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.

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.

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.

[Evaluation of renal lesions in children with tuberous sclerosis - summary of the first year of follow-up program]. / Ocena zmian w nerkach u dzieci chorych na stwardnienie guzowate ­ podsumowanie pierwszego roku programu opieki.

Tuberous sclerosis complex (TSC) is a genetic disease that leads to formation of tumors i.e. in brain kidneys, heart, lungs, and skin. AIM: The aim of the study was to summarize center's experience in the first year of program of nephrologic follow-up in patients with TSC. MATERIALS AND METHODS: During 12 months 30 children with TSC (14 boys and 16 girls aged from 3 months to 17 years 11 months, mean 7.57±5.02 years) were hospitalized. Following parameters were evaluated: genetic and biochemical tests, blood pressure in ambulatory blood pressure monitoring (ABPM), kidney lesions in ultrasonography (30 patients) and in magnetic resonance (14 patients). RESULTS: Genetic tests were performed in 6 children - in 5 TSC2 mutation was found, in one boy with TSC and numerous renal cysts only PKD1 mutation was revealed. Mean GFR was 130.81±23.23 mL/ min/1.73 m2. Four children (13.3%) had arterial hypertension. Renal lesions were found in 28 (93.3%) children: 18 patients had angiomyolipomas (AML) (mean diameter 15.4±12.5, max 38 mm), 23 patients had renal cysts (mean diameter 7.6±7.0, max 30 mm); 13 patients had AMLs and cysts. A dysplastic lesion (39x26x15 mm) in right kidney was found in one girl. Children with AML were older than remaining patients (10.08±4.55 vs. 4.25±3.50 [years], p<0.001). Children with cysts were characterized by higher systolic (p=0.017), diastolic (p=0.027) and mean (p=0.014) arterial pressure, and mean arterial pressure Z-score (p=0.025) in ABPM. Maximal kidney cyst diameter correlated positively with systolic, diastolic, mean arterial pressure, mean arterial pressure Z-score, and diastolic blood pressure load in ABPM (r = 0.61-0.75, p = 0.033-0.005). Two children with numerous AML with diameter >30 mm were treated with sirolimus. CONCLUSIONS: Because of common focal lesions in kidneys children with TSC should be kept under regular nephrologic follow-up. Presence of large renal cysts may predispose children with TSC to arterial hypertension.

[Recurrent urolithiasis as a symptom of primary hyperparathyroidism in a 16-year-old boy]. / Nawracajaca kamica ukladu moczowego jako objaw pierwotnej nadczynnosci przytarczyc u 16-letniego chlopca.

Primary hyperparathyroidism is one of the most common endocrine diseases, however, it is rare in children. In most cases, it is caused by adenoma of these organs. Its most common complications include urolithiasis, nephrocalcinosis and osteoporosis. CASE REPORT: A 16-year-old patient was admitted to our Clinic because of his first-ever renal colic. The ultrasound examination revealed rightsided hydronephrosis caused by the presence of 9 mm stone in the upper part of the right ureter. In addition, the presence of 8 mm stone in the middle calyx of the left kidney was found. Due to the clinical picture, the patient was transferred to the urological department, where the effective ureterorenoscopic lithotripsy (URSL) was performed. Subsequent metabolic diagnostics showed hypercalcemia, hypophosphatemia, elevated levels of parathyroid hormone and hypercalciuria. In addition, the medical history revealed complicated, prolonged healing of a traumatic fracture of both bones of the left forearm in the last 12 months, requiring orthopedic treatment. Due to suspicion of primary hyperparathyroidism, parathyroid scintigraphy with MIBI scan by SPECT/ CT was performed. It revealed a focal lesion that could correspond to adenoma. The patient was referred to endocrinological care, but after 2 months he was readmitted to our Clinic, this time due to left renal colic. A left-sided ureteral stone was identified, which required another urological procedure. CONCLUSIONS: In differential diagnosis of urolithiasis in children, primary hyperparathyroidism should also be considered.

[Influence of intensity, localization and type of deposits in renal biopsy for disease symptoms and follow up in children with IgA nephropathy]. / Wplyw nasilenia, lokalizacji i rodzaju zlogów w biopsji nerki na objawy kliniczne i rokowanie u dzieci z nefropatia IgA.

IgA nephropathy is the most common glomerulonephritis in the world. For diagnosis kidney biopsy is necessary. AIM: The aim of the study was assessment the significance of IgA, C3 and IgG deposits intensity and location in kidney childhood IgA nephropathy (IgAN) for the symptoms of the disease and the follow up. MATERIALS AND METHODS: Study population consisted of 81 children, average 11,45±3,99 years. IgAN was recognized based on renal biopsy, performed 1,2±1,84, median 0,5 years after the onset. We used Oxford classification (OC) to assess the severity of histopatological lesions. In renal biopsy IgA and C3 deposits were found in immunofluorescence in mesangium or in vessels of glomeruli or both, and intensity was defined 0 to +4. We analyzed: proteinuria (mg/kg/day), hematuria, creatinine, GFR (according to Schwartz formula) two times, at the onset of the disease (OOD) and at the follow up (FU). Patients were treated with: ACEI/ARB or steroids alone or with imunossupresion drugs: azathioprine (AZA), cyclophosphamide (CYC), cyclosporine A (CsA), mycopnenolate mophetil (MMF). The follow up was 3,31±2,88 years. We divided the patients into two groups, depending on the intensity of IgA deposits: G1 n=29 (+1/+2), G2 n=52 (+3/+4); depending on the localizations of these deposits, we analyzed 3 groups: A n= 39 (mesangium), B n= 15 (glomeruli vessels), C n=27 (both) and depending on the kind of deposits we analyzed 4 groups: gr. a - n=30 (only IgA), gr. b - n=37 (IgA+C3), gr. c - n=5 (IgA+IgG) gr. d - n= 9 (IgA+IgG+C3). RESULTS: At OOD and FU we not found any differences in G1 vs G2 for: age, proteinuria, GFR and OC in renal biopsy; at FU GFR<90 ml/ min/1,73 m2 FU was observed more frequently in G2 vs G1 (p=0,02). The differences in groups A,B,C and groups a,b,c,d were not found. CONCLUSIONS: Poor prognosis in childhood IgAN may also depend on the intensity of the deposits, irrespective of their location.

Serum GDIgA1 levels in children with IgA nephropathy and Henoch-Schönlein nephritis.

INTRODUCTION: GDIgA1 (galactose deficient IgA1) plays a significant role in the pathogenesis of IgA nephropathy (IgAN) and Henoch-Schönlein nephritis (HSN). AIM OF THE STUDY: The aim of this study was to assess the relevance of serum GDIgA1 level as a prognostic marker in children with IgAN and HSN. MATERIAL AND METHODS: 41 children were included to the study group (15 IgAN, 26 HSN) and 22 to the control group. The following parameters were evaluated at baseline and endpoint: proteinuria, erythrocyturia, serum creatinine, serum IgA, GFR. A kidney biopsy was performed in all patients and evaluated according to the Oxford Classification (1 - present, 0 - absent: M - mesangial hypercellularity; E- endocapillary hypercellularity; S - segmental sclerosis/adhesion; T - tubular atrophy/interstitial fibrosis), and was calculated as the total score (sum of M, E, S, T). At the end of follow-up, the serum GDIgA1 concentration was measured. RESULTS: The serum GDIgA1 concentration in patients with IgAN and HSN was significantly higher than in the control group. No significant differences in mean proteinuria, erythrocyturia, GFR, MEST score, or GDIgA1 in serum, as well as the duration of follow-up between IgAN and HSN were observed. Baseline serum IgA concentration and time to kidney biopsy were significantly higher in children with IgAN than in children with HSN. We observed a positive correlation between GDIgA1 and IgA levels (r = 0.53), and GDIgA1 and serum creatinine levels (r = 0.5), as well as negative correlation between GDIgA1 and GFR (r = -0.37). CONCLUSIONS: Serum GDIgA1 level may have a prognostic value in children with IgAN and HSN; however, to fully elucidate its clinical potential further studies performed in larger patient cohorts are required.

Retrospective cohort study of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis due to CLDN16 mutations.

BACKGROUND: Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder exhibiting a high risk for progressive chronic kidney disease (CKD). METHODS: This is a retrospective multicentre study of 25 paediatric cases with FHHNC in Poland. Median age at diagnosis was 4 years and median follow-up time was 4.8 years. RESULTS: All cases of FHHNC carried recessive mutations in CLDN16. The founder mutation in CLDN16, Leu151Phe, was the most frequent cause of FHHNC in Polish patients, with 13 (52%) cases being homozygous and 5 (20%) carrying Leu151Phe allele in compound heterozygosity. All cases showed nephrocalcinosis, increased urinary fractional excretion of magnesium and hypercalciuria. Other disease features included hypomagnesaemia (76%), hyperparathyroidism (76%), hyperuricaemia (56%) and hypocitraturia (60%). Treatment with thiazides effectively reduced hypercalciuria in most cases. During follow-up, renal function declined in 60% of patients; 12% of patients reached CKD stage 3 or 4 and one patient developed end-stage renal failure. CONCLUSIONS: We report one of the largest cohorts of FHHNC cases caused by CLDN16 mutations. A missense variant of CLDN16, Leu151Phe, is the most common mutation responsible for FHHNC in Poland. Additionally, we found that normomagnesaemia does not exclude FHHNC and the calculation of fractional excretion of Mg can be diagnostic in the setting of normomagnesaemia. We also demonstrate the efficacy of a treatment with thiazides in terms of hypercalciuria in the majority of patients.

Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy.

BACKGROUND: The aim of this study was to evaluate the usefulness of serum immunoglobulin A/complement factor 3 (IgA/C3) ratio for predicting histological severity of kidney lesions in children with IgA nephropathy (IgAN) based on World Health Organization (WHO) and the Oxford classification (OC). METHODS: We studied 89 children with IgAN with a mean age of 11.38 ± 4.1 years (range 2-18 years). Based on available medical records, we retrospectively evaluated clinical data, IgA/C3 ratio, and kidney biopsy findings using the five-grade WHO classification and the OC The mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy/interstitial fibrosis (T) (MEST) score (absent = 0, present = 1) calculated as the sum of M+E+S+T ranging from 0 to 4. RESULTS: Mean IgA/C3 ratio values were significantly higher (P < 0.05) in patients with M1, S1, and T1 compared with M0, S0, and T0, respectively (P < 0.05); there were no differences in the WHO classification. We found a significant positive correlation between the IgA/C3 ratio and proteinuria (r = 0.24) and determined optimal cutoff values of the IgA/C3 ratio, with a corresponding confidence interval for specific MEST scores. CONCLUSIONS: The IgA/C3 ratio in children with IgAN may be a useful marker of the severity of lesions found in kidney biopsy as evaluated using the OC.

Long-term outcomes in idiopathic nephrotic syndrome: from childhood to adulthood.

BACKGROUND: The aim of the study was to assess idiopathic nephrotic syndrome (INS) relapse rate, co-morbidities, and social status of adults diagnosed with INS in childhood. MATERIAL AND METHODS: A written questionnaire was sent to 118 adults treated for INS in childhood. In 61 (51.7%) responders (aged 26.0 ± 6.2 years, range 18 - 51.5 years), we used available medical records to evaluate age at the onset of INS, number of INS relapses below 18 years of age, response to corticosteroids (CS), renal biopsy findings, and immunosuppressive treatment as well as questionnaire to evaluate the number and treatment of INS relapses above 18 years of age, co-morbidities, age at menarche, marital status, offspring, educational status, and occupation. RESULTS: In the group of 61 responders, median age at the onset of INS was 3 (range 1.3 - 14.0) years, median number of INS relapses at < 18 years of age was 5 (1 - 20). Steroid-sensitive nephrotic syndrome (SSNS) was diagnosed in 37 (60.7%) patients, steroid-dependent nephrotic syndrome SDNS in 18 (29.5%) patients, and steroid-resistant nephrotic syndrome (SRNS) in 6 (9.8%) patients. Mesangial proliferation was the most common pattern in renal biopsy (35.7%). All patients received CS, 15 were treated with methylprednisolone pulses, 13 with cyclophosphamide, 11 with chlorambucil, 2 with cyclosporine, and 21 with levamisole. All patients achieved remission and had normal renal function at the age of 18. In adulthood, INS relapsed in 10 (16.4%) patients, including 5 (13.5%) patients with SSNS, 4 (22.2%) with SDNS, and 1 (16.7%) with SRNS (p = 0.72). Median number of relapses was 2 (range 1 - 11). Patients with relapses at > 18 years of age had more (p < 0.005) relapses at < 18 years of age. Hypertension was diagnosed in 8 (16.1%), overweight in 14 (23.0%), obesity in 3 (4.9%), and bone fractures in 12 (19.7%) patients. Five patients had height < 3rd percentile, including 4 with INS onset at < 3 years of age. One patient had growth retardation before the treatment. No myocardial infarctions, strokes, severe infections, or malignancies were reported. Mean age at menarche was 12.9 ± 1.4 years, 37 (60.7%) patients were in a steady relationship/ married, 1/18 (5.6%) patients treated with cytostatic agents and 12/43 (24/7%) patients not treated with cytostatic agents had offspring (p < 0.05). Elementary education was reported by 4 (6.6%), secondary education by 32 (52.5%), and higher education by 25 (40.9%) patients, and 34 (55.7%) patients were professionally active. None of the 6 patients with SRNS developed end-stage renal disease. CONCLUSIONS: 1. High number of INS relapses in childhood is a risk factor for recurrences in adulthood. 2. INS relapses in childhood do not preclude active professional life in adulthood.

Disparities in treatment and outcome of kidney replacement therapy in children with comorbidities: an ESPN/ERA Registry study.

Background: Data on comorbidities in children on kidney replacement therapy (KRT) are scarce. Considering their high relevance for prognosis and treatment, this study aims to analyse the prevalence and implications of comorbidities in European children on KRT. Methods: We included data from patients <20 years of age when commencing KRT from 2007 to 2017 from 22 European countries within the European Society of Paediatric Nephrology/European Renal Association Registry. Differences between patients with and without comorbidities in access to kidney transplantation (KT) and patient and graft survival were estimated using Cox regression. Results: Comorbidities were present in 33% of the 4127 children commencing KRT and the prevalence has steadily increased by 5% annually since 2007. Comorbidities were most frequent in high-income countries (43% versus 24% in low-income countries and 33% in middle-income countries). Patients with comorbidities had a lower access to transplantation {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]} and a higher risk of death [aHR 1.79 (95% CI 1.38-2.32)]. The increased mortality was only seen in dialysis patients [aHR 1.60 (95% CI 1.21-2.13)], and not after KT. For both outcomes, the impact of comorbidities was stronger in low-income countries. Graft survival was not affected by the presence of comorbidities [aHR for 5-year graft failure 1.18 (95% CI 0.84-1.65)]. Conclusions: Comorbidities have become more frequent in children on KRT and reduce their access to transplantation and survival, especially when remaining on dialysis. KT should be considered as an option in all paediatric KRT patients and efforts should be made to identify modifiable barriers to KT for children with comorbidities.

Nephropathic cystinosis in Poland: a 40-year retrospective study.

INTRODUCTION: Nephropathic cystinosis (NC) is a rare, autosomal recessive disorder leading to lysosomal accumulation of cystine. It is caused by mutations in the CTNS gene encoding a cystine cotransporter cystinosin. The infantile (INC) and juvenile (JNC) forms are distinguished. The former, responsible for 95% of cases, is characterized by development of renal Fanconi syndrome, end-stage kidney disease (ESKD), and extrarenal complications. A therapy with cysteamine significantly improves outcomes. There are limited data on NC in the Central Eastern European countries. OBJECTIVES: We aimed to evaluate the prevalence, genetic background, and clinical course of NC in the Polish population. PATIENTS AND METHODS: We performed a retrospective analysis of data of all identified NC patients in Poland. RESULTS: Between 1982 and 2017, 15 patients with NC (13 ICN, 2 JCN) were identified. The most common mutations of the CTNS gene were c.18_c.21delGACT and c.681+1G>A, whereas only 2 patients carried the 57 kb deletion. The majority (11/13) of INC patients with limited access to the cysteamine therapy developed ESKD at a median age of 11 years and 9 of them received kidney transplants. Three INC patients died at a median age of 24 years. In contrast, 2 INC patients treated adequately present normal kidney function and growth at the age of 13 and 11 years. Two JNC patients presented a milder course. CONCLUSIONS: The prevalence of NC in Poland is much lower than in the Western countries and its molecular background appears to be different. The unfavorable course in the majority of INC patients was caused by a limited access to the cysteamine treatment.

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.

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.

Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited.

BACKGROUND: Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. However, neither a causal relationship nor its predictive value have been proven. The purpose of this study was to assess this in children with renal malformations, both with (mut+) and without HNF1B mutations (mut-). METHODS: We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. RESULTS: 108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean sUA was higher and hyperuricemia more prevalent (42.5% vs. 15.4%) in HNF1B carriers. The two groups were similar with respect to respect to age, sex, anthropometric parameters, hypertension, and renal function. Renal function, fractional excretion of uric acid and parathyroid hormone level were independent predictors of sUA. The potential of hyperuricemia to predict mutation was low, and addition of hyperuricemia to a multivariate logistic regression model did not increase its accuracy. CONCLUSIONS: Hyperuricemia is an early and common feature of HNF1B nephropathy. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies.

Health-related quality of life in children with immunoglobulin A nephropathy - results of a multicentre national study.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) may lead to end stage renal disease and severely affect patient functioning and wellbeing. The aim of the study was to evaluate health-related quality of life (HRQoL) in children and adolescents with IgAN, and compare HRQoL in relation to the disease course, social status and psychological factors, such as expressing anger and perceived personal competence. MATERIAL AND METHODS: The multicentre cross-sectional study included 51 patients ≥ 8 years from 7 paediatric nephrology centres in Poland. Psychometric analysis was performed using the Kidscreen-52 questionnaire to evaluate HRQoL, the Anger Expression Scale to evaluate the severity of anger and the Personal Competence Scale to measure general perception of personal competence. RESULTS: Mean age of patients was 14.54 ±3.69 years; duration since the diagnosis of IgAN was 4.98 ±3.9 years. Patients with IgAN rated their psychological wellbeing as significantly worse compared to healthy peers (p < 0.05). The presence of proteinuria was associated with significantly worse physical wellbeing (58.72 ±18.45 vs. 74.44 ±22.97; p < 0.05). Current therapy (steroids/immunosuppressive drugs) had no effect on HRQoL in the study group. Perceived personal competence was rated high by 49% of children in the study group. Children with IgAN were characterized by lower intensity of expressed anger (p < 0.001) and significantly higher intensity of suppressed anger (p < 0.01) compared to reference ranges. Severity of expressed anger correlated positively with the parent relations and school environment dimensions of HRQoL. CONCLUSIONS: We found lower HRQoL in regard to physical and psychological wellbeing in a group of Polish children with IgAN compared to healthy peers. HRQoL should be monitored in this patient group.

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.

Selected Metal Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases as Potential Biomarkers for Tubulointerstitial Fibrosis in Children with Unilateral Hydronephrosis.

Renal tubulointerstitial fibrosis caused by congenital ureteropelvic junction obstruction (UPJO) may lead to the development of obstructive nephropathy (ON) and the impairment of kidney function. Hence, the identification of early biomarkers of this condition might be of assistance in therapeutic decisions. This study evaluates serum and urinary metalloproteinases MMP-1, MMP-2, and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 as potential biomarkers of ON in children with congenital unilateral hydronephrosis (HN) caused by UPJO. Forty-five (45) children with congenital HN of different grades of severity and twenty-one (21) healthy controls were enrolled in the study. Urinary and serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured using specific ELISA kits. The urinary excretions were expressed as biomarker/creatinine (Cr) ratios. To evaluate the extracellular matrix remodelling process activity, the serum and urinary MMP-1, -2, -9/TIMP-1, -2 ratios were also calculated. In comparison with the controls, patients with HN, independent of the grade, showed significantly increased median serum MMP-9, TIMP-1, and TIMP-2, median urinary MMP-9/Cr, and TIMP-2/Cr ratios. Lower median values of serum MMP-2/TIMP-1, MMP-9/TIMP-1 in patients with HN were also revealed. Additionally, higher urinary MMP-2/Cr, lower urinary MMP-2/TIMP-2, and lower serum MMP-9/TIMP-2 ratios were observed in patients with HN grades 3 and 4. Patients with ON diagnosed by renal scintigraphy had a significantly higher median serum MMP-9 concentration and lower median serum MMP-9/TIMP-1, -2 ratios in comparison with those without this condition. Patients with nonglomerular proteinuria had a significantly higher median serum TIMP-1 concentration, a higher median urinary TIMP-2/Cr ratio, and a lower serum MMP-9/TIMP-1 ratio compared to those without this symptom. The relationship between the measured biomarkers and the relative function of the obstructed kidney showed no correlations. The ROC curve analysis showed a promising diagnostic profile for the detection of ON for serum MMP-9 and the serum MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios. In conclusion, the results of this study suggest that patients with HN, particularly with grades 3 and 4, are at higher risk of renal tubulointerstitial fibrosis. The noninvasive markers of this condition considered are urinary MMP-2/Cr and MMP-9/Cr, serum MMP-9, serum and urinary MMP-2, MMP-9/TIMP-1, -2. Additionally, serum MMP-9 and MMP-9/TIMP-1, -2 may become promising markers of ON.

Still diagnosed too late and under-recognized? The first comprehensive report on primary hyperoxaluria in Poland.

INTRODUCTION: Primary hyperoxalurias (PHs) are rare disorders leading to overproduction and increased urinary excretion of oxalate. Three monogenic forms (PH1-PH3) were classified. PHs lead to urolithiasis and chronic kidney disease. There are only sparse data on patients with PH from Eastern European countries including Poland. OBJECTIVES: The aim of the study was to evaluate the prevalence, genetic background, and clinical course of PH in the Polish population. PATIENTS AND METHODS: This was a retrospective multicenter study including data of all identified and genetically confirmed Polish patients with PH. RESULTS: Between 1998 and 2019, 21 patients with PH were identified, including 13 patients with PH1 (62%), 2 with PH2 (9%), and 6 with PH3 (29%). In those with PH1, the most common mutation was c.508G>A in AGXT and in PH3, c.700+5G>T in HOGA1. Nine patients (69%) developed end­stage renal disease at a median age of 13 years and 2 died. In 6 (46%) PH1 cases, the diagnosis was made only after patients had progressed to end­stage renal disease and received isolated kidney transplantation, followed by graft failure. Combined liver­kidney transplantation was performed in 6 patients with PH1. Two siblings with PH2 showed a milder course with slightly decreased renal function in one, at age of 11 years. Despite infantile onset of urolithiasis, all patients with PH3 at a median age of 10 years maintained normal renal function. CONCLUSIONS: The prevalence of PH1 and PH2 in Poland seems to be much lower than in Western countries with PH3 constituting about 30% of all cases. The molecular findings and clinical course are typical, but the underdiagnosis is of concern.