Acute paediatric kidney replacement therapies in Europe: demographic results from the EurAKId Registry.

BACKGROUND: Acute kidney injury (AKI), particularly that requiring dialysis, is a severe complication in hospitalized children that is associated with high morbidity and mortality. A prospective European AKI registry (EurAKId registry, NCT02960867) was created to describe the epidemiology and outcomes of paediatric patients treated with acute dialysis. METHODS: Children were recruited who were between 0 and 18 years of age and were treated both in and outside the paediatric intensive care unit (PICU) with peritoneal dialysis (PD), haemodialysis (HD) or continuous kidney replacement therapy (CKRT) for AKI or metabolic derangement, fluid overload (FO), sepsis or respiratory distress. Five age groups and 12 categories of primary diseases were defined. RESULTS: Data on 340 patients were analysed, of whom 86% received dialysis for AKI and 14% for reasons other than AKI. Boys accounted for 60% of the patients. Illness severity was greater in children with cardiac and haematologic diseases than those with kidney diseases. Most patients received dialysis in the PICU (84%). The most frequently used dialysis modality was CKRT (64%), followed by PD (14%) and HD (14%). The overall survival rate was 65%. Survival was significantly lower in children with three comorbidities than in children with no comorbidities (41% and 83%; P < 0.001). CONCLUSIONS: The EurAKId registry is the first prospective registry considering paediatric acute kidney replacement therapies (KRTs) in both critical and non-critical care settings, focusing on the three dialysis modalities in Europe. The clinical indications for KRT have expanded; our population was characterized by critically ill patients, primarily boys, who frequently received dialysis in the PICU with CKRT.

Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3-5.

BACKGROUND: Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin-angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear. METHODS: In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case-control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3-5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months. RESULTS: In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups. CONCLUSIONS: Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3-5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

BACKGROUND: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. METHODS: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. RESULTS: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher ß2-microglobulin. The HDF cohort had lower ß2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. CONCLUSIONS: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

OBJECTIVE: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis. STUDY DESIGN: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life. RESULTS: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys. CONCLUSIONS: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.

Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study.

BACKGROUND: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population. METHODS: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m2; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38). DISCUSSION: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.

Comparing different estimated glomerular filtration rate equations in assessing glomerular function in children based on creatinine and cystatin C.

BACKGROUND: Glomerular filtration rate (GFR) is the best marker used to assess renal function. Estimated GFR (eGFR) equations have been developed, and the ideal formula is still under discussion. We wanted to find the most practical and reliable GFR in eGFR formulas. We compared serum creatinine (Scr)- and cystatin C (cysC)-based eGFR formulas in the literature. We also aimed to determine the suitability and the reliability of cysC for practical use in determining GFR in children. METHODS: We have enrolled 238 children in the study. Measurement of 24-hour creatinine clearance was compared with eGFR equations which are based on Scr, cysC, and creatinine plus cysC. RESULTS: Of the patients (n = 238), 117 were males (49.2%), and 121 (50.8%) were females with a median age of 9.0 years. The areas under the ROC curves of Counahan-Barratt and Bedside Schwartz were equal and 0.89 (with a 95% CI 0.80-0.97). The areas under the ROC curves were not significantly different in all cystatin C-based eGFR equations. The highest AUC values for differentiating normal vs abnormal renal functions according to CrCl24 were for the CKiD-cysC and CKiD-Scr-cysC equations. CONCLUSIONS: In our study, compared with creatinine-based ones, the cystatin C-based formulas did not show much superiority in predicting eGFR. Still, we think Bedside Schwartz is a good formula to provide ease of use because, in this equation, the constant k is same for all age groups. However, the most valuable equations in determining chronic kidney disease are the CKiD-cysC and CKiD-Scr-cysC equations.

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.

ADCK4-Associated Glomerulopathy Causes Adolescence-Onset FSGS.

Hereditary defects of coenzyme Q10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (>85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.

Growth evaluation in children with vesicoureteral reflux.

BACKGROUND: Vesicoureteral reflux and urinary tract infection predispose children to retardation of growth, hypertension, renal scarring and renal failure. The aim of this study was to evaluate growth pattern in children with vesicoureteral reflux before and after medical/surgical treatment. METHODS: This study was a retrospective cross-sectional study. The study population included 97 children aged 0.5 to 17 years (8.8±5.5). Body weight, height and bone age of the children were measured. Weight Z score and height Z score were calculated during first visits and after medical and/or surgical treatment. Distribution, mean and standard deviation score were evaluated for the descriptive data. T-test and Mann-Whitney U test and Wilcoxon test were used for statistical analysis. RESULTS: Sixty-five percent of 97 children enrolled in this study were girls. About 48.5% of the children had unilateral and mild reflux, while 16.5% had bilateral and severe reflux. The bone age was 8.6 years. Differentiation with chronological age and bone age were not significant (P=0.294). At admission, 54.6% and 50.5% of children had negative Weight Z score and height Z score, respectively. After medical and surgical treatment, Weight Z score and height Z score were increased, however, only the increase in Weight Z score was significant (P=0.039, P=0.031, respectively). A significant reduction in bone age was found in children with renal scars compared to those without renal scars (P=0.048). CONCLUSIONS: High-grade vesicoureteral reflux had a negative impact on indices of growth in children. Medical and/or surgical treatment had positive effect on weight gain.

Association of clearance of middle- and large-molecular-weight substance with arterial stiffness and left ventricular mass in children receiving renal replacement therapy.

BACKGROUND: The prominent cause of mortality in children receiving dialysis treatment is cardiovascular diseases. Risk factors related to chronic renal disease, are effective in the development of cardiovascular diseases. The aim of study was to investigate cardiovascular system (CVS) involvement for functional and structural alterations in children receiving dialysis, and display any association between cardiovascular morbidity and uremic toxins. METHODS: 20 dialysis patients and 20 healthy controls were included to the study. Clearance of small, middle and large molecular-weight uremic toxins was evaluated in blood samples collected 30 minutes before (D0) and 2 hour after dialysis (D2), and change value was calculated as D0-D2/D0. Cardiovascular involvement was determined by comparing arterial stiffness, carotid intima-media thickness (CIMT) and Left Ventricular Mass Index (LVMI) with the control group. RESULTS: Four patients receiving hemodialysis and two patients in continuous ambulatory peritoneal dialysis (CAPD) group who have significant differences in all functional and structural parameters were detected. Four dialysis patients with detected cardiovascular disease have distinctively lower beta-2 microglobulin and homocysteine clearances compared to the patients with no CVS involvement. CONCLUSIONS: The clearance of middle and large molecular-weight substances should be closely monitored in children receiving dialysis.

Are we late for the diagnosis of acute kidney injury in the intensive care units in pediatric patients? A preliminary, retrospective observational study among 66 patients.

BACKGROUND: The purposes of this study were to emphasize the importance of Risk, Injury, Failure, Loss, and End-Stage (RIFLE) classification in early diagnose and prognosis of acute kidney injury (AKI), and to evaluate the practicability of the RIFLE criteria in intensive care units. METHODS: Sixty-six patients applied acute peritoneal dialysis were included into the study. Patients having acute peritoneal dialysis within the first 24 hours of intensive care unit admission were named group 1, between 24-48 hours group 2, and those who had acute peritoneal dialysis 48 hours or more after admission to the intensive care unit were named group 3. Retrospectively, we evaluated patients by RIFLE criteria at the consultation time, and patients who had been just in AKI were called late referral patients. The mean interval time between the onset of AKI and the consultation time was defined as delay time in late referral patients. RESULTS: There were 20 patients in group 1, 15 were in group 2 and 31 in group 3. In total there were 18/66 patients in risk, 13/66 in injury while 35/66 in failure. There was statistically difference between delay times of in risk and failure class in group 3 (P<0.05). Also delayed patient numbers of both risk and failure class were found statistically highly significant (P<0.001). CONCLUSIONS: Most of the patients were in failure class at the time of consultation. We guess that if they would have been diagnosed earlier, prognosis might have been better. Therefore early diagnosis of AKI with RIFLE criteria and early initiation of acute peritoneal dialysis would probably improve prognosis.

Pathogens causing urinary tract infections in infants: a European overview by the ESCAPE study group.

UNLABELLED: Knowledge of the distribution spectrum of causative organisms and their resistance patterns has become a core requirement for the rational and effective management of urinary tract infections. In the context of a prospective trial on the use of antibiotic prophylaxis in infants with underling kidney malformations, we conducted an online survey among paediatric nephrologists on positive urine cultures (July 2010-June 2012) from both hospitalized and non-hospitalized infants under 24 months of age. We collected 4745 urine cultures (UCs) at 18 units in 10 European countries. Escherichia coli was the most frequent bacterium isolated from UCs; however, in 10/16 hospitals and in 6/15 community settings, E. coli was isolated in less than 50% of the total positive UCs. Other bacterial strains were Klebsiella, Enterococcus, Proteus and Pseudomonas not only from hospital settings. E. coli showed a high resistance to amoxicillin and trimethoprim and variable to cephalosporin. Nitrofurantoin had a good rate of efficacy, with 11/16 hospitals and 11/14 community settings reporting a resistance lower than 5%. CONCLUSION: E. coli is the most common organism causing UTIs in infants; however, other bacterial strains are frequently isolated. As a result, antibiotic prophylaxis should be more elastic and adaptable over time in order to guarantee maximum efficacy.

The long-term outlook to final outcome and steroid treatment results in children with idiopathic nephrotic syndrome.

Idiopathic Nephrotic Syndrome (INS) was defined as combination of a nephrotic syndrome and non-specific histological abnormalities of the kidney. Among these abnormalities, minimal change nephrotic syndrome (MCNS) is the most common. We report our experience with MCNS; its clinical course, treatments and outcomes. One-hundred twenty children (66 male, 54 female) with MCNS, admitted to Nephrology Department between 1987-2009 was assessed. Their clinical presentations, treatment and disease courses were reviewed. The mean duration of follow-up was 11.5 ± 1.9 years. Initially, all patients given prednisone 2 mg/kg/ day single dose per four weeks a followed by eight weeks of the same daily dose given every other day. After week 12, prednisone was progressively tapered off at the rate of 0.5 mg/kg per 15 daily intervals until complete discontinuation had been achieved by week 16. Steroid resistance was accepted as no achievement of remission following four weeks of prednisone 2 mg/kg/day followed by three intravenous pulses of corticosteroids. At the end of the initial steroid treatment, 106 (88.3%) patients were determinate steroid responsive while 14 (11.7%) patients were steroid resistance. Thirty-eight patients underwent biopsy. At the end of study recovery rate was increased from 88.3% to 94.1%. In conclusion, most of patients entered remission by our therapy end of follow up time. With the support of our satisfactory results among the whole study group, long-term prednisolone treatment still remains valid.

The long-term outlook to final outcome and steroid treatment results in children with idiopathic nephrotic syndrome.

Idiopathic Nephrotic Syndrome (INS) was defined as combination of a nephrotic syndrome and non-specific histological abnormalities of the kidney. Among these abnormalities, minimal change nephrotic syndrome (MCNS) is the most common. We report our experience with MCNS; its clinical course, treatments and outcomes. One-hundred twenty children (66 male, 54 female) with MCNS, admitted to Nephrology Department between 1987-2009 was assessed. Their clinical presentations, treatment and disease courses were reviewed. The mean duration of follow-up was 11.5 ± 1.9 years. Initially, all patients given prednisone 2 mg/kg/ day single dose per four weeks a followed by eight weeks of the same daily dose given every other day. After week 12, prednisone was progressively tapered off at the rate of 0.5 mg/kg per 15 daily intervals until complete discontinuation had been achieved by week 16. Steroid resistance was accepted as no achievement of remission following four weeks of prednisone 2 mg/kg/day followed by three intravenous pulses of corticosteroids. At the end of the initial steroid treatment, 106 (88.3%) patients were determinate steroid responsive while 14 (11.7%) patients were steroid resistance. Thirty-eight patients underwent biopsy. At the end of study recovery rate was increased from 88.3% to 94.1%. In conclusion, most of patients entered remission by our therapy end of follow up time. With the support of our satisfactory results among the whole study group, long-term prednisolone treatment still remains valid.

The importance of ultrasonographic measurement of peritoneal wall thickness in pediatric chronic peritoneal dialysis patients.

Loss of peritoneal function due to peritoneal fibrosing syndrome (PFS) is a major factor leading to treatment failure in chronic peritoneal dialysis (PD) patients. Although the precise biologic mechanisms responsible for these changes have not been defined, the general assumption is that alterations in peritoneal function are related to structural changes in the peritoneal membrane. Studies of the peritoneal membrane by non-invasive ultrasonography (US) in chronic PD patients are limited. The aim of the present study is to assess the relationship between functional parameters of peritoneum and peritoneal thickness measured by US in children treated by chronic PD. We recruited two groups of patients: 23 subjects (13 females, 10 males) on chronic PD (patient group) and 26 (7 females, 19 males) on predialysis out-patient follow-up (creatinine clearance: 20-60 mL/min/1.73 m(2)) (control group). Age, sex, weight, height, body mass index (BMI), chronic PD duration, episodes of peritonitis and the results of peritoneal equilibration test (PET) were recorded. Hemoglobin (Hb), blood pressure (BP), left ventricular mass index (LVMI) and renal osteodystrophy (ROD) parameters were also obtained. The thickness of the parietal peritoneum was measured by trans-abdominal US in all children. Statistical analyses were performed by using Student's t and Pearson's correlation tests. Mean peritoneal thickness in chronic PD patients (1028.26 ± 157.26 µm) was significantly higher than control patients (786.52 ± 132.33). Mean peritoneal thickness was significantly correlated with mean body height (R(2) = 0.93, p < 0.05), BMI (R(2) = 0.25, p < 0.05), chronic PD duration (R(2) = 0.64, p < 0.05), episodes of peritonitis (R(2) = 0.93, p < 0.05), D/Pcreatinine (R(2) = 0.76, p < 0.05) and D4/D0glucose (R(2) = 0.81, p < 0.05). No correlation was found between peritoneal thickness and Hb, BP, LVMI and ROD parameters. In conclusion, ultrasonographic measurement of peritoneal membrane thickness is a simple and non-invasive method in chronic PD children. This diagnostic tool likely enables to assess peritoneal structure and function in these patients.

Muscarinic Acetylcholine Receptor M3 Mutation Causes Urinary Bladder Disease and a Prune-Belly-like Syndrome.

Urinary bladder malformations associated with bladder outlet obstruction are a frequent cause of progressive renal failure in children. We here describe a muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation in familial congenital bladder malformation associated with a prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the M3 muscarinic acetylcholine receptor, which we show is present in developing renal epithelia and bladder muscle. These observations may imply that M3 has a role beyond its known contribution to detrusor contractions. This Mendelian disease caused by a muscarinic acetylcholine receptor mutation strikingly phenocopies Chrm3 null mutant mice.

The predictive value of urinary UPIb mRNA levels in VUR and recurrent urinary tract infections.

BACKGROUND: Vesicoureteral reflux (VUR) is a risk factor for progressive kidney damage especially when it is accompanied by urinary tract infections (UTIs). Uroplakins (UPs) are integral proteins found in the structure of urothelium. In the present study, we evaluated the usefulness of urinary UPIb messenger ribonucleic acid (mRNA) levels as an early and noninvasive diagnostic tool for VUR and as an indicator for predisposition to UTI. METHODS: Urinary UPIb mRNA levels were determined in patients experiencing their first UTI episode (n = 28) or recurrent UTI (n = 31) as well as patients having UTI with VUR (n = 30). These results were compared to a control group (n = 26). RESULTS: The UPIb mRNA values among patients diagnosed with their first UTI were lower, but not statistically different, than those in the control group. The UPIb mRNA levels of patients with recurrent UTI and UTI with VUR were significantly lower than those observed in control individuals. CONCLUSION: Urine UPIb levels may be useful for predicting the risk of recurrent UTI in patients diagnosed with their first UTI and may also be considered as a noninvasive screening test for VUR.

Success of continuous veno-venous hemodiafiltration treatment in children monitored in the intensive care units.

INTRODUCTION: As intensive care units (ICU) have improved, presence of multiple-organ dysfunctions in majority of patients with acute renal failure (ARF) has become clearer. To facilitate multi-organ support, continuous renal replacement therapy (CRRT) techniques have been developed. This study is the one that reports the experience on children including newborns receiving CRRT monitored in ICU. MATERIALS AND METHODS: The study was performed retrospectively in children who had Continuous Veno- Venous Hemodiafiltration (CVVHDF) as a CRRT modality in ICU. Clinical data, primary cause, consultation time, duration and initiation time of CVVHDF were recorded. Patients were classified as cardiac and non-cardiac in respect to primary dysfunction. Stage of renal failure was evaluated according to pRIFLE criteria. Outcome was identified as primary and secondary. Primary outcome was accepted as the composite correction of uremia and metabolic parameters, and regression of fluid overload, while secondary outcomes were assessed as improvement of hemodynamic instability and survival. RESULTS: A total of 36 patients' files were scanned. There were 10 cases in cardiac group and 26 cases in non-cardiac group. There were statistically better differences between primary and secondary outcome rates of cardiac cases. Although there was no difference between cardiac and non-cardiac cases in terms of primary outcome, secondary outcome was statistically significant. Timing of consultation and CVVHDF was not found to have an effect on the outcome. CONCLUSION: Our results indicated that CVVHDF treatment was successful even in cardiac patients with high mortality and in patients at their later stage of ARF.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

Lack of association between macrophage migration inhibitory factor gene promoter (-173 G/C) polymorphism and childhood Henoch-Schönlein purpura in Turkish patients.

Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity with rash, arthritis, abdominal pain and renal involvements. Macrophage migration inhibitory factor (MIF) is a immunoregulatory proinflammatory cytokine, and a major mediator at the inflammatory sites. The pathogenesis of HSP has not been fully elucidated. Here we aimed to assess the influence of macrophage migration inhibitory factor gene (-173 G/C) polymorphism in the susceptibility and clinical expression of patients with Henoch-Schönlein purpura (HSP). HSP patients (n:139) and ethnically matched healthy controls (n:100) were genotyped by PCR-RFLP. Genotype analysis of both polymorphisms did not reveal a significant deviation from Hardy-Weinberg equilibrium in any group (p > 0.05). No significant difference was obtained in genotype distribution (p > 0.05) and allele frequencies (p > 0.05) between patients and controls. A statistically significant genotype-phenotype correlation was not obtained when HSP patients were stratified by the presence of certain systemic complications and the macrophage migration inhibitory factor gene (-173 G/C) polymorphism (p > 0.05). A significant risk was not observed in the subjects both with the GC+CC genotype (p = 0.06, OR: 0.5538, 95% CI: 0.2985-1.0274) and C allele (odds ratio: C vs. G: 1.799, 95% CI: 1.002-3.23, p = 0.05). Our findings suggest that MIF gene -173 G/C polymorphism is not associated with HSP in the present Turkish population.