Urinary excretion of renin and angiotensinogen in hypertensive children and adolescents.

INTRODUCTION: In recent years hypertension has become an emerging condition in the young population. It has been proposed that the renin-angiotensin system plays an important role in regulation of blood pressure. We assessed whether activation of the intrarenal renin-angiotensin system occurs in hypertensive children and adolescents and what better reflects its activity: urine angiotensinogen (AGT) or urine renin (REN). MATERIAL AND METHODS: The study was conducted on a sample of 58 subjects with primary hypertension (HT) and 29 normotensive children and adolescents. We measured urine REN and AGT excretion and assessed the values in relation to blood pressure (BP) and other clinical parameters. Both REN and AGT values were calculated by urine creatinine: REN/cr. and AGT/cr., respectively. RESULTS: We observed higher urine REN/cr. values in hypertensive subjects in comparison to the reference group (6.99 vs. 2.93, p = 0.003). Hypertensive participants showed positive correlations between urine REN/cr. and diastolic 24-hour BP (r = 0.42, p = 0.002) as well as between urine REN/cr. and urine AGT/cr. (r = 0.266, p = 0.044, respectively). CONCLUSIONS: Increased urine REN/cr. in hypertensive children and adolescents and its positive correlation with BP may indicate its important role in the pathogenesis of HT. Perhaps urine REN/cr. could be a marker of intrarenal renin-angiotensin system activity. Nevertheless, further research should be undertaken to confirm this observation.

Are low birth weight children predisposed to renal loss of carnitine?

Aim: The plasma homeostasis of both free and esterified carnitines is mostly regulated by renal tubular reabsorption, which may be disturbed in low birth weight children. The aim of study was to check whether disturbances in excretion of l-carnitine (LC) and its main ester, acetyl-carnitine (ALC), may be the result of renal dysfunction in low birth weight children (LBW).Methods: This study included 59 LBW children (2165 g [1490-2440]) and 22 children with normal birth weight as a reference group (3500 g [3275-3650]). Subjects were divided into three groups: 0-3 months, 4-12 months and over 1 year at the time of testing. Urinary levels of carnitine were measured spectrophotometrically.Results: The urine excretion of Free LC, Free LC/cr, Total LC and Total LC/cr. Were significantly higher in 0-3 and 4-12-month old LBW infants study groups when compared to the reference groups. We found statistically significant higher urine excretion of ALC and ALC/cr. in all age groups of LBW infants compared to the reference group. There was a negative correlation between birth weight and free LC/cr. (r= -0.3, p < .05), Total LC/cr. (r= -0.34, p < .05), and ALC/cr. (r= -39, p < .05), and in the children >12-month-old strong negative correlation between eGFR and free LC/cr. (r= -0.6, p < .05), Total LC/cr. (r= -0.61, p < .05), ALC/cr. (r= -0.61, p < .05.)Conclusion: Higher urine excretion of both LC and ALC and its negative correlation with birth weight and eGFR may reflect some degree of renal dysfunction in LBW infants.

Upper metastable limit osmolality of urine as a predictor of kidney stone formation in children.

High fluid intake has been universally recommended for kidney stone prophylaxis. We evaluated 24-h urine osmolality regarded as the best biomarker of optimal hydration and upper metastable limit osmolality after water evaporation from urine sample to the onset of spontaneous crystallization and its usefulness as a new risk index that would describe an individual lithogenic potential. We collected 24-h urine from 257 pediatric patients with kidney stones and 270 controls. After volume and osmolality assessment, the urine samples were subjected to volume reduction in vacuum rotavapor continued to the onset of an induced urinary crystallization. The upper metastable limit osmolality of urine sample was calculated based on its initial osmolality value and the amount of water reduction. Pediatric stone formers presented with higher urine volume and lower urine osmolality than healthy controls. Despite that, their urine samples required much lower volume reduction to induce the spontaneous crystallization than those of controls. The ROC analysis revealed an AUC for the upper metastable limit osmolality of 0.9300 (95% CI 0.9104-0.9496) for distinguishing between stone formers and healthy subjects. At the cutoff of 2696 mOsm/kg, the test provided sensitivity and specificity of 0.8638 and 0.8189, respectively. 24-h urine osmolality provided the information about current hydration status, whereas evaporation test estimated the urinary potential to crystalize dependent on urine composition. Upper metastable limit osmolality may estimate the individual lithogenic capability and identify people at risk to stone formation when exposed to dehydration.

Does obesity or hyperuricemia influence lithogenic risk profile in children with urolithiasis?

BACKGROUND: There are indications that obesity and hyperuricemia may influence the formation and composition of urinary stones. The aim of our study was to determine the effect of obesity and hyperuricemia on the urinary lithogenic risk profile in a large cohort of pediatric patients. METHODS: The study population comprised 478 children with urolithiasis and 517 healthy children (reference group). We studied the effects of obesity on the lithogenic profile by dividing the patients with urolithiasis into two groups based on body mass index Z-score (patients who were overweight/obese vs. those with normal weight for age) and comparing the two groups. To study the effect of hyperuricemia on the lithogenic profile, we divided the patients with urolithiasis into two groups based on the presence or not of hyperuricemia (110 patients with urolithiasis accompanied by hyperuricemia vs. 368 patients with urolithiasis and normal serum uric acid levels) and compared the groups. RESULTS: Among the children and adolescents with urolithiasis and hyperuricemia, there was a significantly lower excretion of crystallization inhibitors (citrates, magnesium). We also found significantly negative correlations between serum uric acid levels and the urine citrate/creatinine ratio (citrate/cr.; r = -0.30, p < 0.01), as well as the magnesium/cr. ratio (Mg/cr.; r = -0.33, p < 0.01). There was no statistically significant differences in the urinary excretion of oxalates, citrates, calcium, phosphorus, magnesium and uric acid between children with urolithiasis who were either overweight or obese and children with urolithiasis who had a normal body weight. CONCLUSIONS: In our pediatric patient cohort, hyperuricemia was associated with a decrease in the excretion of crystallization inhibitors in the urine, but the clinical relevance of this observation needs to be confirmed in future studies. Obesity and overweight had no direct influence on the lithogenic risk profile in the urinary stone formers in our study, but there was an indication that higher serum uric acid may be associated with impairment in renal function, which in turn could influence the excretion of lithogenic parameters.

Is symmetric dimethylarginine a sensitive biomarker of subclinical kidney injury in children born with low birth weight?

OBJECTIVE: The aim of this study was to investigate if Symmetric Dimethylarginine (SDMA) is a sensitive biomarker of renal function and may predict subclinical kidney injury in low birth weight (LBW) children. METHODS: We studied 68 LBW children and 20 children as reference group. An enzyme-linked immunosorbent assay was used to measure serum SDMA and Cystatin C (Cys C). RESULTS: SDMA levels were higher in study groups compared to reference groups. There was a strong correlation between SDMA and Cys C, also SDMA negatively correlated with eGFR. CONCLUSION: Elevated SDMA concentration may play an important role in pathogenesis of chronic kidney disease.

Hematological parameters in adolescents with hyperuricemia.

OBJECTIVE: To examine the association between hematological indices and serum uric acid in adolescents with hyperuricemia. METHODS: 10-year retrospective cohort study of 607 patients with hyperuricemia registered with the Pediatric Nephrology Department. RESULTS: There was a statistically significant positive correlation between serum uric acid levels and BMI Z-scores (r=0.406, P<0.001), white and red blood cell counts, hemoglobin and hematocrit. Higher levels of hemoglobin, hematocrit and red blood cells were found in adolescents with metabolic syndrome than in groups without this condition. CONCLUSION: Hematological parameters could be important biological markers of cardiometabolic risk in adolescents with hyperuricemia.

Cerebrospinal fluid oxidative stress during chemotherapy of acute lymphoblastic leukemia in children.

In this study the authors addressed the question whether neurotoxicity due to the chemotherapy of acute lymphoblastic leukemia (ALL) is associated with cerebrospinal fluid (CSF) oxidative stress. Examination of 38 ALL patients revealed significant increases in 8-isoprostane concentration and important decreases in total antioxidative capacity of CSF during therapy. The mean 8-isoprostane level at diagnosis was 9.05 +/- 1.62 pg/mL, and no correlations with initial leukocytosis, organomegaly, and lactate dehydrogenase levels were noted. 8-Isoprostane concentrations were increased on the 59th day of treatment (mean level: 24.85 +/- 7.59 pg/mL [P < .01]) and remained elevated at 4 points of the consolidation phase (17.28 +/- 2.16 pg/mL [P < .05]; 22.72 +/- 6.04 pg/mL [P < .05]; 24.92 +/- 6.31 pg/mL [P < .01]; 32.32 +/- 7.94 pg/mL [P < .01]) as compared to their level at diagnosis. The mean total antioxidative capacity at diagnosis was 203.08 +/- 6.17 mumol/L and was remarkably decreased on the 59th day of treatment (189.76 +/- 1.9 mumol/L [P < .05]) and at one point of the consolidation phase (188.29 +/- 3.46 mumol/L [P < .05]) as compared to the level at diagnosis. This study indicates that neurotoxicity of standard ALL treatment may be related to oxidative stress.

[Sleep disorders in childhood and adolescence, with special reference to allergic diseases]. / Zaburzenia snu w wieku dziecieco-mlodziezowym, ze szczególnym uwzglednieniem chorób alergicznych.

UNLABELLED: Allergic diseases have a significant impact on the quality of life. The aim of the study was to compare sleep parameters of allergic and non-allergic children. MATERIAL AND METHODS: Pediatric Sleep Questionnaire was used to asses sleep quality in 202 participants in a 3-year prospective study: in 122 hospitalized (mean age 7.9 +/- 4.7) (F/M 75/47) due to allergic (n = 70) or non-allergic disease (n = 52), and in 80 healthy children (mean age 6.3 +/- 5.0) (F/M 36/44). Of 70 allergic participants, 26 had atopic dermatitis (SCORAD > or = 20); 25 were with bronchial asthma (GINA' criteria) and 19 with IgE-dependent food allergy confirmed by oral food challenge. Of 52 non-allergic patients, 31 children had gastro-esophageal reflux disease and 21 children had recurrent respiratory infection. RESULTS: The group of patients needed significantly more time to fall asleep than controls (17.9 +/- 13.7 vs 12.8 +/- 8.5 min; p < 0.004). Children with food allergy and atopic dermatitis had greatest problems with falling asleep (21.4 +/- 13.8 vs 12.8 +/- 8.5 min; p < 0.006) and 20.4 +/- 14.9 vs 12.8 +/- 8.5 min; p < 0.024). The number of nights of sound sleep without waking up was lower in the study group than in controls (3.5 +/- 2.6 vs 5.0 +/- 2.7; p < 0.0002). Atopic dermatitis and food allergy were found to predispose to sleep disruption most. Snoring history was revealed in 43.4% of patients and in 6.4% of controls (p < 0.0001), being significantly more common in children with bronchial asthma and recurrent respiratory tract infections. Allergic disease was a risk factor for snoring (OR--2.94; 95%CI--1.72-5.05; p < 0.001). As many as 91% of parents did not inform doctors about poor sleep of their children. CONCLUSIONS: 1. Allergic diseases are accompanied by different sleep disorders included dyssomnias and parasomnias, e.g. bedtime resistance, disrupted sleep or sleep-disordered breathing. 2. Physicians should pay particular attention to sleep quality in children with allergic diseases irrespective of which body system is affected i.e. the skin (atopic dermatitis), the respiratory tract (bronchial asthma) or the alimentary system (food allergy).

Negative correlation between cerebrospinal fluid tau protein and cognitive functioning in children with acute lymphoblastic leukemia.

The aim of the study was to assess whether cerebrospinal fluid tau protein is associated with cognitive changes in children with acute lymphoblastic leukemia (ALL). Examination of 38 ALL patients revealed a statistically significant increase in tau protein on treatment day 59 and at two points during consolidation phase. Cognitive functioning was examined in 19 patients at an average of 3.7 years after diagnosis. The level of tau at the initiation of maintenance therapy was negatively correlated with verbal abilities measured on an intellectual scale. The study suggests that standard ALL treatment may cause a decline in cognitive functioning.

Body composition and bone mass in survivors of childhood cancer.

BACKGROUND: The number of survivors of childhood cancer has increased. Several studies in children and adults have shown relationships between lean mass (LM), fat mass (FM), and bone mineral content (BMC). The objective of the study was to examine the association between body composition and bone mass in young survivors of childhood cancer. METHODS: Sixty-eight postpubertal participants (31 females and 37 males) aged between 15.5 and 27 years who were at least 5 years after completion of treatment for leukemia (n = 30), lymphoma (n = 28), or solid tumors (n = 10) were studied. Anthropometry was performed and dual energy X-ray absorptiometry (DXA) was used to assess BMC in the total body (T) and lumbar spine (S), FM, and LM. RESULTS: There were no observed differences in age or time for cessation of treatment. Body mass index (BMI) was a strong determinant of bone mass in both sexes. TBMC correlated positively with LM (males r = 0.9 and females r = 0.76; P < 0.0001, respectively) and with FM (r = 0.54; P < 0.01 in males and r = 0.8; P < 0.00001 in females). SBMC correlated with LM in both sexes (in males r = 0.77 and in females r = 0.64; P < 0.0001, respectively) but only in females, SBMC also correlated positively with FM (r = 44 P = 0.03). There were no differences between patients who received radiation and those who did not. CONCLUSIONS: The associations between bone mass and body composition differ by sex and skeletal site, however, they are similar in survivors of childhood cancer and compared to healthy individuals during growth. Further prospective research is needed in cancer survivors to determine the long-term effect of anti-cancer therapy on body composition and bone mass.

Level of tau protein in children treated for acute lymphoblastic leukemia.

Long-term neuropsychological complications such as attention and concentration disturbances, poor school performance, hyperexcitability, and even leukoencephalopathy have been described in children after chemotherapy for acute lymphoblastic leukemia. Elevation of the cerebrospinal fluid level of tau protein, associated with neuronal axons, is a neurodegenerative marker. The aim of the study was to assess the level of cerebrospinal fluid tau protein in children with acute lymphoblastic leukemia. The study included 26 patients with acute lymphoblastic leukemia and 19 patients with clinical symptoms of cerebrospinal meningitis (reference group). Tau protein levels were determined by enzyme-linked immunosorbent assay. Cerebrospinal fluid total protein level was not elevated in any of the samples. The examination was performed at diagnosis, after induction treatment, during consolidation, and after reinduction, i.e. before maintenance therapy. Neither age nor sex had an effect on tau protein levels in both groups. The mean tau protein value at diagnosis was 244.84 +/- 98.96 pg/mL in the study group (norm 300 pg/mL) and produced no correlation with initial leukocytosis, lactate dehydrogenase activity, or organomegaly at this point. Dynamic analysis revealed a statistically significant increase in tau protein after induction treatment (431.25 +/- 232.50) as compared with its level at diagnosis (244.84 +/- 98.96, P < 0.008) and later during treatment. The levels of tau protein at various points of treatment did not differ statistically significantly between the groups, except for the values obtained after termination of remission induction. The observed metabolic changes in tau protein, which is a known marker of neuronal damage, indicate that some patients are at a greater risk of central nervous system disorders. This finding requires further studies, also in reference to other central nervous system proteins, and confirms the necessity of long-term follow-up of leukemia patients.

[Biochemical markers of bone formation activity in children with neoplasms]. / Aktywnosc wskazników tworzenia i resorpcji kosci u dzieci z noworozpoznana choroba nowotworowa.

UNLABELLED: The aim of the study was the analysis of biochemical markers of bone turnover in children with neoplasms comparing with the group of healthy children. We explored the relationships between sex, pubertal development and type of neoplastic disease. 85 children (53 boys) with newly diagnosed neoplasms: 48 with acute lymphoblastic leukaemia (ALL), 13 with Hodgkin's disease and 22 with solid tumors (group I) and 111 healthy children (group II) were studied. We measured in plasma: 1. bone specific alkaline phosphatase (BALP), 2. osteocalcin (OST) as the markers of bone formation and 3. ICTP (cross-linked telopeptide of type 1 collagen), 4. parathormon (PTH), as the markers of bone resorption. RESULTS: 1. In the group of boys with neoplasms osteocalcin and BALP values were lower than in healthy boys: OST 51.2 ng/ml +/- 35.3 vs 85.8 ng/ml +/- 35.96, p < 0.0001, BALP 105.6 U/L +/- 56.8, p < 0.0001. The girls had lowered values of osteocalcin (45.55 ng/ml +/- 40.9 vs 71.94 ng/ml +/- 28.75, p < 0.0008) and ICTP (11.25 U/L +/- 3.38 vs 15,47 U/L +/- 5.33, p < 0.0016). The differences were also observed in comparison with the pubertal stage except for the boys in V0Tanner stage. 2. The values of OST and BALP were lower in children with ALL than in the children with solid tumours (p < 0.01). The values of ICTP did not depend on the type of disease, sex and pubertal stage, except the children before puberty. 3. In all group we found the correlation between OST and ICTP (r = 0.45, p < 0.05), BALP and ICTP (r = 0.45, p < 0.05). This correlation was observed in children with leukaemia (r = 0.55, p < 0.05), especially in girls (r = 0.9, p < 0.05). CONCLUSIONS: The markers of bone turnover are decreased in children with newly diagnosed neoplasms, especially with ALL.

[Effect of anticancer treatment on leptin level, fat body mass (FM) and lean body mass (LBM)]. / Wplyw leczenia przeciwnowotworowego na wartosci leptyny w surowicy, wskaznik masy ciala oraz zawartosc masy tluszczowej i beztluszczowej.

UNLABELLED: Leptin plays an important role in the metabolism of adipose tissue. Considering that malignancy and its treatment cans affect normal development in childhood. We analysed the correlations between serum leptin levels and body composition after anticancer treatment. We studied 33 survivors (24 boys and 9 girls) who before our study, have been treated for acute lymphoblastic leukaemia (ALL) (n=23) and Hodgkin disease (n=10) after 7.15+/-3.5 years. Sixteen patients with ALL received cranial irradiation (12Gy). We measured body mass index (BM1) fat mass (FM) and lean body mass (LBM) using dual energy x-ray absorptiometry (DXA). We compared these results to the results obtained from reference values (SD score). Leptin levels were measured with the RIA method. RESULTS: 1. Mean leptin levels were higher in girls after puberty (10.93 ng/mL+/-8.9) than in boys (3.73 ng/mL+/-3. 7). In boys no differences were found in leptin levels between T2-4 and T5 stages. In girls the leptin values increased after puberty. Leptin SD score levels were higher in boys during (1.55 +/-1.0) and after puberty (1.46+/-0.75) and in girls - after puberty (1.19 +/-1.51). We did not find any influence of cranial irradiation (12Gy) or various methotrexate doses (5 g/m(2) vs. 19/m(2)) leptin values. 2. No difference in BMI SD score was found within the whole study group. 3. FM did not change ill boys during and after puberty, although FM SD score were higher during puberty (2.98 +/-4.8). In girls FM and FM SD score were higher after puberty. In boys and girls LBM augmented with pubertal development but LBM SD score in boys were lower after puberty (-1.67 +/-1.7) in comparison to puberty (0.2 +/-1.7). No differences were found between LBM SD score in girls during and after puberty. 4. We found a correlation between leptin levels and BMI (r=0.59 p=0.001) and FM (r=0.77 p=0.0001). 5. Relation of FM to LBM in boys remained unchanged, however in girls it increased within pubertal development. CONCLUSION: l. Anticancer treatment during childhood shows no influence on body mass index although the tendency to higher fat mass in pubertal boys and in post pubertal girls is observed. 2. Leptin values depend on fat mass and do not relate directly to the pubertal stage.