Rituximab-associated hypogammaglobulinemia in children with idiopathic nephrotic syndrome: results of an ESPN survey.

BACKGROUND: There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS). METHODS: A survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded. RESULTS: The majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them. CONCLUSIONS: HGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

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

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

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.

Retrospective analysis of clinical and pathomorphological features of lupus nephritis in children.

PURPOSE: The aim of the study was to evaluate the clinical course and pathomorphological correlations in Polish children with the diagnosis of lupus nephritis (LN). METHODS: We retrospectively analyzed the medical records of 39 children hospitalized due to LN in 7 pediatric nephrology units in Poland between 2010 and 2019. Demographic data, clinical symptoms at the onset of LN and laboratory parameters were reviewed. We analyzed Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), histological LN findings with the activity (IA) and chronicity index (IC). RESULTS: We examined 32 girls and 7 boys, median age at LN onset was 14.75 (IQR 13.0-16.0) years, SLEDAI of 22.0 (IQR 18.0-27.0) points; LN histological class: IV (59.4%), III (18.9%), III/V (10.8%), IV/V (8.1%), VI (2.7%); IA 8.0 (IQR 6.0-11.0) points, IC 1.05 (IQR 0-2.0) points. Children with nephrotic (n â€‹= â€‹22) and non-nephrotic (n â€‹= â€‹17) proteinuria differed in median Hb level (9.55, IQR 8.3-11.2 vs 10.9, IQR 10.1-11.6 â€‹g/L; P â€‹< â€‹0.05), albumin level (2.5, IQR 2.1-3.19 vs 3.6, IQR 3.4-4.1 â€‹g/dL; P â€‹< â€‹0.001), proteinuria (5.76, IQR 3.0-7.5 vs 1.08, IQR 0.53-1.50 â€‹g/day; P â€‹< â€‹0.0001), eGFR (53.9, IQR 27.0-68.8 vs 96.7, IQR 73.8-106.2 â€‹mL/min/1.73 â€‹m2; P â€‹< â€‹0.01) and occurrence of hypertension (77% vs 23%; P â€‹< â€‹0.01). In multivariate analysis Hb level (ߠ​= â€‹8.0; 95%CI, 1.90-14.11) was the significant predictor of eGFR<90 â€‹mL/min/1.73 â€‹m2. CONCLUSIONS: Proliferative forms of LN in children may have a varying clinical presentation. Children with LN with nephrotic range proteinuria have lower Hb level, lower eGFR and higher occurrence of hypertension. Hb level is the significant predictor of eGFR<90 â€‹mL/min/1.73 â€‹m2 in children with LN.

Successful Salvage Haploidentical Alpha-Beta T Cell-Depleted Stem Cell Transplantation After Busulfan-Based Myeloablation in a Patient With IPEX Syndrome: A Case Report.

BACKGROUND: X-linked immunodysregulation syndrome with polyendocrinopathy and enteropathy (IPEX) is caused by FOXP3 gene mutations that block the generation of regulatory T lymphocytes. We report an 18-month-old boy with classic IPEX who underwent 2 hematopoietic stem cell transplantations (HSCTs). METHODS: The first HSCT from an unrelated 8/10 HLA-matched umbilical cord blood donor (UCB) was performed after a conditioning regimen consisting of treosulfan, fludarabine, thiotepa, and thymoglobulin. Due to complete rejection of the UCB transplant, a second transplantation from a 6/10 HLA-matched mother was performed after alpha-beta T-cell depletion. The second conditioning regimen consisted of busulfan, fludarabine, a single dose of cyclophosphamide 1 g/m2, and Grafalon (Neovii Pharmaceuticals, Rapperswil, Switzerland). The T-cell depletion product contained 15.06 x 106 CD34+ cells per kilogram body weight (BW) and 4.19 x 105 alpha-beta T lymphocytes per kilogram BW. Due to acute graft rejection, the boy was treated with thymoglobulin, and full donor chimerism in both T lymphocytes and mononuclear cells was achieved. The immunosuppressive therapy was stopped 1 year after transplantation. To date, the patient remains free from graft-vs-host disease (GVHD) and immunosuppression. CONCLUSIONS: HSCT after busulfan-based reduced-toxicity conditioning in patients with IPEX syndrome is feasible and well tolerated and can result in full donor engraftment. Monitoring of chimerism and aggressive therapy in cases of graft rejection are warranted due to the high reactivity of residual autologous T lymphocytes. T-cell depletion reduces the risk of GVHD and the need for steroid therapy, which is especially challenging in patients with diabetes.

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.

High efficacy of biofeedback therapy for treatment of dysfunctional voiding in children.

INTRODUCTION: Dysfunctional voiding is a frequent condition in children associated with symptoms of incontinence. The aim of this study was to present the efficacy of biofeedback treatment on the resolution of clinical symptoms in a large cohort of children with urodynamically confirmed dysfunctional voiding. MATERIAL AND METHODS: 81 children (75 girls and 6 boys) aged 6-18 years (mean: 10.32 ±3.17 yrs.) with a dysfunctional voiding pattern are presented. 74/81 (92.6%) of children were unresponsive to standard urotherapy and prior pharmacotherapy. Symptoms of bladder dysfunction were evaluated by questionnaire, bladder diary and an urodynamic study according to definitions and standards set by ICCS. The biofeedback training was planned for 2 months. Each session consisted of about 30 repeats of 5 s contraction and 30 s relaxation of pelvic floor muscles and external urethral sphincter. Biofeedback was performed together with standard urotherapy. RESULTS: 67 (82.72%) of the 81 children declared wetting during the day and 41 (50, 62%) - wetting during the night. 32/81 (39.5%) children had increased voiding frequency and 43 (53.08%) had decreased bladder capacity. Following 2 months of biofeedback therapy daytime incontinence resolved in 34/67 (50.7%) children and nighttime incontinence in 22/41 (53.65%). A further 40,3% declared partial improvement in daytime and 26.7% in nighttime wetting. CONCLUSIONS: Biofeedback treatment is an effective therapeutic option for children with dysfunctional voiding. Pelvic floor therapy with biofeedback should be offered to children with dysfunctional voiding resistant to standard urotherapy.

[Preliminary results of a program for the early management of children with congenital hydronephrosis]. / Wstepne wyniki programu wczesnej opieki nefro-urologicznej nad dziecmi z wrodzonym wodonerczem.

UNLABELLED: Antenatal hydronephrosis is one of the most frequently diagnosed congenital abnormalities in the fetus. The aim of the study is to present the preliminary results of a newly launched Pommeranian Program for Early Management of CAKUT in Children. MATERIAL AND METHODS: 105 neonates and infants with hydronephrosis were assessed between Jan and Dec 2007 (27 girls and 78 boys). All patients had postnatal ultrasound performed. Static and dynamic scyntigraphy and cystography were performed according to set indications. Therapeutic decisions were made following a team meeting between pediatric nephrologists and urologists. RESULTS: 56.2% of children with hydronephrosis had documented prenatal findings: 61%--pyelectasis, 15.3% renal cysts, 5.1% unspecified renal pathology, in 18.6% no renal pathology. 82.6% of newborns had term births but perinatal complications were observed in 30.5%. Initial postnatal diagnosis was performed by neonatal wards in 22.8% newborns and by the children's pediatrician in 31.4% of infants. Following referral to nephro-urology centre cystography was performed in 22.9% of infants and scintigraphy in 36.2%. 21.9% of infants were qualified for surgical intervention at an average age of 24 + 13 weeks. CONCLUSIONS: 1. Only half of the children with congenital hydronephrosis are to nephro-urology care following prenatal diagnosis. 2. A large number of perinatal complications are observed in newborns with prenatally diagnosed hydronephrosis. 3. The management of newborn hydronephrosis requires better cooperation between obstetricians, neonatologists, pediatric nephrologists and urologists.

[Evolving pattern of bladder dysfunction in boys with posterior urethral valves (PUV)]. / Przebieg zaburzen funcji pecherza moczowego u pacjentów z zastawka cewki tylnej na podstawie badan urodynamicznych.

UNLABELLED: Bladder dysfunction is present in 50-80% boys born with PUV. THE AIM OF THE STUDY: To assess the effect of age on the pattern of voiding dysfunction. MATERIAL AND METHODS: An analysis of urodynamic findings was performed in 62 boys with PUV divided into younger (mean 6.02 yrs) and older (mean 15.6 yrs) age groups. RESULTS: In younger boys a higher prevalence of decreased bladder compliance (p < 0.0001), detrusor instability (p < 0.001) and detrusor sphincter dyssynergy (p < 0.05) was noted. In older boys a higher prevalence of low detrusor pressure was observed (p < 0.01). CONCLUSION: The pattern of bladder dysfunction in boys with PUV evolves with age.

[Kidney transplantation into a neurogenic bladder in myelomeningocele patient (MMC)]. / Przeszczepienie nerki do pecherza neurogennego u pacjenta z przepuklina oponowo-rdzeniowa.

UNLABELLED: We report a 24-year-old patient with neurogenic bladder due to myelomeningocele (MMC) who received a kidney transplant without prior bladder reconstruction. Following transplantation recurrent episodes of febrile pyelonephritis were observed with elevations of creatinine. A year after Tx a bladder augmentation was performed with appendicostomy to enable intermittent catheterization. Following surgery only sporadic episodes of UTI have been observed and his renal function is stable. CONCLUSION: bladder reconstruction surgery in patients with neurogenic bladder is feasible post transplantation though the optimal timing is prior to a kidney Tx.

[Estimation of GFR from serum creatinine and cystatin C-A comparison of 2 methods in patients with neurogenic bladder due to myelomeningocle (MMC)]. / Szacowanie GFR na podstawie wartosci kreatyniny i cystatyny C--porównanie dwóch metod w grupie pacjentów z pecherzem neurogennym w przebiegu przepukliny oponowo-rdzeniowej (MMC).

UNLABELLED: Glomerular filtration rate (eGFR) calculated from serum creatinine can be overestimated in patients with muscle mass deficits. AIM: The aim of this study was to compare eGFR calculated from serum levels of creatinine and cystatin C in a group of patients with neurogenic bladder due to MMC. MATERIAL AND METHODS: GFR calculations were performed for 67 patients using Schwartz formula for creatinine measured by colorimetric method and Filler formula for cystatin C measured by immunonephelometric method. RESULTS: Statistically significant lower eGFR values were obtained with calculations based on cystatin C levels. CONCLUSION: Cystatin C is a useful marker for GFR estimations in patients with reduced muscle mass.

[Acute renal failure in paediatric oncological disease]. / Ostra niewydolnosc nerek w chorobie nowotworowej u dzieci.

INTRODUCTION: Acute renal failure (ARF) in children with malignancies is a rare clinical situation, but nonetheless it is a serious life threatening condition. It may arise from different clinical situations and may be caused by various factors. The aim of the study was to determine the frequency, aetiology and the course of ARF in children treated for malignancies in the Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical University of Gdansk. MATERIAL AND METHODS: A group of 586 pediatric oncology patients treated between 1992 and 2004 were enrolled in a retrospective study. RESULTS: ARF was diagnosed in 29 cases including: 12 patients with prerenal course of ARF (11 due to septic shock and 1 due to dehydration), 16 patients with intrinsic renal aetiology of ARF (as a complication after cisplatinum and carboplatinum therapy in 2 children, in 2 cases after methotrexate, as a consequence of bilateral nephrectomy due to nephroblastoma in 1 patient and in 11 children with tumour lysis syndrome, including 5 patients with neoplasmatic infiltration of kidneys) and postrenal ARF in 1 patient as a first symptom of a tumour located in the small pelvis (Rhabdomyosarcoma). Renal replacement therapy (dialysis) was necessary in 11 children. Among 29 analysed children, in 20 cases renal failure was reversible. Due to appropriate treatment, ARF in course of tumour lysis syndrome is nowadays reversible. ARF due to septic shock or cytostatics nephrotoxicity is a significant therapeutic problem. In most of the cases it is irreversible. CONCLUSIONS: 1. ARF in these studies occurred in 29 out of 586 children with malignancies (4.9%). 2. Prerenal and renal ARF were the most frequent forms. 3. Implementation of tumour lysis prophylaxis in the treatment of children with blood system proliferative diseases reduces the incidence of ARF. 4. In cases of ARF in children's malignancies close cooperation between paediatric oncologist and nephrologist is necessary.

[Chronic renal disease in boys with posterior urethral valve]. / Przewlekla choroba nerek u chlopców z zastawka cewki tylnej.

UNLABELLED: Posterior urethral valve (PUV) is the most common anatomical cause of bladder outlet obstruction with an incidence ranging from 1/3000 to 1/8000 births. In spite of early valve ablation deterioration of renal function is frequently reported during childhood and adolescence. AIM OF THE STUDY: To evaluate the frequency and progression of chronic renal disease in boys born with PUV. MATERIALS AND METHODS: The presence of chronic renal disease (CRD) in 58 boys with posterior urethral valve (PUV) was assessed by renal ultrasound and estimation of glomerular filtration rate (GFR). GFR was estimated by the method of Schwartz. Chronic renal disease was defined according to NFK K/DOQI Guidelines and classified into 5 stages. RESULTS: 48 (82%) patients with PUV had CRD. Among the patients observed from birth 89% already demonstrated CRD in the first year of life. CONCLUSIONS: 1. The vast majority of boys with PUV (83%) demonstrate symptoms of chronic renal disease. 2. CRD in boys with PUV is frequently evident from the first year of life. 3. PUV patients require regular nephrologic assessment from birth.