The Outcome of Childhood Immunoglobulin A Nephropathy with Acute Kidney Injury at the Onset of the Disease-National Study.

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R-renoprotection, P-prednisone+R, Aza-azathioprine+P+R, Cyc-cyclophosphamide+P+R, CsA-cyclosporine+P+R, MMF-mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A-GFR > 90 mL/min and B-GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0-967) mg/kg/d. Renal biopsy was performed 0.2 (0-7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05-11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients.

Initial Changes in the Heart Conduction System Illustrated by Difference Map Patterns in Adolescent Patients After Kidney Transplantation: A Pilot Study.

BACKGROUND: Cardiovascular complications (CVCs) in patients with end-stage renal disease (ESRD) often require hospitalization and are associated with an increased risk of fatality. Although kidney transplantation (KTx) improves a patient's status, CVCs are still a serious risk factor, so early identification is very important for final therapeutic outcome. METHODS: This study included 5 post-KTx patients (age, 20.8 ± 1.16 years), dialyzed before KTx, and followed up for 6.7 ± 1.71 years. Body surface potential mapping (BSPM) was performed 4 times: twice before and twice after KTx. Electrocardiographic data were processed into map plotting to illustrate differences in ventricular activation times (VATs). RESULTS: A comparative analysis of difference maps, both of dialyzed patients and normal subjects, highlighted certain specificities in the distribution of VAT changes for the left anterior fascicle block (LAFB). The maps clearly showed a significant correlation between the intensity of changes and duration of dialysis before KTx. After KTx, VATs seemed to be similar to those in normal subjects; however, this was true only for patients dialyzed for <1 year. The patients dialyzed for >1 year showed persistent conduction abnormalities on their VAT maps. CONCLUSION: Summary differences in VAT maps can enable diagnostics of initial activation propagation abnormalities in the heart. Short-term dialysis therapy before KTx imposes positive effects with regression of heart conduction changes. These observations need to be verified in a larger study population.

IgA Nephropathy in Children: A Multicenter Study in Poland.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis in pediatric population. The clinical presentation of the disease in children ranges from microscopic hematuria to end-stage kidney disease. The aim of the study was to retrospectively assess clinical and kidney biopsy features in children with IgAN. We assessed a cohort of 140 children, 88 boys, 52 girls with the diagnosis of IgAN in the period of 2000-2015, entered into the national Polish pediatric IgAN registry. The assessment included the following: proteinuria, hematuria, glomerular filtration rate (GFR), arterial blood pressure, and the renal pathological changes according to the Oxford classification and crescents formation, as modifiable and unmodifiable risk factors. The incidence of IgAN in Poland was set at 9.3 new cases per year. The mean age at onset of IgAN was 11.9 ± 4.3 years, and the most common presentation of the disease was the nephritic syndrome, recognized in 52 % of patients. Kidney biopsy was performed, on average, 1.3 ± 2.0 years after onset of disease. Based on the ROC analysis, a cut-off age at onset of disease for GFR <90 mL/min/1.73 m2 (risk factor of progression) was calculated as 13.9 years. Unmodifiable lesions: segmental sclerosis, tubular atrophy/interstitial fibrosis (S1, T1-2) in the Oxford classification and crescents in kidney biopsy were significantly more common in Gr 1 (>13.9 years) compared with Gr 2 (<13.9 years), despite a significantly shorter time to kidney biopsy in the former. We conclude that IgAN in children may be an insidious disease. A regular urine analysis, especially after respiratory tract infections, seems the best way for an early detection of the disease.

Increased Serum IgA in Children with IgA Nephropathy, Severity of Kidney Biopsy Findings and Long-Term Outcomes.

The aim of the study was to determine whether an elevated IgA level at the time of the diagnosis of IgA nephropathy has an effect on the severity of kidney biopsy findings and long-term outcomes in children. We retrospectively studied 89 children with IgA nephropathy who were stratified into Group 1- elevated serum IgA and Group 2 - normal serum IgA at baseline. The level of IgA, proteinuria, hematuria, glomerular filtration rate (GFR) and hypertension (HTN) were compared at baseline and after the end of the follow-up period of 4.0 ± 3.1 years. Kidney biopsy findings were evaluated using the Oxford classification. The evaluation of treatment included immunosuppressive therapy and renoprotection with angiotensin converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), or no treatment. The elevated serum IgA was found in 46 (52 %) patients and normal serum IgA level was found in 43 (48 %) patients. No differences were found between the two groups regarding the mean age of patients, proteinuria, and the number of patients with reduced GFR or HTN at baseline. In kidney biopsy, mesangial proliferation and segmental sclerosis were significantly more common in Group 1 compared with Group 2 (p < 0.05). Immunosuppressive therapy was used in 67 % children in Group 1 and 75 % children in Group 2. The Kaplan-Meier survival curves for renal function (with normal GFR) and persistent proteinuria did not differ significantly depending on the serum IgA level at baseline. We conclude that in IgA nephropathy the elevated serum IgA at baseline may be associated with mesangial proliferation and segmental sclerosis contribute to glomerulosclerosis, but has no effect on the presence of proteinuria or on the worsening of kidney function during several years of disease course.

The rs1800471 Polymorphism of TGFB1 Gene, Serum TGF-Beta1 Level and Chronic Kidney Disease Progression.

The aim of the study was to investigate whether rs1800471 polymorphism in TGFB1 gene is associated with the development and progression of non-diabetic chronic kidney disease. Moreover, we examined the serum TGF-beta1 concentration and its association with that polymorphism and progression of the disease. We applied two different methodological approaches. Firstly, a family based study was carried out, comprised of 109 patients with non-diabetic chronic kidney disease and their 218 healthy parents, using the transmission/disequilibrium test. The rs1800471 polymorphism and serum TGF-beta1 level were determined in all subjects. Serum TGF-beta1 concentration was also measured in 40 healthy controls. Secondly, we performed a case-control orientated study to determine whether rs1800471 polymorphism and other factors influence the progression of renal impairment. We found no relationships between rs1800471 polymorphism allele transfer and the incidence or progression of non-diabetic chronic kidney disease. We found, however, that the serum TGF-beta1 was significantly higher in patients than in controls. In conclusion, rs1800471 polymorphism in TGFB1 gene does not have an impact on the development and progression of non-diabetic chronic kidney disease caused by primary glomerulopathy and chronic interstitial nephritis. The increased serum TGF-beta1 concentration in such patients suggests its role in the pathomechanism of the disease. Circulating TGF-beta1 level is determined in a multifactorial way, not by rs1800471 polymorphism in TGFB1 gene.

Dynamics of changes in heart conduction system in dialyzed young adults after kidney transplantation--pilot study.

BACKGROUND: Cardiovascular complications are the main clinical problem in patients with end-stage renal failure (ESRF). After successful kidney transplantation, this situation improves, although cardiovascular complications remain a risk factor for increased mortality in these patients; therefore, their early identification is of key therapeutic and prognostic significance. This study was designed to determine a dynamics of changes in the heart conduction system in hemodialyzed young adult patients after kidney transplantation in a long-term follow-up, based on the body surface potential mapping (BSPM) method. METHODS: The study comprised 5 patients (mean age, 20.8 ± 1.16 years) after kidney transplantation (KT) who had been chronically dialyzed before. The mean observation period was 6.7 ± 1.71 years. All of the patients were submitted to the following examinations before and after KT: 12-lead electrocardiography (ECG), echocardiography, standard biochemistry, and BSPM (isochronous maps). The mean creatinine concentration was 1.38 ± 0.05 mg/dL. The control group comprised 30 healthy persons. RESULTS: BSPM maps taken from the dialyzed patients demonstrated disturbed spreading of electric impulses within the heart ventricles in a type of left bundle branch block, despite normal 12-lead ECG and echocardiography results. A relationship was demonstrated between the BSPM changes and dialysis duration. After KT, the abnormal distribution of isochrones and ventricular activation times (VAT) presented some significant and specific regression. CONCLUSIONS: 1) In dialyzed patients, BSPM is a more sensitive method than ECG and enables early identification of changes in the heart conduction system presented as left bundle branch block. 2) Dialysotherapy duration before and after KT determines the extent of the BSPM changes. 3) Successful effects of KT bring about regression of intraventricular conduction disorders. 4) The observations need verification in a larger patient group.

Does a late referral to a nephrologist constitute a problem in children starting renal replacement therapy in Poland?--a nationwide study.

BACKGROUND: It is estimated that 20-50% of adult patients start chronic dialysis therapy without prior contact with a nephrologist. The aim of this nationwide study was to assess clinical and metabolic status of children at the start of chronic dialysis in Poland with regard to the timing of the referral to a nephrologist. METHODS: We studied data of 180 children (mean age 14+/-6 years) undergoing chronic dialysis in 13 (out of 14) dialysis pediatric centres in Poland. Patients were classified as early referrals (ERs) when they entered the dialysis programme at least 1 month after the first referral to a nephrologist or late referrals (LRs) when the dialysis was introduced within 1 month from the first visit. RESULTS: Seventy-nine percent of pediatric patients were referred early (ER) to the dialysis centre and 21% were referred late (LR) and had to start dialysis within a month. When starting dialysis, LR patients had significantly higher levels of urea and phosphate as well as lower calcium and haemoglobin in comparison with ERs. Hypertension, pulmonary oedema, fluid overload, treatment in the intensive care unit (ICU) and body mass index (BMI) below 10th percentile turned out to be more frequent in the LR group. Peritoneal dialysis (PD) was used as the first method of dialysis in 59% of ERs and 46% of LRs. The majority of ER patients was treated in the predialysis period with calcitriol, phosphate binders and low protein diet (84%, 89%, 92% of all children, respectively), and 20% of them received epoetin. In the up to 3 years observation of our initial cohort, we also found that the patients who were referred late were less likely to receive kidney transplant (P = 0.02). CONCLUSION: The results of the study indicate that the LR to a pediatric nephrologist was associated with poorer clinical and metabolic status of children entering chronic dialysis programmes.

Soluble adhesion molecules in children and young adults with chronic renal failure treated conservatively.

PURPOSE: Chronic renal failure (CRF) patients present with signs of immunodeficiency, such as increased incidence of infections. Cell adhesion molecules, determining leukocyte migration, may be responsible for the impaired immune response. The aim of the study was to measure soluble (s) vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), P-selectin and L-selectin levels in sera of CRF children and young adults. MATERIAL AND METHODS: The evaluation of adhesion molecule concentrations by ELISA was performed on 15 patients with serum creatinine levels below 265.2 micromol/l (gr. I), 15 patients with serum creatinine levels above 265.2 micromol/l (gr. II) and 15 controls. RESULTS: sVCAM-1, sICAM-1 and sP-selectin concentrations were elevated in both groups vs controls, whereas sL-selectin levels were decreased in all CRF patients. Mean sVCAM-1 and sICAM-1 values in gr. I and gr. II were comparable. sL-selectin and sP-selectin mean values in gr. II were lower than in gr. I. sICAM-1 correlated with haemoglobin and erythrocyte count in both groups and with haematocrit and serum urea--in gr. I. CONCLUSIONS: Enhanced (sVCAM-1, sICAM-1, sP-selectin) and diminished (sL-selectin) adhesion molecule concentrations in both groups show a state of immunologic imbalance, already present in early stages of CRF. Differences in sL-selectin concentrations between gr. I and II imply a progressive character of CRF-related leukocyte dysfunction. sICAM-1 correlation with anaemia markers may suggest the connection between this molecule and the CRF-related disorders.

[The role of collagen in the process of renal fibrosis]. / Udzial kolagenu w procesach wlóknienia nerek.

The progression of chronic renal failure results from the process of fibrosis, which involves the proliferation of renal fibroblasts and the secretion of extracellular matrix proteins (ecm) by these cells. Collagen is the main component of ecm. Renal collagen types in normal kidney and in renal diseases were described. Mediators that stimulate fibroblast proliferation, collagen turnover and factors its regulating were discussed.

[The role of selected cell adhesion molecules in chronic renal failure patients treated conservatively]. / Rola wybranych czasteczek adhezyjnych w przewleklej niewydolnosci nerek leczonej zachowawczo.

Cell adhesion molecules play a pivotal role in many biological processes. Their membrane-bound forms take part in leukocyte migration in case of inflammation and therefore determine effective immune response. Uremia is a state of immunologic imbalance. By comparison with healthy controls, levels of soluble adhesion molecules are either elevated or lowered in chronic renal failure patients. This fact proves conclusively that activation and inhibition of immunocompetent cells coexist in end stage renal disease, thus showing the complexity of immune disorders in uremia. Taking into account the competitive action between circulating adhesins and their bound counterparts, one can come to the conclusion that soluble forms' dysregulation results in the blockage of membrane-bound adhesion molecules and leads to disordered adhesion. Although the effects of change in circulating adhesins' concentrations seem evident, the reason for this change is still unclear.

[Nutritional status of children treated with continuous ambulatory peritoneal dialysis and ambulatory peritoneal dialysis]. / Stan odzywienia dzieci leczonych ciagla ambulatoryjna dializa otrzewnowa i automatyczna dializa otrzewnowa.

Malnutrition is a very important problem in children with ESRD on peritoneal dialysis. Examinations were conducted on 20 children (9 girls, 11 boys), 10 children were treated continuous ambulatory peritoneal dialysis (CAPD) and 10 automated peritoneal dialysis (APD). Anthropometric and serum biochemical parameters were examined. Dialysis adequacy by KT/V, SCCr, PCR were described. The most significant malnutrition was observed in youngest children with lowest BMI values and significant muscle and fat mass deficiency. Increased protein catabolic rate (PCR) in children under 6 years old was an important factor leading to malnutrition.

[The ability to produce nitric oxide by leukocytes in whole blood of children with recurrent urinary tract infections]. / Zdolnosc do produkcji tlenku azotu przez leukocyty pelnej krwi u dzieci chorych na nawracajace zakazenia ukladu moczowego.

We examined 20 children in age from 6 till 18 years old with recurrent urinary tract infection (rUTI). The control group were 15 healthy volunteers in age from 19 till 23 years old. In all cases nitrogen oxide concentration was designated in supernatant of 48 hours leukocytes culture with using colorimetric method with Griess reagent described by Ding. The spontaneous and LPS stimulated ability to nitrogen oxide production in full blood was estimated. The nitrogen oxide index was counted from the difference of concentration of inducated and stimulated nitrogen oxide. The defective response of the leukocytes of full blood to LPS-stimulation for nitrogen oxide productionin aggravation also in remission in children with rUTI and with rUTI in age till 5 years old and above 5 years old comparing to healthy ones.

[Peroxidation of lipids and activity of antioxidant enzymes in children with nephritic syndrome]. / Peroksydacja lipidów i aktywnosc enzymów antyoksydacyjnych u dzieci z zespolem nerczycowym.

UNLABELLED: The aim of the study was to estimate antioxidant status and reliable factors involved in antioxidant protection in children with nephrotic syndrome (NS). 37 children (20 boys, 17 girls) with nephrotic syndrome (NS), aged 2.5-17 (mean 9.5), were included into the study. Erythrocyte Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) and malonylodialdehide (MDA) was estimated using commercial kits produced by Calbiochem and Bioxytech. RESULTS: 1) Decreased mean values of following parameters in children with NS--acute phase comparing to remission phase and the control group: GSH-Px (123.88 +/- 25.02; 187.69 +/- 24.57; 266.49 +/- 21.84 mU/ml; p < 0.001), GSH: (16.6 +/- 5.99; 27.81 +/- 7.68; 43.79 +/- 7.21 mumol/L; p < 0.001). 2) Increased mean values of following parameters in adequate groups: MDA: (18.70 +/- 2.01; 14.63 +/- 1.51; 9.53 +/- 1.48 mumol, p < 0.001), SOD: 536.27 +/- 450.49; 387.16 +/- 219.49; 236.96 +/- 85.71 U/mg). IN CONCLUSION: there is increased lipid peroxidation and insufficient antioxidant defence in children with nephrotic syndrome.

[Levels of selected soluble adhesion molecules in blood serum of children with chronic glomerulonephritis]. / Stezenie wybranych rozpuszczalnych czasteczek adhezyjnych w surowicy krwi dzieci chorych na przewlekle klebuszkowe zapalenie nerek.

Increased concentrations of circulating soluble adhesion molecules have been reported in a variety of disorders. The aim of this study was to evaluate serum sICAM-1, sVCAM-1, sE-selectin, sP-selectin concentrations in 60 children with chronic glomerulonephritis GN (49 patients with GN and syndrome nephroticum, 11--with GN only), aged 3-17 years (mean 9 years) and in 15 healthy children (control group). The histopathological diagnoses of the 27 patients were: minimal change GN--10 cases, lupus nephritis--3, mesangiocapillary GN--4, mesangial GN--4, membranous GN--1, focal glomerulosclerosis--5. It was found a significant increase of tested soluble adhesion molecules in all children with GN compared to the control, independent on the histopathological type of GN. Serum sVCAM-1 and sP-selectin concentrations were higher in children with GN and syndrome nephroticum compared with patients with GN only. The results indicate activation of platelets, leucocytes, endothelium and its damage in GN. It seems, that more advanced vascular endothelium changes and platelets activation occur in children with GN and syndrome nephroticum.

[Epidemiology of HBV infections and possibilities for therapeutic actions in children and adolescents with end-stage renal failure treated with dialysis]. / Epidemiologia zakazen HBV i mozliwosci dzialan terapeutycznych u dzieci i mlodziezy ze schylkowa niewydolnoscia nerek leczonych nerkozastepczo.

Wide spreading of prophylaxis principles of HBV infections in dialysis centers decreased the HBV infection rate in general population of dialyzed patients in Poland last years. There is neither data concerned with HBV infection epidemiology in children and adolescents, nor data about anti-viral treatment possibilities and effects in this group of dialyzed patients. The aim of the study was evaluating of HBV infection rate in patients of pediatric dialysis centers and analysis of causes of infection and efficacy of treatment. Study was based on data sent in a query-answer by 8 biggest pediatric dialysis centers, all of them treating 210 patients. HBV infection was found much more often (16.6%) than in population of all hemodialyzed patients in Poland. More than 75% non-vaccinated patients was infected before dialysis therapy, remaining were infected during vaccination, before the protecting level of antibodies was gained. Big differences in HBV infection rate among centers are observed. Nowadays HCV infections (more than 40% patients infected) are a bigger issue. Only 10 patients in 5 centers had anti-viral treatment (5 with isolated HBV infection, 5 with mixed HBV/HCV infection). In 9 patients interferon-alpha and in 1 patient lamivudine was administered. Efficacy of interferon-alpha treatment was similar to the population of non-uremic children (33.3% vs. 50% of HBeAg elimination). Majority of patients quite well tolerated the drug. Only in 1 case interferon-alpha treatment had to be ceased because of side effects. In a boy treated with lamivudine, after 3 months elimination of viremia and decrease of ALAT activity was observed. HBV infection in patients of pediatric dialysis centers is still a serious matter. More strict applying of vaccination against hepatitis B before dialysis treatment is needed. The possibility of HBV infections therapy is limited, mostly for economical reasons.

Serum concentration of IL-2, IL-6, TNF-alpha and their soluble receptors in children on maintenance hemodialysis.

In chronic renal failure patients a state of immunodeficiency paradoxically coexists with the activation of immune effector cells, including monocytes and lymphocytes. The activation of these cells leads to the release of cytokines. The aim of this study was to estimate the serum concentrations of IL-2, IL-6, TNF-alpha and their soluble receptors: IL-2 sRalpha, IL-6 sR, sTNF RI in children with chronic renal failure and young adults on maintenance hemodialysis (HD). The study included 16 HD patients (11 females, 5 males) aged 11-22 (mean 16.1 +/- 3.1) years and a control group of 15 age-matched healthy children. Only the mean concentration of IL-6 was similar in HD patients and the control group. The levels of the other cytokines were significantly higher in patients undergoing HD compared to the healthy subjects. No significant differences were observed between the pre- and post-dialysis values or between the values obtained using various dialyzer membranes. These data suggest that immune cells in HD children are in an activated state and that neither a single dialysis session nor the type of dialyzer membrane has an influence on the cytokines examined.

[The condition of circulatory system in children and adolescents with ESRD treated by continuous ambulatory peritoneal dialysis and hemodialysis]. / Stan ukladu krazenia u dzieci i mlodziezy ze schylkowa niewydolnoscia nerek leczonych CADO i HD.

Cardio-vascular abnormalities appear very often in end-stage renal failure patients. Because of this we have examined 54 patients, children and adolescents, 35 patients underwent haemodialysis (HD) and 19 continuous ambulatory peritoneal dialysis (CAPD). We can observe that the anatomical status of the heart was dependent upon the time of the treatment. The function of the heart was normal much longer. Structural heart's abnormalities were observed earlier in patients on HD than on CAPD.

[Lupus nephritis in children]. / Toczniowe zapalenie nerek u dzieci.

UNLABELLED: Systemic lupus erythematosus is a very variable and pleomorphic disease. Lupus nephritis with clinical manifestation appears in 65-70% of patients, kidney morphological changes are observed in 80-100%. In this study we analysed clinical course of lupus nephritis in 15 children treated between 1989-1998 (10 girls, 5 boys, aged 9.5-16 years). The following data were considered: inherited susceptibility to the disease, the first symptoms, primary diagnosis, the symptoms at admission to clinical hospital, the time from first symptoms to diagnosis of lupus, laboratory results, clinical course, treatment, outcome of disease. All children underwent percutaneous renal biopsy. 2 patients had class II, 7 patients--class III, 5--class IV and 1 class V of lupus nephritis. In the treatment were used: oral prednisone, intravenous methylprednisolone, methylprednisolone pulse, cyclophosphamide (oral and i.v.), sandimmum. Total or partial remission with normal renal function was observed in 11 children, 1 had stable renal insufficiency, 1 with terminal renal insufficiency started regular HD treatment, 2 patients died. CONCLUSIONS: Lupus nephritis appears the main in young girls aged 12-15 years; the children with renal symptoms need of early renal biopsy and individual treatment; the prognosis of children with IV class lupus nephritis, severe anaemia, low complement, active urinary sediment and quick progress of renal insufficiency is poor.