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

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

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

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

The incidence and prevalence of IgA nephropathy in Europe.

BACKGROUND: This study aimed to determine the incidence and prevalence of immunoglobulin A nephropathy (IgAN) in Europe based on high-quality data from national registries. METHODS: IgAN incidences were obtained from a literature review of European studies of national kidney biopsy registry data in which IgAN diagnosis was biopsy-verified using contemporary techniques. Studies were eligible for the main analysis if published from 1990 to 2020. IgAN point prevalence was defined as the annual IgAN incidence multiplied by the estimated duration of disease. Incidence and prevalence estimates were made for three pooled populations: (i) patients of all ages; (ii) pediatric patients; and (iii) elderly patients. RESULTS: Across 10 European countries, the estimated annual IgAN incidence was 0.76 per 100 000 in patients of all ages. The corresponding pooled IgAN point prevalence was 2.53 per 10 000 (95% confidence interval: 2.51-2.55), ranging from 1.14 per 10 000 in Spain to 5.98 per 10 000 in Lithuania. Applied to 2021 population estimates, the number of expected prevalent IgAN cases was 47 027 across all 10 countries and ranged from 577 in Estonia to 16 645 in Italy. Among pediatric patients, IgAN incidence was 0.20 per 100 000 children and IgAN point prevalence was 0.12 per 10 000 children. Among elderly patients, IgAN incidence was 0.30 per 100 000 and IgAN point prevalence was 0.36 per 10 000. CONCLUSIONS: Based on high-quality data from European national registries, IgAN point prevalence was estimated at 2.53 per 10 000 in patients of all ages. Prevalence was considerably lower in pediatric and elderly populations.

How to take advantage of easily available biomarkers in patients with IgA nephropathy: IgA and C3 in serum and kidney biopsies.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. It is diagnosed based on clinical and histological features including predominant IgA deposits in kidney biopsy. The multi-hit theory, based on the production of GDIgA1 and anti-GDIgA1 antibodies, and complement activation via alternative and lectin pathways and also a genetic tendency are crucial in the pathogenesis of IgAN. The aim of the present review is to summarize the utility of routine diagnostic tests in IgA nephropathy, such as IgA and C3 in serum and kidney biopsy specimens, for predicting the disease progression. The paper also contains data on new markers used in the diagnosis and prognosis of IgA nephropathy.

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

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

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.

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

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

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.

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 Complicated by Both CMV Reactivation and Tuberculosis.

Immunoglobulin A (IgA) vasculitis is the most common systemic vasculitis in the pediatric population. We present the case of a patient with IgA vasculitis with nephritis who developed cytomegalovirus (CMV) infection followed by Mycobacterium tuberculosis infection. In the literature, there are a few cases of IgA nephropathy accompanied by reactivation of CMV or tuberculosis. To the best of our knowledge, this is the first reported case of IgA vasculitis complicated by both CMV reactivation and tuberculosis. It is important to detect infections in patients with IgA vasculitis because they can induce and exacerbate the symptoms of the disease. Effective antimicrobial treatment facilitates the management of proteinuria and slows down the decline of renal function. Immunosuppressive therapy is a risk factor for reactivation of latent infections and makes patients more susceptible to its generalized and complicated course. This can be prevented by actively screening for hidden sites of infection.

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 switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and associated with defective CD46 expression.

The proteasome to immunoproteasome (iPS) switch consists of ß1, ß2 and ß5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4 years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/ß5 and LMP2/ß1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/ß5 (P < 0.0001). The LMP7/ß5 switch was significantly associated with the rate of eGFR loss (P = 0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR >75th centile, i.e. -1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/ß5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/ß5 and low CD46 expression.

[Does Gordon's syndrome always manifest as hypertension? - a case report of one family]. / Czy zespól Gordona zawsze przebiega w postaci nadcisnienia tetniczego? ­ opis przypadku jednej rodziny.

Gordon's syndrome (pseudohipoaldosteronism type II) is a genetically determined, autosomal dominant type of monogenic hypertension caused by excessive reabsorption of chlorine accompanied by reabsorption of sodium and water. CASE REPORTS: The case of a family (2 brothers: 12 and 16 years old and their father), in whom genetic tests confirmed the presence of a mutation characteristic of Gordon syndrome, despite the absence of hypertension in boys. Diagnostics of the family started with a 12-year-old boy because of observed for 2 years hyperkalemia and delayed growth and puberty. The physical examination showed low height (<3c), discreet facial dysmorphic features (close spaced eyelid cracks, low-set ears) and lack of puberty, arterial pressure was normal. In laboratory tests, apart from hyperkalaemia at normal sodium level, hyperchloremia and metabolic acidosis were found. Plasma renin activity and aldosterone concentration were normal. There were no glomerular filtration abnormalities, renal parameters and kidney image in ultrasound examination were normal. Hyperkalemic tubular acidosis type IV was diagnosed and oral treatment with sodium bicarbonate was started. Due to the inability to achieve acidosis control with sodium bicarbonate and positive family history of hyperkalaemia and hypertension in the boy's father, the suspicion of Gordon syndrome was raised. Simultaneously, in the studies performed in the 16-year-old brother of the patient hyperkalemic acidosis, normal blood pressure and growth within normal limits for sex and age were found. The treatment of boys and father with hydrochlorothiazide was started, which resulted in the equalization of acidosis and calemia and rapid normalization of blood pressure in the father. CONCLUSIONS: In patients with tubular hyperkalemic acidosis, despite the absence of hypertension, Gordon's syndrome should be considered in the differentiation.

[Cerebral salt wasting syndrome as a complication of subarachnoid hemorrhage in a girl with nephrotic syndrome - a case report]. / Mózgowy zespól utraty soli jako powiklanie krwawienia podpajeczynówkowego u dziewczynki z zespolem nerczycowym ­ opis przypadku.

INTRODUCTION: Cerebral salt wasting syndrome (CSWS), characterized by natriuresis, polyuria, and hypovolemia, is a rare complication of central nervous system injury or disease. A CASE STUDY: 12-year-old girl was admitted with second attack of nephrotic syndrome (NS). On admission she presents with edema, blood pressure 110/60 mm Hg, proteinuria 145 mg/kg/24h, hypoalbuminemia (1.7 g/dL), GFR 94.4 mL/min/1.73m2, sodium 133 mmol/L. On 5th day the patient developed thrombosis of right subclavian and axillary vein and was treated with recombinant tissue plasminogen activator (0.3 mg/kg/h i.v.). 45 minutes after onset of the infusion severe headache appeared. Computed tomography revealed subarachnoid hemorrhage in a region of left occipital lobe and posterior 1/3 part of sickle of the brain. Control ultrasonography examination revealed resolution of the thrombus. No deficits were found on neurologic examination. Proteinuria subsided on 11th day of hospitalization. After the hemorrhage hypovolemia, hypotension (80/40 - 100/60 mm Hg, heart rate 100/min), polyuria, and pathologic natriuresis (up to 13.0 mmol/kg/24h) were observed. Cerebral salt wasting syndrome was recognized. The girl was supplemented with oral and intravenous sodium (up to 10 mmol/ kg/24h). In following days gradual decrease of diuresis and urinary sodium loss was observed. The patient was discharged home after 41 days with normal diuresis (1.5l/24h) and natriuresis (1.44 mmol/kg/24h). CONCLUSIONS: Treatment of thromboembolic complications in children with NS poses a risk of central nervous system bleeding. Serum sodium concentration and diuresis must be strictly monitored in patients with central nervous system lesion, especially in the course of nephrotic syndrome.

[Accidentally diagnosed distal renal tubular acidosis with nephrocalcinosis - a case report]. / Przypadkowo rozpoznana kwasica kanalikowa dystalna z nefrokalcynoza ­ opis przypadku.

Distal renal tubular acidosis is a defect of acidification of urine in distal tubule. Full-blown form is characterized by polyuria, growth deficiency, nephrolithiasis or nephrocalcinosis. Mutations in genes encoding Cl-/HCO3 - exchanger (autosomal dominant) or H+-ATPase (autosomal recessive) are the most frequent in children. A CASE REPORT: In a boy aged 2,5 years, healthy, with proper development, metabolic acidosis with hyperchloremia, hypokalaemia, normal glomerular filtration rate and alkaline urine was discovered during hospitalization because of pneumonia. USG showed normal length kidney with nephrocalcinosis type IIB. The family history revealed nephrocalcinosis on the part of the boy's father. He also had metabolic acidosis in blood gas test. Genetic test in a boy and his father showed mutation of SLC4A1(17q21-q22) gene encoding Cl-/HCO3 - exchanger. The boy was treated with 8,4% NaHCO3 - orally (1mEq/kg/24h) and KCl (0,3 mEq/kg/24h). We obtained normalization of blood gas test and potassium concentration. CONCLUSIONS: Every child, with accidentally discovered metabolic acidosis, even with normal development, should be diagnosed in case of renal tubular acidosis. Electrolytes, gas blood test, urinalysis and USG are needed in the closest family members of child with diagnosed renal tubular acidosis.

Asymmetric dimethylarginine is not a marker of arterial damage in children with glomerular kidney diseases.

INTRODUCTION: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, correlates with cardiovascular risk especially in patients with chronic kidney disease. The aim of our study was to establish significance of ADMA as a biomarker of arterial damage in children with glomerulopathies. MATERIAL AND METHODS: In 80 children with glomerulopathies (mean age, 11.33 ±4.25 years; 42 with idiopathic nephrotic syndrome [INS], 38 with IgA or Henoch-Schoenlein nephropathy [IgAN/HSN]), we analyzed serum ADMA [nmol/ml], peripheral and central blood pressure, arterial stiffness (augmentation index - AIx75HR, pulse wave velocity - PWV), common carotid artery intima media thickness (cIMT), and selected clinical and biochemical parameters. RESULTS: In the study group, mean ADMA concentration was 1.66 ±1.19 [nmol/ml] and did not differ between INS and IgAN/HSN patients. We found no significant correlations between concentration of ADMA, cIMT [mm]/Z-score, PWV [m/s]/Z-score, and AIx75HR [%] in the whole group and in INS and IgAN/HSN patients. In the whole group of 80 children, ADMA correlated (p < 0.05) with BMI Z-score (r = -0.24), uric acid (r = -0.23), HDL-cholesterol (r = -0.25), and central mean arterial pressure (r = -0.25), in children with INS also with total protein (r = 0.37), albumin (r = 0.36), and total cholesterol (r = -0.40, p = 0.028). In multivariate analysis, serum albumin was the strongest determinant of ADMA in the whole group (ß = 0.536, 95% CI: 0.013-1.060, p = 0.045). CONCLUSIONS: 1. In children with glomerulonephritis, measurement of asymmetric dimethylarginine cannot replace well established and validated methods of assessment of subclinical arterial damage. 2. In children with glomerular kidney diseases, ADMA concentration is related primarily to serum albumin concentration.

[Pulmonary embolism in a girl with nephrotic syndrome and factor V Leiden - case report]. / Zatorowosc plucna u dziewczynki z zespolem nerczycowym i czynnikiem V Leiden ­ opis przypadku.

Thromboembolic complications are found in 2-3% of children with nephrotic syndrome (NS); this increased risk is caused by hypovolemia, hemoconcentration, increased number and activity of platelets, hyperfibrinogenemia and loss of coagulation inhibitors. Risk is even higher in case of additional factors e.g. congenital thrombophilia. CASE REPORT: Girl with NS aged 17 11/12 years was admitted to hospital due to respiratory tract infection with cough and back pain. NS started 9 months earlier and she had two bouts of disease, and was treated only with prednisone (current dose - 60 mg/48h). On admission she was without any abnormalities on auscultation, with BP 111/65 mmHg, HR 80 bpm, satO2 99%. Lab results showed the increase of WBC 18.3×103/µL, D-dimers 23038 µg/L and proteinuria 900 mg/dL. Other values of examined parameters were in normal limits. Chest X-ray and ECG were also normal. Presumptive diagnosis of pulmonary embolism was made and the patient was given 1000IU of antithrombin III and nadroparine (2x90IU/kg/24h s.c.). In ECHO the occlusion of left pulmonary artery and preserved blood flow in right were revealed. In angioCT clot nearly filling lumen of left pulmonary artery, clot in intermediate part of right pulmonary artery, and focus of pulmonary infarction in 10th segment of left lung were found. Doppler USG of lower limb veins did not reveal thrombi or perforator vein incompetence. Treatment with nadroparine was continued, and rapid improvement of clinical condition and disappearance of pain and cough were observed. Mycophenolate mofetil was added, which resulted in subsidence of proteinuria. Rivaroxaban was used in prophylaxis of recurrences of thromboembolism. Tests for thrombophilia revealed factor V Leiden in patient.

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.

[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.