Insight into the Interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in IgA Vasculitis (IgAV).

The pathogenesis of IgAV, the most common systemic vasculitis in childhood, appears to be complex and requires further elucidation. We aimed to investigate the potential role of galactose-deficient immunoglobulin A1 (Gd-IgA1), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE) and protocadherin 1 (PCDH1) in the pathogenesis of IgAV. Our prospective study enrolled 86 patients with IgAV and 70 controls. HMGB1, RAGE, Gd-IgA1 and PCDH1 in serum and urine were determined by the enzyme-linked immunosorbent assay (ELISA) method at the onset of the disease and after a six-month interval in patients and once in the control group. Serum concentrations of HMGB1, RAGE and PCDH1 and urinary concentrations of HMGB1, RAGE, Gd-IgA1 and PCDH1 were significantly higher in patients with IgAV than in the control group (p < 0.001). Concentrations of HMGB1 (5573 pg/mL vs. 3477 pg/mL vs. 1088 pg/mL, p < 0.001) and RAGE (309 pg/mL vs. 302.4 pg/mL vs. 201.3 pg/mL, p = 0.012) in the serum of patients remained significantly elevated when the disease onset was compared with the six-month follow-up interval, and thus could be a potential marker of disease activity. Urinary concentration of HMGB1 measured in the follow-up period was higher in patients with nephritis compared to IgAV without nephritis (270.9 (146.7-542.7) ng/mmol vs. 133.2 (85.9-318.6) ng/mmol, p = 0.049) and significantly positively correlated with the urine albumine to creatinine ratio (τ = 0.184, p < 0.05), the number of erythrocytes in urine samples (τ = 0.193, p < 0.05) and with the outcome of nephritis (τ = 0.287, p < 0.05); therefore, HMGB1 could be a potential tool for monitoring patients with IgAV who develop nephritis. Taken together, our results imply a possible interplay of Gd-IgA1, HMGB1, RAGE and PCDH1 in the development of IgAV. The identification of sensitive biomarkers in IgAV may provide disease prevention and future therapeutics.

Association of Glutathione Transferase M1, T1, P1 and A1 Gene Polymorphism and Susceptibility to IgA Vasculitis.

Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.

The Rationale of Complement Blockade of the MCPggaac Haplotype following Atypical Hemolytic Uremic Syndrome of Three Southeastern European Countries with a Literature Review.

We present eight cases of the homozygous MCPggaac haplotype, which is considered to increase the likelihood and severity of atypical hemolytic uremic syndrome (aHUS), especially in combination with additional risk aHUS mutations. Complement blockade (CBT) was applied at a median age of 92 months (IQR 36-252 months). The median number of relapses before CBT initiation (Eculizumab) was two. Relapses occurred within an average of 22.16 months (median 17.5, minimum 8 months, and maximum 48 months) from the first subsequent onset of the disease (6/8 patients). All cases were treated with PI/PEX, and rarely with renal replacement therapy (RRT). When complement blockade was applied, children had no further disease relapses. Children with MCPggaac haplotype with/without additional gene mutations can achieve remission through renal replacement therapy without an immediate need for complement blockade. If relapse of aHUS occurs soon after disease onset or relapses are repeated frequently, a permanent complement blockade is required. However, the duration of such a blockade remains uncertain. If complement inhibition is not applied within 4-5 relapses, proteinuria and chronic renal failure will eventually occur.

The visibility of the periventricular crossroads of pathways in preterm infants as a predictor of neurological outcome and occurrence of neonatal epileptic seizures.

AIM: To evaluate the relationship between the neurological outcome, neonatal epileptic seizures, and signal-intensity visibility of the frontal and parietal periventricular crossroads of pathways on brain magnetic resonance imaging (MRI) in preterm infants at term-equivalent age. METHODS: The study enrolled 48 preterm infants born between 2012 and 2016. The signal-intensity characteristics of the frontal and parietal periventricular crossroads were evaluated and classified into four grades. A non-favorable outcome was defined as a motor and functional disorder with developmental delay and/or cerebral palsy. RESULTS: Neonatal seizures, epilepsy, pathological EEG and brain ultrasound finding, and brain MRI abnormalities were mostly found in neonates with non-favorable outcomes. Visible frontal and parietal periventricular crossroads were associated with a normal neurologic outcome (P=0.0004; P=0.0009, respectively). Not-visible or slightly visible periventricular crossroads were associated with non-favorable outcomes in the case of frontal crossroads (P=0.036) and not-visible periventricular crossroads in the case of both frontal and parietal crossroads (P=0.001, P=0.015, respectively). The visibility of the frontal and parietal periventricular crossroads was associated with a lack of neonatal epileptic seizures (P=0.03; P=0.02, respectively). The frontal crossroads were more frequently slightly visible, while the parietal periventricular crossroads were more frequently visible. CONCLUSION: Poor visibility of the frontal and parietal crossroads of pathways on MRI is associated with neonatal epileptic seizures and poor neurological outcomes in preterm infants at term-equivalent age.

A CHILD WITH DENSE DEPOSIT DISEASE AND DECREASED CLASSIC COMPLEMENT PATHWAY ACTIVITY.

We report a rare case of nephritic syndrome underlying dense deposit disease (DDD) with alternative complement pathway dysfunction explained with both C3 nephritic factor (C3NeF) antibodies and DDD associated polymorphism of factor H. An 8-year-old boy presented with macroscopic hematuria, hypertension and periorbital edema followed by persistently low C3 during the 8-week follow-up. Positive C3 staining on immunofluorescence microscopy, supported by dense deposits within the glomerular basement membrane on electron microscopy, confirmed the diagnosis of DDD. Preliminary tests for complement activation showed decreased classic pathway and deficient alternative complement pathway, as well as slightly positive C3NeF, supporting the diagnosis of DDD. Genetic analysis revealed a polymorphism of the complement factor H gene with an increased risk of developing DDD. Supportive therapy led to satisfactory recovery of renal function and normalization of C3. Given the poor prognosis of the disease, proper approach to such specific glomerulopathy is important to avoid or at least slow down progression to end-stage renal disease.

Genotype-phenotype Correlation of ß-Thalassemia in Croatian Patients: A Specific HBB Gene Mutations.

An analysis of genotype-phenotype correlation was performed for 14 patients with beta-thalassemia who had been registered in Referral Centre for hematology and oncology of the University Hospital Centre, Zagreb, Croatia. HBB gene mutations were determined using a gene-specific Q5 High-Fidelity PCR analysis with direct DNA sequencing of amplified transcripts. Mahidol score index used for classification of thalassemia severity was found to be low for all the patients enrolled in the study, indicating a mild ß-thalassemia phenotype with no signs of disease progression. Most of the patients have already described gene mutations: IVS-II-666 C>T (HBB:c.316-185C>T) and IVS-II-16 G>C (HBB:c.315+16G>C). Each of the aforementioned mutations was found in (11/14; 78,57%) and (10/14; 71,43%) of our patients, respectively. Recently published HBB:c.9T>C mutation was found in 8 of 14 (57,14%) in our study group. IVSII-74 T>G (HBB:c.315+74T>G) is a worldwide mutation found in 6 of 14 (42.86%) of our patients. All these mutations occur among Croatian children with no obvious Indian/Near Eastern/Iranian ancestry. We also identified 7 de novo mutations (c.316-135het_dupT, c.316-133A>G, c.93-54G>A, c.316-68_316-67het_insCGG, c.316-342delA, c.316-312delT, c.316-209delT) of mild severity phenotype according to Mahidol classification score index. We did not find children or adults with thalassemia major severity phenotype.

Calcium oxalate urolithiasis in children: urinary promoters/inhibitors and role of their ratios.

Diagnostic criteria for determination of inclination towards idiopathic calcium oxalate (CaOx) urolithiasis based on biochemical urine parameters are not sufficiently well defined in children. The aim of this study was to determine the risk of CaOx urolithiasis in children from concentrations of calcium, oxalate, citrate, and glycosaminoglycans in urine and their ratios, all standardized in respect to creatinine. We collected and analyzed 24-h urine samples of children with CaOx urolithiasis (n = 61) and compared with urine samples of matched control group of healthy children (n = 25). The study has showed that all stone formers have higher excretion of calcium (mmol/mmol creatinine), calcium/citrate (mol/mmol), and oxalate/(citrate × glycosaminoglycans) ratio (mol Ox × mol cr)/(mol Cit × g GAGs). ROC analysis of these variables gave criteria (>0.28, >1.07, and >0.08, respectively) for distinguishing stone formers from healthy children. Biochemical urine parameters and their ratios (calcium, calcium citrate, and oxalate/(citrate × glycosaminoglycans) enable one to discriminate idiopathic calcium oxalate stone formers from healthy children. Oxalate/(citrate × glycosaminoglycans) ratio per se can serve as an independent risk for stone formation. CONCLUSION: Using biochemical urine parameters and their ratios such as calcium, calcium/citrate, and oxalate/(citrate × glycosaminoglycans) enables one to determine diagnostic criteria towards idiopathic calcium oxalate urolithiasis in children. What is known: • The role of urine calcium as a promoter in calcium oxalate urolithiasis is well established. • Seldom used calcium/citrate ratio is acknowledged as a risk factor for calcium/oxalate urolithiasis. What is new: • The values of calcium and citrate in clinically and genetically proven idiopathic calcium oxalate urolithiasis make calcium/citrate ratio useful for diagnostic purposes in such stone formers. • Rarely used calcium independent oxalate/(citrate x glycosaminoglycans) ratio serves as the second best high specificity marker for idiopathic calcium oxalate urolithiasis.

Rational Therapy of Urinary Tract Infections in Children in Croatia

Resistance to chemotherapeutics used in the treatment of urinary tract infection is increasing throughout the world. Taking into account clinical experiences, as well as current bacterial resistance in Croatia and neighboring countries, the selection of antibiotic should be the optimal one. Treatment of urinary tract infection in children is particularly demanding due to their age and inclination to severe systemic reaction and renal scarring. If parenteral antibiotics are administered initially, it should be switched to oral medication as soon as possible. Financial aspects of antimicrobial therapy are also very important with the main goal to seek the optimal cost/benefit ratio. Financial orientation must appreciate the basic primum non nocere as a conditio sine qua non postulate as well.

Demographic characteristics and metabolic risk factors in Croatian children with urolithiasis.

The aim of this study was to assess demographic data, clinical presentation, metabolic features, and treatment in 76 children with urolithiasis presented from 2002 to 2011. Urolithiasis is responsible for 2.5/1,000 pediatric hospitalizations, with new cases diagnosed in 1.1/1,000 admissions. From the observed period, two-fold rise of incidence rate was observed. Compiling the data from other pediatric institutions in our country, we estimated present overall incidence rate in Croatia as 6.5/100,000 children under 18 years. There were 41 boys and 35 girls (ratio 1.17:1). The mean age at diagnosis was 9.7 (range 0.8-16) years and follow-up duration was 5.3 (range 1.8-10) years. Renal colic (75.0 %) and hematuria (57.89 %) were the main symptoms. In 65.78 % of children, stones were unilateral. Stones were located in kidney in 52.63 %, in the ureter in 26.32 %, and in bladder in 6.58 % cases. Stone analysis showed calcium oxalate in 75.0 % of the cases. Associated urinary tract abnormalities were found in 19.73 % children. Most common metabolic disturbances were hypercalciuria (47.37 %) and idiopathic or mild hyperoxaluria (18.42 %). Urine saturation (EQUIL2) was elevated in 61.84 % cases. Spontaneous stone evacuation occurred in 51.21 % children. Extracorporeal shock wave lithotripsy, surgical evacuation, and endoscopic removal of calculi were performed in 21.0, 6.58, and 5.26 % of cases, respectively. Follow-up conservative therapy, consisting of fluid/diet recommendations and additional potassium citrate and/or chlorothiazide in children with increased risk, was sufficient for stone recurrence prevention in 92.1 % of children. In conclusion, the study gave insight in epidemiology and metabolic disturbances of urinary stone disease in Croatian children.

Renal thromboembolism during treatment with recombinant activated factor VII (rFVIIa) in a child with hemophilia B with factor IX inhibitors.

BACKGROUND: Serious thromboembolic events connected with rFVIIa therapy in hemophilia patients are rare. Only three cases are reported in children, all of them with hemophilia A. CASE PRESENTATION: We present unique case of patient with hemophilia B and high titer inhibitors to coagulation FIX, who developed severe renal damage due to thromboembolic event during rFVIIa therapy, associated with unsuspected renovascular anomalies. CONCLUSION: Caution is necessary if hematuria B requires administration of rFVIIa. US color doppler renal imaging before and after drug administration should be sufficient as an early warning.

Ultrasound distinction between simple recurrent urinary tract infections and a specific bladder wall inflammatory entity called cystitis cystica.

A specific representative of recurrent urinary tract infections (UTI) called cystitis cystica (CC) was assessed by ultrasound. The aim of the study was to delineate, by means of ultrasound measurement (US) of bladder wall thickness (BWT), the children with mere repeated UTI from those prone to frequent UTI due to CC. Two groups were compared, the control group of 30 with recurrent UTI without US CC BWT changes, and the group of 30 children with characteristic CC bladder wall thickening in whom cystoscopy was performed for verification the diagnosis of CC. BWT of > 3 mm (> 2.8 mm and > 3.3 mm) was found as cut-of value for distinction of CC versus simple recurrent UTI. US BWT measurement is useful in diagnosing CC and therefore valuable in decision about need of UTI prophylaxis.

Vesicoureteral reflux and urodynamic dysfunction.

INTRODUCTION: The concept of vesicoureteral reflux (VUR) as a consequence of congenital anomaly of vesicoureteral junction has undergone changes owing to the finding that such children may have lower urinary tract dysfunction, which produces high intravesical pressure and consequently a predisposition for VUR. PATIENTS AND METHODS: The urodynamics was investigated by pressure-flow-EMG study in 132 children with VUR and 162 refluxing units. RESULTS: Only 33 (25.0%) patients had normal urodynamic finding. The most frequent pathological finding was overactive bladder (OAB), found in 59 (44.7%) children, followed by dysfunctional voiding (DV) in 25 (18.9%) children. Children with VUR grades I and II had a higher percentage of pathological urodynamic findings than children with VUR grades III and IV. OAB was more frequent in children under 5 years of age with unilateral and lower grade VUR. It was found equally in children with and without uroinfections. DV was more frequent in children older than 5 years, with bilateral VUR, higher grade VUR and uroinfections. CONCLUSIONS: Children with VUR have a high incidence of urodynamic disorders. The results of the study indicate the possible role of urodynamic dysfunction in the pathogenesis of VUR, especially mild one.

An innovative diagnostic procedure in children: videourodynamics with contrast-enhanced voiding urosonography.

Contemporary videourodynamic (VUD) investigation combines voiding cystourethrography (VCUG) and urodynamics into one study, which allows simultaneous visualization of the urinary tract by ionizing radiation alongside the measurement of sensation, capacity, compliance, and detrusor pressure during bladder filling and voiding using one double lumen catheter. Today VUD is a benchmark for evaluating the lower urinary tract disorders in children because it evaluates urinary bladder and sphincter function and visualizes bladder morphology and vesicoureteral reflux (VUR) presence at the same time. Several previous studies of fluoroscopic videourodynamics issued concerns regarding radiation exposure. This technical report aims to describe a new modality of VUD in children by replacing fluoroscopic VCUG with contrast-enhanced voiding urosonography (ceVUS). ceVUS using second-generation contrast media and harmonic imaging is a radiation-free and highly sensitive imaging modality used to detect VUR in children. We simultaneously performed an infusion of ultrasound contrast through the double lumen urodynamic catheter during urodynamic evaluation. This article describes the advantages of this method compared with a conventional technique. In addition to being radiation-free, this procedure of advanced videourodynamics method can better detect vesicoureteral reflux and intrarenal reflux combined with urodynamic disorders associated with VUR.

Differentinating between non-transfusion dependant ß-thalassemia and iron deficinecy anemia in children using ROC and logistic regression analysis: two novel discrimination indices designed for pediatric patients.

Introduction: This cross-sectional study enrolled a group of 271 children with microcytic anemia in order to test the performance of 41 single and 2 composite formulas andindices in distinguishing between ß-thalassemia (ß-thal) and iron deficiency anemia (IDA) in the pediatric population. Methods: Optimal pediatric cut-off values from the previously published formulas and indices were generated using ROC analysis. Logistic regression in R using generalized linear models (GLM) generated two new indices. Results: Formulas and indices with optimal cut-offvalues in children with accuracy ≥90% were (in descending order): Matos & Carvalho index, MDHL(Telmissani) formula, England and Fraser formula, Pornprasert index, Sirachainan index, Telmissani (MCHD) formula, CRUISE index, Hameed index, Sargolzaie formula and Zaghloul II index. The CroThalDD-LM1 index has an accuracy of 93.36% (AUC 0.986, 95% CI 0.975-0.997), while the second CroThalDD-LM2 index utilizes absolute reticulocyte count alongside CBC variables, with an accuracy of 96.77% (AUC 0.985, 95% CI 0.988-0.999). Discussion and conclusion: We recommend using aforementioned formulas and indices with corrected cut-off values and accuracy >90% alongside two new proposed indices. A comparison of both native and these new indices is encouraged. These are the first discrimination indices generated and designed precisely for the pediatric population, which includes preschool children.

Rehabilitation approach and results of using the biofeedback method (GIGER MD device) in children with neurogenic bladder.

Background: GIGER MD device applies a biofeedback method through stimulated coordinated rhythmic and dynamic movements of the trunk and extremities in an anti-gravity position, thus helping to regain lost motor functions. Methods: In this article, the performance of the GIGER MD device was evaluated in 36 children with neurogenic bladder measuring gait speed, voiding bladder capacity, deviation from the age-adjusted bladder capacity (measured using the Koff scale), and urinary incontinence. Results: Children using the GIGER MD device had an increase in voiding bladder capacity (33.79%, median volume increase of 50 ml) with a subsequent median decrease in median age-adjusted bladder capacity by 45.50% (median deviation before was 36% vs. 16% after treatment). The number of urinary incontinence episodes also reduced by 55.57% (7-3 episodes per day), and the 20-meter motor gait speed increased by 14.26% (from 23 to 19 s). Conclusion: Children who follow the GIGER MD therapy regularly for a period of 6 months show that CNS functional damage can be significantly improved.

Case report: Autoimmune hemolytic anemia caused by warm and cold autoantibodies with complement activation-etiological and therapeutic issues.

Introduction: Research on mixed warm and cold autoantibodies in autoimmune hemolytic anemia (AIHA) targeting erythrocytes [red blood cells (RBCs)] and platelets is scarcely reported. Case presentation: In this study, we present the case of a 5-year-old boy with positive direct [anti-IgG (1+), anti-IgG-C3d (3+)], and indirect antiglobulin (Coombs) tests. The RBCs were coated with polyspecific-positive, warm IgG autoantibodies alongside activated complement components. Plasma-containing immunoglobulin M (IgM) class autoantibodies were found in 1:64 titers with a wide temperature range of 4°C-37°C. The platelets were also coated with IgM autoantibodies. There was a reduction in the levels of the classical and alternative complement pathways, such as C3, C4, ADAMTS13 metalloprotease activity, factor H antigen, complement factor B antigen, and C1q antigen alongside the elevated sC5b-9 terminal complement complex. Hematuria and/or proteinuria, reduced diuresis, and elevated levels of serum creatinine were absent. The kidney ultrasound report was normal. A recent combination of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection was found. The first-line treatment consisted of intravenous methylprednisolone [4 mg/kg/body weight for the first 72 h (q12 h), followed by 2 mg/kg body weight for 21 consecutive days with a slow steroid reduction until plasmapheresis (PLEX)]. After the patient showed limited response to corticosteroid therapy, rituximab (375 mg/m2) was administered once a week (five doses in total), with vitamins B9 and B12. These strategies also showed limited (partial) therapeutic benefits. Therefore, the treatment was switched to PLEX (five cycles in total) and intravenous immunoglobulin (IVIg) (1 g/kg/5 days). This combination significantly improved RBC count and platelet levels, and C3 and C4 levels returned to normal. A follow-up of 2.5 years after treatment showed no sign of relapse. A genetic analysis revealed a rare heterozygous intronic variation (c.600-14C > T) and heterozygous Y402H polymorphism of the CFH gene. c.600-14C > T mutation was located near the 5' end of exon 6 in the gene encoding the complement C3 protein of unknown significance. We presumed that the complement regulators in our patient were sufficient to control complement activation and that complement blockade should be reserved only for devastating, life-threatening complement-related multiorgan failure. Conclusion: We believe that EBV and CMV triggered AIHA, thus activating the complement cascade. Hence, we used corticosteroids, rituximab, vitamins B9 + B12, PLEX, and fresh frozen plasma (FFP) as treatment. Final remission was achieved with PLEX and FFP. However, an additional late effect of B12 rituximab and the disappearance of long-lived circulating plasma cells should not be completely ignored. Complement activation with a genetic background should be assessed in severe warm and cold hemolytic anemias caused by autoantibodies.

Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

Idiopathic nephrotic syndrome in children: review of 282 Croatian cases.

Recent data suggests increased incidence of focal segmental glomerulosclerosis (FSGS) among children with idiopathic nephrotic syndrome (INS). To determine the causes and possible longitudinal changes in the etiology of INS, 282 Croatian children diagnosed with INS between 1990 and 2009 were evaluated. In total, 122 children were assessed as having minimal change nephrotic syndrome (MCNS) based on their initial presentation, laboratory findings and clinical course. Kidney biopsy was performed in the remaining 160 children. MCNS was present in 18.1% of all biopsies performed. Total incidence of MCNS (assessed + biopsy proven) was only 53.5%. In contrast, FSGS was found in 40.6% of all biopsies and accounted for 23.1% of all cases. Mesangial proliferative glomerulonephritis (MesPGN) was the third most common diagnosis, present in 26.9% of the biopsies, and accounted for 15.2% of all cases. There were no significant longitudinal differences in the incidence of different causes of INS. The overall response to steroids at presentation was 71.6%. A higher proportion of initial steroid responders among children with FSGS (43.1%) and MesPGN (67.4%) than previously reported was noted. A longitudinal tendency of increasing steroid resistance in FSGS and MesPGN groups was observed.