Urinary procollagen III aminoterminal propeptide and ß-catenin - New diagnostic biomarkers in solitary functioning kidney?

PURPOSE: We aimed at evaluating urinary levels of procollagen III aminoterminal propeptide (PIIINP) and ß-catenin and the relationship between these markers and clinical and laboratory variables in children with a solitary functioning kidney (SFK). PATIENTS AND METHODS: The study group consisted of 98 (M/F: 62/36) children with an SFK with a median age of 8 years. An age-matched control group contained 54 healthy peers. Urinary levels of procollagen III aminoterminal propeptide and ß-catenin were measured using a commercially available immunoassay kit. RESULTS: The urinary values of PIIINP (UPIIINP) were significantly increased in patients with SFK versus controls (p < 0.01). Our analysis revealed no significant differences in urinary ß-catenin levels between the SFK patients and control subjects (p > 0.05). Only urinary PIIINP levels were correlated to renal function tests, such as serum creatinine, urea, uric acid, and estimated glomerular filtration rate (p<0.05). CONCLUSIONS: An increased urinary level of PIIINP may indicate early kidney impairment in children with SFK. Urinary ß-catenin does not seem to play any important role as a marker of renal function in children with SFK. Further long-term studies are required in order to evaluate the clinical usefulness of these markers and their predictive value of chronic kidney disease (CKD) progression.

Is urine intercellular adhesion molecule-1 a marker of renal disorder in children with ureteropelvic junction obstruction?

AIM: We aimed to investigate whether urine intercellular adhesion molecule-1 (ICAM-1) might serve as a marker of renal disorder in children with ureteropelvic junction obstruction. MATERIAL AND METHODS: Twenty-nine children with severe hydronephrosis (HN) were compared with 23 participants with mild HN and with 19 healthy peers. RESULTS: Urine ICAM-1/uCre levels were significantly higher in HN children than healthy controls (P<0.01), and in severe HN when compared with mild HN (p<0.05). CONCLUSIONS: It seemed to us that uICAM-1 is a biomarker of renal disorder, and might have the potential to predict which patients will require surgery.

Normal values for urine renalase excretion in children.

BACKGROUND: The objective of this study was to establish age-dependent values for urinary renalase/creatinine (renalase/Cr) ratio in healthy children and adolescents. METHODS: The study was conducted on a random sample of 157 healthy children and adolescents (0.1-17.9 years) divided into six age groups in 3-year intervals. Urine renalase concentration was measured using an enzyme-linked immunosorbent assay (ELISA) kit (Uscn Life Science, Wuhan, China). RESULTS: We analyzed median urine renalase/Cr ratio in particular age groups with the use of analysis of variance (ANOVA). Renalase/Cr levels were significantly higher in the youngest children < 3 years in comparison with other age groups (4.07 ng/mg Cr, p < 0.05). There was a statistically significant negative correlation between urine renalase/Cr and body mass index (BMI) Z-score (r = -0.22, p < 0.05) and both systolic (r = -0.22, p < 0.05) and diastolic (r = -0.21, p < 0.05) blood pressure. We constructed the reference renalase/Cr percentiles according to age in 3-year intervals. CONCLUSIONS: To the best of our knowledge, this study is the first to present reference values of urine renalase excretion in a healthy pediatric population. Further studies should concentrate on the influence of increased blood pressure or obesity on urine renalase excretion in children and teenagers.

Urinary angiotensinogen as a novel marker of obstructive nephropathy in children.

AIM: Obstructive nephropathy due to congenital or acquired urinary tract obstruction is one of the most important causes of chronic renal failure in children. There is a need for identification of new noninvasive urinary biomarkers to provide the clinician with fast, specific and reliable diagnostic and prognostic tool. The aim of the study was to determine whether urinary angiotensinogen (uAGT) may be a useful marker of obstruction in children with hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO). METHODS: The study cohort consisted of surgical group (SG): 31 children with severe HN who required surgery; nonsurgical group (NSG): 20 patients with mild HN, and reference group (RG): 19 healthy children. Urinary concentrations of angiotensinogen were measured using immunoenzymatic ELISA commercial kit and were expressed in ng/mg Cre (uAGT/uCre). RESULTS: uAGT/uCre level was higher in SG when compared to NSG (p < 0.01) and healthy participants (SG vs. RG: p < 0.01). The difference between the uAGT/uCre in NSG and RG was not statistically significant (p > 0.05). uAGT/uCre was correlated negatively with differential renal function (r = -0.46; p < 0.01). CONCLUSION: The present pilot study has clearly demonstrated that children with UPJO showed increased uAGT levels, which correlated negatively with differential renal function in radionuclide scan.

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

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.

Is plasma symmetric dimethylarginine a suitable marker of renal function in children and adolescents?

OBJECTIVE: The purpose of this cross-sectional study was to identify whether plasma symmetric dimethylarginine (pSDMA) is a useful marker of renal function in children. MATERIAL AND METHODS: The study group consisted of 35 patients with chronic kidney disease (CKD) stages 1-5 (median age 11.5 years), classified on the basis of estimated glomerular filtration rate (eGFR) and divided into three groups: group A, patients with CKD stages 1 and 2; group B, CKD stage 3; and group C, CKD stages 4 and 5. A control group included 42 age-matched healthy children. Commercial enzyme-linked immunosorbent assay kits were used to measure pSDMA and serum cystatin C (sCysC) concentrations. RESULTS: The pSDMA and sCysC levels were significantly elevated in all CKD patients in comparison with healthy controls (p < 0.05). The pSDMA level in children was increased in the mild CKD (group A) (p < 0.01). There were also a significant difference in pSDMA concentration between groups A and B (p < 0.01). No differences in pSDMA levels were found between groups B and C. Receiver operating characteristics analyses showed that pSDMA was a better diagnostic tool than sCysC for identifying CKD stage among all the examined children and for detecting patients from group A (eGFR >60 ml/min/1.73 m(2)). CONCLUSIONS: Increased pSDMA and sCysC levels were found in CKD children. Further studies are required to confirm potential applications of pSDMA and CysC as useful biomarkers for the diagnosis and progression of CKD.

Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of cyclosporine nephrotoxicity?

The aim of work was to investigate whether serum and urinary neutrophil gelatinase-associated lipocalin(sNGAL and uNGAL, respectively) are potential biomarkers of early cyclosporine A (CsA) nephrotoxicity in steroid-dependent nephrotic children (SDNS). The study group (I) consisted of 19 children with SDNS aged 9.46+/-5.52 years treated with CsA. The children were examined four times: at proteinuria relapse, prior to CsA treatment,then after 3, 6, and 12 months of CsA treatment. The control group (II) consisted of 18 healthy children aged 3-15 years. A commercial enzyme-linked immunosorbent assay method was used to measure NGAL concentration.The sNGAL level in SDNS children prior to the administration of CsA was similar to that in the healthy controls (p>0.05), but it increased significantly during the course of treatment (p<0.01). The uNGAL/creatinine (cr) ratio in SDNS patients was higher before the withdrawal of CsA therapy (p<0.05), and was also increased at the consecutive examinations (p<0.01). There was a positive correlation between both sNGAL and uNGAL levels and CsA serum level. However, based on the serum and urinary NGAL/cr receiver operating characteristic curve and area under the curve (AUC) analysis, it remains uncertain whether uNGAL is a good predictor of cyclosporine nephropathy. Both sNGAL and uNGAL concentrations increased during the course of CsA treatment. Further studies in larger groups of patients are therefore necessary to confirm our experimental data that increased NGAL levels may be a non-invasive marker for the early detection of tubulointerstitial damage in CsA nephrotoxicity.

[Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in the urine of children with pyelonephritis]. / Metaloproteinazy 2 i 9 oraz ich tkankowe inhibitory 1 i 2 w moczu dzieci chorych na odmiedniczkowe zapalenie nerek.

UNLABELLED: In small children, pyelonephritis (PN) is an important cause of scarring in the renal and disturbed in the production and degradation of extracellulare matrix proteins (ECM). Aim of the study was to assess the urinary levels metalloproteinases 2 and 9 (MMP-2 and MMP-9) and their inhibitors 1 and 2 (TIMP-1 and TIMP-2) in children with pyelonephritis (PN). MATERIALS AND METHODS: Study group (I) consisted of 42 children with PN, aged 1-15 years, examined twice: A--prior to treatment (1-3 days of fever), B--after antibacterial treatment (10-14 days). The control group (K) consisted of 30 healthy children. Enzyme-linked immunosorbent assay kits were used for measurements of total human MMP-2, MMP-9, TIMP-1 and TIMP-2 in first morning urine. RESULTS: In children with PN (I) prior to treatment (A), urinary concentration of all parameters were increased as compared to the control (K) (p<0.05). After treatment (B), only the levels of TIMP-1 was still elevated (p = 0.02). In PN before (A) and after (B) treatment MMP-9/TIMP-1 ratio. However MMP-2/TIMP-2 ratio was normal. CONCLUSION: In children with PN the balance MMP-9/TIMP-1 is disturbed, with the predominance of TIMP-1 production over MMP-9. It may lead to renal fibrosis.

Reference values of plasma oxalate in children and adolescents.

Oxalate homeostasis is a derivative of absorption and transportation in the digestive system and renal/intestinal excretion of oxalate. The objective of this cross-sectional study was to determine normative values of plasma oxalate in relation to age, gender, and body size. A group of 1,260 healthy Caucasian children and adolescents aged 3 months to 18 years [mean +/- standard deviation (SD) 10.5 +/- 4.3] was studied. Each 1-year group comprised 70 subjects. Oxalate levels were assessed in blood plasma samples obtained from fasted individuals using the precipitation-enzymatic method with oxalate oxidase. Median oxalate levels in healthy infants was 3.20 micromol/L (5th-95th percentiles: 1.56-5.58) and was higher compared with older children [2.50 micromol/L (5th-95th percentiles: 0.95-5.74); p < 0.01]. No differences were found in plasma oxalate levels between boys and girls. There were no associations between plasma oxalate levels and anthropometric traits. In the healthy population aged 1-18 years, plasma oxalate concentration is independent of age, gender, and body size. Infants demonstrate higher plasma oxalate levels compared with older children, which suggests possible immature mechanisms of renal excretion. This study appears to be the first extensive report providing normative data for plasma oxalate in children and adolescents.