Agata Korzeniecka-Kozerska

Urinary MMP-9/NGAL ratio as a potential marker of FSGS in nephrotic children

BACKGROUND: The study was undertaken to develop a potential new markers for distinguishing minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) in children. We hypothesized that matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) is a better marker of focal sclerosis in the glomerulus then matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) and matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-2 MMP2/TIMP-2. METHODS: The present study used a sample of 36 children and adolescents subdivided into two groups: I – 20 children with MCNS, subjected to examination twice: A – in relapse of nephrotic syndrome, before treatment and B – after regression of proteinuria; II – 16 children with FSGS. MMPs and TIMPs and NGAL levels were measured in the urine using ELISA kit. MMP-9/TIMP-1, MMP-2/TIMP-2 and MMP-9/NGAL ratios were calculated. RESULTS: Median NGAL/cr. was significantly higher in MCNS and FSGS patients when compared to healthy controls. Both, NGAL and MMP-9 urinary levels were significantly elevated in FSGS subjects, as compared with control subjects. Contrary to FSGS children, in MCNS group, before treatment only NGAL/cr., but not MMP-9/cr. was increased. Urinary concentrations of NGAL and MMP-9 were highly associated with each other (NGAL/cr. vs. MMP-9/cr., r = 0.485, p < 0.01). Median urine MMP-9/NGAL ratio in FSGS patients was significantly higher than in patients with MCNS. We also found that significant increase in MMP-9/NGAL was associated with FSGS [odds ratio (OR) – 9.0; confidence interval (CI) 1.97–41.07]. CONCLUSION: MMP-9/NGAL ratio may serve as differentiation marker between MCNS and FSGS in nephrotic children.

Functional bladder capacity and urine osmolality in children with primary monosymptomatic nocturnal enuresis

Objective To assess functional day-time bladder capacity (DBC) and urine osmolality in children with primary monosymptomatic nocturnal enuresis (PMNE) according to age and sex. Material and methods A total of 263 children with PMNE were divided into two groups: Group I, 160 children (63 girls, 97 boys) aged 5–9 years (mean age 7.14±1.47 years); and Ggroup II, 103 children (25 girls, 78 boys) aged 10–15 years (mean age 12.26±1.52 years). DBC (milliliters) was the largest void of the day measured over four 24-h periods, irrespective of the diet applied. Urine osmolality was determined three times: in the evening before bed-time; at night, 2–4 h after falling asleep; and in the morning in the nocturnal void. Results DBC was smaller in Group I than in Group II (151.27 vs 199.46 ml; p<0.05). No statistically significant differences were found in relation to sex (p>0.05). The mean osmolality of the nocturnal void in the morning was 854.15 and 909.22 mOsmol/kg H2O in Groups I and II, respectively (p>0.05). Differences between boys and girls were not statistically significant (p>0.05). No correlation was found between DBC and urine osmolality (p>0.05). A detailed analysis of the results revealed DBC below the 5th percentile or above the 95th percentile in 23/263 cases (8.7%), reduced osmolality (< 800 mOsmol/kg H2O) in 76/263 (28.8%), a familial nature of nocturnal enuresis in 124/263 (47.1%) and difficulty waking in 86/263 (32.7%). Conclusions In children with PMNE aged 5–15 years, functional DBC increases with age and does not differ between the sexes; the mean nocturnal urine osmolality is neither age- nor sex-dependent.

Assessment of Lithogenic Risk in Children Based on a Morning Spot Urine Sample

PURPOSE The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on 24-hour urine collection. We studied whether the Bonn Risk Index could be measured in spot urine samples and which part of the day is most suitable for this purpose. MATERIALS AND METHODS We collected total and fractionated 24-hour urine (in a 6-hour nocturnal portion and 9 consecutive 2-hour diurnal samples) in 42 children and adolescents with calcium oxalate urolithiasis and 46 controls. Bonn Risk Index values determined from each of the urine fractions were compared to those obtained from related 24-hour urine collections. RESULTS Both groups exhibited similar circadian patterns of Bonn Risk Index values. Median Bonn Risk Index for the nighttime portion of urine in the stone group was 1.4 times higher than that obtained from the total 24-hour urine. The morning hours between 08:00 and 10:00 showed the peak lithogenic risk, and this fraction had the highest sensitivity and selectivity regarding discrimination between stone formers and healthy subjects. The afternoon hours demonstrated lower and less fluctuating crystallization risk. Despite diurnal fluctuations in Bonn Risk Index, there was still a well-defined cutoff between the groups. CONCLUSIONS Bonn Risk Index determined from urine samples collected between 08:00 and 10:00 appears optimal in separating stone formers from healthy subjects, and appears as useful as the value determined from 24-hour urine collection. Investigation of this diurnal sample simplifies diagnosis in pediatric stone disease without loss of clinical information.

Urinary nerve growth factor level in children with neurogenic bladder due to myelomeningocele

Abstract Objective. Myelomeningocele is the most common physically disabling birth defect in humans. It is caused by the failure of the neural tube to close and is most common in the lumbosacral area. Because of associated neurogenic bladder dysfunction, children with myelomeningocele have an increased risk of urinary tract infections and, ultimately, of kidney damage. Nerve growth factor (NGF) is an important mediator inducing bladder overactivity in many pathological conditions. The aim of this study was to evaluate urinary NGF excretion in children with neurogenic bladder caused by myelomeningocele. Material and methods. The investigation was conducted into two groups. Group 1 comprised 28 children with neurogenic bladder, and group 2 comprised 20 healthy children with no abnormalities in the urinary and nervous systems. Urinary NGF levels were measured by enzyme-linked immunosorbent assay. Results. Median urinary NGF concentration in group 1 was higher when compared with healthy controls. Positive correlations between urinary NGF level and detrusor pressure at maximum bladder capacity, and negative correlations between NGF and bladder wall compliance were found. Conclusions. Urinary NGF levels were significantly elevated in patients with myelomeningocele. Future studies are needed to examine further the significance of urinary NGF levels in the pathogenesis of neurogenic bladder in this clinical condition.

Dyslipidaemia in overweight children and adolescents is associated with an increased risk of kidney stones.

There is conflicting evidence about the role of obesity in paediatric nephrolithiasis. This Polish study explored the influence of nutritional status and lipid disturbances on urinary lithogenic factors and the risk of kidney stone formation in children and adolescents from three to 18 years of age.

Asymmetric and symmetric dimethylarginine in adolescents with hyperuricemia.

The purpose of this work was to investigate if in adolescents with hyperuricemia serum levels of asymmetric and symmetric dimethylarginine (ADMA, SDMA) are increased and if their levels correlate with serum uric acid (UA). Patients and Methods. The study group consisted of 58 hyperuricemic patients aged median 16.15 Q1–Q3 (14–17). The reference group contained 27 healthy individuals with normal serum UA level. ADMA and SDMA were measured by immunoenzymatic ELISA commercial kits and expressed in μmol/L. Serum UA was measured by the colorimetric method. Results. In hyperuricemic patients serum ADMA values did not differ between two estimated groups (P > 0.05); however, SDMA was significantly higher than in reference group (P < 0.01). Serum ADMA and SDMA correlated positively with UA (r = 0.34, P < 0.01) (r = 0.31, P < 0.01) and hs-CRP (r = 0.20, P < 0.05) (r = 0.36, P < 0.01), respectively. Conclusion. We demonstrated increased SDMA but not ADMA levels in adolescents with hyperuricemia and their correlation with serum uric acid levels. However, at the moment it is difficult to answer the question if it is just coexistence of these factors or any mechanism linking uric acid and methylated arginines really exists.

Urodynamic Findings and Renal Function in Children with Neurogenic Bladder after Myelomeningocele.

Introduction: Myelomeningocele (MMC) is a congenital central nervous system malformation caused by a failure of the neurulation process in early pregnancy. Patients with MMC present many abnormalities and the nervous, skeletal and urinary systems are the most affected. The aim of this study was to clinically evaluate patients with MMC, estimate renal and lower urinary tract (LUT) function and to ascertain whether urodynamic findings can predict the deterioration of urinary tract function. Materials and Methods: Medical records of 112 patients were gathered from a database and evaluated retrospectively. The data included age, sex, BMI Z-score WHO, physical activity, urodynamic parameters and diagnosis and renal function. Results: A total of 112 patients with MMC were enrolled in the study. There were no differences in age, sex, BMI Z-score WHO, physical activity, renal function and urodynamic findings (apart from cystometric capacity) between boys and girls. Detrusor overactivity was the most frequent urodynamic diagnosis in all groups of physical activity, level of lesion and in catheterized and non-catheterized children. The correlations between urodynamic findings and renal function tests were found. Conclusions: Patients with neurogenic bladder after MMC most often present detrusor overactivity. LUT function is disturbed in all MMC patients independent of lesion level and physical activity.

Urinary nerve growth factor in patients with detrusor overactivity

BackgroundDetrusor overactivity (DO) is one of the most frequent bladder dysfunctions in children up to the age of 18. Nowadays, the only way to confirm DO is by urodynamic investigation, which is an invasive procedure. Among the many mediators influencing bladder function, nerve growth factor (NGF) plays an important role. The present study was designed to measure urinary NGF (uNGF) levels in patients with DO diagnosed by urodynamic study in comparison with healthy controls.MethodsThe investigation was conducted on 44 children, divided into two groups (24 patients with DO, 20 healthy children). Uroflowmetry was performed in all enrolled to the study and cystometry only to patients. uNGF levels were estimated in both studied groups.ResultsThe median uNGF level in patients with DO before treatment was higher compared with healthy controls. There were no differences between uNGF levels in patients after anticholinergic treatment and the controls. We found differences in uroflowmetry parameters between the reference group and the patients. We found correlations between uroflowmetry parameters and uNGF/cr. level.Conclusions1.The uNGF level could be used for detecting DO in children and adolescents.2.Measuring uNGF level is a simple, noninvasive procedure and very useful for choosing therapy in patients with DO in various clinical conditions.