Circulating Levels of Soluble α-Klotho and FGF23 in Childhood Cancer Survivors: Lack of Association with Nephro- and Cardiotoxicity-A Preliminary Study.

Background/Objectives: The survival rate among pediatric cancer patients has reached 80%; however, these childhood cancer survivors (CCSs) are at a heightened risk of developing chronic conditions in adulthood, particularly kidney and cardiovascular diseases. The aims of this study were to assess the serum α-Klotho and FGF23 levels in CCSs and to determine their association with nephro- and cardiotoxicity. Methods: This study evaluated a cohort of 66 CCSs who remained in continuous remission, with a mean follow-up of 8.41 ± 3.76 years. Results: The results of this study revealed that CCSs exhibited significantly higher levels of soluble α-Klotho compared to healthy peers (1331.4 ± 735.5 pg/mL vs. 566.43 ± 157.7 pg/mL, p < 0.0001), while no significant difference was observed in their FGF23 levels. Within the participant cohort, eight individuals (12%) demonstrated a reduced estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m2. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). No correlations were found between potential treatment-related risk factors, such as chemotherapy or radiation therapy, serum levels of α-Klotho and FGF23, and nephro- and cardiotoxicity. Conclusions: In conclusion, this preliminary cross-sectional study revealed elevated levels of α-Klotho among childhood cancer survivors but did not establish a direct association with anticancer treatment. The significance of elevated α-Klotho protein levels among CCSs warrants further investigation.

Revealing novel biomarkers for diagnosing chronic kidney disease in pediatric patients.

Pediatric chronic kidney disease (CKD) is a clinical condition characterized by progressive renal function deterioration. CKD diagnosis is based on glomerular filtration rate, but its reliability is limited, especially at the early stages. New potential biomarkers (citrulline (CIT), symmetric dimethylarginine (SDMA), S-adenosylmethionine (SAM), n-butyrylcarnitine (nC4), cis-4-decenoylcarnitine, sphingosine-1-phosphate and bilirubin) in addition to creatinine (CNN) have been proposed for early diagnosis. To verify the clinical value of these biomarkers we performed a comprehensive targeted metabolomics study on a representative cohort of CKD and healthy pediatric patients. Sixty-seven children with CKD and forty-five healthy children have been enrolled in the study. Targeted metabolomics based on liquid chromatography-triple quadrupole mass spectrometry has been used for serum and plasma samples analysis. Univariate data analysis showed statistically significant differences (p < 0.05) in the concentration of CNN, CIT, SDMA, and nC4 among healthy and CKD pediatric patients. The predictive ability of the proposed biomarkers was also confirmed through specificity and sensitivity expressed in Receiver Operating Characteristic curves (AUC = 0.909). In the group of early CKD pediatric patients, AUC of 0.831 was obtained, improving the diagnostic reliability of CNN alone. Moreover, the models built on combined CIT, nC4, SDMA, and CNN allowed to distinguish CKD patients from healthy control regardless of blood matrix type (serum or plasma). Our data demonstrate potential biomarkers in the diagnosis of early CKD stages.

Urinary Beta-2-Microglobulin and Late Nephrotoxicity in Childhood Cancer Survivors.

The objectives of this study were to evaluate urinary beta-2-microglobulin (ß2M) levels in long-term childhood cancer survivors and to establish its association with anticancer drug-induced nephrotoxicity. The study consisted of 165 childhood cancer survivors (CCS) who were in continuous complete remission. We reported that CCS had a significantly higher level of ß2M (p < 0.001) and ß2M/Cr. ratio (p < 0.05) than healthy peers. Among all participants, 24 (14.5%) had decreased eGFR (<90 mL/min/1.73 m2). A significant positive correlation between ß2M/Cr. ratio and body mass index (coef. 14.48, p = 0.046) was found. Furthermore, higher levels of urinary ß2M were detected among CCS with a longer follow-up time (over 5 years) after treatment. Subjects with decreased eGFR showed statistically higher urinary ß2M levels (20.06 ± 21.56 ng/mL vs. 8.55 ± 3.65 ng/mL, p = 0.007) compared with the healthy peers. Twelve survivors (7.2%) presented hyperfiltration and they had higher urinary ß2M levels than CCS with normal glomerular filtration (46.33 ± 93.11 vs. 8.55 ± 3.65 ng/mL, p = 0.029). This study did not reveal an association between potential treatment-related risk factors such as chemotherapy, surgery, radiotherapy, and the urinary ß2M level. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). We demonstrated that urinary beta-2-microglobulin may play a role in the subtle kidney injury in childhood cancer survivors; however, the treatment-related factors affecting the ß2M level remain unknown. Further prospective studies with a longer follow-up time are needed to confirm the utility of urinary ß2M and its role as a non-invasive biomarker of renal dysfunction.

Galectin-3-A New Player of Kidney Damage or an Innocent Bystander in Children with a Single Kidney?

The aim of this study was to evaluate the galectin-3 (Gal-3) level in children with a congenital solitary functioning kidney (cSFK) and determine its association with common renal function parameters. The study consisted of 68 children (49 males) with cSFK. We demonstrated that children with cSFK had a lower level of galectin-3 than that of healthy subjects (p < 0.001). No significant differences in serum cystatin C (Cys C) levels between the cSFK children and the reference group were found. The subjects with cSFK and reduced estimated glomerular filtration rate (eGFR) had significantly higher levels of Gal-3 and Cys C compared to those with normal eGFR (p < 0.05). Children with eGFR <60 mL/min/1.73 m2 showed significant statistical differences between the values of area under ROC curve (AUC) for Gal-3 (AUC 0.91) and Cys C (AUC 0.96) compared to that for creatinine level (AUC 0.76). Similar analyses carried out among cSFK children with eGFR <90 mL/min/1.73 m2 revealed an AUC value of 0.69 for Gal-3, 0.74 for Cys C, and 0.64 for creatinine; however, no significant superiority was shown for any of them. The receiver operating characteristic (ROC) analyses for identifying the SFK children among all participants based on the serum levels of Gal-3 and Cys C did not show any diagnostic profile (AUCs for Gal-3 and Cys C were 0.22 and 0.59, respectively). A positive correlation between the Gal-3 and Cys C concentrations was found (r = 0.39, p = 0.001). We demonstrated for the first time that Gal-3 might play an important role in the subtle kidney damage in children with cSFK. However, further prospective studies are required to confirm the potential applicability of Gal-3 as an early biomarker for kidney injury and possible progression to CKD.

Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Selected Cytokines-Potential Biomarkers in Children with Solitary Functioning Kidney.

This study was performed to explore serum tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its dependent cytokines urinary excretion: monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T cell expressed and secreted chemokine (RANTES) with their relation to the kidney function parameters in children with solitary functioning kidney (SFK). The study included 80 children and adolescents (median age 9.75 year) with congenital and acquired (after surgical removal) SFK. Serum TWEAK and urinary MCP-1 and RANTES levels were significantly higher in SFK patients (p < 0.05). The serum TWEAK was positively related to serum creatinine (r = 0.356; p < 0.001). Moreover, in SFK the receiver operating characteristic analyses revealed good diagnostic profile for serum TWEAK with AUC (Area Under The Curve)-0.853, uRANTES-0.757, and for RANTES/cr.: AUC-0.816. Analysis carried out to identify children with impaired renal function (albuminuria and/or decreased estimated glomerular filtration rate < 90 mL/min/1.73 m2 and/or hypertension) showed good profile for TWEAK (AUC-0.79) and quite good profile for uRANTES and RANTES/cr. (AUC 0.66 and 0.631, respectively). This is the first study investigating serum TWEAK and urinary excretion of MCP-1 and RANTES together in children with SFK. Obtained results indicate that TWEAK and RANTES may serve as potential markers of renal impairment.

Urine NGAL and KIM-1-Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study.

The deterioration of renal function after childhood solid tumors treatment is the result of using the intensive multimodal therapy. In recent years, urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL) have been introduced as potential promising biomarkers of early kidney damage. The aim of the present study was to determine whether anticancer treatment has any effect on the concentration of KIM-1 and NGAL and its association with renal impairment in survivors of childhood solid tumors. Sixty patients previously treated for solid tumors were involved in this study. The median time after end of treatment was 8.35 years. Urine KIM-1 and NGAL levels were measured using immunoenzymatic ELISA commercial kits. Higher levels of urine NGAL, KIM-1/cr. (creatinine), and NGAL/cr. ratios were found in comparison with healthy controls (p < 0.0001). Among all subjects, 23% were found to have decreased estimated glomerular filtration rate (eGFR). A strong correlation between KIM-1/cr. and a cumulative dose of ifosfamide was observed (r = 0.865, p < 0.05). In addition, a moderate correlation between NGAL/cr. and a cumulative dose of cisplatin was identified (r = 0.534, p < 0.05). The AUC for KIM-1/cr. was 0.52, whereas NGAL/cr. showed a diagnostic profile describing the AUC of 0.67. Univariable regression showed significant associations between NGAL/cr. ratio and subjects after unilateral nephrectomy (coeff. 63.8, p = 0.007), cumulative dose of cisplatin (coeff. 0.111, p = 0.033), and age at diagnosis (coeff. 3.75, p = 0.023). The multivariable model demonstrated only cumulative dose of cisplatin as an independent factor influence on NGAL/cr. ratio. The results of our study showed increased levels of urine KIM-1 and NGAL many years after completion of the childhood solid tumors treatment, which correlated positively with a cumulative dose of ifosfamide and cisplatin. This study also suggests that unilateral nephrectomy could affect the concentration of the studied biomarkers.

Urine NGAL and KIM-1: tubular injury markers in acute lymphoblastic leukemia survivors.

INTRODUCTION: Nephrotoxicity is a potential adverse effect of anticancer treatment in childhood. Cytostatics, abdominal radiotherapy, total body irradiation (TBI) and some agents used in supportive care may induce acute kidney injury (AKI) or lead to chronic kidney disease (CKD). The aim of this study was to test the hypothesis whether urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are increased in acute lymphoblastic leukemia (ALL) survivors. METHOD: The study cohort consisted of 86 patients (42 females) previously treated for ALL. The median time after cessation of treatment was 6.55 (IQR: 1.96-9.93) years and median age at the time of study: 12 (IQR: 6.76-16.00). The control group included 53 healthy peers. Immunoenzymatic ELISA commercial kits were used to measure urine KIM-1 and NGAL levels. RESULTS: The median levels of urine uNGAL (p < 0.05), uNGAL/creatinine (cr.) ratio (p < 0.0001) and uKIM-1/creatinine ratio (p < 0.0001) were significantly higher in ALL survivors in comparison with healthy controls. Female patients had significantly higher levels of NGAL and NGAL/cr. than males (mean 8.42 ± 7.1 vs. 4.59 ± 4.5 ng/mL and 86.57 ± 77 vs. 37.7 ± 37 ng/mg, respectively; p < 0.01). Of all the study participants, 11 (13%) presented eGFR below 90 mL/min/1.73 m2. The NGAL/cr. ratio seemed to be the best predictor of decreased eGFR (AUC = 0.65). The cumulative dose of methotrexate and cyclophosphamide did not predict the values of the urine NGAL, NGAL/cr., KIM-1/cr. and eGFR. Five years after the end of treatment, the patients had higher levels of uKIM-1 (1.02 ± 0.8 vs. 0.62 ± 0.6 ng/mL, p < 0.01), uNGAL (7.9 ± 6.7 vs. 4.6 ± 5 ng/mL, p < 0.01) and lower eGFR (114 ± 29 vs. 134 ± 35 mL/min/1.73 m2, p < 0.01) in comparison with ALL survivors with the observation period of less than 5 years. CONCLUSION: We demonstrated that ALL survivors have higher levels of urine NGAL, NGAL/cr. and uKIM-1/cr. ratio as compared to the control group. Further long-term follow-up studies are necessary to assess the significance of the NGAL and KIM-1 and their relationship to kidney damage after anticancer treatment in childhood.

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

OBJECTIVE: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis. STUDY DESIGN: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life. RESULTS: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys. CONCLUSIONS: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.

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.

Urine exoglycosidases are potential markers of renal tubular injury in children with ureteropelvic junction obstruction.

AIM: Hydronephrosis caused by ureteropelvic junction obstruction (UPJO) is an important problem in children and young adults. The aim of this pilot study was to determine the urine profiles of a number of lysosomal exoglycosidases to see whether they indicated tubular renal damage in children with UPJO. METHODS: We measured lysosomal exoglycosidases urine activities in 32 patients with UPJO, dividing them into three groups. The surgical group comprised 16 children with severe hydronephrosis who required surgery, the nonsurgical group comprised 16 patients with mild hydronephrosis, and the reference group comprised 42 healthy children. The following indicators were measured: N-acetyl-ß-hexosaminidase and its A and B isoenzymes, α-fucosidase, ß-galactosidase, α-mannosidase and ß-glucuronidase. RESULTS: The urine activities of all exoglycosidases were significantly higher in children with UPJO than children in the reference group (p < 0.01). A strong positive correlation was also found between most of the urine exoglycosidases and the urine albumin/creatinine ratio (p < 0.01). CONCLUSION: Our findings demonstrated that children with UPJO showed increased renal activities of assessed exoglycosidases, which correlated positively with the urine albumin/creatinine ratio. A larger multicentre study is required to confirm the clinical applications of these observations.

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.

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 cytokine profiles in unilateral congenital hydronephrosis.

BACKGROUND: We aimed to evaluate possible clinical application of urinary monocyte chemotactic protein-1 (MCP-1), osteopontin (OPN), and regulated upon activation, normal T-cell expressed and secreted (RANTES) chemokine as useful noninvasive markers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction (UPJO). METHODS: The study cohort consisted of surgical cases (study group 1), comprising 15 children with severe HN who required surgery (median age 1.03 years), conservative cases (study group 2), comprising 21 patients with mild, nonobstructive HN, and control group, comprising 19 healthy children. All children had normal renal function. Urinary (u) concentrations of MCP-1, OPN, and RANTES were measured using immunoenzymatic enzyme-linked immunosorbent assay (ELISA) commercial kits and were expressed in nanograms per milligram creatinine. Increased levels of MCP-1 and OPN were found in children with HN in comparison with study group 2 and controls (p < 0.05). UMCP-1/Cr correlated with half-time (T(1/2)) of the elimination phase of tracer excretion of technetium-99m-mercaptoacetyltriglycine ((99m)Tc-MAG-3) (p < 0.05). RESULTS: Receiver operator characteristic (ROC) analyses revealed good diagnostic profile for uMCP-1 only in identifying children (<40 %) with abnormal differential renal function (DRF) [area under the curve (AUC) 0.862], and in detecting kidney injury in all examined children (AUC 0.704). CONCLUSIONS: Additional studies with larger number of patients are required to confirm a potential application of uMCP-1 as a promising parameter for early identification of kidney obstruction.

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.

[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.

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.

[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.

[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.