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.

KIM-1 and NGAL: new markers of obstructive nephropathy.

Congenital obstructive nephropathy is the primary cause of chronic renal failure in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. The aim of our study was to determine whether urinary (u) kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be useful non-invasive biomarkers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction. The study cohort consisted of 20 children with severe HN who required surgery (median age 2.16 years) and two control groups (control group 1: 20 patients with mild, non-obstructive HN; control group 2: 25 healthy children). All of the children had normal renal function. Immunoenzymatic ELISA commercial kits were used to measure uKIM-1 and uNGAL concentrations. The preoperative median uKIM-1/creatinine (cr.) and uNGAL levels were significantly greater in the children with severe HN than in both control groups. Three months after surgery, uNGAL had decreased significantly (p<0.05) in the children with severe HN, but was still higher than that in control group 2 children (p<0.05). Receiver operator characteristic analyses revealed a good diagnostic profile for uKIM-1 and uNGAL in terms of identifying a differential renal function of <40% in HN patients (area under the curve (AUC) 0.8 and 0.814, respectively) and <45% in all examined children (AUC 0.779 and 0.868, respectively). Based on these results, we suggest that increasing uNGAL and uKIM-1 levels are associated with worsening obstruction. Further studies are required to confirm a potential application of uKIM-1 and uNGAL as useful biomarkers for the diagnosis and progression of chronic kidney disease.

Effect of cyclosporin A on proteinuria in the course of glomerulopathy associated with WT1 mutations.

Denys-Drash syndrome (DDS) is characterized by progressive glomerulopathy caused by diffuse mesangial sclerosis (DMS), genitourinary defects, and a higher risk of developing Wilms' tumor. It is commonly assumed that the DMS is unresponsive to any medications. In this report, we present a patient with Denys-Drash syndrome, in whom the cyclosporine A (CsA) was found to induce total remission. This observation and observations of other authors confirm that in genetic forms of nephrotic syndrome, the proteinuric effect of CsA may be due to a non-immunologic mechanism. We confirm the beneficial effect of CsA treatment in DDS; however, the potential nephrotoxicity of this drug will probably not allow long-term use.

[Serum and urinary concentration of selected metalloproteinases and their tissue inhibitors in children with vesicoureteral reflux]. / Stezenie wybranych metaloproteinaz i ich tkankowych inhibitorów w surowicy i moczu dzieci z odplywami pecherzowo-moczowodowymi.

UNLABELLED: Vesicoureteral reflux (VUR) in children may lead to the renal fibrosis and scarring due to the overproduction and accumulation of extracellular matrix proteins (ECM) in interstitial tissue. Metalloproteinases produced in the kidneys are called biological markers of fibrosis. THE AIM OF THE STUDY was to assess if the presence of VUR in children disturb the balance between the serum and urinary concentrations of matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 (TIMP-1) and 2 (TIMP-2) and predispose to excessive renal fibrosis. MATERIAL AND METHODS. The study was performed in 88 children, median aged 5.5 years (0.08-16 yrs) with VUR confirmed by voiding cystouretrography (VCUG). In 95% of estimated children the pyelonephritis indicated for VCUG performance. Control group consisted of 30 healthy children at similar age. Concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were estimated using immunoenzymatic ELISA method in urine of all examined children, additionally all the mentioned parameters in children with high (ll-V) grade of VUR were assessed in serum. RESULTS revealed that the urinary and serum concentrations of TIMP-1 and TIMP-2 were higher in healthy controls (p < 0.05). MMP-9 levels were higher only in the urine (p < 0.05) and MMP-2 in serum (p < 0.05). Increase in TIMP concentrations was connected with parallel increase in MMP levels in children with I-V grades of VUR, what was confirmed by the normal values of MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios (p > 0.05). Only children with Ill-rd grade of VUR revealed reduced values of MMP/TIMP ratios (p < 0.05). Children's with Ill-V grade VUR revealed higher increase in serum concentrations of TIMP than in MMP, it was also seen in decrease in MMP/TIMP ratios (p < 0.05). No correlation was found between serum and urinary results of estimated parameters (p > 0.05). CONCLUSION: MMP-2 and MMP-9 and TIMP-1 and TIMP-2 play role in pathogenesis of VUR disturbances, what was confirmed by the change in their serum and urinary concentrations. In serum and urine of children with high (Ill-V) grade VUR the biggest disturbances were observed in MMPs: TIMPs system with the TIMP levels higher than MMP values, what indirectly indicated ECM degradation disturbances and increase in renal fibrosis.

Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children.

Receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) play key roles in the pathogenesis of glucocorticoid-induced osteoporosis (GIO). The aim of our study was to determine whether the cumulative glucocorticoid dose (CGCS) in children with idiopathic nephrotic syndrome (INS) has any effect on the concentration of serum RANKL and OPG and the RANKL/OPG ratio. The study population consisted of 90 children with INS, aged 3-20 years, who were treated with GCS. These children were divided into two groups according to the CGCS: low (L)<1 g/kg body weight (BW) and high (H)>or=1 g/kg BW, respectively. The control group (C) consisted of 70 healthy children. RANKL concentration was observed to be significantly higher and OPG significantly lower in INS children than in the reference group: 0.21 (range 0.01-1.36) versus 0.15 (0-1.42) pmol/l (p<0.05), respectively, and 3.76 (1.01-7.25) versus 3.92 (2.39-10.23) pmol/l (p<0.05), respectively. The RANKL/OPG ratio was significantly higher in INS children (p<0.01). The concentration of RANKL, similar to the RANKL/OPG ratio, was significantly higher in Group H children than in Group L children: 0.46 (0.02-1.36 ) versus 0.19 (0.01-1.25) (p<0.01) and 0.14 (0.01-0.71) versus 0.05 (0.002-0.37) (p<0.01), respectively. The concentration of OPG was similar in both groups. There was a positive correlation between CGCS and the concentration of sRANKL as well as the RANKL/OPG ratio (in both cases r=0.33, p<0.05). Based on these results, we suggest that long-term exposure to GCS results in a dose-dependent increase in serum RANKL concentration and the RANKL/OPG ratio, but not in the level of serum OPG.

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.

[WT1 mutation as a cause of progressive nephropathy in Frasier syndrome--case report]. / Mutacja genu WT1 jako przyczyna postepujacej nefropatii w zespole Frasiera--opis przypadku.

Frasier syndrome is an uncommon genetic disorder featuring progressive glomerulopathy, male pseudohermaphroditism and gonadal dysgenesis. It is caused by mutations in intron 9 of the WT1 gene. Because of its rarity there is limited literature available on the diagnosis and treatment of this syndrome. The aim of the study was to present the clinicopathological findings and molecular analysis of phenotypically female adolescent presenting with severe proteinuria and primary amenorrhea. The significance of early recognition of Frasier syndrome and its differentiation from Denys-Drash syndrome was discussed. WT1 mutation analysis should be routinely done in females with steroid-resistant nephritic syndrome.

[Urinary laminin and fibronectin level in children with nephritic syndrome]. / Stezenie lamininy i fibronektyny w moczu dzieci z zespolem nerczycowym.

UNLABELLED: Laminin (LN) and fibronectin (FN) are important extra cellular matrix (ECM) proteins. Disturbance between production and degradation of ECM proteins contributes to renal scarring. The aim of the study was evaluation the levels of urinary LN and FN in children with proteinuria in nephrotic syndrome (NS). MATERIALS AND METHODS: Examinations were conducted on 71 children, 3-15 years old: (A)--44 children with NS (proteinuria above 50 mg/kg b.v./24 hours); (B)--27 children without proteinuria (remission NS). Control group (K)--30 healthy children. Concentration of LN and FN were determined by EIA. RESULTS: In urine of children with NS (A) urinary concentration of LN significantly increased, in comparison to control (K) (p<0.05), but FN was normal (p>0.05). In children with remission of NS (B) urinary concentration of LN was unchanged (p>0.05), but concentration of FN significantly decreased (p<0.05). In renal biopsies majority children of A group presented minimal changes, but majority children of B group presented hyalinization of renal tubules. CONCLUSION: Nephrotic proteinuria disturbs production of LN and increases its urinary excretion, but did not influence on urinary excretion of FN.

[Role of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) in nephrology]. / Rola metaloproteinaz (MMP) i ich tkankowych inhibitorów (TIMP) w nefrologii.

Metalloproteinases (MMP) and their tissue inhibitors (TIMP) play a crucial role to keep the balance between the synthesis and degradation of extracellular matrix protein. Balance disturbances of those two systems lead to abnormal tissue remodeling. There is evidence that matrix metalloproteinases activity changes in many pathological conditions, including inflammatory, degenerative disorders as well as tumor progression. Recent investigations indicate that MMPs and TIMPs play a pivotal role in pathogenesis of most of kidney diseases. Studies describing dysregulated activity of MMPs and/or their tissue inhibitors in various experimental and clinical models of kidney disease, including chronic kidney disease, glomerulonephritis, pyelonephritis, diabetic and hypertensive nephropathy, polycystic kidney disease and renal cancer are reviewed.

[The evaluation of urinary tract dysfunction in children with monosymptomatic primary nocturnal enuresis]. / Ocena czynnosci dolnych dróg moczowych u dzieci z pierwotnym izolowanym moczeniem nocnym (PIMN).

UNLABELLED: The reason for our search was various investigations about urinary tract dysfunctions in enuretic children. AIM: The aim of our study was estimation of lover urinary tract function in children with monosymptomatic primary nocturnal enuresis without positive reaction for a long non pharmacological therapy. MATERIAL AND METHODS: 54 children after 9-12 months behavioral therapy and short pharmacological treatment (desmopresin) was undergoing urodynamic investigation (uroflowmetry and cystometry). RESULTS: Urodynamic disorders was found in 44/54 of estimated children. In 34 of children it was overactive bladder, in 6 patients we found detrusor-sphincter discoordination. Five children had decreased bladder capacity. Next to non pharmacological treatment we used anticholinergic or Baclofen depending on the results of urodynamic tests. The response to the treatment (non bedwetting at all) we observed in 34 children (in 9 of them after 3 months of therapy, in 16 after 6 months of therapy and in 12 after 12 months of therapy). The rest of children had decreased number of wet night per month. CONCLUSION: The pharmacological treatment of urodynamic disorders helps to children with monosymptomatic primary nocturnal enuresis to lost this symptom.

[Analysis of vesicoureteral reflux (VUR) course in children]. / Analiza przebiegu odplywów pecherzowo-moczowodowych (OPM) u dzieci.

UNLABELLED: A small number of reports evaluating early effects of vesicoureteral reflux conservative therapy in children, based on antibacterial prophylaxis combined with correction of the of lower urinary tract function inspired us to perform the study. THE AIM OF THE STUDY was to assess the effects of vesicoureteral reflux (VUR) management in children according to grade, sex and way of treatment. MATERIAL AND METHODS: The study group consisted of 108 children, who were treated in 2000-2007 due to VUR. There were 162 refluxing ureters (grades I-V) diagnosed by voiding cystourethrography (VCU). In 82 children cystometry and (or) uroflowmetry were additionally performed, which revealed lower urinary tract disorders in 41 (60 refluxing ureters), mostly detrusor hyperactivity or detrusor-sphincter dyscoordination. All children had conservative treatment, A - in 67 (102 refluxing ureters) only antibacterial prophylaxis, B - in 41 of children (60 refluxing ureters) in combination with pharmacological treatment of urodynamic abnormalities. RESULTS: The check-up VCU was performed after 23+/-15 months on average. VUR was observed to subside in 44/162 (28%) of refluxing ureters, including 22/108 (22%) of those treated managed with method A and 22/60 (37%) with method B. Fifty three of refluxing ureters were qualified for further conservative therapy and 65/162 (40%) for surgery (especially endoscopic). Following 2-3 years medical and surgical treatment, 87/162 (54%) refluxing ureters resolved. CONCLUSION: In the diagnostics of VUR in children we should take into consideration the assessment of lower urinary tract function, as treatment of these abnormalities increases the effects of VUR conservative management. However it should be confirmed on a larger group of patients.

Response to prednisone in relation to NR3C1 intron B polymorphisms in childhood nephrotic syndrome.

UNLABELLED: The variation in time required to obtain cessation of proteinuria in children with nephrotic syndrome (NS) represents one aspect of the variations shown by these children in response to glucocorticoid (GC) treatment. Polymorphism of the GC receptor gene (NR3C1) has been postulated as one factor that would partially explain differences in both the clinical presentation and the reaction to treatment in GC-treated diseases. We genotyped 118 children diagnosed with NS who initially responded to oral GC treatment [steroid-responsive nephrotic syndrome (SRNS) group] and 136 healthy children for three intron B single nucleotide polymorphisms of NR3C1, namely Bcl I (C/G), rs33389 (C/T) and rs33388 (A/T). In the SRNS group, we performed a three-marker haplotype analysis of NR3C1 in relation to the response to prednisone, represented as time to proteinuria resolution (TPR) as categorical and ordinal variable. RESULTS: The distribution of individual polymorphisms and three-marker haplotypes was similar in healthy children and SRNS patients (all p values >0.05). The GTA haplotype was associated with a higher GC sensitivity, as determined by TPR, and was found to be more prevalent in early (response 7 days) prednisone responders (27.7 vs. 14.5%, hap-score = -2.22, p = 0.05 adjusted for biopsy results). These results are in agreement with those reported earlier on an association of intron B haplotypes with GC sensitivity. The distribution of GC polymorphisms among the residents of north-eastern Poland was also determined.

[Evaluation of inflammatory and renal injury markers in youngest children with pyelonephritis]. / Ocena wskazników zapalenia i uszkodzenia nerek u najmlodszych dzieci chorych na odmiedniczkowe zapalenie nerek.

UNLABELLED: Pyelonephritis (PN) is frequent bacterial infections in young infants and very important because may cause parenchymal scarring. Early confirmation of bacterial infection and application the appropriate treatment before obtaining result of urine culture, reduce probability of parenchymal scarring. THE AIM OF THE STUDY: To evaluate the useful of inflammatory and renal injury markers: serum procalcitonin (PCT), tumor necrosis factor alpha (TNF-alpha) and injury renal marker alpha1--microglobulin (A1M) measurement, in comparison with C-reactive protein concentration and abnormal urinary tract, in neonates and young infants with pyelonephritis. MATERIAL AND METHODS: Investigation was performed in two groups: I group--23 children with PN (1 to 24 weeks of age), and K group--30 healthy children aged from 1 to 24 weeks. Serum concentration of CRP was measured by immunonephelometric assay, PCT by immunoluminometric assay, TNF alpha by ELISA method, and urinary A1M by nephelometric assay. RESULTS: In control group (K) medians of all investigated markers were below minimum of detection. PN patients (I) had the highest PCT TNF-alpha, A1M and CRP concentration before treatment and normal results after antibiotic treatment. Using a cut-off: of 0.5 mg/dl for CRP, 0.5 ng/ml for PCT 15 pg/ml for TNF-alpha and 10 mg/g cr for A1M, sensitivity and specificity in children with pyelonephritis were: for CRP 100% and 62.5%, for PCT 81.8% and 87.2%, for TNF alpha 77.1% and 93.1% and A1M 70.4% and 56.1%, respectively. A positive correlation between serum PCT and CRP and TNF alpha was found. Very high concentration all markers were in patients with vesicoureteral reflux and 1 patient with hydronephrosis. CONCLUSION: In early diagnostics of PN (before obtaining results of urine culture) in youngest children, determination of concentration PCT and TNF alpha, has higher value than determination of CRP, taking into concentration high sensitivity and specificity for bacterial infection.

[Serum cystatin C concentration in children with urinary stones]. / Stezenie cystatyny C w surowicy dzieci z kamica moczowa.

UNLABELLED: Stone formation precedes long period, when the crystals are accumulated in basement membranes of renal tubules and intestinal tissue. Accumulated, inside of renal tubules crystals and stones in urinary tract cause urinary tract obstruction, what may lead to impairment of renal function. The aim of work was the assessment of serum cystatin C (cys C) concentration in children with urolithiasis, confirmed by the presence of renal stones in renal pelvis in comparison to serum creatinine concentration and creatinine clearance (Cr cl). MATERIAL AND METHODS: Examined group (B) consisted of 30 children aged (13.08 +/- 4.14 years) with urolithiasis, which was divided into 3 subgroups (I, II, Ill) in dependence on stones' diameter (0.35-1.6cm). Control group (C) consisted of 26 healthy children at the same age. Nephelometric method was used to determine serum cystatin C level, Jaffe method to assess serum creatinine and the Schwartz formula to estimate glomerular filtration rate. RESULTS: In control group (C) serum cys C did not exceed 0.95 mg/l. In group B serum cystatin C and serum creatinine concentration and Cr cl was similar to the results of control group (p > 0.05). However in 16% of children with urolithiasis, in whom the stones of 0.8-1.6cm diameter were found in both renal pelvis, the concentration of serum cys C exceed 1.2 mg/l, and the value differed significantly from the results of control group (p < 0.05). A weak positive correlation between cys C and creatinine concentration and also between cys C and Cr cl was found. The serum cys C concentration in children with single stones of 0.35-0.8 diameter was normal. CONCLUSION: Serum cystatin C increases with increased degrees of urolithiasis assessed by stone size and their number in kidney.

[Urinary TGF-beta1 excretion in children with renal cysts]. / Wydalanie TGF-beta1 w moczu dzieci z torbielowatoscia nerek.

UNLABELLED: Autosomal dominant polycystic disease is characterised by abnormal polycystin, protein, which is a component of basement membrane and extracellular matrix. Transforming growth factor (TGF-beta1) is a cytokine, which takes part in development of renal tubule epithelium and stimulates the synthesis of extracellular matrix proteins. The aim of work was the assessment of TGF-beta1 concentration in children with renal polycystic disease. MATERIAL AND METHODS: The examined group (I) consisted of 33 children aged (median 14.7 years, range 4.0-17.9): A--11 children with solitary cyst, B--22 with polycystic renal disease. Control group (C) consisted of 20 healthy children at the same age. The concentration of urinary TGF-b1 was measured using immunoenzymatic ELISA method. The results showed that mean concentration of urinary TGF-beta 1 (121.9 +/- 168 pg/mg cr.) was lower than in group B, in which it was 207.2 +/- 361 pg/mg cr. However the difference was not statistically significant (p>0.05). In both subgroups (A and B) urinary excretion of TGF-beta1 was higher than in control group (C) (p<0.05). In 4 (36%) children from group A and 8 (36%) from group B the urinary concentration of TGF-beta 1 was below the sensitivity of the method. No correlation between TGF-beta 1 and children's age, urinary osmolality and GRF according to Schwartz was found. It was a positive correlation between urinary TGF-betal concentration and total diameter of renal cysts. CONCLUSIONS: TGF-betal takes part in renal cyst formation and increased urinary excretion of TGF-b1 in proportion to the dimension of renal cysts may be an evidence of that fact.

Glucocorticoid receptor and vascular endothelial growth factor in nephrotic syndrome.

AIM: The aim of the study was to assess plasma and urine concentrations of vascular endothelial growth factor (VEGF) in nephrotic syndrome children (NS) depending on the total dose of glucocorticoids (GC) and the percentage of lymphocytes with glucocorticoid receptor expression (CD3/GCR). METHODS: We examined 51 children (2-15 years), allocated to three groups: group I: 13 children with the first NS onset, group II: 13 children with NS relapse, group C: 25 healthy children. The NS patients were examined: (A) before treatment and (B) 4-5 weeks after prednisone administration at a dose of 60 mg/m2/24 h. Plasma and urinary VEGF levels were determined using the immunoenzymatic ELISA method. Flow cytometry was applied to assess CD3/GCR expression. RESULTS: Higher plasma and urinary VEGF concentrations were noted in NS children before treatment (A), as compared to control subjects (C). Following prednisone therapy (B), VEGF level was reduced but it was still higher than in the control group. Positive correlation was observed between VEGF and protein in the urine (group I r = 0.660, P < 0.05, group II r = 0.818, P<0.01) and a weak positive correlation between VEGF in plasma and urine (group I r = 0.531, P<0.05, group II - r = 0.581, P<0.05). CD3/GCR expression was lower in group II. In both groups, the correlation between plasma VEGF and CD3/GCR was positive (P<0.05). CONCLUSIONS: 1. Plasma and urinary VEGF levels increase during nephrotic syndrome onset. 2. Glucocorticoid treatment reduces plasma and urinary VEGF levels in NS children.

Assessment of serum cystatin C in children with congenital solitary kidney.

The aim of the study was to assess serum cystatin C level in children with a congenital solitary kidney, depending on their age and compensatory overgrowth of the kidney. The study group (I) consisted of 36 children, 3-21 years of age (median 10.8 years), with a congenital solitary kidney and no other urinary defects. The control group (C) contained 36 healthy children, 5-21 years old (median 10.9 years). Nephelometric methods were used to determine serum cystatin C level, the Jaffe method to assess creatinine concentration and the Schwartz formula to estimate glomerular filtration rate. Kidney length was measured with the patient in a supine position, and overgrowth was estimated (O%) in comparison with the respective kidney in the control group. Serum cystatin C level in group I was higher than that in the control group (P<0.05). Increased values, above 0.95 mg/l, were found in 16/36 (44%) children aged 12-21 years. Glomerular filtration rate (GFR, estimated by the Schwartz formula) and creatinine level in group I were similar to those of the control group (P>0.05). Increased kidney length was found (median 18.2%). Cystatin C concentration was positively correlated with O% (r=0.406, P<0.01) and kidney length to child height ratio (L/H) (r=0.376, P<0.05). We conclude that Increased serum cystatin C concentration in patients with a unilateral congenital solitary kidney occurs after 12 years of age and correlates with compensatory overgrowth of the kidney.

Vascular endothelial growth factor in children with nephrotic syndrome treated with cyclosporine A.

AIM: To assess the effect of cyclosporine A (CyA) on the level of vascular endothelial growth factor (VEGF) in the plasma and urine of nephrotic syndrome children. METHODS: The study material consisted of 15 children (F 6, M 9; group I) who were subjected to the following examinations: A) at the time of proteinuria relapse, before treatment with CyA, B) after 3 mo, C) after 6 mo, and D) after 12 mo of CyA administration with prednisone and convertase inhibitor. The control group (II) contained 20 healthy children. The immunoenzymatic ELISA method (R&D Quantikine) was used to determine plasma and urinary VEGF levels, while the immunofluorescence method was applied to assess CyA concentration in the plasma. The statistical program Statistica 6.0 was used for statistical analysis of the results. RESULTS: In the present study, plasma VEGF level in examination A was higher than in the control group (p<0.01). After proteinuria regression (B), it did not differ from the level observed in healthy children (p>0.05). After 6 and 12 mo of CyA administration, VEGF concentration increased and was higher than in the control group (p<0.05). In all the examinations, urinary excretion of VEGF was higher than in the control group, increasing proportionally with the duration of treatment and plasma CyA level. A positive correlation was observed between plasma and urinary VEGF levels and between VEGF and CyA concentrations in the plasma. CONCLUSION: Long-term CyA treatment of nephrotic syndrome children leads to an increase in plasma and urinary VEGF.

[Urinary concentration of proinflammatory cytokines with regard to infected urinary tract region]. / Stezenie cytokin prozapalnych w moczu w zaleznosci od umiejscowienia zakazenia w drogach moczowych.

UNLABELLED: Uropathogenic bacteria stimulate epithelial cells of interstitial tissue and macrophages to secrete proinflammatory cytokines: interleukin I (IL-1beta), interleukin 6 (IL-6) and interleukin 8 (IL-8). The aim of the study was to check: 1) if the concentration of proinflammatory cytokines (IL-1beta, IL-6, IL-8) differs in dependence on region and clinical picture of urinary tract infection, 2) what is the influence of antibacterial treatment on their concentration. MATERIAL: We examined 67 children, aged 1-15 years, who were divided into 3 groups: 27 children with acute pyelonephritis (AP), caused by E. coli (group I), in whom the examination was carried out twice: A - before treatment, B - after 14 days of antibacterial treatment, 10 children with chronic urinary tract infection (UTI) associated with neurogenic bladder (group II) and 30 healthy children (group K). METHOD: Urinary concentration of examined cytokines was assessed using ELISA immunoenzymatic method and was expressed in pg/mg creatinine. Results showed that in group I before treatment the urinary concentration of examined cytokines was increased (p<0.05). After antibacterial treatment concentration of IL-1beta was normal and concentration of IL-6 and IL-8 decreased but was still higher than in control group (p<0.05). In group II before treatment the increase in concentration of IL-1beta and IL-8 was not so high (p<0.05) and the urinary concentration of IL-6 was normal (p>0.05). In examination A in children from group I and II a positive correlation between examined cytokines and C reactive protein was shown. We have also found a positive correlation between urinary concentration of IL-1beta a IL-8. CONCLUSIONS: 1. Urinary concentration of examined proinflammatory cytokines is different in children with AP and UTI associated with neurogenic bladder and correlates with concentration of C-reactive protein. 2. In most of children with AP after 14-days of antibacterial treatment the urinary concentration of proinflammatory cytokines has been increased.

Evaluation of bladder instability in children with recurrent urinary tract infections.

BACKGROUND: Impairment in the functions of the lower urinary tract can be the cause of recurrent urinary tract infections (UTI) and vesicoureteral reflux (VUR) in children. The purpose of our research was to evaluate the frequency of occurrence of bladder instability in children with UTI. MATERIAL/METHODS: The research involved 114 children (21 boys, 93 girls), ranging in age from 5 to 16. Group I consisted of 61 children with a history of recurrent UTI, while Group II included 53 children with recurrent UTI and VUR. Urodynamic tests (uroflowmetry and cystometry) were done on all the children, while in selected cases profilometry was also performed, using a Duet apparatus (Dantec Medical A/S). RESULTS: Abnormal functioning of the lower urinary tract was found in 45 children (74%) from Group I and 44 children (84%) from Group II. The most common dysfunction was instability of the detrusor muscle, which was found in 52 children (45%), including 23 (38%) from Group I and 29 (55%) from Group II. In 19 children detrusor instability was accompanied by reduced bladder volume, and in 8 cases there was a lack of detrusor-sphincter coordination. In both groups ca. 20% of the children did not present with symptoms indicating urination dysfunctions. Ca. 80% reported various symptoms, of which the most common were nocturnal wetting and urinary urgency. In half of the children from Group I and one-fourth of the children from Group II there were several co-occurring symptoms: nocturnal and diurnal wetting, pollakiruria, and urinary urgency, or all three symptoms simultaneously. CONCLUSIONS: The most common disturbance of lower urinary tract functioning in these children with recurrent UTI was instability of the detrusor muscle, which occurred more often in children with VUR.