship between ghrelin levels and parameters of renal function, nutritional status, and selective hormones were investigated. ESRD patients had higher total ghrelin levels than those with mild CKD or control individuals. However, acyl ghrelin did not differ between groups, indicating that the excess circulating ghrelin was desacylated. Since desacyl ghrelin has been shown to inhibit appetite, increased levels might contribute to protein-energy wasting in pediatric renal patients. When all 43 renal patients were combined, multiple regression analysis found age and glomerular filtration rate (GFR) to be significant negative predictors of total ghrelin. Acyl ghrelin was influenced negatively by age and positively by energy intake. Acyl to total ghrelin ratio related positively to GFR and energy intake. The results indicate that total but not acyl ghrelin is influenced by low GFR in children with CKD and suggests that ghrelin activation may be impaired in these patients. Since energy intake is a positive predictor of acyl ghrelin, the physiological control of ghrelin secretion appears to be altered in pediatric renal patients.

Hemolytic Uremic Syndrome in Pediatric Intensive Care Units in São Paulo, Brazil

The hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) is one of the most frequent causes of pediatric acute renal failure. The aim of this study was to report the clinic and microbiologic features associated with 13 post-diarrheal HUS cases identified in pediatric intensive care units in the city of São Paulo, Brazil, from January 2001 to August 2005. Epidemiologic, clinic, and laboratorial information, along with fecal and serum samples, were collected for identifying the genetic sequences of Stx and for studying antibodies directed against LPS O26, O111 and O157. STEC was isolated from three patients, and serotypes O26:H11, O157:H7 and O165:H- were identified. In nine patients, high levels of IgM against LPS O111 (n=2) and O157 (n=7) were detected. Dialysis was required in 76.9% of the patients; arterial hypertension was present in 61.5%, neurological complications were observed in 30.7%, and only one patient died. During a 5–year follow-up period, one patient developed chronic kidney disease. The combined use of microbiologic and serologic techniques provided evidence of STEC infection in 92.3% of the HUS cases studied, and the importance of O157 STEC as agents of HUS in São Paulo has not been previously highlighted.The hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) is one of the most frequent causes of pediatric acute renal failure. The aim of this study was to report the clinic and microbiologic features associated with 13 post-diarrheal HUS cases identified in pediatric intensive care units in the city of Sao Paulo, Brazil, from January 2001 to August 2005. Epidemiologic, clinic, and laboratorial information, along with fecal and serum samples, were collected for identifying the genetic sequences of Stx and for studying antibodies directed against LPS O26, O111 and O157. STEC was isolated from three patients, and serotypes O26:H11, O157:H7 and O165:H - were identified. In nine patients, high levels of IgM against LPS O111 (n=2) and O157 (n=7) were detected. Dialysis was required in 76.9% of the patients; arterial hypertension was present in 61.5%, neurological complications were observed in 30.7%, and only one patient died. During a 5-year follow-up period, one patient developed chronic kidney disease. The combined use of microbiologic and serologic techniques provided evidence of STEC infection in 92.3% of the HUS cases studied, and the importance of O157 STEC as agents of HUS in Sao Paulo has not been previously highlighted.

CEREBRAL SINOVENOUS THROMBOSIS IN A NEPHROTIC CHILD

Nephrotic syndrome in infancy and childhood is known to be associated with a hypercoagulable state and thromboembolic complications, but cerebral sinovenous thrombosis (CST) is a very rare and serious one, with only a few isolated reports in the literature. A case is presented of a 9-year-old boy with nephrotic syndrome that acutely developed signs and symptoms of intracranial hypertension syndrome. CST was diagnosed on cranial CT and MRI and he gradually recovered after treatment with anticoagulants. The diagnosis of CST should be considered in any patient with nephrotic syndrome who develops neurologic symptoms. The discussion of this case, coupled with a review of the literature, emphasizes that early diagnosis is essential for institution of anticoagulation therapy and a successful outcome. This report also illustrates the difficulties that may be encountered in managing such a patient.

Síndrome de Lowe: relato de cinco casos

INTRODUCTION Lowe Syndrome, or Oculocerebrorenal Dystrophy (OCRL), has a recessive inheritance linked to X chromosome. It presents cataracts and glaucoma, delay in neuropsychomotor development, cognitive deficits, and renal Fanconi syndrome. OBJECTIVE Describe five patients with OCRL, attended at Tubulopathy outpatient clinic. METHOD We performed a retrospective assessment of 5 male patient clinical charts of OCRL patients. RESULTS Mean age at first consultation was 76.5 and mean follow up interval was 30.5 months (8-53 months). Symptoms and clinical signs included cataracts and nystagmus. Neuropsychomotor development and weight and height deficits were present in whole cases, as well as polyuria, polydipsia, and intestinal constipation, metabolic acidosis, phosphaturia, bicarbonaturia, proteinuria, hypercalciuria, hyperuricosuria. Nephrocalcinosis was identified in one, renal lithiasis in three, and reduced kidney size in two patients. We found pathological fractures and rachitism in two, bone rarefaction and delay of bone age in all of the patients. One patient presented a reduction in the rhythm of glomerular filtration. Therapeutically, all patients received alkali, phosphorus and vitamin D reposition in addition to a dietary orientation adequate to their needs. CONCLUSION This study emphasizes the importance of early diagnosis and medico-nutritional followup, to avoid complications related to metabolic disturbances.

Histochemical study of the skeletal muscle in children with chronic renal failure in dialysis treatment

Among the modifications occurring in the uremic organism, in addition to the consequences of dialysis, myopathy and peripheral neuropathy are very significant. Children are particularly affected, as their growth and development are jeopardized. Histochemistry of muscular biopsy was used to study eighteen children with end-stage renal failure under dialysis during a ten-month period. According to our results, the skeletal muscular tissue presented the following types of alterations: atrophy, type grouping, lipidosis, glycogen depletion and mitochondrial proliferation.

Avaliação nutricional de crianças com doença renal crônica

OBJECTIVE:Malnutrition is a frequent complication among children with renal diseases. Short stature is the main clinical sign. The aim of this study is to analyze the nutritional status of children with renal disease using anthropometry. METHODS: This cross sectional study enrolled 21 (43%) boys and 28 (57%) girls with age ranging from 5.3 to 19.5 years. They were divided in three groups based on their creatinine clearance (mL/min/1.73m2): Group 1, >37 (n=19); Group 2, between 15 and 37 (n=9) and Group 3, <15 (n=21). Weight and height were obtained in order to calculate the following indexes: Weight/age (W/A), height/age (H/A) and body mass index (BMI); then, Z scores were obtained. Malnutrition was defined as Z scores below -2. ANOVA test was used to compare groups. RESULTS: There were no differences among the groups for anthropometric data. 19 patients (38.8%) presented short-stature and 22 (44.8%) low-weight. Z scores were similar among groups relative to W/A, H/A and BMI values. W/A Z score values were: Group 1: -1.9±1.8; Group 2: -2.6±3.1 and Group 3: -2.5±1.4 (p=0.47). H/A Z scores values were: Group 1: -1.5±1.2; Group 2: -2.3±1.8 and Group 3: -2.1±1.1 (p=0.18). The calculated BMI Z scores were: Group 1: -1.2±1.4; Group 2: -1.7±3.9 and Group 3: -1.6±1.3 (p=0.82). 19 children presented short stature and 22 presented low weight. There were no differences between the studied groups. CONCLUSIONS: The sample presented high prevalence of malnutrition. Even considering the disease stage, there were no nutritional differences between the studied groups.

Tubular urinary enzymes in acute post-infectious glomerulonephritis.

Abstract. Tubular function of 17 pediatric patients with a mild form of acute post-infectious glomerulonephritis was prospectively evaluated by assessment of the urinary activity of proximal and distal tubule enzymes. Neutral-like endopeptidase (NEP-like) and angiotensin-converting enzyme (ACE) were the proximal tubule enzymes assessed, while prolyl-endopeptidase (PE) and serine-endopeptidase H1 and H2 were the distal tubule enzymes analyzed. Urine was collected at diagnosis (T0) and after 2 (T2) and 6 (T6) months of follow-up. NEP-like enzyme activity (nmol/mg creatinine; median±quartile range) was increased at diagnosis, and this remained stable during the first 6 months (T0 18.30±83.26, T2 17.32±49.56, T6 23.38±107.18). Urinary activity of the other enzymes was as follows: ACE (mU/ml per mg creatinine) T0 0.08±0.16, T2 0.06±0.10, T6 0.18±0.29; PE (nmol/mg creatinine) T0 6.70±84.87, T2 9.55±69.00, T6 13.67±28.70; serine-endopeptidase H1 (nmol/mg creatinine) T0 7.86±26.95, T2 17.17±59.37, T6 18.19± 79.14; and serine-thiol-endopeptidase H2 (nmol/mg creatinine) T0 3.06±21.97, T2 12.06±32.42, T6 16.22± 44.06. Thirty other healthy children matched for age and gender were considered as a control group. This group was assessed once and the results were: NEP-like activity 6.05±10.54, ACE 0.11±0.22, PE 7.10±13.36, H1 5.00±17.30, and H2 6.00±20.16. In conclusion, we observed that NEP-like and H1 enzymes exhibited significant increased urinary activity 6 months after the diagnosis. This increase occurred in spite of the disappearance of clinical symptoms, which occurred 2 months after the diagnosis. We believe that the increase in urinary enzymatic activity could be a manifestation of a silent tubular dysfunction following an episode of acute post-infectious glomerulonephritis.