Antibiotic Prophylaxis in Infants with Grade III, IV, or V Vesicoureteral Reflux.

BACKGROUND: The efficacy of continuous antibiotic prophylaxis in preventing urinary tract infection (UTI) in infants with grade III, IV, or V vesicoureteral reflux is controversial. METHODS: In this investigator-initiated, randomized, open-label trial performed in 39 European centers, we randomly assigned infants 1 to 5 months of age with grade III, IV, or V vesicoureteral reflux and no previous UTIs to receive continuous antibiotic prophylaxis (prophylaxis group) or no treatment (untreated group) for 24 months. The primary outcome was the occurrence of the first UTI during the trial period. Secondary outcomes included new kidney scarring and the estimated glomerular filtration rate (GFR) at 24 months. RESULTS: A total of 292 participants underwent randomization (146 per group). Approximately 75% of the participants were male; the median age was 3 months, and 235 participants (80.5%) had grade IV or V vesicoureteral reflux. In the intention-to-treat analysis, a first UTI occurred in 31 participants (21.2%) in the prophylaxis group and in 52 participants (35.6%) in the untreated group (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P = 0.008); the number needed to treat for 2 years to prevent one UTI was 7 children (95% CI, 4 to 29). Among untreated participants, 64.4% had no UTI during the trial. The incidence of new kidney scars and the estimated GFR at 24 months did not differ substantially between the two groups. Pseudomonas species, other non-Escherichia coli organisms, and antibiotic resistance were more common in UTI isolates obtained from participants in the prophylaxis group than in isolates obtained from those in the untreated group. Serious adverse events were similar in the two groups. CONCLUSIONS: In infants with grade III, IV, or V vesicoureteral reflux and no previous UTIs, continuous antibiotic prophylaxis provided a small but significant benefit in preventing a first UTI despite an increased occurrence of non-E. coli organisms and antibiotic resistance. (Funded by the Italian Ministry of Health and others; PREDICT ClinicalTrials.gov number, NCT02021006; EudraCT number, 2013-000309-21.).

Subcutaneous C.E.R.A. for the Maintenance Treatment of Anemia in Pediatric Patients With CKD: A Phase 2, Open-Label, Single-Arm, Multicenter Study.

RATIONALE & OBJECTIVE: The optimum starting dose of intravenous continuous erythropoietin receptor activator (C.E.R.A.) has been previously determined; this study ascertains the optimum starting dose of subcutaneous C.E.R.A. administration in pediatric patients. STUDY DESIGN: Phase 2, open-label, single-arm, multicenter study. SETTING & PARTICIPANTS: Patients aged 3 months to 17 years with renal anemia and chronic kidney disease (CKD; including those treated with maintenance dialysis and those not treated with dialysis) who were receiving maintenance treatment with erythropoiesis-stimulating agents (ESAs). INTERVENTION: Subcutaneous C.E.R.A. administration every 4 weeks (starting dose was based on defined conversion factors). OUTCOME: The primary outcome was the change in hemoglobin concentration between the baseline and evaluation period for each patient. Secondary efficacy measures and safety were also evaluated. RESULTS: Forty patients aged 0.4-17.7 years were enrolled. The study achieved its primary outcome: the mean change in hemoglobin concentration was an increase of 0.48g/dL; the 95% confidence interval (0.15-0.82) and standard deviation (±1.03) were within the prespecified boundaries (-1 to 1g/dL and<1.5g/dL, respectively). Mean hemoglobin concentrations were maintained within the target 10-12g/dL range in 24 of 38 patients and within±1g/dL of the baseline in 19 of 38 patients, and the median C.E.R.A. subcutaneous dose decreased over time. Efficacy in key subgroups (age group, dialysis type, prior ESA treatment) was consistent with the primary outcome. Thirty-eight patients completed the core period; 25 chose to enter the safety extension period. Safety was consistent with prior studies, with no new signals. LIMITATIONS: Single-arm and open-label study; small sample size. CONCLUSIONS: Pediatric patients with anemia secondary to CKD who were on, or not on, dialysis could be safely and effectively switched from maintenance ESAs to subcutaneous C.E.R.A. administered every 4 weeks, using defined dose-conversion factors to determine the optimum starting dose. FUNDING: F. Hoffmann-La Roche Ltd. TRIAL REGISTRATION: The SKIPPER trial registered at ClinicalTrials.gov with study number NCT03552393. PLAIN-LANGUAGE SUMMARY: Anemia, a complication of chronic kidney disease, is associated with poor quality of life and an increased risk of hospitalization and mortality. The current treatments for anemia include iron therapy and erythropoiesis-stimulating agents (ESAs); however, the relatively short half-lives of the ESAs epoetin alfa/beta or darbepoetin alfa may require more frequent dosing and hospital visits compared with the ESA known as continuous erythropoietin receptor activator (C.E.R.A.). A previous study demonstrated that children aged 5 years or more with anemia associated with chronic kidney disease who were on hemodialysis could be switched to intravenous C.E.R.A. from their existing epoetin alfa/beta or darbepoetin alfa treatment. This study provides evidence that subcutaneous C.E.R.A. can safely and effectively treat anemia in children, including those aged<5 years and regardless of whether they were on dialysis or the type of dialysis they received (peritoneal dialysis or hemodialysis).

Effects of Puberty on Blood Pressure Trajectories - Underlying Processes.

Puberty is a complex process leading to physical, sexual, and psychosocial maturation. The changes in morphology and organ function during puberty also affect blood pressure (BP) regulation, and as a consequence (BP) values change noticeably, reaching values often higher than after reaching full maturity. In children entering puberty, BP, especially systolic, increases and then reaches adult values by the end of puberty. The mechanisms responsible for this process are complex and not fully understood. Sex hormones, growth hormone, insulin-like growth factor-1, and insulin, whose production increases during puberty, significantly regulate BP through complex and overlapping mechanisms. During puberty, the incidence of arterial hypertension also increases, especially in children with excess body weight. The present paper presents the current state of knowledge regarding the influence of processes occurring during puberty on blood pressure.

Endothelial dysfunction as a factor leading to arterial hypertension.

Hypertension remains the main cause of cardiovascular complications leading to increased mortality. The discoveries of recent years underline the important role of endothelial dysfunction (ED) in initiating the development of arterial hypertension. The endothelium lines the interior of the entire vascular system in the body and acts as a physical barrier between blood and tissues. Substances and mediators produced by the endothelium exhibit antithrombotic and anti-inflammatory properties. Oxidative stress and inflammation are conditions that damage the endothelium and shift endothelial function from vasoprotective to vasoconstrictive, prothrombotic, and pro-apoptotic functions. A dysfunctional endothelium contributes to the development of hypertension and further cardiovascular complications. Reduced nitric oxide (NO) bioavailability plays an essential role in the pathophysiology of ED-associated hypertension. New technologies provide tools to identify pathological changes in the structure and function of the endothelium. Endothelial dysfunction (ED) contributes to the development of arterial hypertension and should be considered in therapeutic strategies for children with hypertension.

Nocturnal non-dipping on 24-h Ambulatory Blood Pressure Monitoring in children and adolescents with obesity is associated with higher total cholesterol levels.

BACKGROUND: Few studies indicate the occurrence of abnormal nocturnal dipping of blood pressure (BP) in 35-50% of children and adolescents with obesity. The relation between that phenomenon and metabolic complications of obesity remains unclear. To evaluate the association between disorders of glucose and lipid metabolism, and nocturnal non-dipping in pediatric patients with obesity. METHODS: In 207 children (53.14% girls, mean age 14 (range 2-17), mean BMI Z-SCORE 4.38, range 2.07-10.74) standard 24-h Ambulatory Blood Pressure Monitoring was performed. Normal dipping was defined as a ≥ 10% decline in BP during the night. RESULTS: There were 106 (51.21%) cases of non-dippers. The mean 24-h nocturnal systolic BP (SBP) reduction (%) was 9.9 ± 5.5. The mean 24-h nocturnal diastolic BP (DBP) reduction (%) was 15.8 ± 8.5. There was a significant correlation between BMI Z-SCORE and mean day-time SBP (r = 0.14 P = .042). There are positive correlations between 24-h heart rate (beats/min) and BMI Z-SCORE (r = 0.15, P = .027), between fasting glucose and systolic BP Z-SCORE (r = 0.17, P = .03) and between mean diastolic BP and LDL cholesterol (r = 0.23, P = .004). Total cholesterol level was significantly higher in non-dippers (4.34 vs. 3.99 mmol/L, P = .034). There were no significant differences between non-dippers and dippers regarding fasting glucose (4.6 vs. 4.8 mmol/L), 120'post load glucose (5.7 vs. 5.9 mmol/L), insulin (19 vs. 20.2 µIU/mL), HOMA-IR (2.36 vs. 2.44), LDL cholesterol (2.64 vs. 2.51 mmol/L), HDL cholesterol (1.06 vs. 1.03 mmol/L) or triglycerides (1.36 vs. 1.34 mmol/L) levels. CONCLUSION: Nocturnal non-dipping is frequent in pediatric patients with obesity. It is associated with higher total cholesterol levels.

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.

Mild X-linked Alport syndrome due to the COL4A5 G624D variant originating in the Middle Ages is predominant in Central/East Europe and causes kidney failure in midlife.

A study of 269 children enrolled into a National Registry for children with persistent glomerular hematuria identified 131 individuals with genetically confirmed X-linked Alport Syndrome. A single variant c.1871G>A p.Gly624Asp (G624D) in COL4A5 was predominant and accounted for 39% of X-linked Alport Syndrome in unrelated Polish families (44 of 113). To evaluate its origins, the genetic variation in a 2.79 Mb segment encompassing the COL4A5 locus on chromosome X was assessed. All G624D alleles were found on the same rare haplotype background, indicating a founder effect dating back to the 12-13th century. The phenotypic data of 131 children with X-linked Alport Syndrome and their 195 affected adult relatives revealed that the G624D variant was associated with a significantly milder clinical course in comparison to other pathogenic COL4A5 variants. Furthermore the clinical course of this genetically uniform cohort was milder than that observed in individuals with other COL4A5 missense mutations. In spite of the benign clinical manifestation throughout childhood and early adulthood, the G624D variant confers significant risk for both kidney failure and deafness in males, albeit 20-30 years later than that observed in individuals with other COL4A5 pathogenic variants (50% cumulative risk of starting dialysis at 54 years (95% confidence interval: 50-62) v. 26 years (95% confidence interval: 22-30)). Thus, males with G624D are candidates for existing and emerging therapies for Alport Syndrome.

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.

BACKGROUND: The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS: We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS: We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10-14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS: We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).

Multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab in children with steroid-resistant nephrotic syndrome.

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

Neutral pH and low-glucose degradation product dialysis fluids induce major early alterations of the peritoneal membrane in children on peritoneal dialysis.

The effect of peritoneal dialysates with low-glucose degradation products on peritoneal membrane morphology is largely unknown, with functional relevancy predominantly derived from experimental studies. To investigate this, we performed automated quantitative histomorphometry and molecular analyses on 256 standardized peritoneal and 172 omental specimens from 56 children with normal renal function, 90 children with end-stage kidney disease at time of catheter insertion, and 82 children undergoing peritoneal dialysis using dialysates with low-glucose degradation products. Follow-up biopsies were obtained from 24 children after a median peritoneal dialysis of 13 months. Prior to dialysis, mild parietal peritoneal inflammation, epithelial-mesenchymal transition and vasculopathy were present. After up to six and 12 months of peritoneal dialysis, blood microvessel density was 110 and 93% higher, endothelial surface area per peritoneal volume 137 and 95% greater, and submesothelial thickness 23 and 58% greater, respectively. Subsequent peritoneal changes were less pronounced. Mesothelial cell coverage was lower and vasculopathy advanced, whereas lymphatic vessel density was unchanged. Morphological changes were accompanied by early fibroblast activation, leukocyte and macrophage infiltration, diffuse podoplanin presence, epithelial mesenchymal transdifferentiation, and by increased proangiogenic and profibrotic cytokine abundance. These transformative changes were confirmed by intraindividual comparisons. Peritoneal microvascular density correlated with peritoneal small-molecular transport function by uni- and multivariate analysis. Thus, in children on peritoneal dialysis neutral pH dialysates containing low-glucose degradation products induce early peritoneal inflammation, fibroblast activation, epithelial-mesenchymal transition and marked angiogenesis, which determines the PD membrane transport function.

Efficacy and safety of sevelamer carbonate in hyperphosphatemic pediatric patients with chronic kidney disease.

BACKGROUND: Treatment for hyperphosphatemia in chronic kidney disease (CKD) involves dietary control of phosphorus intake, dialysis, and treatment with oral phosphate binders, none of which were approved by the Federal Food and Drug Administration in pediatric patients at the time of this study. METHODS: This was a phase 2, multicenter study (NCT01574326) with a 2-week, randomized, placebo-controlled, fixed-dose period (FDP) followed by a 6-month, single-arm, open-label, dose-titration period (DTP), with the aim to evaluate the safety and efficacy of sevelamer carbonate (SC) in hyperphosphatemic pediatric patients with CKD. Following a 2-4 week screening phase, pediatric patients with a serum phosphorus level higher than age-appropriate levels were randomized to receive either SC or placebo as powder/tablets in 0.4-1.6 g doses, based on body surface area. The primary efficacy outcome was the change in serum phosphorus from baseline to end of the FDP in the SC versus placebo arms (analysis of covariance). The secondary outcome was mean change in serum phosphorus from baseline to end of DTP by treatment group and overall. Treatment-emergent/serious adverse events (AEs) were recorded. RESULTS: Of 101 enrolled patients (29 centers), 66 completed the study. The majority of patients were adolescents (74%; mean age 14.1 years) and on dialysis (77%). Renal transplant was the main reason for discontinuation. SC significantly reduced serum phosphorus from baseline levels (7.16 mg/dL) during the FDP compared to placebo (least square mean difference - 0.90 mg/dL, p = 0.001) and during the DTP (- 1.18 mg/dL, p < 0.0001). The safety and tolerability of SC and placebo were similar during the FDP, with patients in both groups reporting mild/moderate gastrointestinal AEs during the DTP. CONCLUSIONS: Sevelamer carbonate significantly lowered serum phosphorus levels in hyperphosphatemic children with CKD, with no serious safety concerns identified.

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.

[B-type natriuretic peptide as a marker of cardiac dysfunction in children with chronic kidney disease]. / Peptyd natriuretyczny typu B jako marker uszkodzenia serca u dzieci z przewlekla choroba nerek.

Left ventricular hypertrophy is the most common organ damage in children with chronic kidney disease (CKD). AIM: The aim of the study was to assess the usefulness of B-type natriuretic peptide (BNP) as a marker of heart injury in children with CKD. MATERIALS AND METHODS: We included 66 children (41 boys and 25 girls) aged 0.7 to 18.6 (median 11.6) years with CKD stage 1-5. The concentrations of urea, creatinine, cystatin C and BNP in blood serum were assessed, and the estimated glomerular filtration rate (eGFR) was calculated from the Schwartz and Filler formulas. Patients were divided into groups depending on the CKD stage [group 1: CKD stages 1 + 2 (GFR> 60 ml/min/1.73 m2), group 2: stage 3 (GFR = 30-59 ml/min/1.73 m2), group 3: CKD stage 4 (GFR 15-29 ml/min/ 1.73 m2), group 4 - stage 5 (dialyzed children)]. On the basis of echocardiography, the left ventricular mass (LVM) was calculated, which was indexed for height (left ventricular mass index, LVMI). Left ventricular hypertrophy (LVH) was diagnosed if the LVMI value was > 95th percentile for sex and age. RESULTS: Depending on the CKD stage the median BNP concentrations for group 1, group 2, group 3, and group 4 were 2.5 pg/ml, 6.0 pg/ml, 9.3 pg/ml and 18.0 pg/ml, and the LVH prevalence 27.3%, 33.3%, 60.0% and 63.6% , respectively. Significant correlations between BNP concentration and LVH expressed by LVMI (R=0.256, p=0.038), creatinine (R=0.453, p<0.001), cystatin (R=0.494, p<0.001) and eGFR (R=-0.473, p<0.001) were found. CONCLUSIONS: In children with chronic kidney disease, BNP is an indicator of heart failure correlating with renal function parameters and left ventricular mass index.

[Mycophenolate mofetil (MMF) as the first choice immunosuppressive drug in treatment of steroid-dependent nephrotic syndrome in children]. / Mykofenolan mofetilu (MMF) jako lek immunosupresyjny pierwszego wyboru w leczeniu steroidozaleznego zespolu nerczycowego (SZZN) u dzieci.

Most children diagnosed with nephrotic syndrome show favourable response to corticosteroid therapy, nonetheless 30% of patients have frequent relapses or a steroid-dependent course of disease. Cyclophosphamide, cyclosporin A or MMF are being used in treatment of steroid-dependent nephrotic syndrome in search of a drug with highest long-term effectiveness and least amount of side effects. AIM: The aim of study was to assess of the efficacy of MMF as the first choice immunosuppressive drug in children with nephrotic syndrome after determining a steroid-dependency. MATERIALS AND METHODS: 23 children with steroid-dependent nephrotic syndrome were enrolled in the study. Mean age at disease onset was 3.8 years. Mean disease duration time before introducing MMF was 21.3 months. Mean treatment time with MMF was 23.6 months. Patients previously treated with immunosuppressive drug, except for prednisone were excluded from the study. RESULTS: Per year of treatment with MMF 56,5% of patients had not more than 1 relapse of the disease, 5 patients had more than 1, but less than 2 relapses. After the mean time of 23.6 months MMF treatment was discontinued in 15 patients (62,5%). 11 patients (48%) from that group significantly benefited from treatment in the form of no further relapses, defer of steroid-dependence or the possibility to reduce the dose of corticosteroids to minimal. CONCLUSIONS: MMF has advantage over cyclophosphamide and calcineurin inhibitors in reference to side effect profile, especially glomerular filtration markers, hypertension and frequent drug dependency. Treatment with MMF is effective in maintaining long-term remission and enables the reduction of cumulative steroid dose. Regarding nearly 50% of patients with benefits after MMF treatment and good treatment tolerance, it seems justified to introduce MMF as the first choice immunosuppressive drug in patients with steroiddependent nephrotic syndrome.

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease.

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.

Filter Size Not the Anticoagulation Method is the Decisive Factor in Continuous Renal Replacement Therapy Circuit Survival.

BACKGROUND/AIM: As continuous renal replacement therapy (CRRT) has emerged as a standard therapy in pediatric intensive care units (PICU), many related issues that may have an impact on circuit survival have gained in importance. Objective of the study was an evaluation of factors associated with circuit survival, including anticoagulation (ACG). METHODS: Retrospective study that included 40 patients, who in total received 7636 hours of CRRT during 150 sessions (84 filters, 4260 hours with heparin anticoagulation (Hep-ACG); 66 filters, 3376 hours with regional citrate anticoagulation (RCA)). RESULTS: The Kaplan-Meier analysis of the total circuit survival time depending on the type of ACG did not demonstrate a significant difference between Hep-ACG and RCA. The percentage of clotted filters was significantly higher in case of smaller filters (HF20: 58.8%; ST60: 29.5%; ST100: 15.8%), and their lifetime was significantly lower regardless of ACG (the mean and median lifetime for HF20: 38.7/27.0 h; for ST60: 54.1/72.0 h., for ST100: 62.1/72.0 h, respectively). CONCLUSIONS: Irrespectively of filter size, filter clotting occurs within the first 24 hours after the initiation of CRRT. Most commonly, clotting affects small filters, and their lifetime is significantly shorter as compared to larger filters regardless of the type of the ACG.

Circadian blood pressure profiles and ambulatory arterial stiffness index in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in relation to their genotypes.

OBJECTIVE: Lifelong steroid therapy and exposure to adrenal androgen excess in 21-hydroxylase deficient (21-OHD) congenital adrenal hyperplasia (CAH) children and adolescents may modify circadian blood pressure profile and result in vascular complications. The objective of the study was to evaluate vascular abnormalities in 21-OHD children and adolescents in relation to their genotypes. DESIGN: A cross-sectional study conducted at a tertiary referral center. PATIENTS: Seventy patients with 21-OHD CAH (27 boys), aged from 3 to 17.9 years: 9 with nonclassic CAH, 61 with classic CAH: 10 with simple virilising (SV) and 51 with salt wasting CAH (13-Del/Del, 8-Del/I2G, 7-I2G/I2G and 23-other genotypes). MAIN OUTCOMES MEASURES: The assessment of systolic and diastolic BP (SBP, DBP) loads, night dip% and arterial ambulatory stiffness index (AASI) in 21-OHD CAH patients.

Modification of the Schwartz equations for children increases their accuracy at eGFR > 60 mL/min/1.73 m(2).

AIM: Estimation of eGFR in children with normal kidney function using the Schwartz equations results in underestimating real GFR. MATERIALS AND METHODS: We propose modification of three Schwartz equations - two based on creatinine concentration (eGFRScrBS bedside) and (eGFRScr) and one 3-marker based on creatinine, urea and cystatin C concentrations (eGFRS3M). The iohexol test (reference method) was performed 417 times in 353 children >2 years with mean GFR: 98 ± 31.6 ml/min/1.73m(2). The assessment included also the Filler and Zappitelli equations. The modification was performed using methods: (1) based on equation, eGFRcor = a [eGFR - T] + T, where T = 50, if eGFR > T, and a equals for: eGFRScrBS 1.4043, for eGFRScr 2.0048, for eGFRS3M 1.2951, and (2) based on correction of all coefficients of the original equation. RESULTS: For comparison of all the results and for children with GFR< 60, 60-90, 90-135 and > 135 ml/min/1.73m(2) the correlation coefficient, relative error (RE) and root mean square relative error (RMSRE) was employed and revealed improvement of RE from 25.9 to 6.8 and 3.9% (depending on the correction method) for eGFRScr; from 19 to 8.1 and 3.9% for eGFRScrBS and: from 11.6% to 2.0 and 2.3% for eGFRS3M (respectively). The RMSRE values changed from 30 to 21.3 and 19.8% for eGFRScr, from 25.1 to 21.6 and 19.8% for eGFRScrBS and from 19.1 to 15.8 and 15.3 % for eGFRS3M. CONCLUSIONS: Modifications of Schwartz equations at GFR > 60 ml/min/1.73m(2) significantly improves the accuracy of calculating eGFR. The 3-markers equation is more accurate and should be employed frequently.

[Office and 24-hour ambulatory blood pressure measurements in hypertension assessment in children with chronic kidney disease].

Introduction: Hypertension (HT) is one of the major risk factors of chronic kidney disease (CKD) progression and cardiovascular complications. The aim of the study was to analyze blood pressure (BP) values and assess the usefulness of clinical measurements in BP monitoring in children with chronic kidney disease. Material and methods: The study was conducted in 62 children (40 boys and 22 girls) aged 4,2-18,6 years (median age 12.4 (9.1; 16.0) with CKD stages 1 + 2 (n = 9), 3 (n = 17), 4 (n = 15) and 5. Creatinine concentration was measured and glomerular filtration rate was calculated using the Schwartz formula. Each of the patients underwent clinical BP measurements and 24-hour ambulatory blood pressure monitoring (ABPM). Results: Based on clinical meaurements elevated BP values were found in 25 patients (40.3%): in stages 1 + 2 in 33.3%, in stage 3 in 41.2%, in stage 4 in 46.6% and in stage 5 in 38.1% patients. Hypertension was diagnosed with ABPM in 30 patients (48.4% of the studied population): in stages 1 + 2 - 3 patients (33.3%), in stage 3 - 8 patients (47, 1%), in stage 4 - 7 patients (46.7%) and stage 5 - 12 patients (57.1%). Only 12 patients (19.4%) had hypertension diagnosed in both clinical and ABPM measurements. White coat effect was found in 13 children (21.0%) and masked HT in 18 children (29.0%). In 24-hour BP monitoring the highest values of systolic, diastolic and mean BP values were found in children with masked HT. In children with masked HT higher values of 24-hour systolic (120 vs. 105.5 mmHg, p<0.001) and diastolic (75 vs. 65 mmHg, p<0.001) BP compared with clinical values were detected. Children with masked HT had significantly higher nighttime diastolic BP compared with children with HT (1.43 vs. 0.74 z-score, p<0.001). Conclusions: The large percentage of children with masked hypertension is an indication for frequent ABPM measurements in children with chronic kidney diseses. Office measurements are not sufficient to detect HT in children with CKD. The best diagnostic method to confirm and monitor hypertension in patients with CKD is 24-hour ambulatory blood pressure monitoring.