Lymphocyte to monocyte ratio and blood pressure variability in childhood hypertension-a pilot study.

BACKGROUND AND AIMS: The investigation of inflammatory background of hypertension (HTN) concentrates mainly on patients with primary HTN. The aim of the study was to analyze the role of new parameters of inflammation-lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR), in the population of children with primary (pHTN) and secondary renal hypertension (rHTN). MATERIAL AND METHODS: The study group consisted of 70 children with pHTN, 46 patients with rHTN, and 30 age-matched normotensive controls. The retrospective analysis focused on the evaluation of LMR, NLR, and PLR values in relation to blood pressure (BP) parameters from in-office and ambulatory BP monitoring measurements. Twenty-four hours, daytime, and nighttime periods were evaluated. Blood pressure variability (BPV) was defined by standard deviation and coefficient of variation of analyzed values. RESULTS: LMR and NLR values in HTN patients differed significantly vs. controls. Dippers with pHTN demonstrated significant correlations between LMR, NLR, PLR, and markers of BPV, in 24 h and daytime diastolic BP and mean arterial pressure. In dippers with rHTN such correlations concerned only LMR. CONCLUSIONS: LMR may become a promising marker of BPV, useful in children with primary and secondary hypertension. IMPACT: Lymphocyte to monocyte ratio is a novel marker of blood pressure variability, connected to target-organ damage, in children with primary and secondary renal hypertension. Our study analyzes for the first time the connections between blood cell count-driven inflammatory markers (lymphocyte to monocyte, neutrophil to lymphocyte, and platelet to lymphocyte ratios) and parameters of blood pressure variability, and compares those ratios in children with primary and secondary hypertension. The increasing incidence of hypertension among children urges the search for simple methods of assessment of its complications. LMR may be of added value in the analysis of the inflammatory background of hypertension.

Emerging Role of Microbiome in the Prevention of Urinary Tract Infections in Children.

The microbiome of the urinary tract plays a significant role in maintaining health through the impact on bladder homeostasis. Urobiome is of great importance in maintaining the urothelial integrity and preventing urinary tract infection (UTI), as well as promoting local immune function. Dysbiosis in this area has been linked to an increased risk of UTIs, nephrolithiasis, and dysfunction of the lower urinary tract. However, the number of studies in the pediatric population is limited, thus the characteristic of the urobiome in children, its role in a child's health, and pediatric urologic diseases are not completely understood. This review aims to characterize the healthy urobiome in children, the role of dysbiosis in urinary tract infection, and to summarize the strategies to modification and reshape disease-prone microbiomes in pediatric patients with recurrent urinary tract infections.

Relationship between Gd-IgA1 and TNFR1 in IgA nephropathy and IgA vasculitis nephritis in children - multicenter study.

AIM OF THE STUDY: To evaluate the relationship between serum Gd-IgA1 (sGd-IgA1) and serum and urine TNFR1 (sTNFR1, uTNFR1) levels as possible prognostic factors in IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN). MATERIAL AND METHODS: From 299 patients from the Polish Registry of Pediatric IgAN and IgAVN, 60 children (24 IgAN and 36 IgAVN) were included in the study. The control group consisted of 20 healthy children. Proteinuria, haematuria, serum creatinine as well as IgA and C3 levels were measured and glomerular filtration rate (GFR) was calculated at onset and at the end of the follow-up. Kidney biopsy findings were evaluated using the Oxford classification. Serum Gd-IgA1 and serum and urine TNFR1 levels were measured at the end of follow-up. RESULTS: Serum Gd-IgA1 level was significantly higher in IgAN and IgAVN patients in comparison to the control group. Urine TNFR1 was significantly higher in IgAN than in IgAVN and the control group. We did not observe any differences in sTNFR1 level between IgAN, IgAVN and control groups. We found a positive correlation between Gd-IgA1 and creatinine (r = 0.34), and negative between Gd-IgA1 and GFR (r = -0.35) at the end of follow-up. We observed a negative correlation between uTNFR1/creatinine log and albumin level and protein/creatinine ratio. We did not find any correlations between Gd-IgA1 and TNFR1. CONCLUSIONS: The prognostic value of sGd-IgA1 in children with IgAN and IgAVN has been confirmed. TNFR1 is not associated with Gd-IgA1 and is not a useful prognostic marker in children with IgAN/IgAVN and normal kidney function.

New markers of cell migration and inflammation in children with chronic kidney disease.

Context: Chronic kidney disease (CKD) is characterized by immunocompetent cell migration and inflammation. Monocyte chemoattractant protein (MCP)-1 and macrophage colony-stimulating factor (MCSF) stimulate monocyte migration and transition into macrophages with subsequent release of neopterin. Objective: The aim of the study was to analyze these parameters in children with various stages of CKD. Material and methods: The study group consisted of 41 CKD children, 19 patients on haemodialysis (HD), 22 children on automated peritoneal dialysis (APD) and 23 controls. Serum concentrations of MCP-1, MCSF and neopterin were assessed by ELISA. Correlations to matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) were analyzed. Results: MCP-1, MCSF and neopterin were significantly elevated in all patients versus controls and the highest values concerned HD children. A single HD session lessened the concentrations of all parameters, yet they rose back before the next HD session. All markers correlated with MMPs and TIMPs in different combinations. Conclusions: Systemic inflammation and cell migration are triggered by CKD and additionally aggravated by chronic dialysis, with the more evident negative impact of HD than APD. Discrepancies in MCP1, MCSF and neopterin serum concentrations suggest they may serve as new markers of cellular and inflammatory responses in children with CKD.

Multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab in children with steroid-resistant nephrotic syndrome.

The aim of the study was a multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab (Rtx) in children with steroid-resistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in eight paediatric nephrology centres in Poland. The children were administered a single initial infusion of rituximab at the dose of 375 mg/m2 of the body surface area. Proteinuria, the daily supply of glucocorticoids, and cyclosporine were assessed at the moment of the start of the treatment and after 6 months since its commencement. Before Rtx therapy, complete remission was found in 13 patients (43%) and partial remission was found in 8 patients (26%). These numbers increased to 16 (53%) and 12 (40%), respectively. At the start of the treatment 23 patients (76.6%) were treated with cyclosporine A. After 6 months, this number decreased to 15 patients (35%). At the start of the treatment, 18 patients (60%) were treated with prednisone. After 6 months, this number decreased to 8 patients (44%). Children with SRNS may potentially benefit from Rtx treatment despite relative risk of side effects. The benefits may include reduction of proteinuria or reduction of other immunosuppressants.

Skin Autofluorescence, as a Measure of AGE Accumulation in Individuals Suffering from Chronic Plaque Psoriasis.

BACKGROUND: Psoriasis is currently regarded as a chronic systemic inflammatory disease associated with increased cardiovascular risk. Advanced glycation end products (AGEs) contribute to the development of atherosclerosis. OBJECTIVES: The aim of the study was the assessment of skin autofluorescence (SAF), as a measure of AGE accumulation, in individuals suffering from chronic plaque psoriasis without any comorbid conditions. METHODS: A study group consisted of 70 patients with chronic plaque psoriasis without any comorbid conditions and 59 healthy controls, matched by age and gender. AGE accumulation was assessed by SAF (AGE Reader, DiagnOptics BV) which is a validated and noninvasive technique. Relations between SAF and some clinical and laboratory data were assessed. RESULTS: SAF was positively correlated with age both in patients with psoriasis and controls (R = 0.722, p < 0.00001 and R = 0.613, p < 0.00001, respectively). There was significantly increased SAF in patients with psoriasis with elevated levels of C-reactive protein (CRP) and increased erythrocyte sedimentation rate (ESR) compared to controls (p < 0.00001; p < 0.00001, respectively, after adjustment to age). Increased SAF was found in psoriatic patients with prediabetes (HbA1c 5.7-6.4%) compared to controls (p < 0.0012, after adjustment to age). CONCLUSION: Systemic inflammation (increased CRP level), prediabetes, and aging may influence enhanced AGE accumulation in patients with psoriasis without any comorbidities. SAF may be considered as a useful, noninvasive method to identify patients with psoriasis at increased cardiovascular risk.

[Chronic kidney disease in children up to 2 years of age - a single center data analysis]. / Przewlekla choroba nerek u dzieci do 2. roku zycia ­ analiza danych z jednego osrodka.

Although anomalies in the urinary tract are the leading cause of chronic kidney disease (CKD) in the pediatric population, there are few studies focusing on etiological discrepancies between younger and older children. AIM: The aim of the study was to perform a comparative analysis of etiology of CKD in children hospitalized in the Department of Pediatric Nephrology at the Wroclaw Medical University, with reference to the patients' age and gender. MATERIALS AND METHODS: The retrospective analysis considered medical records of 174 patients aged 0-18 years, diagnosed with CKD, hospitalized in our Department in the years 2011-2017. The analyzed population was divided regarding the patients' age. Group A contained children up to 2 years of age (45 patients), group B - children aged 2-18 years (129 patients). RESULTS: In younger children, boys prevailed, in older children gender distribution was equal. The most common causative factors of CKD in group A were: urinary tract anomalies (66,7%), perinatal acute kidney injury (17,8%) and hereditary renal disorders (8,9%). In children over 2 years of age, urinary tract anomalies were also the leading cause of CKD (48,8%), followed by glomerulopathies (16,3%) and hereditary renal disorders (15,5%). CONCLUSIONS: Anomalies within the urinary tract are the predominant cause of CKD in children, irrespective of age. Male predominance concerned only children up to 2 years of age. The second causative factor for CKD in the youngest children is acute kidney injury, mainly in the perinatal period. Glomerulopathies and hereditary renal disorders are significant etiological factors for CKD in older children.

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.

Epidermal growth factor, growth differentiation factor-15, and survivin as novel biocompatibility markers in children on chronic dialysis.

CONTEXT: Chronic dialysis results in aggravation of apoptosis and cell damage, triggered by bioincompatibility of dialysis membranes and peritoneal fluids. OBJECTIVE: The aim of study was to assess the usefulness of epidermal growth factor (EGF), growth differentiation factor (GDF)-15, and survivin as novel markers of biocompatibility in dialyzed children. MATERIALS AND METHODS: Parameters were assessed by ELISA in 19 patients on hemodialysis and 22 children on peritoneal dialysis. RESULTS: Serum concentrations of analyzed parameters in children on chronic dialysis differed significantly from controls and depended strongly on the dialysis technique. CONCLUSIONS: EGF, GDF-15, and survivin may serve as new biocompatibility markers in children on chronic dialysis.

Urine survivin, E-cadherin and matrix metalloproteinases as novel biomarkers in children with chronic kidney disease.

CONTEXT: Epithelial-mesenchymal transition (EMT) leads to renal fibrosis and chronic kidney disease (CKD). OBJECTIVE: The aim of this study was to assess the usefulness of survivin, E-cadherin and metalloproteinases (MMPs) as biomarkers of CKD-related complications. MATERIAL AND METHODS: Survivin, E-cadherin, MMP-2, MMP-9 and TGFbeta1 were assessed by ELISA in 41 children with CKD stages 3 to 5 and in 23 controls. RESULTS: The serum and urine values of analyzed parameters were significantly elevated in CKD patients versus controls and correlated with each other. CONCLUSIONS: The observed parameter changes indicate apoptosis, tissue remodeling and fibrosis in CKD children. Urine survivin may become a new biomarker of kidney-specific EMT.

Skin autofluorescence as a novel marker of vascular damage in children and adolescents with chronic kidney disease.

BACKGROUND: Skin autofluorescence (sAF) was examined as a marker of the accumulation of advanced glycation end products (AGEs) in tissues of children with chronic kidney disease (CKD) in relation to renal function, dialysis modality and markers of endothelial inflammation and dysfunction. METHODS: A total of 76 children with CKD were enrolled in the study, of whom 20 children were on hemodialysis (HD), 20 were on peritoneal dialysis (PD) and 36 were treated conservatively. A control group of 26 healthy subjects was also included in the study. In all children, sAF intensity, carotid intima-media (cIMT) thickness and plasma concentrations of sE-selectin, matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and plasminogen activator inhibitor type 1 (PAI-1) were measured. RESULTS: Compared to the controls, children with CKD had significantly elevated sAF levels. sAF in the children with CKD was positively correlated with sE-selectin, MMP-9, TIMP-1, ADMA, SDMA and PAI-1 levels. In the predialysis group (conservative treatment) sAF levels were positively correlated with sE-selectin and ADMA levels and negatively correlated with glomerular filtration rate. Multiple regression analysis showed a significant association of sAF with sE-selectin and MMP-9 in CKD children. CONCLUSIONS: The results reveal that AGEs were accumulated in the children with CKD. This accumulation was related to early vascular changes and a number of biochemical vascular risk markers. sAF measurement, as a noninvasive method, may be useful for identification of clinical risk factors of vascular disease in CKD children.

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.

Expression of chemokine receptors on peripheral blood T cells in children with chronic kidney disease.

Chemokine receptors play a role in leukocyte recruitment, activation, and maintaining effector functions and regulate adaptive immune response and angiogenesis. The study aimed at flow cytometric analysis of T cell subsets with selected surface chemokine receptors (CCR4, CCR5, CCR7, CXCR3, and CXCR4) or receptor combination in peripheral blood of children with chronic kidney disease (CKD) on hemodialysis (HD). The percentage of T lymphocytes with CD8 and combined CD28,CCR7 expression was higher in HD children. The percentage of T lymphocytes expressing CCR7, CD28,CCR7, and CXCR4,CD8 was increased in children on conservative treatment. Total number (tn) of CXCR4+ cells was reduced in children on hemodialysis. The tn of T CXCR3+ cells was lower in children on conservative treatment. During HD the percentage of T CD4+ cells was higher and of T CXCR3+ lymphocytes was lower after HD session as compared to 15 min of session duration. During HD tn of T cells with expression of CCR4, CCR5, CCR7, CXCR3, and CXCR4 was constant. The alteration of chemokine receptors expression in children with CKD occurs early in the development. Diminished expression of CXCR3, CXCR4 on T cells in patients with CKD on HD might result in impaired inflammatory response. Increased CCR7+ T cell percentage could be responsible for the alteration of migration of cells into secondary lymphatic organs.

Urine matrix metalloproteinases and their extracellular inducer EMMPRIN in children with chronic kidney disease.

BACKGROUND: Transforming growth factor (TGF)beta1 and matrix metalloproteinases (MMPs) play an essential role in CKD-related tissue remodeling. However, there are no data on urine MMPs and their extracellular inducer EMMPRIN in CKD patients. The aim of study was to assess the concentrations of MMP-2, MMP-7, MMP-9, EMMPRIN and TGFbeta1 in serum and urine of CKD children and to analyze the potential relations between those parameters. METHODS: Forty-one pre-dialysis CKD children and 23 age-matched controls were enrolled in the study. The concentrations of analyzed parameters were assessed by ELISA. RESULTS: Serum and urine values of MMP-2, MMP-7, MMP-9, EMMPRIN and TGFbeta1 were significantly elevated in CKD patients versus controls. The MMP-2 and MMP-9 levels in urine correlated significantly with the corresponding values in serum, whereas MMP-7, EMMPRIN and TGFbeta1 urine concentrations did not. There were also significant correlations between urine values of all parameters. CONCLUSIONS: The increased urine levels of MMPs, EMMPRIN and TGFbeta1 indicate enhanced proteolysis and renal tissue remodeling. In the case of MMP-7, EMMPRIN and TGFbeta1 those disturbances seem independent of enhanced serum activity of the corresponding enzymes. The urine MMP-7 and EMMPRIN concentrations may serve as new independent indices of tissue remodeling and renal interstitial fibrosis in children with CKD.

The impact of dialysis modality on novel markers of stress reaction, matrix remodeling and endothelial damage in children on chronic dialysis.

BACKGROUND/AIMS: Dialysis triggers stress reaction, matrix remodeling and endothelial damage, but little is known about the changes it induces on selected heat shock proteins (Hsp90α), adhesion molecules (E-cadherin, sE-selectin), metalloproteinases (MMP-8) and their extracellular inducer (EMMPRIN). The aim of this study was to assess serum concentrations of the above-mentioned parameters in children on chronic dialysis. METHODS: 19 patients on hemodialysis (HD), 22 children on peritoneal dialysis (PD) and 30 age-matched controls were examined. Serum concentrations of parameters were assessed by ELISA. RESULTS: Hsp90α, MMP-8, EMMPRIN and E-cadherin concentrations were significantly increased in children on dialysis vs. controls and higher levels were in HD than PD patients. There was no difference in the level of sE-selectin between HD and PD modalities. A single HD session diminished Hsp90α, MMP-8, EMMPRIN and E-cadherin values, but had no impact on sE-selectin levels. CONCLUSIONS: Hemodialysis evokes stress reaction, matrix and endothelium destruction, to a greater extent than peritoneal dialysis. Single hemodialysis influences circulating cells rather than endothelial cells.

Is TCF7L2 variant associated with non-diabetic chronic kidney disease progression? Results of a family-based study.

INTRODUCTION: It is assumed that genetic factors may play a significant role in CKD development. The aim of the study was to investigate the role of rs7903146 polymorphism in the TCF7L2 gene in development and progression of non-diabetic chronic kidney disease (CKD). MATERIAL/METHODS: 109 children and young adults with CKD caused by primary glomerulopathy and tubulointerstitial nephropathy, stages 3-5, and their 218 biological parents with no renal dysfunction were included in the study. We tested the transmission of alleles of rs7903146 polymorphism in the TCF7L2 gene from heterozygous parents to offspring affected with CKD using the transmission/disequilibrium test. We also analysed whether rs7903146 polymorphism had any impact on the loss of glomerular filtration rate. RESULTS: The rs7903146 polymorphism in TCF7L2 allele transmission from heterozygous parents to their affected children was not different from a random proportion expected for no association, in the whole group of subjects, and in the subgroups, depending on CKD aetiology. Lack of association between the analysed polymorphism and the loss of glomerular filtration rate was found in the total group of patients as well as in the subgroups, regarding the cause of CKD. CONCLUSIONS: This study found no association between rs7903146 polymorphism in the TCF7L2 gene and the increased risk for development of CKD caused by primary glomerulopathy and analysed tubulointerstitial nephropathy. The progression rate of CKD of non-diabetic aetiology does not depend on this polymorphism.

The Role of TNF-α in the Pathogenesis of Idiopathic Nephrotic Syndrome and Its Usefulness as a Marker of the Disease Course.

Background: The pathogenesis of idiopathic nephrotic syndrome (INS) has not been fully explained. Among the likely factors, tumor necrosis factor - alpha (TNF-α) is considered. We aimed to evaluate the TNF-α (sTNF-α, uTNF-α) levels in the serum and urine of INS children, with the aim of determining its association with proteinuria, and of determining its usefulness as a marker of the disease severity. Methods: Fifty-one examined patients were divided into subgroups depending on the number of relapses as follows: group IA-first episode; group IB-more than two relapses, and according to treatment modality; group IIA-glucocorticosteroids (GS) alone; and group IIB-GS with immunosuppressants. Healthy age-matched children served as the control group. Results: sTNF-α and uTNF-α levels were significantly increased in active phases in the whole INS group compared to the control group. They decreased in remission, but remained significantly higher when compared to the control group. During remission in the IB group, sTNF-α levels were significantly higher than in IA, whereas, in the relapse phase, these values were similar. In the IA group, a positive correlation between proteinuria and sTNF-α was demonstrated. Conclusions: Our findings suggest that TNF-α plays a role in the development of INS, and may be used as a prognostic marker, as well as an indicator for the continuation of therapy. Additional research is required to verify this statement.

Physical Activity and Its Potential Determinants in Obese Children and Adolescents under Specialist Outpatient Care-A Pilot Cross-Sectional Study.

(1) Background: this study aimed to assess the physical activity of obese pediatric patients under specialized outpatient care and its potential determinants. (2) Methods: A total of 83 subjects aged 7-18 years with simple obesity and their parents were enrolled. Data were collected with the use of physical activity questionnaires (PAQs) for children and adolescents and additional questions concerning selected socio-demographic characteristics. (3) Results: The mean final PAQ score was 2.09 ± 0.69. The most frequently chosen types of physical activity included walking, gymnastics, and jogging or running. We found a weak correlation inversely proportional between the child's age and mean final PAQ score (r = -0.25; p = 0.02). Younger children were more active during lunchtime at school and after school compared to adolescents (p = 0.03 and p = 0.04). The final PAQ score differed according to the place of residence; the lowest score was obtained by subjects living in cities >100,000 inhabitants (p = 0.025). We found a positive correlation between PAQ-Ch score and the father's physical activity, and between PAQ-A score and the mother's education. (4) Conclusions: The physical activity of obese pediatric patients is low, particularly in adolescents. It seems that age and place of residence have an impact on the physical activity of obese children and adolescents. The PAQs used in this study are useful in physical activity assessment and identification of time segments during the day in which activity might be improved. However, this requires confirmation in a larger group of pediatric patients.

New markers of apoptosis in children on chronic dialysis.

Enhanced apoptosis is characteristic for chronic kidney disease (CKD). A specific type of apoptosis, anoikis, is connected with the extracellular matrix turnover and cell detachment. Although E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase (MMP)-8 may play an important role in this process, they have not been analyzed in any nephrological aspect, either in CKD. The aim of study was to evaluate the serum concentrations of E-cadherin, EMMPRIN and their potential regulators (MMP-8, MMP-7, TIMP-1, TIMP-2), with relevance to apoptosis/cell damage markers (sFas, sFasL, Hsp27), in children with CKD. 39 CKD children stages 3-4, 26 CKD children stage 5 still on conservative treatment, 19 patients on hemodialysis (HD), 22 children on automated peritoneal dialysis (APD) and 30 controls were examined. Serum concentrations of those parameters were assessed by ELISA. Median E-cadherin, EMMPRIN and MMP-8 values were significantly increased in patients on dialysis versus those in pre-dialysis period and versus controls. The highest values were noticed in the HD subjects. Regression analysis revealed that EMMPRIN and MMP-8 predicted various apoptosis markers, whereas E-cadherin turned out the best predictor of both apoptosis (Hsp27, sFas, sFasL) and matrix turnover (MMP-7, TIMP-1, TIMP-2) indexes in dialyzed patients. Children with CKD are prone to E-cadherin, EMMPRIN and MMP-8 elevation, aggravated by the dialysis commencement and most evident on hemodialysis. Correlations between parameters suggest their role as indexes of apoptosis in children on dialysis. E-cadherin seems the most accurate marker of anoikis in this population.

Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene.

Cranioectodermal dysplasia (CED) is a disorder characterized by craniofacial, skeletal, and ectodermal abnormalities. Most cases reported to date are sporadic, but a few familial cases support an autosomal-recessive inheritance pattern. Aiming at the elucidation of the genetic basis of CED, we collected 13 patients with CED symptoms from 12 independent families. In one family with consanguineous parents two siblings were affected, permitting linkage analysis and homozygosity mapping. This revealed a single region of homozygosity with a significant LOD score (3.57) on chromosome 3q21-3q24. By sequencing candidate genes from this interval we found a homozygous missense mutation in the IFT122 (WDR10) gene that cosegregated with the disease. Examination of IFT122 in our patient cohort revealed one additional homozygous missense change in the patient from a second consanguineous family. In addition, we found compound heterozygosity for a donor splice-site change and a missense change in one sporadic patient. All mutations were absent in 340 control chromosomes. Because IFT122 plays an important role in the assembly and maintenance of eukaryotic cilia, we investigated patient fibroblasts and found significantly reduced frequency and length of primary cilia as compared to controls. Furthermore, we transiently knocked down ift122 in zebrafish embryos and observed the typical phenotype found in other models of ciliopathies. Because not all of our patients harbored mutations in IFT122, CED seems to be genetically heterogeneous. Still, by identifying CED as a ciliary disorder, our study suggests that the causative mutations in the unresolved cases most likely affect primary cilia function too.