Development of a tool for predicting HNF1B mutations in children and young adults with congenital anomalies of the kidneys and urinary tract.

BACKGROUND: We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT). METHODS: The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%). A random forest model was constructed to predict HNF1B mutations. The recursive feature elimination algorithm was used for feature selection for the model, and receiver operating characteristic curve statistics was used to verify its predictive effect. RESULTS: A total of 213 patients were analyzed, including HNF1B-positive (mut + , n = 109) and HNF1B-negative (mut - , n = 104) subjects. The majority of patients had mild chronic kidney disease. Kidney phenotype was similar between groups, but bilateral kidney anomalies were more frequent in the mut + group. Hypomagnesemia and hypermagnesuria were the most common abnormalities in mut + patients and were highly selective of HNF1B. Hypomagnesemia based on age-appropriate norms had a better discriminatory value than the age-independent cutoff of 0.7 mmol/l. Pancreatic anomalies were almost exclusively found in mut + patients. No subjects had hypokalemia; the mean serum potassium level was lower in the HNF1B cohort. The abovementioned, discriminative parameters were selected for the model, which showed a good performance (area under the curve: 0.85; sensitivity of 93.67%, specificity of 73.57%). A corresponding calculator was developed for use and validation. CONCLUSIONS: This study developed a simple tool for predicting HNF1B mutations in children and young adults with CAKUT.

Outcome of immunosuppression in children with IgA vasculitis-related nephritis.

BACKGROUND AND HYPOTHESIS: IgA vasculitis with nephritis (IgAVN) is the most common vasculitis in children. Treatment recommendations are, due to a lack of evidence, based on expert opinion resulting in variation. The aim of this study was to describe clinical presentation, treatment and outcome of an extremely large cohort of children with biopsy proven IgAVN to identify prognostic risk factors and signals of treatment efficacy. METHODS: Retrospective data were collected on 1148 children with biopsy proven IgAVN between 2005 and 2019 from 41 international paediatric nephrology centres across 25 countries and analyzed using multivariate analysis. The primary outcome was estimated glomerular filtration rate (eGFR) and persistent proteinuria at last follow up. RESULTS: The median follow up was 3.7 years (IQR 2-6.2). At last follow up, 29% of patients had an eGFR < 90 ml/min/1.73m2, 36% had proteinuria and 3% had chronic kidney disease stage 4-5. Older age, lower eGFR at onset, hypertension and histological features of tubular atrophy and segmental sclerosis were predictors of poor outcome. There was no evidence to support any specific second line immunosuppressive regimen to be superior to others, even when further analysing subgroups of children with reduced kidney function, nephrotic syndrome or hypoalbuminemia at onset. Delayed start of immunosuppressive treatment was associated with a lower eGFR at last follow up. CONCLUSION: In this large retrospective cohort, key features associated with disease outcome are highlighted. Importantly there was no evidence to support that any specific immunosuppressive treatments were superior to others. Further discovery science and well-conducted clinical trials are needed to define accurate treatment and improve outcomes of IgAVN.

A rare cause of steroid-resistant nephrotic syndrome - a case report.

Steroid resistance is a common condition occurring in children with nephrotic syndrome. Until now, over 50 genes involved in steroid-resistant nephrotic syndrome (SRNS) pathogenesis have been identified, among which the most prevalent are NPHS1, NPHS2, CD2AP, and PTPRO. The patterns of inheritance of SRNS are autosomal recessive, autosomal dominant, or mitochondrial, and tissues of those patients show focal segmental glomerulosclerosis (FSGS) signs in histopathological image analysis. We present a case of a 6-year-old girl who was admitted to the pediatric nephrology department due to nephrotic range proteinuria and edema of the lower leg. We started therapy with prednisone at a dose of 45 mg (60 mg/m2), enalapril as a nephroprotection, and antihistamines as an additional treatment. During in-patient treatment, we detected increased blood pressure. Due to persistent proteinuria in spite of 6-week treatment with steroids at the maximal dose, we confirmed disease resistance to steroids. Additionally, FSGS signs were confirmed in kidney biopsy samples. After genetic screening for SRNS and detection of the rare gene mutation NUP93 we reduced prednisone but maintained nephroprotective treatment and administered cyclosporin A. The girl remains currently under the care of nephrologists with normal arterial blood pressure, trace proteinuria in follow-up examination, and normal kidney function. NUP93 mutation is extremely rare; therefore few cases have been described to date. The onset of the symptoms in all pediatric patients appeared before the age of 8 and they developed end stage kidney disease (ESKD). They might manifest symptoms from the other systems.

Thrombotic complications in children with first-episode steroid-sensitive nephrotic syndrome: A single-center experience.

OBJECTIVE: The aim of the study was to evaluate the clinical course and risk factors of venous thromboembolic complications (VTEC) in children with a first episode of steroid-sensitive nephrotic syndrome (SSNS). MATERIALS AND METHODS: We retrospectively analyzed the medical records of children hospitalized due to SSNS in one pediatric nephrology unit between 2012 and 2019. Demographic data, clinical symptoms at the onset of NS, and laboratory parameters were compared between patients with and without VTEC. RESULTS: Among 106 children (4.7 ± 3.06 years of age) with a first episode of SSNS, 5 VTEC were diagnosed during 2 - 60 days after onset of NS, on the basis of clinical symptoms and/or results of imaging studies. These were thromboses of femoral vein, central part of the kidney, dorsal veins of the hand, venous sinuses of the brain, and superficial vein in the popliteal fossa region. We found significant higher serum fibrinogen level (p = 0.022) and D-dimers (p = 0.0001) in children with VTEC vs. those without VTEC, but AUC analysis showed that only D-dimers significantly differentiate thrombosis. The clinical risk factors of VTEC were vascular cannulation (100%), infections (80%), and diuretics (80%). In children with VTEC, low molecular weight heparin was used. The outcome was a full recovery in all patients. CONCLUSION: VTEC occurs in 4.72% of children with a first episode of SSNS. The course of VTEC in children with SSNS may be asymptomatic. The clinical risk factors of VTEC in children with SSNS are vascular cannulation, infections, and diuretics. High D-dimer levels are a sensitive indicator of thrombosis.

Epidemiology and Risk Factors of UTIs in Children-A Single-Center Observation.

Urinary tract infections (UTIs) are one of childhood's most common bacterial infections. The study aimed to determine the clinical symptoms, laboratory tests, risk factors, and etiology of different UTIs in children admitted to pediatric hospitals for three years. Methods: Patients with positive urine cultures diagnosed with acute pyelonephritis (APN) or cystitis (CYS) were analyzed for clinical symptoms, laboratory tests, risk factors, and etiology, depending on their age and sex. Results: We studied 948 children with UTIs (531 girls and 417 boys), with a median age of 12 (IQR 5−48 months). A total of 789 children had clinical symptoms; the main symptom was fever (63.4% of patients). Specific symptoms of UTIs were presented only in 16.3% of patients. Children with APN had shown significantly more frequent loss of appetite, vomiting, lethargy, seizures, and less frequent dysuria and haematuria than children with CYS. We found significantly higher median WBC, CRP, and leukocyturia in children with APN than with CYS. The risk factors of UTIs were presented in 46.6% of patients, of which 35.6% were children with APN and 61.7% with CYS. The main risk factor was CAKUT, more frequently diagnosed in children with CYS than APN, mainly in children <2 years. The most commonly isolated bacteria were Escherichia coli (74%). There was a higher percentage of urine samples with E. coli in girls than in boys. Other bacteria found were Klebsiella species, Pseudomonas aeruginosa, Proteus mirabilis, and Enterococcus species. Conclusions: Patients with APN were younger and had higher inflammatory markers. Often, fever is the only symptom of UTI in children, and other clinical signs are usually non-specific. The most common UTI etiology is E. coli, regardless of the clinical presentation and risk factors.

Nephrological and urological symptoms in patients with Robinow syndrome - a report of two cases.

Robinow syndrome is a rare congenital syndrome described in 1969 by Meinhard Robinow. The genetic background is heterogeneous - mutations of DVLI1, DVLI3, WNT5A genes (mild, autosomal dominant inheritance) or ROR2 gene (severe, autosomal recessive inheritance) are responsible for the syndrome. The syndrome is characterized by facial dysmorphism, skeletal defects, short stature, cardiovascular and urinary system abnormalities. CASE REPORT: We report nephrological and urological problems in two 4-year-old male patients with Robinow syndrome. The first patient has a horseshoe kidney located mainly on the right side, right vesicoureteral reflux grade II, dysfunctional voiding, buried penis, and retractile testicles. The second patient has recurrent urinary tract infections; diagnostic findings include left kidney duplication, grade II left vesicoureteral reflux, large posterior urethral diverticulum, dysfunctional voiding, buried penis, glanular hypospadias, and bilateral cryptorchidism. CONCLUSIONS: Patients with Robinow syndrome require multidisciplinary care, including nephrology-urology care. Nephrological and urological manifestations in children with Robinow syndrome are diverse, and urinary tract defects may be atypical and complex.

Reduced Blood Pressure Dipping Is A Risk Factor for the Progression of Chronic Kidney Disease in Children.

Background: Elevated blood pressure and proteinuria are well-established risk factors for chronic kidney disease (CKD) progression in children. This study aimed to analyze risk factors for CKD progress, emphasizing detailed ambulatory blood pressure (ABPM) data. Methods: In 55 children with CKD II−V, observed for ≥1 year or until initiation of kidney replacement therapy, we analyzed ABPM, clinical, and biochemical parameters. Results: At the beginning, the glomerular filtration rate (eGFR) was 66 (interquartile range­IQR: 42.8−75.3) mL/min/1.73 m2, and the observation period was 27 (16−36) months. The mean eGFR decline was 2.9 ± 5.7 mL/min/1.73 m2/year. eGFR decline correlated (p < 0.05) with age (r = 0.30), initial proteinuria (r = 0.31), nighttime systolic and mean blood pressure (r = 0.27, r = 0.29), and systolic and diastolic blood pressure dipping (r = −0.37, r = −0.29). There was no relation between mean arterial pressure during 24 h (MAP 24 h Z-score) and eGFR decline and no difference in eGFR decline between those with MAP 24 h < and ≥50 th percentile. In multivariate analysis, systolic blood pressure dipping (beta = −0.43), presence of proteinuria (beta = −0.35), and age (beta = 0.25) were predictors of eGFR decline. Conclusions: Systolic blood pressure dipping may be a valuable indicator of CKD progression in children.

Circadian Blood Pressure Profile in Pediatric Patients with Primary Hypertension.

Our study aimed to evaluate factors affecting circadian BP profile and its association with hypertension-mediated organ damage (HMOD) in pediatric patients with primary hypertension (PH). The study included 112 children (14.7 ± 2.1 age, 79 boys, 33 girls) with untreated PH. Non-dipping was defined as a nocturnal drop in systolic or diastolic BP (SBP, DBP) < 10%, and a nocturnal drop >20% was defined as extreme dipping. The nocturnal SBP drop was 10.9 ± 5.9 (%), and the DBP drop was 16.2 ± 8.5 (%). Non-dipping was found in 50 (44.6%) children and extreme dipping in 29 (25.9%) patients. The nocturnal SBP decrease correlated with BMI Z-score (r = −0.242, p = 0.010) and left ventricular mass index (LVMI) (r = −0.395, p = 0.006); diastolic DBP decrease correlated with augmentation index (AIx75HR) (r = 0.367, p = 0.003). Patients with a disturbed blood pressure profile had the highest LVMI (p = 0.049), while extreme dippers had the highest augmentation index (AIx75HR) (p = 0.027). Elevated systolic and diastolic BP dipping were risk factors for positive AIx75HR (OR 1.122 95CI (1.009−1.249) and OR 1.095 95CI (1.017−1.177). We concluded that disturbed circadian BP profile was common in children with PH and should not be considered a marker of secondary hypertension. A disturbed circadian BP profile may be associated with higher body weight. In pediatric patients with PH, non-dipping is associated with increased left ventricular mass, and extreme dipping may be a risk factor for increased arterial stiffness.

Evaluation of Active Renin Concentration in A Cohort of Adolescents with Primary Hypertension.

Our study aimed to assess active renin concentration in children with primary hypertension. Thus, we evaluated active renin concentration, clinical parameters, office and ambulatory blood pressure, and biochemical parameters in 51 untreated adolescents with primary hypertension (median: 14.4 [interquartile range-IQR: 13.8-16.8] years) and 45 healthy adolescents. Active renin concentration did not differ between patients with hypertension and healthy children (median: 28.5 [IQR: 21.9-45.2] vs. 24.9 [IQR: 16.8-34.3] [pg/mL], p = 0.055). In the whole group of 96 children, active renin concentration correlated positively with serum potassium and office and ambulatory systolic and diastolic blood pressures. Among children with hypertension, patients with isolated systolic hypertension had lower renin concentration than patients with systolic-diastolic hypertension (26.2 [IQR: 18.6-34.2] vs. 37.8 [IQR: 27.0-49.6] [pg/mL], p = 0.014). The active renin concentration did not differ between patients with isolated systolic hypertension and healthy children. In multivariate analysis, diastolic blood pressure Z-score (beta = 0.238, 95 confidence interval [0.018-0.458], p = 0.035) was the only predictor of active renin concentration in the studied children. We concluded that active renin concentration is positively associated with blood pressure and potassium in children, and diastolic blood pressure was the strongest predictor of renin level. Patients with isolated systolic hypertension may differ from patients with systolic-diastolic hypertension in less severe activation of the renin-angiotensin-aldosterone system.

Serum and urine periostin and cytokeratin-18 in children with congenital obstructive nephropathy.

Congenital obstructive nephropathy (CON) is one of the most common causes of chronic kidney disease in children. The aim of the study was to investigate serum and urine periostin and cytokeratin-18 (CK-18) in children with CON in relation to CON etiology, treatment, and kidney injury. We evaluated 81 children with CON secondary to ureteropelvic junction obstruction (UPJO), ureterovesical junction obstruction (UVJO), posterior urethral valves (PUV) and 60 controls. Neither biomarker demonstrated any relation to CON etiology. However, all patients showed significantly higher urine periostin (uPeriostin) and uPeriostin/Cr levels than the controls. Also, UVJO patients showed higher sCK-18 and uCK-18/Cr levels, and PUV patients showed higher uCK-18/Cr levels than the controls. Neither biomarker was found to have any relation to CON treatment. However, conservatively treated children and those before and after surgery showed significantly higher uPeriostin and uPeriostin/Cr levels than the controls. uPeriostin strongly correlated with differential renal function (DRF) < 40%. The ROC analysis demonstrated the best area under the curve (AUC) for uPeriostin (0.831) and uPeriostin/Cr (0.768), and low for sPeriostin (0.656) and uCK-18 (0.615) for detecting renal injury. In conclusion, although serum and urine periostin and CK-18 did not display any relation to etiology or the type of CON treatment, uPeriostin seems to be a useful tool for detecting renal injury in children with CON, especially due to its strong negative correlation with DRF < 40%.

The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study.

This study aimed to evaluate the usefulness of vanin-1 and periostin in urine as markers of the autoimmune process in kidneys and renal fibrosis in IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). From a group of 194 patients from the Department of Pediatrics and Nephrology, who were included in the Polish Pediatric Registry of IgAN and IgAVN, we qualified 51 patients (20 with IgAN and 31 with IgAVN) between the ages of 3 and 17, diagnosed based on kidney biopsy, for inclusion in the study. All of the patients received glucocorticosteroids, immunosuppressive drugs, or renoprotective therapy. The control group consisted of 18 healthy individuals. The concentration of vanin was significantly higher in the IgAN and IgAVN groups than in the control group. The concentration of vanin/creatinine correlates positively with the level of IgA and negatively with the serum level of C3 at the end of the observation. Urinary vanin-1 concentration may be useful as a marker of the active autoimmune process in IgAN and IgAVN in children, but the study needs confirmation on a larger group of children, along with evaluation of the dynamics of this marker. Urinary periostin is not a good marker for children with IgAN and IgAVN, especially in stage 1 and 2 CKD.

Burnout Syndrome among Pediatric Nephrologists-Report on Its Prevalence, Severity, and Predisposing Factors.

BACKGROUND AND OBJECTIVES: Burnout is an occupation-related syndrome comprising emotional exhaustion, depersonalization, and reduced feelings of work-related personal accomplishments. There are reports on burnout among adult nephrologists and general pediatricians, but little is known about burnout among pediatric nephrologists. The aim of our study was to assess the prevalence and severity of burnout syndrome among Polish pediatric nephrologists. MATERIALS AND METHODS: A 25-item study survey consisting of abbreviated Maslach Burnout Inventory and additional self-created questions about work-related factors was completed by 97 physicians affiliated with the Polish Society of Pediatric Nephrology. Women comprised 75.3%, with median time of professional experience in the study group was 15 years. RESULTS: A high level of emotional exhaustion, depersonalization, and reduced feeling of personal accomplishments were observed in 39.2%, 38.1%, and 21.6% of the participants, respectively. At least a medium level of burnout in all three dimensions were observed in 26.8% of the participants and 8.2% of them presented high three-dimensional burnout. About 41.2% of the participants stated that they would like to take part in burnout prevention and support programs. According to the study participants, excessive bureaucracy in healthcare systems, rush at work, and overtime work were the main job-related problems that could influence burnout intensity. CONCLUSIONS: Burnout is an important factor in the professional landscape of pediatric nephrology. Actions aimed at reducing the risk of occupational burnout among pediatric nephrologists should be applied, both at the personal and institutional levels.

Developmental Abnormalities of Teeth in Children With Nephrotic Syndrome.

INTRODUCTION: Treatment with glucocorticoids in children with nephrotic syndrome can be the cause of developmental disorders of the masticatory organ and bone or teeth abnormalities. The aim was to assess the frequency and type of dental abnormalities and the correlation of their occurrence with a dosage of glucocorticoids and treatment time in children with idiopathic nephrotic syndrome. METHODS: The study group consisted of 31 patients aged 5 to 17 diagnosed with idiopathic steroid-sensitive nephrotic syndrome and 33 overall healthy children. The studies included clinical evaluation of dentition, radiologic diagnostics, and statistical analysis. RESULTS: In the study group, 77.4% of patients were diagnosed with abnormalities in dental development. Tooth number disorders, presence of persistent deciduous teeth and impacted teeth, abnormal crown or root shape, developmental defects of enamel, pulp stones, and bone structure disorders were identified. Statistical analysis showed significant differences in the average treatment time of glucocorticoids in patients without and with tooth developmental abnormalities. CONCLUSIONS: Long-term use of glucocorticoids in children with nephrotic syndrome promotes the occurrence of developmental abnormalities of the teeth, calcification of the pulp, and disorders of bone tissue metabolism. For this reason, patients with steroid-sensitive nephrotic syndrome should be under the constant care of a dentist.

24-hour central blood pressure and immune system activation in adolescents with primary hypertension - a preliminary study.

Introduction: Adult and pediatric data suggest a positive relationship between the extent of subclinical inflammation, blood pressure, and hypertension-mediated organ damage (HMOD) in primary hypertension (PH). 24-hour (24-h) ambulatory blood pressure (ABPM) and central blood pressure (CBP) are strong predictors of HMOD. Our study aimed to analyze the relationship between 24-h central ABPM, subclinical inflammation, and clinical data in adolescents with PH. Material and methods: In 28 untreated adolescents with PH (14.50 ±2.27 years) and 25 healthy peers (14.76 ±2.83 years), we analyzed 24-h peripheral and central ABPM, markers of subclinical inflammation (neutrophil-to-lymphocyte ratio - NLR, platelet-to-lymphocyte ratio - PLR, mean platelet volume - MPV), and clinical and biochemical data. Results: Patients with PH had higher 24-h peripheral and central blood pressure than healthy peers. In all 53 patients, we found significant (p < 0.05) positive correlations between NLR, PLR and 24-h central systolic, diastolic, and mean blood pressure (24-h cSBP, 24-h cDBP, 24-h cMAP), between 24-h central augmentation index corrected for heart rate 75 (24-h cAIx75HR) and platelet count. In 28 patients with PH, 24-h cAIx75HR correlated with low-density lipoprotein (LDL) cholesterol (R = 0.442), and ambulatory arterial stiffness index with body mass index (BMI) (R = 0.487), uric acid (R = 0.430), and high-density lipoprotein (HDL) cholesterol (R = -0.428). Conclusions: Increased central 24-h blood pressure may be associated with immune system activation in adolescents with primary hypertension. In adolescents with primary hypertension, dyslipidemia and hyperuricemia are risk factors for increased arterial stiffness. Further studies on central and peripheral blood pressure in terms of their relationship with inflammation in these patients are needed.

Early Vascular Aging in Children With Tuberous Sclerosis Complex.

Objectives: Experimental data indicate that activating mutations in the mTOR (mammalian target of rapamycin) pathway may lead to abnormal arterial wall structure. Vascular anomalies like arterial stenoses are reported in pediatric patients with tuberous sclerosis complex (TSC). In addition, large renal lesions (angiomyolipoma-AML and cysts) are risk factors for arterial hypertension in adult patients with TSC. This study aimed to assess blood pressure, including central blood pressure and arterial damage (early vascular aging-EVA) in children with TSC. Materials and Methods: In a group of 33 pediatric patients with TSC (11.13 ± 4.03 years, 15 boys, 18 girls), we evaluated peripheral and central office blood pressure, 24-h ambulatory blood pressure, and arterial damage: aortic pulse wave velocity (aPWV) [m/s], [Z-score], augmentation index (AIx75HR [%]), common carotid artery intima-media thickness (cIMT) [mm], [Z-score], stiffness of common carotid artery (E-tracking), renal lesions in magnetic resonance and ultrasonography, and selected biochemical parameters. The control group consisted of 33 healthy children (11.23 ± 3.28 years, 15 boys, 18 girls). Results: In TSC group 7 (21.2%) children had arterial hypertension, 27 (81.8%) children had renal angiomyolipomas, 26 (78.8%)-renal cysts, and 4 (12.1%) patients were treated with mTOR inhibitors (2 patients with everolimus and 2 patients with sirolimus) at the moment of evaluation. Children with TSC had higher central systolic blood pressure (AoSBP) (98.63 ± 9.65 vs. 90.45 ± 6.87 [mm Hg], p < 0.001), cIMT (0.42 ± 0.05 vs. 0.39 ± 0.03 [mm], p = 0.011), cIMT Z-score (0.81 ± 1.21 vs. 0.16 ± 0.57, p = 0.007), aPWV (4.78 ± 0.81 vs. 4.25 ± 0.56 [m/s], p = 0.003) and aPWV Z-score (-0.14 ± 1.15 vs. -0.96 ± 0.87, p = 0.002) compared to healthy children, without differences in AIx75HR (8.71 ± 15.90 vs. 5.24 ± 11.12 [%], p = 0.319) and stiffness of common carotid artery. In children with TSC AoSBP correlated positively with serum cystatin C concentration (r = 0.377, p = 0.030) and with maximum diameter of renal cyst (R = 0.419, p = 0.033); mean arterial pressure (MAP) 24 h Z-score correlated with serum cystatin C concentration (R = 0.433, p = 0.013); and aPWV Z-score with daily urinary albumin loss [mg/24 h] (R = 0.412, p = 0.029). Conclusions: Children with tuberous sclerosis complex are at risk of elevated central blood pressure and early vascular aging. In children with TSC, blood pressure and arterial stiffness are related to renal involvement.

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.

Arterial stiffness in children with primary hypertension is related to subclinical inflammation.

INTRODUCTION: The immune system can trigger an inflammatory process leading to blood pressure elevation and arterial damage. The aim of the study was to assess the relation between subclinical inflammation and arterial damage in pediatric patients with primary hypertension (PH) and to establish the usefulness of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios, and mean platelet volume (MPV) as markers of arterial damage in these subjects. MATERIAL AND METHODS: In 119 children with PH (14.94 ±2.76 years) and 45 healthy children (14.91 ±2.69 years) we analyzed markers of subclinical inflammation (NLR, PLR, MPV), clinical and biochemical parameters, office blood pressure, ambulatory blood pressure monitoring (ABPM), central blood pressure, aortic pulse wave velocity (aPWV), augmentation index corrected for heart rates 75 (AIx75HR), carotid intima media thickness (cIMT), and common carotid artery stiffness (E-tracking). RESULTS: Children with PH were characterized by significantly higher neutrophil (3.9 ±1.7 vs. 3.0 ±1.0 [1000/µl], p < 0.001) and platelet counts (271.9 ±62.3 vs. 250.3 ±60.3 [1000/µl], p = 0.047), NLR (1.9 ±1.5 vs. 1.3 ±0.4, p = 0.010), PLR (131.4 ±41.9 vs. 114.7 ±37.6, p = 0.020), aPWV (5.36 ±0.88 vs. 4.88 ±0.92 m/s, p = 0.004), and cIMT (0.46 ±0.07 vs. 0.43 ±0.07 mm, p = 0.002) compared to healthy children. In PH children NLR correlated positively (p < 0.05) with: systolic, diastolic and mean blood pressure in ABPM (r = 0.243, r = 0.216, r = 0.251), aPWV [m/s] (r = 0.241), aPWV Z-score (r = 0.204), and common carotid artery PWVbeta [m/s] (r = 0.202). CONCLUSIONS: There is a link between arterial stiffness and subclinical inflammation in pediatric patients with primary hypertension. Neutrophil-to-lymphocyte ratio may serve as a promising marker of arterial stiffness in pediatric patients affected by primary hypertension.

Treatment of idiopathic nephrotic syndrome with two steroid dosing regimens - one-year observational study.

INTRODUCTION: The aim of the study was to compare the first year of disease in children with idiopathic nephrotic syndrome (INS) treated according to two prednisone dosing regimens: a weight-based schedule (2 mg/kg/24 h in the 1st month, 2 mg/kg/48 h in the 2nd month, with dose tapering during the following 4 months), and a body surface area (BSA)-based schedule (60 mg/m2/24 h in the 1st month, 40 mg/m2/48 h in the 2nd month, with dose tapering during the following 4 months). MATERIAL AND METHODS: In 2 groups of children treated with weight- and BSA-based regimens (20 patients, 3.13 ±1.01 years, treated in 2010-2013 and 20 patients, 5.13 ±2.86 years, treated in 2014-2016) clinical and anthropometrical parameters, number of INS relapses, total prednisone dose (mg/kg/year), and steroid adverse effects were compared during the first year of disease. RESULTS: Children treated with the weight-based steroid regimen received a higher total annual prednisone dose (259.06 ±79.54 vs. 185.83 ±72.67 mg/kg/24 h, p = 0.004) and had a shorter (though not significantly) period without prednisone (38.25 ±55.83 vs. 75.90 ±73.06 days, p = 0.062) compared to patients treated with the BSA-based regimen. There was no difference in number of relapses between groups (2.20 ±1.64 vs. 1.60 ±1.67, p = 0.190) but more patients relapsed in the weight-based group (19/20 vs. 13/20, p = 0.044). No differences in Z-score values of height, weight, and body mass index (BMI) were observed. No steroid-related adverse events were noted except for arterial hypertension (4/20 vs. 5/20 patients, p = 1.000). CONCLUSIONS: The BSA-based regimen of prednisone dosing in children with INS reduces exposure to steroids and risk of relapse, as well as increases days off steroids in the first year compared to the weight-based regimen with a high second-month dose.

The Usefulness of Urinary Periostin, Cytokeratin-18, and Endoglin for Diagnosing Renal Fibrosis in Children with Congenital Obstructive Nephropathy.

Congenital obstructive nephropathy (CON) leads to renal fibrosis and chronic kidney disease. The aim of the study was to investigate the predictive value of urinary endoglin, periostin, cytokeratin-18, and transforming growth factor-ß1 (TGF-ß1) for assessing the severity of renal fibrosis in 81 children with CON and 60 controls. Children were divided into three subgroups: severe, moderate scars, and borderline lesions based on 99mTc-ethylenedicysteine scintigraphy results. Periostin, periostin/Cr, and cytokeratin-18 levels were significantly higher in the study group compared to the controls. Children with severe scars had significantly higher urinary periostin/Cr levels than those with borderline lesions. In multivariate analysis, only periostin and cytokeratin-18 were independently related to the presence of severe and moderate scars, and periostin was independently related to borderline lesions. However, periostin did not differentiate advanced scars from borderline lesions. In ROC analysis, periostin and periostin/Cr demonstrated better diagnostic profiles for detection of advanced scars than TGF-ß1 and cytokeratin-18 (AUC 0.849; 0.810 vs. 0.630; 0.611, respectively) and periostin for detecting borderline lesions than endoglin and periostin/Cr (AUC 0.777 vs. 0.661; 0.658, respectively). In conclusion, periostin seems to be a promising, non-invasive marker for assessing renal fibrosis in children with CON. CK-18 and TGF-ß1 demonstrated low utility, and endoglin was not useful for diagnosing advanced scars.

IgA vasculitis nephritis clinical course and kidney biopsy - national study in children.

The aim of the study was to investigate the relationship between the severity of typical clinical symptoms, severity of histopathological lesions in kidney biopsies in IgA vasculitis nephritis (IgAVN) and to propose indications for kidney biopsy in children. MATERIAL AND METHODS: This retrospective study enrolled 106 patients, included in the IgAVN registry of Polish children, diagnosed by kidney biopsy. Renal and extrarenal symptoms at onset of the disease were analyzed. Biopsy results were assessed using Oxford classifications (MEST-C). The patients were divided into 3 groups depending on the severity of proteinuria: A-nephrotic proteinuria with hematuria; B-non-nephrotic proteinuria with hematuria; C-isolated hematuria. RESULTS: The first symptoms of nephropathy were observed at the 0.7 (1-128.4) months from the onset of extrarenal symptoms. Kidney biopsy was performed on 39 (6-782) days after the onset of nephropathy symptoms. MEST-C score 4 or 5 was significantly more frequent in children from group A than in groups B and C. Significantly higher mean MEST-C score was found in patients with abdominal symptoms than without. In group A: S0 and T0 we found in significantly shorter time to kidney biopsy than in S1, T1-2 p < 0.05) and in group B the significantly shorter time in T0 compare to T1-2 p < 0.05). The ROC analysis shows that S1 changes appear in kidney biopsies in group A with cut off 21 days (AUC 0,702, p = 0.004, sensitivity 0.895 specificity 0.444) T1-2 changes after 35 days (AUC 0.685, p = 0.022, sensitivity 0.750, specificity 0.615), and in goupn B T1-2 cut off is 74 days (AUC 0,738, p = 0.002, sensitivity 0.667, specificity 0.833). CONCLUSIONS: In childhood IgAVN, the severity of changes in the urine is clearly reflected in the result of a kidney biopsy. The biopsy should be performed in patients with nephrotic proteinuria no later than 3 weeks after the onset of this symptom in order to promptly apply appropriate treatment and prevent disease progression. Accompanying abdominal symptoms predispose to higher MESTC score.