Markers of systemic inflammation in children with hyperuricemia.

AIM: The purpose of the study was to investigate serum concentrations of the monocyte chemoattractant protein-1 (MCP-1) and high-sensitivity CRP (hs-CRP) in children with hyperuricemia and to evaluate its association with obesity. PATIENTS AND METHODS: The study involved 52 hyperuricemic patients with mean age of 15.53 ± 1.7 years. Twenty-seven healthy individuals with normal serum uric acid (SUA) level were selected as the control group (C). Serum MCP-1 and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA) and immunonephelometry, respectively. RESULTS: Hyperuricemic patients showed increased sMCP-1 (median: 69.58 pg/mL) and hs-CRP (median: 0.53 mg/L) vs. controls (48.39 pg/mL, 0.24 mg/L; respectively) (p < 0.01). The obese children also presented significantly higher levels of sMCP-1 and hs-CRP (median, 81.69 and 1.18 mg/L, respectively) in comparison with nonobese (median, 59.62 and 0.41 mg/L, respectively; p < 0.01). Only hs-CRP correlated positively with body mass index Z-score (r = 0.33, p < 0.05). Receiver operator characteristic analyses checking the sensitivity and specificity of examined markers for hyperuricemia revealed the higher area under the curve (AUC) for sMCP-1; however, the difference between AUC for sMCP-1 and for hs-CRP was not significant (p > 0.05). CONCLUSION: Serum MCP-1 and hs-CRP are elevated in hyperuricemic patients, but the role of obesity in inflammation markers needs further investigation.

[Serum and urinary homocysteine in children with steroid-dependent nephrotic syndrome]. / Homocysteina w surowicy i moczu dzieci ze steroidozaleznym zespolem nerczycowym.

UNLABELLED: Hyperhomocysteinemia is independent risk factor of cardiovascular diseases. Similarly to nephrotic syndrome (NS) predisposes to vein thrombosis. THE AIM OF THE STUDY: To evaluate serum and urinary total homocysteine (stHcy and utHcy) levels in children with the symptoms of SN, and to determine a correlation between its concentration and some parameters of hemostasis, as well as doses and the time of prednisone therapy and serum cortisol level. MATERIAL AND METHODS: The examined group consisted of 18 children with NS, aged 7.64 +/- 5.1 years, divided on two groups: A--in time o proteinuria; B--during treatment with prednisone after regression of proteinuria. Control group (C) consisted of 20 children, aged 8.5 +/- 3.6 years. Serum and urinary tHcy levels were assayed by enzyme-linked immunosorbent assay method using the Axis-Shield set. RESULTS: Serum total Hcy concentration in groups A and B did not differ from the control group (p > 0.05). Urinary total Hcy concentration in groups A and B was significantly higher than that of control (p < 0.05). A positive correlation was observed between stHcy and serum albumin as well as cortisol levels, and between utHcy and serum AT III level. CONCLUSIONS: In children with steroid-dependent NS, subclinical disturbances in hemostasis were independent of serum tHcy concentration. There was no correlation between serum tHcy and cumulated doses, as well as time of prednisone treatment, however positive correlation was found with serum cortisone. Urinary excretion of Hcy significantly increases, in comparison to control, and correlates with serum AT III level.

High-sensitivity C-reactive protein and mean platelet volume in paediatric hypertension.

The purpose of the study was to investigate serum uric acid (SUA), high-sensitivity C-reactive protein (hs-CRP) and mean platelet volume (MPV) in pre-hypertensive (PH) and hypertensive (HT) children and adolescents. The study group consisted of 80 patients aged 10-19 years subdivided into PH and HT groups according to mean daytime or night-time systolic or diastolic blood pressure (BP) levels (> 90th percentile, but < 95th percentile and > or = 95th percentile, respectively). The control group (C) contained 25 normotensive subjects. Serum hs-CRP level was determined by a nephelometric method (Behring); platelets (PLTs) were counted, and MPV was assessed by a Coulter Analyzer MAXM. SUA was measured with an Hitachi instrument. The median SUA and hs-CRP levels in PH and HT subjects were significantly higher than those of the controls (P < 0.01) and were higher in the HT group than in the PH group (P < 0.05). An increase in SUA above 5.5 mg/dl was associated with an increase in hs-CRP [odds ratio (OR) 4.8; confidence interval (CI) 1.3-17.4; P < 0.01]. MPV values in the PH group did not differ from those of the controls (P > 0.05), but it was significantly higher in HT patients (P < 0.01). Serum hs-CRP and MPV concentrations were positively correlated with all BP measurements except night-time diastolic blood pressure (DBP). We demonstrated that, in HT children and adolescents, increased SUA with a parallel increase in hs-CRP and PLTs with MPV is observed. Although large, multicentre, prospective studies are needed to confirm this observation, hyperuricaemia seems to be associated with an increase in hs-CRP in PH and HT patients.

[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.

[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.

[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.

[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.

IgA nephropathy in a girl with psoriasis and seronegative arthritis.

IgA nephropathy is one of the most common forms of glomerulonephritis, but the coexistence of IgA nephropathy and psoriasis is very rare, especially in children. Herein we report the case of an 8-year-old girl with both psoriasis and IgA nephropathy who responded to treatment with cyclosporine A for both conditions.

[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.

[The effect of cyclosporine A in steroid-dependent nephrotic syndrome in children]. / Ocena skutecznosci leczenia cyklosporynq steroidozaleinego zespolu nerczycowego u dzieci.

UNLABELLED: The aim of study was the analysis of cyclosporine A (CyA) treatment efficacy in children with steroid-dependent nephrotic syndrome (NS). MATERIAL AND METHODS: The examined group consisted of 21 children (F--8, M--16) at the mean age 12.1 +/- 4.6 years with the relapses NS in the course of minimal change nephrotic syndrome (MCSN) in 9 (43%) and focal segmental glomerulosclerosis (FSGS) in 12 (57%) cases. All children were administrated CyA (Sandimun Neoral f. Novartis Pharma AG), together with prednisone (Encorton f. Polfa Pabianice) (0.2 - 0.5 mg/kg b.w./24 h) and ACE inhibitor (Enap f. Krka). The concentration of cyclospornine A in serum was measured by monoclonal antibody fluorescence polarization immunoassay. Serum concentration of creatinine, uric acid, albumin, cholesterol and creatinine clearance (Schwartz method) and proteinuria was analysed: A - before treatment, B--in 3rd day, C--in 3rd month, D--in 6th month, E--in 12th month of CyA treatment and F--after 3-6 months after finishing treatment. Blood pressure was measured by ABPM in examination A, D, E, and F. RESULTS: During administration of CyA the urinary protein excretion decreased successively and in 12th month of treatment was 4.5 +/- 3.9 mg/kg bw/24 h. The serum creatinine concentration increased by 33.9%, and uric acid by 52.8% in comparison to the initial level. Mean systolic blood pressure (RRs) in ambulatory blood pressure monitoring (ABPM) during 24 hours was 120.5 +/- 9.2 mmHg before treatment and increased by about 6% after 12 months of treatment. Respectively diastolic blood pressure (RRr) was 66.7 +/- 4.3 mmHg and increased to 71.0 +/- 2.5 mmHg at the end of 12 h month. The nocturnal fall of RRs before treatment was 14.2 +/- 2.8%, and RRr 14.9 +/- 2.1%. During treatment nocturnal fall of both RRs and RRr decreased to 9.2 +/- 2.7% for RRs and 9.8 +/- 2.7% for RRr after 6 months of treatment. After 12 months of treatment and in remission the nocturnal fall of blood pressure was still below 10%. CONCLUSIONS: CyA is an effective drug in children with relapses of steroid-dependent in the course of MCSN and FSGS. Side effects after CyA treatment, under the control of its concentration in serum and parameters of renal function are occasional and transient. Cyclosporine A disturbs the 24 hours rhythm of arterial blood pressure.

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.

High-sensitivity C-reactive protein (hs-CRP) level in children with nephrotic syndrome.

The aim of this study was to assess the serum concentration of high-sensitivity C-reactive protein (hs-CRP) in children with nephrotic syndrome (NS) treated with prednisone and cyclosporine A (CyA). Patients were divided into three groups: (I) 20 NS children (aged 4-14 years) in relapse and examined twice, (A) before treatment and (B) after proteinuria regression (a 3-4 week course of prednisone therapy); (II) 20 children with steroid-dependent or steroid-resistant NS, treated with CyA, also examined twice, (D) before treatment with CyA, (E) 6 months after therapy. A control group (C) consisted of 20 healthy children. Serum hs-CRP level was determined by a nephelometric method with a Behring Nephelometer 100 Analyzer, Dade Behring. The results showed that median hs-CRP concentration was the highest in children with relapsing steroid-sensitive NS before treatment (IA). After proteinuria regression (IB), the hs-CRP level had decreased and did not differ from that of healthy controls (C) (P>0.05). In group II, before CyA administration (IID), the level of hs-CRP was normal, but it had increased after 6 months of treatment (IIE) up to a level six-times higher than that of the control group (P<0.01). We concluded that, in children with steroid-sensitive nephrotic syndrome in relapse, the serum hs-CRP level is increased but returns to normal after 3-4 weeks of glucocorticoid treatment. In children chronically treated with CyA due to NS, serum hs-CRP level increases significantly during the therapy.

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.