Elevated level of lysophosphatidic acid among patients with HNF1B mutations and its role in RCAD syndrome: a multiomic study.

INTRODUCTION: Patients with hepatocyte nuclear factor-1 beta (HNF1B) mutations present a variable phenotype with two main symptoms: maturity onset diabetes of the young (MODY) and polycystic kidney disease (PKD). OBJECTIVES: Identification of serum metabolites specific for HNF1Bmut and evaluation of their role in disease pathogenesis. METHODS: We recruited patients with HNF1Bmut (N = 10), HNF1Amut (N = 10), PKD: non-dialyzed and dialyzed (N = 8 and N = 13); and healthy controls (N = 12). Serum fingerprinting was performed by LC-QTOF-MS. Selected metabolite was validated by ELISA (enzyme-linked immunosorbent assay) measurements and then biologically connected with HNF1B by in silico analysis. HepG2 were stimulated with lysophosphatidic acid (LPA) and HNF1B gene was knocked down (kd) by small interfering RNA. Transcriptomic analysis with microarrays and western blot measurements were performed. RESULTS: Serum levels of six metabolites including: arachidonic acid, hydroxyeicosatetraenoic acid, linoleamide and three LPA (18:1, 18:2 and 20:4), had AUC (the area under the curve) > 0.9 (HNF1Bmut vs comparative groups). The increased level of LPA was confirmed by ELISA measurements. In HepG2HNF1Bkd cells LPA stimulation lead to downregulation of many pathways associated with cell cycle, lipid metabolism, and upregulation of steroid hormone metabolism and Wnt signaling. Also, increased intracellular protein level of autotaxin was detected in the cells. GSK-3alpha/beta protein level and its phosphorylated ratio were differentially affected by LPA stimulation in HNF1Bkd and control cells. CONCLUSIONS: LPA is elevated in sera of patients with HNF1Bmut. LPA contributes to the pathogenesis of HNF1B-MODY by affecting Wnt/GSK-3 signaling.

Relationship between Gd-IgA1 and TNFR1 in IgA nephropathy and IgA vasculitis nephritis in children - multicenter study.

AIM OF THE STUDY: To evaluate the relationship between serum Gd-IgA1 (sGd-IgA1) and serum and urine TNFR1 (sTNFR1, uTNFR1) levels as possible prognostic factors in IgA nephropathy (IgAN) and IgA vasculitis nephritis (IgAVN). MATERIAL AND METHODS: From 299 patients from the Polish Registry of Pediatric IgAN and IgAVN, 60 children (24 IgAN and 36 IgAVN) were included in the study. The control group consisted of 20 healthy children. Proteinuria, haematuria, serum creatinine as well as IgA and C3 levels were measured and glomerular filtration rate (GFR) was calculated at onset and at the end of the follow-up. Kidney biopsy findings were evaluated using the Oxford classification. Serum Gd-IgA1 and serum and urine TNFR1 levels were measured at the end of follow-up. RESULTS: Serum Gd-IgA1 level was significantly higher in IgAN and IgAVN patients in comparison to the control group. Urine TNFR1 was significantly higher in IgAN than in IgAVN and the control group. We did not observe any differences in sTNFR1 level between IgAN, IgAVN and control groups. We found a positive correlation between Gd-IgA1 and creatinine (r = 0.34), and negative between Gd-IgA1 and GFR (r = -0.35) at the end of follow-up. We observed a negative correlation between uTNFR1/creatinine log and albumin level and protein/creatinine ratio. We did not find any correlations between Gd-IgA1 and TNFR1. CONCLUSIONS: The prognostic value of sGd-IgA1 in children with IgAN and IgAVN has been confirmed. TNFR1 is not associated with Gd-IgA1 and is not a useful prognostic marker in children with IgAN/IgAVN and normal kidney function.

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

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

Clinical profile of a Polish cohort of children and young adults with cystinuria.

BACKGROUND: Cystinuria is an inherited disorder that results in increased excretion of cystine in the urine. It accounts for about 1-2% of pediatric kidney stones. In this study, we sought to identify the clinical characteristics of patients with cystinuria in a national cohort. METHODS: This was a retrospective study involving 30 patients from the Polish Registry of Inherited Tubulopathies. Initial data and that from a 6-month follow-up were analyzed. Mutational analysis was performed by targeted Sanger sequencing and, if applicable, MLPA analysis was used to detect large rearrangements. RESULTS: SLC7A9 mutations were detected in 15 children (50%; 10 males, 5 females), SLC3A1 mutations in 14 children (47%; 5 males, 9 females), and bigenic mutations in one male patient. The first clinical symptoms of the disease were detected at a median of 48 months of age (range 3-233 months). When individuals with different mutations were compared, there were no differences identified in gender, age of diagnosis, presence of UTI or urolithiasis, eGFR, calcium, or cystine excretion. The most common initial symptoms were urolithiasis in 26 patients (88%) and urinary tract infections in 4 patients (13%). Urological procedures were performed in 18 out of 30 (60%). CONCLUSIONS: The clinical course of cystinuria is similar among patients, regardless of the type of genetic mutation. Most patients require surgery before diagnosis or soon after it. Patients require combined urological and pharmacological treatment for prevention of stone recurrence and renal function preservation.

"Apple does not fall far from the tree" - subclinical atherosclerosis in children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) increases the risk of atherosclerosis in children and adults. Atherosclerotic cardiovascular disease in young patients FH is usually subclinical but recognition of children with more pronounced changes is crucial for adjusting effective management. Aim of this research was to use ultrasonography with two-dimensional speckle tracking (2DST) and tonometry to evaluate atherosclerotic changes in patients with FH (parents and their offspring). METHODS: Applanation tonometry and carotid arteries sonography with evaluation of the intima-media complex thickness (IMCT) and application of the 2DST were performed in 20 families with FH (20 parents and 29 children). The same size control group (age and sex matched) was included. Results were compared between peers and between generations together with the correlation analysis. RESULTS: Adults with FH, in comparison with healthy peers, presented significantly more atherosclerotic plaques (9 vs. 2, p = 0.0230), had significantly thicker IMC (0.84 ± 0.19 vs. 0.56 ± 0.06 mm, p < 0.0001) and had stiffer arterial wall (for stain: 6.25 ± 2.3 vs. 8.15 ± 2.46, p = 0.0103). In children from both groups there were no atherosclerotic plaques and IMCT did not differ significantly (0.42 ± 0.07 vs. 0.39 ± 0.04, p = 0.1722). However, children with FH had significantly stiffer arterial wall according to 2DST (for strain: 9.22 ± 3.4 vs. 11.93 ± 3.11, p = 0.0057) and tonometry (for the pulse wave velocity: 4.5 ± 0.64 vs.3.96 ± 0.62, p = 0.0047). These parameters correlated with atherosclerosis surrogates in their parents (p < 0.001) but were not significantly affected by presence of presumed pathogenic gene variant. CONCLUSIONS: Children with FH presented subclinical atherosclerosis manifested as decreased arterial wall elasticity. Degree of stiffening was associated with advancement of atherosclerosis in their parents but did not present significant association with gene variants. Sonography with application of 2DST seems to be a good candidate for comprehensive evaluation of atherosclerosis in families with FH.

A single-center study to evaluate the efficacy of a fetal urine peptide signature predicting postnatal renal outcome in fetuses with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUVs) account for 17% of pediatric renal failure. The management of pregnancies involving fetuses with PUV is hampered by the fact that current clinical parameters obtained from fetal ultrasound and/or fetal urine biochemistry are insufficient to predict postnatal renal function. We previously have developed a fetal urine peptide signature (12PUV) that predicted with high precision postnatal renal failure at 2 years of age in fetuses with PUV. Here, we evaluated the accuracy of this signature to predict postnatal renal outcome in fetuses with PUV in an independent single-center study. METHODS: Thirty-three women carrying fetuses with suspected PUV were included. Twenty-five fetuses received vesicoamniotic shunts during pregnancy. PUV was confirmed postnatally in 23 patients. Of those 23 fetuses, 2 were lost in follow-up. Four and 3 patients died in the pre- and perinatal periods, respectively. Follow-up renal function at 6 months of age was obtained for the remaining 14 patients. The primary outcome was early renal failure, defined by an eGFR < 60 mL/min/1.73 m2 before 6 months of age or pre- or perinatal death. RESULTS: The peptide signature predicted postnatal renal outcome in postnatally confirmed PUV fetuses with an AUC of 0.94 (95%CI 0.74-1.0) and an accuracy of 90% (95%CI 78-100). The signature predicted postnatal renal outcome for the suspected PUV cases with an AUC of 0.89 (95%CI 0.72-0.97) and an accuracy of 84% (95%CI 71-97). CONCLUSIONS: This single-center study confirms the predictive power of the previously identified 12PUV fetal urinary peptide signature.

Glomerular filtration decrease after diagnostic cardiac catheterisation in children with congenital cardiac malformation - the role of serum creatinine, cystatin C, neutrophil gelatinase and urine output monitoring.

INTRODUCTION: Diagnosis of contrast induced-nephropathy (CIN) by a classic renal biomarker such as creatinine concentration can be delayed because of various factors that can influence this marker. Changes in new biomarkers such as neutrophil-gelatinase associated lipocalin (NGAL) and cystatin C are postulated to be more sensitive for recognizing patients prone to CIN-acute kidney injury (AKI). AIM: To investigate the role of NGAL and cystatin C as early biomarkers in the diagnosis of kidney injury after cardiac catheterisation. MATERIAL AND METHODS: The study group consisted of 50 patients with congenital heart malformation admitted for scheduled cardiac catheterisation. The biomarkers serum creatinine, serum NGAL and serum cystatin C were tested at 5 time-points sequentially from start to 48 h after the procedure. RESULTS: Significant changes were noted during the research in the serum creatinine concentration (p < 0.001) and serum NGAL concentration (p < 0.001). CIN-AKI, diagnosed by the modified Schwartz formula, occurred in 16 (32%) patients after 24 h and in 8 (16%) after 48 h. Subsequent analysis showed that serum creatinine significantly rose in the first 2 h of the study with simultaneous reduction in the eGFR. Maximum growth in serum NGAL occurred at 6 h after contrast administration and then returned to the baseline values at 24 h. Serum cystatin C level did not significantly change during the study. CONCLUSIONS: We observed a transient decrease in eGFR and a rise of serum NGAL after 2 h but NGAL was most pronounced at 6 h after the procedure. The potential role of cystatin C as a biomarker of CIN-AKI was not proved.

Grayscale ultrasound characteristics of autosomal dominant polycystic kidney disease severity - an adult and pediatric cohort study.

INTRODUCTION: The most common hereditary kidney condition is autosomal dominant polycystic kidney disease. It is the cause of 5-10% of end-stage renal disease. Its symptoms are generally late-onset, typically leading to development of hypertension and chronic kidney disease. Ultrasonography is the imaging modality of choice in its diagnosis and management. The aim of this study is to determine the diagnostic value of grayscale ultrasound imaging in evaluating disease severity. MATERIALS AND METHODS: The study group consisted of 81 patients diagnosed with autosomal dominant polycystic kidney disease, 35 adults and 46 children. Inclusion criterion for adults was the presence of at least 10 large cysts in each kidney; children included into the study had developed at least 1 large renal cyst in each kidney. The number of large cysts, echogenicity of kidney parenchyma, cortical thickness and presentation of cortex/medulla boundary were assessed with the use of Logiq E9 apparatus (GE Healthcare, Netherlands). Patients were divided into groups, based on these morphological parameters. Kidney function was assessed according to serum creatinine concentration and creatinine clearance. Statistical analysis was performed, with p-value lower than 0.05 considered as significant. RESULTS: The number of cysts and the degree of parenchymal dysfunction were the determinants of creatinine level and creatinine clearance, with the second predictor proving stronger. CONCLUSIONS: We recommend that an ultrasound kidney examination in patients with polycystic kidney disease should include evaluating renal parenchyma and the number of cysts for better assessment of disease severity.

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.

Blood concentration of aminothiols in children with relapse of nephrotic syndrome.

BACKGROUND: The role of idiopathic nephrotic syndrome (INS) in the pathogenesis of atherosclerosis in childhood has not been clearly elucidated. However, antioxidative defense in INS is thought to be imbalanced. This study aimed to assess the changes of plasma concentration of selected aminothiols in the blood of children with INS at various stages of the disease. METHODS: This cross-sectional study was conducted in 125 children aged 2-18 years. The children were divided into 4 groups: group A, early relapse (n=37); group B, early remission for 4-6 weeks from the onset (n=37); group C, late steroid-free remission (n=31); and group D, long-term remission for 2-5 years (n=20). Control group (E) consisted of 30 age- and gender-matched healthy children. The study protocol comprised an analysis of plasma concentrations of glutathione, homocysteine, cysteine and cysteinylglycine by high-performance liquid chromatography. Fractions of protein-bound and free aminothiols were measured. Endothelial injury was assessed by thrombomodulin, PAI-1 concentration, and von Willebrand factor activity. RESULTS: The children with INS had unbalanced aminothiol metabolism only in relapse and early remission, that shifted towards increased oxidative processes. Administration of cyclosporine A caused a significant increase in homocysteine and cysteine concentration. Changes in aminothiol metabolism were significantly related to endothelial injury. CONCLUSIONS: The findings of this study may be helpful in elucidating the pathogenesis of premature atherosclerosis in patients with INS refractory to the treatment or in the case of frequent relapse.

Clinical validity of urinary interleukin 18 and interleukin 6 determinations in preterm newborns.

INTRODUCTION: Preterm newborns are at a particular risk of acute kidney injury (AKI) and sepsis. PURPOSE: Assessment of urinary interleukin 18 (ulL-18) and urinary interleukin 6 (ulL-6) concentrations in association with AKI and sepsis respectively in newborns hospitalized in Neonatal Intensive Care Unit (NICU). MATERIAL AND METHODS: An evaluation was carried out of the dependence of ulL-18 on neonatal birth weight (BW) and AKI as well as ulL6 on sepsis. In prospective study, the evaluation included 58 children with BW up to 2000 g. Clinical observations spanned the period between the 1st and 28th day of life. RESULTS: The mean gestational age was 30.3 Hbd, mean BW was 1361.9 g. AKI was diagnosed in 35 (60.3%), sepsis in 22 (39.7%) neonates. For median values of uIL-18 and ulL-18/mgCr, as well as for mean logarithmically transformed values of ulL-18 and ulL-18/mgCr, negative, statistically significant linear correlations were demonstrated for BW. In population, median value of ulL-18 and ulL-18/mgCr decreased respectively by 8.21 pg/ml and 84.8 pg/mgCr per each 100 g increment of BW. A negative, statistically significant linear correlation with an average strength was noted for the dependency of the duration of AKI and BW. No significant differences were observed in uIL-18 and ulL-181 mgCr values between the investigated days of AKI and reference group. There was noted a significant increase of the values of uIL-6 and uIL-6/ mgCr on day 0 of sepsis confirmed by the ROC analysis with AUROC 78% and 74%, respectively. CONCLUSIONS: ulL-18 and ulL-18/mgCr values might be a reliable marker of renal tubules maturation in newborns; ulL-18 is not a reliable marker in diagnosing AKI in neonatal population; ulL-6 and uIL-6/ mgCr concentration values measured on actual days may be regarded an early marker of sepsis; AKI duration in preterm neonates is negatively correlated with BW.

Clinical manifestation of pediatric granulomatosis with polyangiitis - the experience of two regions in Poland.

BACKGROUND: The purpose of this study was to describe clinical manifestations, laboratory findings and outcome of granulomatosis with polyangiitis (GPA) in pediatric patients living in two regions (Southern and Central) of Poland. METHODS: Retrospective analysis of patient hospital records from four large hospitals during a period from 1995 to 2013. Patients with confirmed diagnosis of GPA according to American College of Rheumatology (ACR) and EULAR/PRINTO/PRES criteria for GPA were analyzed. All patients were subjected to clinical, laboratory, radiological and immunological assessment. RESULTS: During this 18-year period only 9 children with confirmed diagnosis of GPA (6 girls, 3 boys) were identified. The average age of the disease onset was 12 years (range: 8-16 years). Average delay between first symptoms and diagnosis was approx. 20 months (range: 0-84 months). Organ system involvement at presentation included: kidneys 88.8% (8/9), lungs 77.7% (7/9), ear/nose/ throat 55.5% (5/9), gastrointestinal tract 55.5% (5/9), skin 44.4% (4/9), joints 22.2% (2/9), eyes 11.1% (1/9) and nervous system 11.1% (1/9). In 5 children disease course was progressive (constant progression of sinusitis in one case, end-stage renal disease in two, chronic kidney disease stage IV in one and one child died due to alveolar hemorrhage). CONCLUSION: The majority of our patients were females. Clinical features of pediatric GPA were similar to those described in adults. None of our patients developed subglottic stenosis and in only 2 children saddle-nose deformity was observed. Although GPA was treated according to contemporary standards care, disease progression was observed in more than a half of children.

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.

Anaemia treatment in chronically dialysed children: a multicentre nationwide observational study.

OBJECTIVE: Erythropoiesis-stimulating agents (ESAs) are applied as a standard therapy in children with anaemia in chronic kidney disease. The aim of this study was to describe the efficacy and details of ESA treatment in a population of dialysed children in Poland. MATERIAL AND METHODS: The study had a prospective observational design and was performed in 12 dialysis centres. The study group comprised 117 dialysed children with a mean age at enrolment of 165.33 (97.18-196.45) months. RESULTS: Dialysed children were treated mostly with epoietin beta and darbepoietin. The mean dose of ESA was 99 (68-147) U/kg/week with a significant difference between patients on peritoneal dialysis [83 (54-115)] and haemodialysis [134 (103-186)] (p < 0.0001). The mean haemoglobin of all the time-point tests during 6 months was 10.91 ± 1.18 g/dl. The efficacy of anaemia treatment was unsatisfactory in 52% of subjects. In multivariate analysis, initial haemoglobin level <10 g/l, any infection, younger age at first dialysis, malnutrition and inadequate ESA dosage remained significant predictors of anaemia. CONCLUSIONS: The study revealed that anaemia treatment in Polish children is unsatisfactory. Late commencement of the treatment, inadequate dosing, malnutrition and infections could constitute risk factors for therapy failure.

The effect of peritoneal dialysis method on residual renal function in children.

We set out to assess the effect of continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) on residual renal function (RRF) in children with end-stage renal disease (ESRD). In 101 children (age: 8.84 +/- 5.25 years; 44 on CAPD, 57 on APD) over 36 months, we evaluated RRF [as daily diuresis (DD) in mL/kg/24 h and mL/m2/24 h], glomerular filtration rate [GFR (in mL/min/1.73 m2)], ESRD cause, presence of arterial hypertension (HTN), biochemical parameters, peritoneal equilibration test (PET), adequacy [as total weekly Kt/V (twKt/V) and creatinine clearance (twCCr)], and infectious complications of PD. Initially, the CAPD and APD groups did not differ significantly in DD, but mean GFR was significantly higher in the APD group (p < 0.05). In the CAPD group, the volume of high osmolarity PD fluid was significantly lower (p < 0.05), and the rates of peritonitis and exit-site infection and of aminoglycoside use were higher (p < 0.001, p < 0.05, and p < 0.005 respectively). Over 36 months, the mean twKt/V and twCCr were within norms in both groups, but were higher in APD, significantly so (p < 0.05) for twKt/V at 24 and 36 months and for twCCr initially. In both groups, RRF decreased systematically, with a significantly lower (p < 0.05) rate of DD (mL/m2/24 h) and GFR decline in the first year in CAPD, but without a difference in the next 2 years. The longest RRF preservation was in children with tubulointerstitial nephropathies, particularly hypoplasia and dysplasia (p < 0.05). Children with hemolytic uremic syndrome (HUS) and hereditary nephropathy were at the highest anuria risk. Compared with the 22 children (7 CAPD, 15 APD) who became anuric, the 20 children (10 CAPD, 10 APD) with RRF preserved for 36 months had a higher DD and GFR before dialysis onset; higher hemoglobin and albumin; and lower HTN prevalence, cholesterol, triglycerides, and proteinuria (p < 0.05). Risk of anuria during 36 months did not differ significantly between the CAPD and APD groups. In children on CAPD or APD, risk factors for RRF loss include HUS, hereditary nephropathy, low diuresis and GFR before dialysis onset, HTN, anemia, hypoalbuminemia, hyperlipidemia, and proteinuria. Compared with children on APD, those on CAPD show better preservation of RRF during year 1, although the risk of anuria seems to be the same for both methods. In children with risk factors for rapid diuresis loss, CAPD might be considered the preferred initial dialysis method.

[Calcium-phosphate disturbances in dialysed children and adolescents--one centre analysis between 1991-2008]. / Zaburzenia gospodarki wapniowo-fosforanowej u dzieci i mlodziezy dializowanych w latach 1991-2008--doswiadczenia jednego osrodka.

UNLABELLED: Disturbances of calcium-phosphate metabolism are one of the most prominent complications of chronic kidney disease with high impact on cardiovascular complications and outcome. The aim of the study was to assess the clinical efficacy of CKD-related calcium-phosphate homeostasis treatment in children and adolescents on chronic dialysis in a tertiary reference centre between 1991 to 2008. MATERIAL AND METHODS: Study group consisted of 81 subjects (29F, 52M): 40 hemodialysis and 41 peritoneal dialysis patients (aged at start of dialysis: 1m.-17 y.). Treatment period ranged from 7 to 150 months. 9 subjects died on dialysis. A retrospective analysis of medical records was performed for serum calcium, phosphate, parthormon, alkaline phosphatase, CaxP product and applied treatment (conservative or surgery). The analysis was conducted in 4-5 y time intervals. RESULTS: We did not observed significant differences in the most of analyzed parameters apart a tendency to increase in PTH levels in last 9 years. Conservative treatment comprised a diet, calcium phosphate binders, vitamin D metabolites and non-calcium phosphate binders (since 2003). Parathyroidectomy was performer as surgery. CONCLUSIONS: The efficacy of treatment of CKD-related calcium-phosphate disturbances in children and adolescents on chronic dialysis has not changed in last several years despite introduction of new methods of treatment.

[Homocysteine and glutathione metabolism in steroid-treated relapse of idiopathic nephrotic syndrome]. / Metabolizm homocysteiny i glutationu w zaostrzeniu idiopatycznego zespolu nerczycowego leczonym glikokortykosteroidami.

UNLABELLED: Changes in metabolism of aminothiols may have an influence on endothelial function or change the red-ox balance. The aim of study was designed to assess changes in plasma aminothiols': proatherogenic (homocysteine-HCY) and antiatherogenic (glutathione-GSH) metabolism in nephrotic syndrome in children. MATERIAL AND METHODS: The study group included 77 nephrotic children (aged 2-18 years) divided into four groups, i.e. in acute phase of the disease (24), during steroid-induced (24), steroid-free (12) and in long-term remission (17). Twenty five healthy children served as controls. GSH and HCY in plasma were assessed by high-performance liquid chromatography. Fraction of protein-bound and free aminothiols was assessed and albumin saturation was calculated. RESULTS: GSH and its fractions' concentrations were comparable to healthy subject, however in early relapse free fraction was significantly higher than in late remission. The albumin saturation with GSH was significantly higher in early than in late relapse. Total HCY concentration was decreased in early relapse, elevated after 2 week and comparable to controls after 8 week of treatment. HCY free fraction and albumin saturation were elevated within first 2 weeks. Children in long-term remission showed elevated total concentration of HCY and GSH and their protein bound fractions when compared to controls. Albumin saturation with these aminoacids was higher as well. CONCLUSION: The study showed aminothiol imbalance in children in first weeks of relapse of nephrotic syndrome.

[Pyelonephritis with massive renal tissue necrosis in child with urinary tract malformation--a case report]. / Odmiedniczkowe zapalenie nerek z rozlegla martwica miazszu nerek na podlozu wady wrodzonej ukladu moczowego--opis przypadku.

The aim of the case report is presentation of unusual and heavy clinical course of pyelonephritis with renal tissue necrosis in a child with urinary tract malformation. Nine month old girl was admitted to hospital in heavy clinical status due to pyelonephritis--urosepsis. It was complicated by acute renal insufficiency. Patient was treated by broad-spectrum antibiotics and parenteral nutrition. She was feverish for 14 days. Computed tomography done in order to exclude abdominal abscess showed massive renal tissue necrosis of on both sides. Antibiotic treatment was successful after 6 weeks. Urological evaluation revealed bilateral vesico-ureteral refluxes grade IV. Scintigraphy showed multiple scars. Patient was treated Deflux injections (twice). We noted 5 urinary tract recurrences despite antibiotic profilaxis. GFR of 75 ml/min/1.73 m2 was estimated at age of 16 m. Immunodeficiency or malignancy as background of clinical course were excluded. The case we describe presents severe clinical course of pyelonephritis due to complex urinary tract malformation that is to be considered despite based on modern publications "sparing" strategies of diagnosis and profilaxis in urinary tract malformations.

Ectopic mediastinal parathyroid carcinoma as a cause of dialysis-dependent renal failure.

Carcinoma of the parathyroid gland is infrequent in patients with secondary hyperparathyroidism. Typical clinical symptoms are related to the presence of a neck mass and hypercalcemia. We describe a case of a 55-year-old man in whom primary parathyroid carcinoma led most likely to the development of end-stage dialysis-dependent renal failure, and the diagnosis of the cancer was delayed due to ectopic localization of the tumor, and dramatic complications in the clinical course of the disease, including acute pancreatitis and peritionitis. However, 6 months after successful surgery and subsequent radiotherapy, the patient is well and free from recurrences but remains chronically dialysis-dependent.

Continuous veno-venous hemodiafiltration in children after cardiac surgery.

OBJECTIVE: Acute renal failure (ARF) is still a frequent complication following extensive cardiac surgery. Renal replacement therapy (RRT) modality preferences to treat critically ill children have shifted from peritoneal dialysis to continuous renal replacement therapy (CRRT), although the experience with the latter is still highly limited in the infants. METHODS: We describe our results with continuous veno-venous hemodiafiltration (CVVHDF) in 25 children (15 males, 10 females) who underwent CRRT from 2001 to 2006 and were retrospectively reviewed. RESULTS: We performed continuous veno-venous hemodiafiltration (CVHDF) using PRISMA (Hospal). The mean age at the onset of CRRT was 26 months (ranging from 7 days to 11.2 years) and the mean body weight was 14 kg. The mean duration of RRT was 67 h (8-243 h) with ultrafiltration rate 4.9 ml/(h kg); the mean filter "lifetime" was 31.5h. Anticoagulation was achieved with non-fractioned heparin infusion (21/25 cases) and enoxaparin (2/16). The mean creatinine concentrations at the beginning, 24, 48 and 72 h were as follows: 171, 100, 65 and 88 micromol/l. Of these 25 treated children, 19 died in the postoperative period (8 during CVVHDF). The mortality rate for the entire group was 76%. The main cause of death was cardiac failure and sepsis with multiorgan dysfunction (MODS). The main complication during CRRT was bleeding, transient hypothermia, thrombocytopenia and filter clotting which occurred in about one-third of the patients. CONCLUSIONS: We conclude that CVVHDF may be an alternative method of renal support for critically ill children after cardiac surgery in experienced centers, but a significant number of specific complications should be taken into account.