Beata Leszczyńska

Background: Pierson syndrome (PS) is a rare, genetically determined primary glomerulopathy characterized by hereditary nephrotic syndrome, early-onset chronic kidney disease (CKD), and a spectrum of ocular defects including microcoria. Neurological deficits may also be present. Case Report: We present the case of a 15-year-old girl in whom proteinuria and hematuria were first detected at 2 months of age. During the first year of life, proteinuria was sub-nephrotic, without edema, and with preserved urine output. Nephrotic-range proteinuria, hypoalbuminemia, and hypercholesterolemia were subsequently documented after referral to a tertiary nephrology center at 13 months of age. A renal biopsy at 14 months showed minimal-change disease with negative immunofluorescence. Full-dose glucocorticoids were initiated. Due to a lack of remission, cyclosporine A was added; after one year, it was discontinued because of nephrotoxicity. From age 4 onward, the patient received only renoprotective therapy. Hypertension was treated with amlodipine. Severe myopia was diagnosed during the preschool years, followed by the development of peripheral degenerative retinal changes in subsequent years. Genetic testing revealed a point variant c.173G>A and a large deletion of exons 5–17 of the LAMB2 gene. The results point compellingly to the diagnosis of PS. The patient subsequently progressed to end-stage kidney disease and underwent deceased-donor kidney transplantation at 15 years and 3 months of age with standard triple immunosuppression (tacrolimus, glucocorticoids, and mycophenolate mofetil). Conclusions: LAMB2-associated nephropathy should be considered in children with early-onset glomerular proteinuria accompanied by ocular abnormalities, even in the absence of microcoria. Comprehensive genetic testing, including CNV analysis when initial sequencing identifies only one potentially causative variant, may establish the diagnosis and help avoid prolonged empirical immunosuppression in patients with genetically mediated steroid-resistant nephrotic syndrome.

Background/Objectives: Hemolytic uremic syndrome (HUS) is a known cause of acute kidney injury in children, but there are few recent reports on its epidemiology and outcome. We aimed to investigate trends in the incidence and the long-term outcomes of both Shiga toxin-producing Escherichia coli -HUS (STEC-HUS) and atypical HUS (aHUS) in Poland over the last 12 years (2012—2023), based on the Polish Pediatric HUS and Pediatric Renal Replacement Therapy (RRT) Registries. Methods: A total of 436 patients (301 with STEC-HUS and 135 with aHUS) were included. Results: The incidence of STEC-HUS increased during the observation period, with a mean of 3.9 cases per million age-related population (marp). The incidence of aHUS was relatively constant with a mean of 1.8/marp. The majority of patients fully recovered, although kidney sequelae were observed at 5-year follow-ups in 31% of children with STEC-HUS, 57% of aHUS subjects in the pre-eculizumab era, and 37% of aHUS subjects who had received eculizumab. The overall mortality rate was 2% for STEC-HUS and 3.7% for aHUS, with no deaths reported in children on eculizumab and mortality mainly attributed to neurological damage. A decreasing incidence of chronic kidney disease stage 5 (CKD5) due to HUS was observed. Conclusions: Despite an unchanging incidence of aHUS and an increasing incidence of STEC-HUS, the kidney outcomes of both diseases have improved significantly over the last 12 years. Mortality from HUS has dropped due to improved symptomatic treatment and the introduction of anti-C5 therapy. The development of CKD5 in childhood as a consequence of HUS has become exceptional.

Introduction: Netrin-1 (NTN-1) is an anti-inflammatory protein secreted by proximal tubule epithelial cells in reaction to hypoxic or toxic injury. We determined the utility of urinary NTN-1 as an early marker for detecting AKI in patients after cardiac surgery.Material and methods: Our study included 40 children at age 1-36 months and 20 healthy controls. We measured serum creatinine and urinary NTN-1 in patients, who underwent cardiac surgery in cardiopulmonary bypass (CPB).Results: Urinary NTN-1 was higher in the study group than in the control group. The detection ratio of urinary NTN-1 was higher pre-surgery than 6 and 24 hours after (55%, 27.5%, and 32.5%, respectively). We found no correlations between NTN-1 at any point ΔeGFR, decline eGFR, AKI after 48 h. The initial NTN-1/creatinine ratio negatively correlated with ΔGFR (r=-0.36, p=0.031), NTN-1/creatinine ratio after 24 h did not correlate with aortic clamping time, CPB time, ΔGFR. In our study, AKI occurred in 12.5% of patients and none required RRT. The occurrence of AKI correlated with CPB time (r=0.35, p=0.027) and aortic clamping time (r=0.44, p=0.005). NTN-1 concentration and NTN-1/creatinine ratio in the AKI group were not significantly higher preoperatively and 24 hours post-surgery than in patients without AKI.Conclusions: The role of urinary NTN-1 in children after cardiac surgery as an early marker of AKI was not confirmed. No factors affecting the NTN-1/creatinine ratio were found in the study group. Patients who have longer CPB time and aortic clamping time belong to the high-risk group of AKI after surgery.

Shiga toxin-producing Escherichia coli (STEC) are zoonotic pathogens causing hemorrhagic colitis and hemolytic uremic syndrome (HUS) in children and the elderly. Stool samples were collected from 180 children hospitalized in five pediatric centers in Poland in 2018–2022. Direct stx1 / stx2 gene detection by PCR in feces and E. coli isolates was performed. Antibiotic susceptibility was tested according to EUCAST v.12. Randomly selected isolates were serotyped with O157 antiserum and genotyped by pulsed-field gel electrophoresis (PFGE). A total of 44 E. coli isolates were confirmed as STEC by PCR. Among them, 84.4% were positive for stx2 , and equally 6,8% for only stx1 and both stx1 and stx2 genes. The stx1 gene was also found in one Citrobacter freundii isolate. E. coli serotype O157 was present in 97.6% of the isolates. STEC infections most often occurred between June-October with a peak in July and August (51%). The highest, 77.8% of STEC isolates were found in the 1–5 years old group. No extended-spectrum β-lactamases (ESBL) were found. Resistance only to amoxicillin/clavulanic acid (24.4%), piperacillin/tazobactam (3%), cefotaxime (6%), gentamicin (6%), ciprofloxacin (3%), azithromycin (3%), trimethoprim/sulfamethoxazole (24,2%) was detected. PFGE analysis showed 18 PFGE types with no clonal distribution. Eight isolates with A, B, and C PFGE types showed genetic relatedness in the type with no detection of transmission way of distribution. STEC strains pose a serious threat to human health, therefore demographic and epidemiological characteristics are crucial for their surveillance.

Background. Children with chronic kidney disease (CKD) experience a lot of mental and emotional stress, which can lead to the development of depressive disorders. The prevalence of depressive disorders in CKD children is estimated to be between 7% and 35%. Objectives. The aim of our study was to analyze the prevalence and characteristics of depression and depressive symptoms in children and adolescents with CKD treated conservatively.Materials and methods. The crosssectional, multicenter study was conducted in 73 CKD children aged 8-18 and in 92 of their parents. To assess the mental wellbeing of CKD children, Kovacs's Children's Depression Inventory 2 (CDI2) was used as CDI2: SelfReport and CDI2: Parent Form.Results. The majority of CKD children acquired medium scores in CDI2, 11% of participants reported symptoms suggesting depressive disorder, and among them 8.2% met the criteria for depression. A significant relationship was found between age and interpersonal problems, age at CKD diagnosis, and total score and ineffectiveness, CKD duration and total score/emotional problems. Depressive symptoms were associated with the stage of CKD, and they differed significantly between stages III and IV. We noticed the child-parent disagreement on reported depressive symptoms. Parents perceive their children's mental state as worse than the children themselves. Conclusions. There is a problem of depression in children with CKD treated conservatively. Variables associated with depressive symptoms in CKD children treated conservatively require further study. Key factors predisposing to the development of depression seem to be age at the time of diagnosis, disease duration, and progression of CKD from stage III to IV. Disparities between depressive symptoms self-reported by CKD children and their parents' assessment require further analysis. However, these disparaties indicate that the final diagnosis of the occurrence of depressive disorders should be based on a multidimensional assessment of the patient's situation.

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 range—IQR: 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.

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.

Atypical hemolytic uremic syndrome (aHUS) is a rare disease triggered by dysregulation of the alternative complement pathway, consisting of a characteristic triad of nonimmune hemolytic anemia, thrombocytopenia, and renal failure. The risk of aHUS onset, recurrence, and allograft loss depends on the genetic background of a patient. We show a series of cases from a single family whose five members were affected by aHUS and presented distinct clinical outcomes. Next-generation sequencing revealed combined mutations in both complement factor H and membrane cofactor protein CD46. Out of eight siblings, aHUS affected three adult brothers, and, subsequently, affected two children of an unaffected sister. The first patient died due to aHUS, and two other brothers underwent successful kidney transplantation with no aHUS recurrence. The younger, 10-month-old child presented with a severe course of the disease with cardiac involvement and persistent hemolytic anemia limited by eculizumab, while the 2-year-old recovered completely on eculizumab. The study shows a highly variable disease penetrance.

Introduction: GDIgA1 (galactose deficient IgA1) plays a significant role in the pathogenesis of IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSN) Aim and 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).

INTRODUCTION AND AIMS: Children with idiopathic nephrotic syndrome (NS) treated with high doses of glucocorticoids (GCs) have increased apetite and are overweight. Changes in serum levels of leptin, ghrelin and obestatin - peptides regulating apetite, may influence severity of obesity. The aim of the study was to evaluate the serum concentrations of leptin, ghrelin and obestatin in children with nephrotic syndrome.