Urinary Concentration of Renal Biomarkers in Healthy Term Neonates: Gender Differences in GST-pi Excretion.

BACKGROUND Serum creatinine, the criterion standard in assessment of renal function, is not reliable for the neonatal period because of its dependence on renal immaturity and maternal creatinine levels. Thus, it is important to study other biomarkers of renal function in neonates. The present study aimed to measure the urinary concentration of renal biomarkers: calbindin, clusterin, GST-pi (glutathione-S-transferase-alpha), KIM-1 (kidney injury molecule 1), MCP-1 (monocyte chemoattractant protein-1), and B2M (beta 2-microglobulin) in healthy term neonates. MATERIAL AND METHODS In the study, we included 80 healthy term neonates - 40 females and 40 males. We collected the neonates' urine on their first day of life. Urinary concentrations of calbindin, clusterin, KIM-1, MCP-1, and B2M were assessed using an immunoassay for kidney toxicology research. Because dilution of the urine affects the concentrations of urinary biomarkers, we normalized them to the concentration of urinary creatinine (Cr) and present them as biomarker/Cr ratios. RESULTS We obtained the following values of the assessed biomarker/Cr ratios (median [Q1-Q3]): calbindin/Cr.: 197.04 (56.25-595.17), KIM-1/Cr: 0.09 (0.04-0.18), MCP-1/Cr: 0.05 (0.02-0.14), B2M/Cr: 126.12 (19.03-342.48), GST-pi/Cr in boys: 1.28 (0.46-3.77), GST-pi/Cr in girls: 8.66 (2.51-27.82), clusterin/Cr: 4.55 (1.79-12.97) ng/mg Cr. CONCLUSIONS We showed the urinary levels of calbindin, clusterin, GST-pi, KIM-1, MCP-1, B2M in white, West Slavic, healthy term neonates. We found that in there is an association between female sex and a higher urinary GST-pi excretion, but urinary excretion of calbindin, clusterin, KIM-1, MCP-1, and B2M is sex-independent. The urinary levels of the assessed biomarkers do not depend on the method of delivery.

Current Status of Protein Biomarkers in Urolithiasis-A Review of the Recent Literature.

Urolithiasis is an increasingly common clinical problem worldwide. The formation of stones is a combination of metabolic status, environmental factors, family history and many other aspects. It is important to find new ways to quickly detect and assess urolithiasis because it causes sudden, severe pain and often comes back. One way to do this is by exploring new biomarkers. Current advances in proteomic studies provide a great opportunity for breakthroughs in this field. This study focuses on protein biomarkers and their connection to kidney damage and inflammation during urolithiasis.

Steroid-Resistant Nephrotic Syndrome Caused by NUP93 Pathogenic Variants.

BACKGROUND: Although steroid therapy is a standard of care for nephrotic syndrome treatment, 15-20% of patients do not respond to it. Finding the genetic background is possible in >10% of steroid-resistant nephrotic syndrome (SRNS) cases. Variants in genes encoding nuclear pore complex proteins are a novel cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent studies suggest NUP93 variants to be a significant cause of paediatric onset SRNS. The clinical data on certain variants and disease history are still very limited. METHODS AND RESULTS: We report the SRNS case of a 12-year-old boy with two detected NUP93 variants, which are pathogenic and possibly pathogenic. The onset of the disease was early and severe. The patient was admitted to the paediatric nephrology department due to nephrotic-range proteinuria and hypoalbuminemia with a long medical history of steroid and non-steroid immunosuppressive treatment. The genetic panel targeting 50 genes, clinically relevant for nephrotic syndrome, was performed. The only gene which was found to be affected by mutations, namely c.2326C>T and c.1162C>T, respectively, was NUP93. Conclusions: NUP93 variants are rarely identified as causes of SRNS. Clinical data are of utmost importance to establish the standard of care for SRNS patients suffering from this genetic disfunction. This is the first case of a heterozygous patient with the c.2326C>T and c.1162C>T variants and confirmed clinical history of the SRNS described so far. Our data suggest the clinical relevance of the c.1162C>T variant.

The Urinary Concentration of Trefoil Factor 3 (TFF3) in the Term and Preterm Neonates.

BACKGROUND: Distinguishing between a pathologic state and renal development is important in neonatology. Because the assessment of serum creatinine in neonates is not reliable, better biomarkers are needed. Trefoil factor 3 (TFF3) is proposed as a biomarker of kidney injury. The study aimed to assess its urinary concentration in healthy term and stable preterm neonates. MATERIAL AND METHODS: The study included 80 term and 20 preterm neonates born in the Department of Perinatology of the University Clinical Hospital in Bialystok. Urine was obtained from the term neonates on the 1st day of life and from the preterm neonates on the 1st, 8th, 15th and 22nd day of life. The urinary concentration of TFF3 was determined using a commercially available immunoassay and was normalized for the urinary creatinine concentration (cr.). RESULTS: The values of TFF3/cr. were higher in the preterm than in the term neonates (p < 0.05) (median (Q1-Q3): 1486.85 (614.92-3559.18) and 317.29 (68.07-671.40) ng/mg cr.). They did not differ in the subsequent days of the preterm neonates' lives. The ROC curve for TFF3/cr. in the preterm and term neonates showed AUC = 0.751 (cut-off value = 1684.25 ng/mg cr.). CONCLUSIONS: Prematurity is associated with higher urinary excretion of TFF3. Male gender is associated with an increased urinary TFF3 excretion in term neonates.

Protein Biomarkers in Chronic Kidney Disease in Children-What Do We Know So Far?

Chronic kidney disease (CKD) in children is a major concern of medical care and public health as it is related to high morbidity and mortality due to progression to end-stage kidney disease (ESKD). It is essential to identify patients with a risk of developing CKD to implement therapeutic interventions. Unfortunately, conventional markers of CKD, such as serum creatinine, glomerular filtration rate (GFR) and proteinuria, have many limitations in serving as an early and specific diagnostic tool for this condition. Despite the above, they are still the most frequently utilized as we do not have better. Studies from the last decade identified multiple CKD blood and urine protein biomarkers but mostly assessed the adult population. This article outlines some recent achievements and new perspectives in finding a set of protein biomarkers that might improve our ability to prognose CKD progression in children, monitor the response to treatment, or even become a potential therapeutic target.

The Role of Complement Component C3 Activation in the Clinical Presentation and Prognosis of IgA Nephropathy-A National Study in Children.

The aim of the study was to evaluate the influence of the intensity of mesangial C3 deposits in kidney biopsy and the serum C3 level on the clinical course and outcomes of IgAN in children. The study included 148 children from the Polish Pediatric IgAN Registry, diagnosed based on kidney biopsy. Proteinuria, creatinine, IgA, C3 were evaluated twice in the study group, at baseline and the end of follow-up. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The intensity of IgA and C3 deposits were rated from 0 to +4 in immunofluorescence microscopy. The intensity of mesangial C3 > +1 deposits in kidney biopsy has an effect on renal survival with normal GFR in children with IgAN. A reduced serum C3 level has not been a prognostic factor in children but perhaps this finding should be confirmed in a larger group of children.

Urinary excretion of renin and angiotensinogen in hypertensive children and adolescents.

INTRODUCTION: In recent years hypertension has become an emerging condition in the young population. It has been proposed that the renin-angiotensin system plays an important role in regulation of blood pressure. We assessed whether activation of the intrarenal renin-angiotensin system occurs in hypertensive children and adolescents and what better reflects its activity: urine angiotensinogen (AGT) or urine renin (REN). MATERIAL AND METHODS: The study was conducted on a sample of 58 subjects with primary hypertension (HT) and 29 normotensive children and adolescents. We measured urine REN and AGT excretion and assessed the values in relation to blood pressure (BP) and other clinical parameters. Both REN and AGT values were calculated by urine creatinine: REN/cr. and AGT/cr., respectively. RESULTS: We observed higher urine REN/cr. values in hypertensive subjects in comparison to the reference group (6.99 vs. 2.93, p = 0.003). Hypertensive participants showed positive correlations between urine REN/cr. and diastolic 24-hour BP (r = 0.42, p = 0.002) as well as between urine REN/cr. and urine AGT/cr. (r = 0.266, p = 0.044, respectively). CONCLUSIONS: Increased urine REN/cr. in hypertensive children and adolescents and its positive correlation with BP may indicate its important role in the pathogenesis of HT. Perhaps urine REN/cr. could be a marker of intrarenal renin-angiotensin system activity. Nevertheless, further research should be undertaken to confirm this observation.

Health-related quality of life in children with immunoglobulin A nephropathy - results of a multicentre national study.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) may lead to end stage renal disease and severely affect patient functioning and wellbeing. The aim of the study was to evaluate health-related quality of life (HRQoL) in children and adolescents with IgAN, and compare HRQoL in relation to the disease course, social status and psychological factors, such as expressing anger and perceived personal competence. MATERIAL AND METHODS: The multicentre cross-sectional study included 51 patients ≥ 8 years from 7 paediatric nephrology centres in Poland. Psychometric analysis was performed using the Kidscreen-52 questionnaire to evaluate HRQoL, the Anger Expression Scale to evaluate the severity of anger and the Personal Competence Scale to measure general perception of personal competence. RESULTS: Mean age of patients was 14.54 ±3.69 years; duration since the diagnosis of IgAN was 4.98 ±3.9 years. Patients with IgAN rated their psychological wellbeing as significantly worse compared to healthy peers (p < 0.05). The presence of proteinuria was associated with significantly worse physical wellbeing (58.72 ±18.45 vs. 74.44 ±22.97; p < 0.05). Current therapy (steroids/immunosuppressive drugs) had no effect on HRQoL in the study group. Perceived personal competence was rated high by 49% of children in the study group. Children with IgAN were characterized by lower intensity of expressed anger (p < 0.001) and significantly higher intensity of suppressed anger (p < 0.01) compared to reference ranges. Severity of expressed anger correlated positively with the parent relations and school environment dimensions of HRQoL. CONCLUSIONS: We found lower HRQoL in regard to physical and psychological wellbeing in a group of Polish children with IgAN compared to healthy peers. HRQoL should be monitored in this patient group.

Are low birth weight children predisposed to renal loss of carnitine?

Aim: The plasma homeostasis of both free and esterified carnitines is mostly regulated by renal tubular reabsorption, which may be disturbed in low birth weight children. The aim of study was to check whether disturbances in excretion of l-carnitine (LC) and its main ester, acetyl-carnitine (ALC), may be the result of renal dysfunction in low birth weight children (LBW).Methods: This study included 59 LBW children (2165 g [1490-2440]) and 22 children with normal birth weight as a reference group (3500 g [3275-3650]). Subjects were divided into three groups: 0-3 months, 4-12 months and over 1 year at the time of testing. Urinary levels of carnitine were measured spectrophotometrically.Results: The urine excretion of Free LC, Free LC/cr, Total LC and Total LC/cr. Were significantly higher in 0-3 and 4-12-month old LBW infants study groups when compared to the reference groups. We found statistically significant higher urine excretion of ALC and ALC/cr. in all age groups of LBW infants compared to the reference group. There was a negative correlation between birth weight and free LC/cr. (r= -0.3, p < .05), Total LC/cr. (r= -0.34, p < .05), and ALC/cr. (r= -39, p < .05), and in the children >12-month-old strong negative correlation between eGFR and free LC/cr. (r= -0.6, p < .05), Total LC/cr. (r= -0.61, p < .05), ALC/cr. (r= -0.61, p < .05.)Conclusion: Higher urine excretion of both LC and ALC and its negative correlation with birth weight and eGFR may reflect some degree of renal dysfunction in LBW infants.

[Liddle syndrome as a rare cause of hypertension - a case report]. / Zespól Liddle'a jako rzadka przyczyna nadcisnienia tetniczego ­ opis przypadku.

Liddle syndrome is an uncommon genetic disorder featuring hypertension, hypokalemia, metabolic alcalosis, decreased rennin and aldosterone secretion. It is caused by a point mutation of a gene encoding one of the three subunits of the epithelial sodium channel (ENaC). Because of its rarity, the availability of the literature on the diagnosis of this syndrome is limited. A CASE REPORT: The 14 years old adolescent with resistant hypertension was analyzed genetically, because of the family history. The significance of it and biochemical findings in recognition of Liddle Syndrome was discussed. It has been concluded that performing a genetic test at the suspicion of monogenic background of hypertension allows for accurate and effective treatment.

The Possible Impact of Hyperuricemia on Serum Soluble Receptor for Advanced Glycation end Products (sRAGE) Levels in Teenagers: A Case Control Study.

BACKGROUND: Dietary advanced glycation end products (AGEs) and their interactions with the soluble receptors for AGEs (RAGE) play a crucial role in the pathogenesis of cardiovascular diseases. OBJECTIVE: This study was set out to assess, whether there was any association between serum sRAGE level and serum uric acid level in children with hyperuricemia. METHODS: This case-control study involved 53 patients (12 girls, 41 boys) with hyperuricemia (defined as serum uric acid >4.8 and >5.5 mg/dl in girls and boys, respectively) aged (median [IQR]) (15.5 [13.5-15.5] years). Thirty-six healthy individuals with normal serum uric acid level were selected as a reference group. Additionally, the study group with hyperuricemia was divided into two groups: HU-HT (hypertensive n=25) and HU-NT (normotensive n=28) teenagers. The serum concentration of human sRAGE was measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: We found statistically significant differences in serum sRAGE levels between normotensive subjects with hyperuricemia (median [IQR]) (169.8 [148.3-231.1] pg/ml) and reference group (median [IQR]) (129 [107.4-175.3] pg/ml), p<0.01. Univariate analysis of the data revealed a positive correlation between serum sRAGE and serum uric acid in the study group (r=0.306, p<0.05). CONCLUSION: Our data showed that serum soluble receptors for AGEs are increased in teenagers with hyperuricemia. In contrast, neither hypertension nor increased BMI had a significant influence on serum sRAGE concentration. Further studies are needed to discover the possible mechanism on the influence of uric acid on sRAGE levels and to assess its possible clinical significance.

Serum GDIgA1 levels in children with IgA nephropathy and Henoch-Schönlein nephritis.

INTRODUCTION: GDIgA1 (galactose deficient IgA1) plays a significant role in the pathogenesis of IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSN). AIM OF THE STUDY: The aim of this study was to assess the relevance of serum GDIgA1 level as a prognostic marker in children with IgAN and HSN. MATERIAL AND METHODS: 41 children were included to the study group (15 IgAN, 26 HSN) and 22 to the control group. The following parameters were evaluated at baseline and endpoint: proteinuria, erythrocyturia, serum creatinine, serum IgA, GFR. A kidney biopsy was performed in all patients and evaluated according to the Oxford Classification (1 - present, 0 - absent: M - mesangial hypercellularity; E- endocapillary hypercellularity; S - segmental sclerosis/adhesion; T - tubular atrophy/interstitial fibrosis), and was calculated as the total score (sum of M, E, S, T). At the end of follow-up, the serum GDIgA1 concentration was measured. RESULTS: The serum GDIgA1 concentration in patients with IgAN and HSN was significantly higher than in the control group. No significant differences in mean proteinuria, erythrocyturia, GFR, MEST score, or GDIgA1 in serum, as well as the duration of follow-up between IgAN and HSN were observed. Baseline serum IgA concentration and time to kidney biopsy were significantly higher in children with IgAN than in children with HSN. We observed a positive correlation between GDIgA1 and IgA levels (r = 0.53), and GDIgA1 and serum creatinine levels (r = 0.5), as well as negative correlation between GDIgA1 and GFR (r = -0.37). CONCLUSIONS: Serum GDIgA1 level may have a prognostic value in children with IgAN and HSN; however, to fully elucidate its clinical potential further studies performed in larger patient cohorts are required.

[Influence of intensity, localization and type of deposits in renal biopsy for disease symptoms and follow up in children with IgA nephropathy]. / Wplyw nasilenia, lokalizacji i rodzaju zlogów w biopsji nerki na objawy kliniczne i rokowanie u dzieci z nefropatia IgA.

IgA nephropathy is the most common glomerulonephritis in the world. For diagnosis kidney biopsy is necessary. AIM: The aim of the study was assessment the significance of IgA, C3 and IgG deposits intensity and location in kidney childhood IgA nephropathy (IgAN) for the symptoms of the disease and the follow up. MATERIALS AND METHODS: Study population consisted of 81 children, average 11,45±3,99 years. IgAN was recognized based on renal biopsy, performed 1,2±1,84, median 0,5 years after the onset. We used Oxford classification (OC) to assess the severity of histopatological lesions. In renal biopsy IgA and C3 deposits were found in immunofluorescence in mesangium or in vessels of glomeruli or both, and intensity was defined 0 to +4. We analyzed: proteinuria (mg/kg/day), hematuria, creatinine, GFR (according to Schwartz formula) two times, at the onset of the disease (OOD) and at the follow up (FU). Patients were treated with: ACEI/ARB or steroids alone or with imunossupresion drugs: azathioprine (AZA), cyclophosphamide (CYC), cyclosporine A (CsA), mycopnenolate mophetil (MMF). The follow up was 3,31±2,88 years. We divided the patients into two groups, depending on the intensity of IgA deposits: G1 n=29 (+1/+2), G2 n=52 (+3/+4); depending on the localizations of these deposits, we analyzed 3 groups: A n= 39 (mesangium), B n= 15 (glomeruli vessels), C n=27 (both) and depending on the kind of deposits we analyzed 4 groups: gr. a - n=30 (only IgA), gr. b - n=37 (IgA+C3), gr. c - n=5 (IgA+IgG) gr. d - n= 9 (IgA+IgG+C3). RESULTS: At OOD and FU we not found any differences in G1 vs G2 for: age, proteinuria, GFR and OC in renal biopsy; at FU GFR<90 ml/ min/1,73 m2 FU was observed more frequently in G2 vs G1 (p=0,02). The differences in groups A,B,C and groups a,b,c,d were not found. CONCLUSIONS: Poor prognosis in childhood IgAN may also depend on the intensity of the deposits, irrespective of their location.

Urine fibroblast growth factor 23 levels in hypertensive children and adolescents.

AIM: To determine the correlation of urinary fibroblast growth factor 23 (FGF23) excretion with blood pressure and calcium-phosphorus metabolism. METHODS: The study included 42 hypertensive (17 girls) and 46 healthy children and adolescents (17 girls) aged 6-18 years admitted to the Department of Pediatrics and Nephrology, Medical University of Bialystok between January 2013 and December 2013. FGF23 in urine was measured using Human Intact FGF-23 ELISA Kit. RESULTS: Hypertensive participants had significantly higher urine FGF23/creatinine values than the reference group (8.65 vs 5.59 RU/mg creatinine, P=0.007). Urine FGF23/creatinine positively correlated with systolic blood pressure in all participants. In hypertensive patients, urine FGF23/creatinine positively correlated with serum calcium and negatively with serum 25(OH)D, urinary calcium, phosphorus, and magnesium. CONCLUSION: This study found that FGF23 may play an important role in the pathogenesis of hypertension in children and adolescents, but our results should be confirmed by further studies.

[FGF23 and Klotho protein--the role in the pathogenesis of hypertension]. / Rola FGF23 i bialka Klotho w patogenezie nadcisnienia tetniczego.

Fibroblast growth factor 23 (FGF23) is a relatively new phosphatonin, which is produced mainly by bone cells. It is responsible for the regulation of calcium- phosphate homeostasis in the body. FGF23 is one of hormones with phosphaturic effect. It inhibits renal reabsorbtion of phosphate and increases its urinary excretion. Moreover, FGF23 decreases serum concentration of 1,25(OH)2D by inhibition of lα-hydroxylase and stimulation of 24-hydroxylase. The current knowledge on FGF23 and its cofactor-Klotho protein in disturbances of calcium-phosphate balance or in Chronic Kidney Disease is quite obvious. Still we need to know more about the influence of FGF23 on the cardiovascular system and its role in the pathogenesis of hypertension thus this will be the main aspect of our study.

Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy.

BACKGROUND: The aim of this study was to evaluate the usefulness of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio for predicting histological severity of kidney lesions in children with IgA nephropathy (IgAN) based on World Health Organization (WHO) and the Oxford classification (OC). METHODS: We studied 89 children with IgAN with a mean age of 11.38 ± 4.1 years (range 2-18 years). Based on available medical records, we retrospectively evaluated clinical data, IgA/C3 ratio, and kidney biopsy findings using the five-grade WHO classification and the OC The mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy/interstitial fibrosis (T) (MEST) score (absent = 0, present = 1) calculated as the sum of M+E+S+T ranging from 0 to 4. RESULTS: Mean IgA/C3 ratio values were significantly higher (P < 0.05) in patients with M1, S1, and T1 compared with M0, S0, and T0, respectively (P < 0.05); there were no differences in the WHO classification. We found a significant positive correlation between the IgA/C3 ratio and proteinuria (r = 0.24) and determined optimal cutoff values of the IgA/C3 ratio, with a corresponding confidence interval for specific MEST scores. CONCLUSIONS: The IgA/C3 ratio in children with IgAN may be a useful marker of the severity of lesions found in kidney biopsy as evaluated using the OC.

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.

Paediatric normative data for urine NGAL/creatinine ratio.

AIM: The objective of this study was to establish age-dependent urine NGAL (neutrophil gelatinase-associated lipocalin)/creatinine ratio values in healthy children and adolescents. METHODS: The study was performed using a random sample of 172 healthy children and adolescents (M-88, F-84), aged median 9.75 (0.2-17.9) years. Urine NGAL concentration was measured using a commercially available ELISA kit (R&D Systems, USA). RESULTS: Median concentrations of urine NGAL/creatinine in particular age groups were analysed using anova. The differences between the youngest group of children under the age of 6 years and the rest of examined population were statistically significant. There were no differences in urine NGAL/creatinine between other age groups. Statistically significant negative correlation between urine NGAL/creatinine and age of subjects was found (r = -0.29, p < 0.05). CONCLUSION: In the study, normative values of urine NGAL/creatinine for subjects aged 0.2-17.9 years have been established. These data may help clinicians and researchers to improve the interpretation of urine NGAL/creatinine ratio in children and adolescents. However, further studies using numerous data should be conducted to add reference values for urine NGAL partitioned by age and gender.

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.