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Background Diabetic ketoacidosis (DKA) and hyperglycaemia without ketoacidosis are common acute complications of diabetes. Their association with acute kidney injury (AKI) and diabetic kidney disease (DKD) was studied. Methods The study group consisted of 197 children with type 1 diabetes with average diabetes duration of 8.08 ± 2.32 years. The medical history of the patients was retrospectively reviewed. The number of children with severe hyperglycaemia, DKA and AKI was assessed. The association with the risk of chronic kidney disease (CKD) was analysed. Results AKI was found in 14% of cases hospitalised for DKA and 8% of cases hospitalised for hyperglycaemia. Patients with AKI showed a significantly increased corrected sodium (141.23 ± 5.09 mmol/L, p = 0.035). Patients with AKI in DKA showed a significant increase in WBC (20.73 ± 8.71 × 103/µL, p = 0.0009). Follow-up analysis after a minimum of 5 years of diabetes revealed that a single episode of DKA was found in 63 patients and a single episode of AKI in 18 patients. Two or more episodes of DKA were found in 18 patients, and nine cases were complicated by AKI. These patients showed a significant increase in urinary albumin excretion (44.20 ± 64.21 mg/24 h), the highest values of eGFR and the worst glycaemic control. Conclusions Diabetic children can develop AKI in the course of DKA and hyperglycaemia without ketoacidosis, which is associated with volume depletion and reflected by corrected sodium concentration. AKI in DKA seems to be complicated by stress and inflammation activation. AKI and poor glycaemic control with repeated DKA episodes can magnify the risk of progression to DKD. Graphical abstract

Background For therapeutic drug monitoring (TDM) of mycophenolic acid (MPA), which is frequently proposed, saliva might be a suitable and easy-to-obtain biological matrix. The study aimed to validate an HPLC method with fluorescence detection for determining mycophenolic acid in saliva (sMPA) in children with nephrotic syndrome. Methods The mobile phase was composed of methanol and tetrabutylammonium bromide with disodium hydrogen phosphate (pH 8.5) at a 48:52 ratio. To prepare the saliva samples, 100 µL of saliva, 50 µL of calibration standards, and 50 µL of levofloxacin (used as an internal standard) were mixed and evaporated to dryness at 45 °C for 2 h. The resulting dry extract was reconstituted in the mobile phase and injected into the HPLC system after centrifugation. Saliva samples from study participants were collected using Salivette® devices. Results The method was linear within the range of 5–2000 ng/mL, was selective with no carry-over effect and met the acceptance criteria for within-run and between-run accuracy and precision. Saliva samples can be stored for up to 2 h at room temperature, for up to 4 h at 4 °C, and for up to 6 months at − 80 °C. MPA was stable in saliva after three freeze–thaw cycles, in dry extract for 20 h at 4 °C, and for 4 h in the autosampler at room temperature. MPA recovery from Salivette® cotton swabs was within the range of 94–105%. The sMPA concentrations in the two children with nephrotic syndrome who were treated with mycophenolate mofetil were within 5–112 ng/mL. Conclusions The sMPA determination method is specific, selective, and meets the validation requirements for analytic methods. It may be used in children with nephrotic syndrome; however further studies are required to investigate focusing on sMPA and the correlation between sMPA and total MPA and its possible contribution to MPA TDM is required. Graphical abstract

Background Steroid resistant (SR) nephrotic syndrome (NS) affects up to 30% of children and is responsible for fast progression to end stage renal disease. Currently there is no early prognostic marker of SR and studied candidate variants and parameters differ highly between distinct ethnic cohorts. Methods Here, we analyzed 11polymorphic variants, 6 mutations, SOCS3 promoter methylation and biochemical parameters as prognostic markers in a group of 124 Polish NS children (53 steroid resistant, 71 steroid sensitive including 31 steroid dependent) and 55 controls. We used single marker and multiple logistic regression analysis, accompanied by prediction modeling using neural network approach. Results We achieved 92% (AUC = 0.778) SR prediction for binomial and 63% for multinomial calculations, with the strongest predictors ABCB1 rs1922240, rs1045642 and rs2235048, CD73 rs9444348 and rs4431401, serum creatinine and unmethylated SOCS3 promoter region. Next, we achieved 80% (AUC = 0.720) in binomial and 63% in multinomial prediction of SD, with the strongest predictors ABCB1 rs1045642 and rs2235048. Haplotype analysis revealed CD73_AG to be associated with SR while ABCB1_AGT was associated with SR, SD and membranoproliferative pattern of kidney injury regardless the steroid response. Conclusions We achieved prediction of steroid resistance and, as a novelty, steroid dependence, based on early markers in NS children. Such predictions, prior to drug administration, could facilitate decision on a proper treatment and avoid diverse effects of high steroid doses.

Some studies have shown that the area under the concentration-time curve (AUC) of mycophenolic acid (MPA) should be higher for children with nephrotic syndrome (NS) than after renal transplantation. The pharmacodynamic aspect of MPA, the activity of inosine monophosphate dehydrogenase (IMPDH), has not been studied in children with NS. The study included 21 children (4-16 years old) with NS treated with mycophenolate mofetil. MPA and its glucuronide plasma concentrations were determined using validated high-performance liquid chromatography-ultraviolet (HPLC-UV). The separate HPLC-UV method was applied for IMPDH activity determination. The variability was expressed by the coefficient of variation (CV). IMPDH activity and MPA concentration (C

Background: Late failure of arterial aortocoronary conduits may result from abnormal activity of cells found in the vessel wall, including macrophages. The purpose of this study was to assess if there are any associations between the number of macrophages and overexpression of matrix metalloproteinases (MMPs) in the wall of arterial grafts, as well as their clinical significance. Methods: This study involved 128 consecutive patients with a mean age of 64.9 ± 9.7 years who underwent elective surgery for coronary artery disease (CAD). The surplus segments of internal thoracic artery (ITA) and radial arteries (RA) were taken for immunohistochemical analysis of macrophage numbers and MMPs expression. The participants who reached the clinical primary end-point (cardiacrelated death, acute coronary syndrome or progression of CAD) had a follow-up angiography. Results: The mean numbers of macrophages were higher on RA (70 [24; 112]) than ITA cross-sections (44 [24; 59]; p < 0.001). Median expression of both MMP2 and MMP9 were stronger in the ITA than RA cross-sections (p < 0.001). A significant positive correlation of MMP2 expression and a number of macrophages infiltrating the tunica media of arterial segments were noted on both ITA and RA cross-sections. In addition, the arterial segments of the 6 patients who reached clinical end-point had higher numbers of macrophages and stronger MMP2 expression when compared to the rest of the participants. Conclusions: Macrophage infiltration of arterial wall grafts prior to harvesting may be associated with higher risk of late occlusion and MMP2 might be facilitating this process.

(1) Background: A rarely discussed effect of obesity-related glomerulopathy (ORG) may slowly lead to irreversible glomerular damage and the development of chronic kidney disease. These patients need to undertake medical care, but whether they should be included in intensive oral care is still not mandatory. The study aimed to assess a relationship between renal, metabolic, and oral health indicators among pediatric patients affected by simple obesity. (2) Methods: 45 children and adolescents with simple obesity hospitalized (BMI 34.1 ± 4.8 kg/m2, age 15.4 ± 2.3) and compared with 41 aged-matched healthy controls (BMI 16.4 ± 2.4 kg/m2, age 15.4 ± 2.7). Echocardiography, 24-h ambulatory blood pressure monitoring, ultrasound exam with Doppler, and laboratory tests including kidney and metabolic markers were performed. Oral status was examined regarding the occurrence of carious lesions using decay missing filling teeth (DMFT), gingivitis as bleeding on probing (BOP), and bacterial colonization as plaque control record (PCR). (3) Results: The strongest correlation was revealed between BMI and concentration of uric acid, cystatin C, GFR estimated by the Filler formula (r = 0.74, r = 0.48, r = −0.52), and between oral variables such as PCR and BOP (r = 0.54, r = 0.58). Children and adolescents with obesity demonstrated untreated dental caries, less efficient in plaque control and gingivitis. (4) Conclusions: No specific relation to markers of kidney disease were found, however, more frequent gingivitis/bacterial colonization and significant differences in oral status between obese and non-obese patients were revealed. Susceptibility to inflammation may be conducive to developing metabolic syndrome and kidney damage in the form of obesity-related glomerulopathy and contribute to future dental caries. Uric acid seems to indicate metabolic syndrome and cardiovascular complications (LVMI &gt, 95 percentiles). Cystatin C and uric acid might aspire to be early markers of kidney damage leading to obesity-related glomerulopathy.

RECOMMENDATIONS OF THE POLISH SOCIETY OF HYPERTENSION GUIDELINE EDITORS: Andrzej Tykarski, Krzysztof J. Filipiak, Andrzej Januszewicz, Mieczyslaw Litwin, Krzysztof Narkiewicz, Aleksander Prejbisz, Danuta Ostalska-Nowicka, Krystyna Widecka, Katarzyna Kostka-Jeziorny EXPERTS: Marcin Adamczak, Marta Buraczewska, Ludwina Szczepaniak-Chichel, Marzena Chrostowska, Danuta Czarnecka, Piotr Dobrowolski, Grzegorz Dzida, Zbigniew Gaciong, Jerzy Gąsowski, Tomasz Grodzicki, Dagmara Hering, Beata Wozakowska-Kaplon, Przemyslaw Kosinski, Beata Begier-Krasinska, Jan Krekora, Jacek Manitius, Malgorzata Myśliwiec, Anna Niemirska, Arkadiusz Niklas, Łukasz Obrycki, Agnieszka Olszanecka, Sylwester Prokurat, Grazyna Brzezinska-Rajszys, Marek Rajzer, Katarzyna Stolarz-Skrzypek, Agnieszka Szadkowska, Filip M. Szymanski, Anna Szyndler, Andrzej Wiecek, Barbara Wizner, Jacek Wolf, Tomasz Zdrojewski

RECOMMENDATIONS OF THE POLISH SOCIETY OF HYPERTENSION GUIDELINE EDITORS: Andrzej Tykarski, Krzysztof J. Filipiak, Andrzej Januszewicz, Mieczyslaw Litwin, Krzysztof Narkiewicz, Aleksander Prejbisz, Danuta Ostalska-Nowicka, Krystyna Widecka, Katarzyna Kostka-Jeziorny EXPERTS: Marcin Adamczak, Marta Buraczewska, Ludwina Szczepaniak-Chichel, Marzena Chrostowska, Danuta Czarnecka, Piotr Dobrowolski, Grzegorz Dzida, Zbigniew Gaciong, Jerzy Gąsowski, Tomasz Grodzicki, Dagmara Hering, Beata Wozakowska-Kaplon, Przemyslaw Kosinski, Beata Begier-Krasinska, Jan Krekora, Jacek Manitius, Malgorzata Myśliwiec, Anna Niemirska, Arkadiusz Niklas, Łukasz Obrycki, Agnieszka Olszanecka, Sylwester Prokurat, Grazyna Brzezinska-Rajszys, Marek Rajzer, Katarzyna Stolarz-Skrzypek, Agnieszka Szadkowska, Filip M. Szymanski, Anna Szyndler, Andrzej Wiecek, Barbara Wizner, Jacek Wolf, Tomasz Zdrojewski

Limited sampling strategy (LSS) is a precise and relatively convenient therapeutic drug monitoring method. We evaluated LSSs for mycophenolic acid (MPA) in children with nephrotic syndrome treated with mycophenolic mofetil (MMF) and validated the LSSs using two different approaches. We measured MPA plasma concentrations in 31 children using HPLC-UV method and received 37 MPA pharmacokinetic profiles (0–12 h). For six children, MPA profiles were estimated twice after two MMF doses. LSSs were developed using multilinear regression with STATISTICA and R software and validated using validation group and bootstrap method, respectively. The best three time point equations included C1, C3, C6 (good guess 83%, bias − 2.78%; 95% confidence interval (CI) − 9.85–0.46); C1, C2, C6 (good guess 72%, bias 0.72%; 95% CI − 5.33–7.69); and C1, C2, C4 (good guess 72%, bias 2.05%; 95% CI − 4.92–13.01) for STATISTICA software. For R software, the best equations consisted of C1, C3, C6 (good guess 92%, bias − 2.69%; 95% CI − 27.18–33.75); C0, C1, C3 (good guess 84%, bias − 2.11%; 95% CI − 24.19–22.29); and C0, C1, C2 (good guess 84%, bias − 0.48%; 95% CI − 30.77–54.07). During validation, better results were obtained for R evaluations, i.e., bootstrap method. The most useful equations included C0, C1, C3 and C0, C1, C2 time points; however, the most precise included C1, C3, C6 time points because of MPA enterohepatic recirculation. Better results were obtained for bootstrap validation due to greater number of patients. Validated LSS should be used only in the population for which it was developed. As there is growing evidence that underexposure of MPA is associated with insufficient treatment response, we recommend the introduction of therapeutic drug monitoring for MPA in children with nephrotic syndrome.

We evaluated mycophenolic acid (MPA) limited sampling strategies (LSSs) established using multiple linear regression (MLR) in children with nephrotic syndrome treated with mycophenolate mofetil (MMF). MLR-LSS is an easy-to-determine approach of therapeutic drug monitoring (TDM). We assessed the practicability of different LSSs for the estimation of MPA exposure as well as the optimal time points for MPA TDM. The literature search returned 29 studies dated 1998–2020. We applied 53 LSSs (n = 48 for MPA, n = 5 for free MPA [fMPA]) to predict the area under the time-concentration curve (AUCpred) in 24 children with nephrotic syndrome, for whom we previously determined MPA and fMPA concentrations, and compare the results with the determined AUC (AUCtotal). Nine equations met the requirements for bias and precision ±15%. The MPA AUC in children with nephrotic syndrome was predicted the best by four time-point LSSs developed for renal transplant recipients. Out of five LSSs evaluated for fMPA, none fulfilled the ±15% criteria for bias and precision probably due to very high percentage of bound MPA (99.64%). MPA LSS for children with nephrotic syndrome should include blood samples collected 1 h, 2 h and near the second MPA maximum concentration. MPA concentrations determined with the high performance liquid chromatography after multiplying by 1.175 may be used in LSSs based on MPA concentrations determined with the immunoassay technique. MPA LSS may facilitate TDM in the case of MMF, however, more studies on fMPA LSS are required for children with nephrotic syndrome.

Background Glomerular hyperfiltration, initiating development of obesity-related glomerulopathy, results in an enlargement of the glomeruli and unsealing of the filtration barrier. It can be followed by adaptive focal segmental glomerulosclerosis and chronic kidney disease (CKD). The aim of the study was to determine the expression pattern of lipid metabolism and selected kidney damage markers in obese adolescents and to identify potential factors which can predict CKD. Methods The study group consisted of 142 adolescents with a BMI z-score > 2. Sixty-two healthy and normal-weight individuals served as controls. The factors associated with the rate of glomerular filtration in obese adolescents were assessed by linear regression methods using univariate and multivariate analyses. The risk of developing CKD was estimated using the Fisher’s exact test. Results The study group was divided into “elevated,” “normal,” and “decreased” glomerular filtration rate (GFR) patients. Increased urine galectin-3 (Gal-3) concentration was diagnosed in all patients. “Decreased GFR” subjects expressed increased urine concentration of neutrophil gelatinase-associated lipocalin (NGAL) and daily megalin excretion. Thirty-nine study participants developed CKD. Increased uric acid (UA) concentration was associated with CKD development both in “normal” and “decreased GFR” patients. Additionally, in “normal” GFR patients, increased concentrations of cholesterol (Ch), triglycerides (TG), and NGAL were associated with CKD. Conclusions Increased serum concentrations of Ch, TG, and UA and increased urine concentration of NGAL might predict CKD development in obese adolescents with normal and decreased GFR. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

The aim of this case&ndash, control study was the evaluation of the association between biomarkers of early primary arterial hypertension (HA) and oral diseases among children and adolescents. Material and methods. Subjects suspected of primary HA (n = 180) underwent a complex evaluation of their vascular status: blood pressure, heart rate, vascular stiffness, sympathetic activity in a 24 h ambulatory examination, followed by measurement of serum uric acid (UA), cystatin C, and creatinine. This procedure allowed the identification of children with primary (n = 58) and secondary HA (n = 74), as well as of children with normal arterial blood pressure, who served as a control group (n = 48). All subjects with secondary HA were excluded from further investigation. Oral examination included the measurement of caries intensity (using the decayed, missing, filled index for permanent teeth DMFT /primary teeth dmft), bacterial plaque (by the plaque control record index, PCR%), and gingivitis (by the bleeding on probing index, BOP%). For statistical analysis, a linear regression model and Spearman rank correlation were used. Results. UA, cystatin C, and creatinine were not altered in the HA group. However, the number of decayed permanent teeth (DT) and the DMFT, PCR%, and BOP% indexes were significantly higher in the primary HA group compared to the control group (p = 0.0006, p = 0.02, p = 0.0009, p = 0.003). Our results are not sufficient to prove the important role of caries and gingival inflammation in the modulation of HA symptoms, although they prove the association of oral diseases with primary HA symptoms. This may indicate future strategies for preventive measures for hypertensive children and adolescents.

BACKGROUND Hypertension is a growing clinical problem in pediatric population. Also, the cause of hypertension is usually unknown and it may result from systemic inflammation related to tooth decay. AIM To estimate the potential association in cross-sectional study between tooth decay and hypertension in children and adolescents. PATIENTS AND METHODS Study group-65 children diagnosed with primary arterial hypertension; control subjects-44 normotensive children. Blood pressure, dental examination, measurement of salivary cortisol, alpha-amylase, secretory IgA, and lysozyme concentrations were performed in all of the children. RESULTS Hyper- and normotensive children had similar peripheral blood morphology and serum biochemical parameters, except of uric acid concentration, which was significantly higher in the study group (p = .047). Salivary evening concentrations of cortisol and alpha-amylase were significantly higher in hypertensive children (p = .002 and p = .004, respectively). Although 24-hr systolic blood pressure (SBP), including daytime and nighttime SBP, correlated with "decay," "microalbuminuria," "BMI," and "glomerular filtration rate" (r > .75, r > .7, r

BACKGROUND The early impact of type-1 diabetes mellitus (DM1), increased blood pressure and glomerular hyperfiltration (GHF) on kidney damage in adolescents using two urinary markers of kidney injury - neutrophil gelatinase-associated lipocalin (uNGAL) and transferrin (uTransf) was assessed. METHODS The study group consisted of 80 adolescents with DM1, of whom 42 were patients with increased blood pressure (IBP), and 38 were patients with normal blood pressure (NBP). Blood pressure was assessed by 24-hour ambulatory bloodpressure monitoring. All patients showed estimated glomerular-filtration rates (eGFRs) above 90 ml/min/1.73m2. The control group consisted of 19 healthy, age and gender-matched adolescents. RESULTS All diabetic children showed a significant increase in uNGAL (p

In pediatric nephrotic syndrome, recommended mycophenolic acid (MPA) pharmacokinetics are higher than those for transplant recipients. In MPA therapeutic monitoring, inosine-5&prime, monophosphate dehydrogenase (IMPDH) activity may be useful. We modified the method established for renal transplant recipients and determined IMPDH activity in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and children (4&ndash, 16 years) with nephrotic syndrome treated with mycophenolate mofetil (MMF). From children, four blood samples were collected, and MPA concentrations were also determined. IMPDH activity was calculated using xanthosine monophosphate (XMP) normalized with adenosine monophosphate (AMP), both determined with the HPLC-UV method. The modified method was accurate, precise, and linear for AMP and XMP within 0.50&ndash, 50.0 &mu, moL/L. Mean IMPDH activity in volunteers was 45.97 &plusmn, 6.24 &micro, moL&middot, s&ndash, 1&middot, moL&ndash, 1 AMP, whereas for children, the values were variable and amounted to 39.23 &plusmn, 27.40 &micro, 1 AMP and 17.97 &plusmn, 15.24 &micro, 1 AMP before the next MMF dose and 1 h afterward, respectively. The modified method may be applied to IMPDH activity determination in children with nephrotic syndrome treated with MMF. IMPDH activity should be determined after one thawing of PBMCs due to the change in AMP and XMP concentrations after subsequent thawing. For children, the lowest IMPDH activity was observed concomitantly with the highest MPA concentration.

The aim of the study was a multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab (Rtx) in children with steroid-resistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in eight paediatric nephrology centres in Poland. The children were administered a single initial infusion of rituximab at the dose of 375 mg/m2 of the body surface area. Proteinuria, the daily supply of glucocorticoids, and cyclosporine were assessed at the moment of the start of the treatment and after 6 months since its commencement. Before Rtx therapy, complete remission was found in 13 patients (43%) and partial remission was found in 8 patients (26%). These numbers increased to 16 (53%) and 12 (40%), respectively. At the start of the treatment 23 patients (76.6%) were treated with cyclosporine A. After 6 months, this number decreased to 15 patients (35%). At the start of the treatment, 18 patients (60%) were treated with prednisone. After 6 months, this number decreased to 8 patients (44%). Children with SRNS may potentially benefit from Rtx treatment despite relative risk of side effects. The benefits may include reduction of proteinuria or reduction of other immunosuppressants.

BACKGROUND Clean intermittent catheterization (CIC) is a standard treatment for patients who are unable to empty the bladder. In the absence of the urethra or if catheterization through the urethra is problematic, a continent vesicostomy is used as a catheterizable conduit. The Malone procedure is an established treatment option for children with neurogenic constipation and fecal incontinence. OBJECTIVES The aim of the study was to report the authors' experience with continent catheterizable conduits (CCCs) in children, to review the results and to determine the efficacy of the technique, with an emphasis on continence and the need for revision. MATERIAL AND METHODS The retrospective study involved children who underwent catheterizable conduit procedures from 2000 to 2015. Two kinds of continent stomas were performed: Mitrofanoff vesicostomies for CIC and Malone antegrade continence enemas (MACEs). The 115 patients treated included 66 girls and 49 boys. A total of 134 operations were performed; 62 were Mitrofanoff vesicostomies and 72 were Malone appendicostomies. In 19 cases, both Mitrofanoff and Malone appendicostomies were formed out of 1 appendix divided into 2 parts. In 5 children vesicocutaneous stomas were constructed using Monti's procedure, and in 1 it was constructed from an intussuscepted ileal loop. In 27 patients Malone procedures were performed laparoscopically. RESULTS The mean follow-up period was 8.6 years. There was no serious morbidity in relation to the surgery. In 9 children local wound infection was noted, and in 9 others stomal stenosis developed. Out of the 62 children with catheterizable vesicostomies, 59 were continent. The MACE procedure was successful in all 72 patients; problems with constipation and fecal incontinence were resolved in all cases. None of the laparoscopies needed conversion. CONCLUSIONS Continent catheterizable conduits help patients achieve both fecal and urinary continence. Laparoscopy is effective in performing the Malone procedure. Stoma-related complications could be avoided using end-to-side appendix anastomoses to the skin. Stomal incontinence is rare even when a simplified technique is employed, using the appendix without cecoplication.

Patient: Female, 7 Final Diagnosis: Xanthogranulomatosus pyelonephritis Symptoms: Leucocyturia Medication: — Clinical Procedure: Nephrectomy Specialty: Nephrology Objective: Unusual clinical course Background: Xanthogranulomatous pyelonephritis (XP) is an extremely rare, severe, atypical form of chronic renal parenchymal inflammation accompanied by hydronephrosis and/or urolithiasis. The pathomechanism of XP is not yet fully understood. Microscopically, XP is indicated by the presence of multinucleated giant cells and lipid-laden macrophages, as well as inflammatory infiltration and intensive renal fibrosis. The lipid accumulation in kidney parenchyma may be secondary to the altered flow of low-density lipoprotein (LDL)-derived cholesterol particles inside the affected cells. Physiologically, the process of LDL-derived cholesterol transport from lysosomes to the sites of its esterification is dependent on vimentin, which is a molecule comprising the cytoskeleton in mesenchymal cells. Case Report: A 7-year old girl was hospitalized because of the finding of unexplained kidney lesions on an abdominal ultrasound examination (an enlarged and deformed collecting system of the right kidney with hyperechogenic, solid, staghorn lesions in the calyces). Three months earlier, the patient had experienced recurrent urinary tract infection. Based on the subsequent laboratory and imaging diagnostics, the final diagnosis of XP was established and the girl was qualified for right-sided nephrectomy Microscopic examination revealed numerous foci of granuloma formations with no evident exponents of dysplastic or neoplastic abnormalities. Significant CD68-positive cell infiltrations and scattered foam cells arranging the numerous foci of granuloma inflammation were noticed. Renal parenchyma, adjacent to granuloma lesions, presented a vimentin expression. Conclusions: Vimentin expression in XP may confirm a focal character of chronic granuloma formation and may suggest the complexity of XP pathogenesis involving not only macrophage and fibroblast activation but also local lipid deregulation and fibrosis.

Nephrotic-range proteinuria as a paraneoplastic syndrome (PNS) is an exceptional presentation, especially in children. It is usually associated with hematologic malignancies. Solid tumors are very rare causes of proteinuria. We present the case of a 7-year-old boy with an extremely rare atypical thymic carcinoid accompanied by nephrotic-range proteinuria as PNS. The kidney biopsy was consistent with minimal change disease (MCD). Tests for a neuroendocrine tumor were performed due to symptoms of hypercortisolemia and an elevated concentration of chromogranin A in the serum. The chest computed tomography revealed a tumor in the anterior mediastinum, which was diagnosed as an atypical thymic carcinoid. A complete resolution of the nephrotic-range proteinuria was observed within 1 week after the first thoracoscopic surgery, with almost complete reduction of the tumor mass. This extremely rare case shows that MCD can occur as a PNS even in children. Nephrotic-range proteinuria can be a symptom of malignant solid tumor. This case highlights the possibility of secondary causes of MCD in children.

Patients after a cardiac surgery in cardiopulmonary bypass often present an acute kidney failure. Continuous renal replacement therapy (CRRT) is often required. The aim of this study was to present effectiveness and safety of CRRT with regional citrate anticoagulation (RCA-CRRT) in small children after cardiac surgery. A retrospective analysis was conducted on 15 patients after cardiac surgery and who had RCA-CRRT performed in 2014. The established protocol was followed. Mean time on the RCA-CRRT was 192 h 40 min with the circuit mean lifetime of 43 h 33 min. Clotting was found to be a cause of shutdown in 29% of circuits. No severe electrolyte and metabolic disorders were observed. The RCA-CRRT is a safe procedure for critically ill children with contraindications to the CRRT with heparin anticoagulation. To avoid adverse effects related to metabolic disorders a proper procedure protocol has to be followed.

Crohn's disease belongs to the group of autoimmune diseases, known as inflammatory bowel disease. The inflammation may span the entire depth of the intestinal wall. In effect the typical complications of Crohn's disease can be the formation of fistulas: external (perianal, between the bowel and skin) and internal (between two loops of bowel, between the bowel and bladder, between the bowel and vagina). These complications may occur in about 30–40% of patients. The study describes a 17-year-old patient hospitalized for recurrent urinary tract infections. The first symptoms of the disease were tonic abdominal pain, anemia, recurrent diarrhea, fever of unknown etiology. The cause of these problems was a urinary tract infection, which persistently recurred despite aggressive treatment. After the transfer to the Department, the diagnostic process revealed the suspicious thickening of the walls of the ileum. The diagnostics was expanded in the direction of inflammatory bowel diseases. In addition to urinary tract infections, Crohn's disease was diagnosed and confirmed. Owing to persistent dysuria, a fistula between the bowel and bladder was suspected. After confirmation of this diagnosis a parenteral nutrition was applied and the treatment was continued in the Department of Gastroenterology. This case illustrates the potential difficulties in identifying the cause of urinary tract infections and shows the need for an accurate diagnostic process, especially in cases of recurrent. The cause can sometimes be very surprising.

Phakomatoses are a group of neurocutaneous disorders whose origin is derived from the embryonic ectoderm. These disorders affect the central nervous system, the eyes, and the skin. This article presents phakomatoses and cutaneous manifestations associated with moyamoya disease and syndrome. Moyamoya disease is a progressive and occlusive disorder of the cerebral vasculature often presenting with particular phakomatoses. This article aims to reveal why patients with phakomatoses qualify for detailed neuroimaging.

The aim of the study was to estimate target values of mycophenolate mofetil (MMF) pharmacokinetic parameters in children with proteinuric glomerulopathies by calculating the pharmacokinetic parameters of MMF metabolites (mycophenolic acid [MPA], free MPA [fMPA] and MPA glucuronide [MPAG]) and assessing their relation to proteinuria recurrence. One hundred and sixty-eight blood samples were collected from children, aged 3-18 years, diagnosed with nephrotic syndrome or lupus nephritis. MMF metabolites concentrations were examined before drug administration (Ctrough) and up to 12h afterward employing high-performance liquid chromatography. Dose-normalized MPA Ctrough and area under the concentration-time curve from 0 to 12h (AUC12) were within 0.29-6.47 μg/mL/600 mg/m(2) and 9.97-105.52 μg h/mL/600 mg/m(2), respectively. MPA Ctrough was twofold lower (p=0.024) in children with proteinuria recurrence. MPA, fMPA and MPAG concentrations correlated positively to respective AUC12. It may be suggested MMF metabolites monitoring in children with proteinuric glomerulopathies is justified by MPA Ctrough2 μg/mL in patients at risk of the proteinuria recurrence. Such a recurrence is most probably caused by not sufficient MPA concentration during proteinuric glomerulopathies treatment. MPA Ctrough3 μg/mL may be considered as an efficient one to avoid proteinuria recurrence. Finally, MPA target AUC12 should exceed 60 μg h/mL to ensure the safe and effective treatment in children with nephrotic syndrome, however, the upper limit is still to be established.

Salicylate intoxication is possible by ingestion and topical application of creams or lotions. Symptoms of salicylate poisoning include: vomiting, abdominal pain, fever, dizziness and hallucinations. Moreover metabolic acidosis or coagulations disorders can be observed. In case of severe poisoning potential symptoms may include: acute renal failure, pulmonary edema and gastrointestinal bleeding. As there is no antidote, only symptomatic treatment such as : gastric lavage, supplying with active carbon and advocated alkaline diuresis can be applied. Compensation of acid-base and electrolyte fluctuations may be of crucial importance. This paper presents the case of a 7-year-old girl, who was admitted to Department of Pediatric Cardiology and Nephrology at University of Medical Sciences in Poznan, due to intoxication by salicylates. Before hospitalization the patient was treated with 30% salicylate ointment because of scabies. After dermatological consultation, the medication was applied twice a day on whole skin except the face, without cleaning (for next three days). Patient received a total dose of 30 g of salicylic acid. First symptoms appeared after 24 hours of the first application. She was admitted to neighboring Hospital, where the preliminary diagnosis was gastro-intestinal infection. Next day the patient started to present neurological symptoms. She was transported to another hospital, where measurement of salicylates level in serum was performed. Finally the patient was admitted to Department of Pediatric Cardiology and Nephrology in Poznan for hemodialysis, due to very high, toxic level of salicylates (7 times higher than therapeutic dose of the drug). Gradual reduction of the concentration of salicylic acid in the blood serum was accompanied by clinical improvement of the patient. Because of high ratio of the skin surface to the body weight as well as clinically significant absorption into the body, substances topically applied on children with low safety margin should be dosed with caution.

Background Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children. Methods This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69 ± 5.63 kg. RCA-CRRT was performed with a commercially available pre-dilution citrate solution (Prismocitrate 18/0). Results The mean time on RCA-CRRT and HA-CRRT was 148.73 ± 131.58 and 110.24 ± 105.38 h, respectively. Circuit lifetime was significantly higher in RCA-CRRT than in HA-CRRT (58.04 ± 51.18 h vs. 37.64 ± 32.51 h, respectively; p = 0.030). Circuit clotting was observed in 11.63 % of children receiving RCA-CRRT and 34.15 % of those receiving HA-CRRT. Episodic electrolyte and metabolic disturbances were more common in children receiving RCA-CRRT. The survival at discharge from the hospital was 37.5 and 14.3 % among children receiving RCA-CRRT and HA-CRRT, respectively. Conclusions In critically ill children with a low body weight, RCA appeared to be safe and easy to used. Among our patient cohort, RCA was more effective in preventing circuit clotting and provided a better circuit lifetime than HA.

The mechanism of steroid resistance in children with the nephrotic syndrome is yet unknown. About 20% of patients demonstrate steroid unresponsiveness and progress to end stage renal disease. Aberrant SOCS3 and SOCS5 expression in steroid resistant and sensitive patients has previously been demonstrated. Here, we investigate genetic and epigenetic mechanisms of regulation of SOCS3 and SOCS5 transcription in nephrotic children. 76 patients with the nephrotic syndrome (40 steroid resistant and 36 steroid sensitive) and 33 matched controls were included in this study. We performed genotyping of a total of 34 single nucleotide polymorphisms for SOCS3 and SOCS5 promoters and evaluated their methylation status using MS-PCR and QMSP methods. Steroid resistant patients had a significantly lower methylation of one region of SOCS3 promoter in comparison with steroid sensitive patients and controls (p < 0.0001). However, the relative methylation level in the steroid sensitive patients and controls differed significantly even before the first steroid dose (p = 0.001758). Other SOCS3 and SOCS5 promoter regions displayed no differences in methylation or were fully methylated/unmethylated in all study groups, showing site-specific methylation. The allele and genotype distribution for SOCS3 and SOCS5 markers did not differ statistically between the groups. We demonstrate an epigenetic mechanism of SOCS3 up-regulation in steroid resistant children with the nephrotic syndrome. The assessment of methylation/unmethylation of SOCS3 promoter might be an early marker for steroid responsiveness in NS patients.

Atherosclerosis commonly affects the arteries harvested from patients 70 years of age or older. Saphenous vein grafts appear to maintain a higher patency rate after coronary artery bypass grafting in these subjects. The infiltration of macrophages is an early step in saphenous vein graft atherosclerosis; however, little is known regarding the underlying mechanisms of infiltration. The objective of the present report is to evaluate the presence of CD68-positive cells in the saphenous vein wall and correlate initial CD68-positive infiltration to specific clinical and biochemical parameters and the graft patency rate as estimated in patients undergoing coronary artery bypass grafting. A total of 309 patients were allocated into two groups: A1 patients, who were between 50 and 70 years of age, and A2 patients, who were 70 years or older at the time of vein harvesting. CD68 expression was evaluated by immunohistochemistry. There were no significant differences between A1 and A2 patients regarding macrophage expression within any of the analyzed vascular regions. Saphenous vein macrophages were never present in the tunica intima unless they were also expressed in the media or the adventitia. The patients with CD68-positive cells in the tunica intima had a significantly higher number of bypass stenoses when compared with the subjects who did not have CD68-positive cells in this layer. These findings suggest that the CD68-positive cells (those that have not yet developed into foam cells) present in the intima of saphenous vein grafts might serve as a very early marker of graft occlusion.

The studies aimed at identifying a prognostic significance of angiogenesis-related factors: CD105 and placental growth factor (PlGF) in a course of acute lymphoblastic leukaemia (ALL). Research protocol was based on detection of RNA and protein expressions in bone marrow blasts using quantitative PCR and immunocytochemical assays respectively. Kaplan–Meier statistics revealed CD105 and PlGF expression as managed separately do not correlate with relapse-free time in ALL patients. On the other hand, an associated analysis of CD105 and PlGF demonstrated a significantly shorter progression-free time in children who were CD105+ and PlGF+ or CD105− and PlGF+ at the moment of ALL diagnosis.

Suppressors of Cytokine Signaling (SOCS) inhibit Signal Transducers and Activators of Transcription (STATs) phosphorylation by binding and inhibiting Janus Kinases (JaKs). The aim of the present study was to evaluate the influence of glucocorticosteroids on the JaK/STAT signaling pathway in the leukocytes of nephrotic syndrome (NS) patients. The study group was composed of 34 steroid sensitive NS (SSNS) children and 20 steroid resistant NS (SRNS) subjects. Gene expression was assessed by real-time PCR using pre-designed human JaK/STAT PCR array. Protein expression was evaluated using ELISA assay (plasma concentration) and immunofluorescence (in situ protein expression). In SSNS children, the initial increased expression of JaK1, JaK2, JaK3, STAT1, STAT2, STAT6, TYK2, SOCS1, SOCS2, SOCS3, SOCS4 and SOCS5 was reduced back to the control limits. Similarly, in SRNS patients the increased levels of almost all mRNA expressions for the abovementioned genes were decreased, with the exceptions of SOCS3 and SOCS5 expressions. These mRNA expressions were still significantly increased and correlated with early unfavorable course of nephrotic syndrome in children. Plasma levels of SOCS3, SOCS5, IL-6 and IL-20 were significantly increased in SRNS subjects after six weeks of steroids medication compared to SSNS and control participants. We conclude that SOCS3 and SOCS5 increased mRNA expressions might predict initial resistance to steroids in NS patients. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 719–728)

Streszczenie Toczen rumieniowaty ukladowy (SLE) jest autoimmunologiczną chorobą tkanki lącznej o szerokim zakresie objawow klinicznych. U dzieci choroba wystepuje znacznie rzadziej niz u doroslych, ale az u 70–80% z nich wystepuje toczniowe zapalenie nerek (NT), ktore jest jednym z najpowazniejszych czynnikow rokowniczych SLE. W celu indukcji, a nastepnie podtrzymania remisji choroby stosowane jest intensywne leczenie immunosupresyjne obarczone mozliwością wystąpienia powaznych skutkow ubocznych. Cel pracy Celem pracy byla retrospektywna analiza przebiegu i wynikow leczenia toczniowego zapalenia nerek u dzieci. Material i metody Grupe badaną stanowilo 10 dzieci hospitalizowanych w Klinice Nefrologii Dzieciecej UM w Poznaniu. Analizowano objawy kliniczne, parametry laboratoryjne oraz wyniki leczenia immunosupresyjnego w okresie 24 miesiecy. Wyniki Średnia wieku w chwili zachorowania wynosila 14 lat i 3 miesiące. Wśrod pacjentow przewazaly dziewczynki. U 7 dzieci nefropatia toczniowa wystąpila w postaci zespolu nerczycowego, a u 6 jako ostra niewydolnośc nerek. U 7 pacjentow stwierdzono IV klase NT wg klasyfikacji WHO. W leczeniu stosowano steroidy (GK), cyklofosfamid (CF), cyklosporyne (CsA), plazmaferezy oraz u 3/10 mykofenolan mofetylu (MMF). U 2 chorych stosowano CsA w indukcji remisji. Wszyscy pacjenci uzyskali remisje kliniczną i biochemiczną w okresie indukcji. U 3 pacjentow leczonych MMF remisja wystąpila w pierwszych trzech miesiącach leczenia. Wnioski NT u dzieci przebiega z duzą aktywnością kliniczną oraz postepującą glomerulopatią, ktora wymaga intensywnego leczenia immunosupresyjnego. Zastosowanie MMF w okresie indukcji remisji moze przyspieszyc osiągniecie remisji oraz prowadzic do ograniczenia liczby pulsow cyklofosfamidowych i wydluzenia okresu remisji.

The aim of this study was to investigate acute and subacute oral toxicity of an ionic liquid, didecyldimethylammonium acesulfamate [DDA][Ace], in rats. The compound tested was classified to the fourth toxicity class with a fixed LD(50) cut-off value of 500 mg/kg. Organ pathology induced by [DDA][Ace] in acute experiments included exfoliation of the surface layer of the digestive tract and alveolar septa in lung parenchyma. In a subacute experiment, rats were administered 10, 50, and 100 mg/kg/day [DDA][Ace] for 28 days. Reduced body weight gain and reduced food consumption was observed in mid- and high-dose rats. Statistically significant hematology changes were found mostly in high-dose groups of both sexes: increases in hematocrit, mean corpuscular volume, and mean platelet volume. Statistically significant changes in clinical chemistry parameters included increases in the GGT, SDH, and LDH activity and bilirubin concentration, and decreases in triglycerides, glucose, and inorganic phosphorus concentration. No treatment-related microscopic changes were observed. Under the conditions of this study, the lowest-observed-adverse-effect level of [DDA][Ace] was considered to be 10 mg/kg/day.

The aim of the present research was to investigate the possible in vitro stimulatory effect of substance P (SP) on blasts induction in childhood common acute lymphoblastic leukaemia (ALL). Bone marrow aspirates were incubated with SP receptor agonist or antagonist (spantide) and subsequently assayed for the presence of human interleukin (IL)-1b using ELISA kit. Blast cells incubated with SP receptor agonist were found to result in a significant increase of IL-1b concentration while incubated with spantide resulted in control levels of IL-1b. These findings suggest the novel possible role of SP in blasts proliferation in childhood ALL of common (CD10) origin.