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Children with a solitary functioning kidney (SFK) have an increased risk of kidney injury. The exact risk of and risk factors for kidney injury remain unknown, which impedes personalized care. Here, we recruited a nationwide multicenter cohort of 944 patients with SFK to get more insight into this by consenting patients born in 1993-2020 and diagnosed with congenital or acquired SFK before adulthood. The median follow-up was 12.8 years and four indications of kidney injury were studied: urine protein-creatinine ratios, blood pressure, estimated glomerular filtration rate and use of anti-hypertensive/proteinuric medication. For each indicator except medication use, separate cut-off values for any injury and severe injury were used. Survival analyses indicated that at 18 years of age, any or severe kidney injury were present in 75% and 39% of patients with congenital SFK, respectively. Risk factors for kidney injury included kidney agenesis as cause of the SFK, anomalies in the SFK, and high body mass index at last follow-up. Kidney agenesis and being overweight were specifically associated with proteinuria and high blood pressure, whereas anomalies in the SFK were associated with reduced estimated glomerular filtration rates. The high prevalence of kidney injury in patients with SFK emphasizes the need for long-term follow-up, in which lifestyle is an important topic to address. More research into the etiological role of risk factors will help to translate our findings into individualized care strategies. Thus, our study shows that a significant proportion of children with SFK will develop kidney injury over time.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional signals. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. We conducted a multi-population GWAS meta-analysis in 38,463 participants (2,440 cases) and population specific GWAS, discovering twelve significant associations (eight novel). Fine-mapping implicated specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk signal. Non-HLA loci colocalized with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs was lacking, but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associated with earlier disease onset in two independent cohorts. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cellspecific insights into its molecular drivers.

Nephrotic syndrome in childhood is a common entity in the field of pediatric nephrology. The optimal treatment of children with nephrotic syndrome is often debated. Previously conducted studies have shown significant variability in nephrotic syndrome management, especially in the choice of steroid-sparing drugs. In the Netherlands, a practice guideline on the management of childhood nephrotic syndrome has been available since 2010. The aim of this study was to identify practice variations and opportunities to improve clinical practice of childhood nephrotic syndrome in the Netherlands. A digital structured survey among Dutch pediatricians and pediatric nephrologists was performed, including questions regarding the initial treatment, relapse treatment, kidney biopsy, additional immunosuppressive treatment, and supportive care. Among the 51 responses, uniformity was seen in the management of a first presentation and first relapse. Wide variation was found in the tapering of steroids after alternate day dosing. Most pediatricians and pediatric nephrologists (83%) would perform a kidney biopsy in case of steroid-resistant nephrotic syndrome, whereas for frequent relapsing and steroid-dependent nephrotic syndrome this was 22% and 41%, respectively. Variation was reported in the steroid-sparing treatment. Finally, significant differences were present in the supportive treatment of nephrotic syndrome.Conclusion: Substantial variation was present in the management of nephrotic syndrome in the Netherlands. Differences were identified in steroid tapering, use of steroid coverage during stress, choice of steroid-sparing agents, and biopsy practice. To promote guideline adherence and reduce practice variation, factors driving this variation should be assessed and resolved. What is Known:• National and international guidelines are available to guide the management of childhood nephrotic syndrome.• Several aspects of the management of childhood nephrotic syndrome, including the choice of steroid-sparing drugs and biopsy practice, are controversial and often debated among physicians.What is New:• Significant practice variation is present in the management of childhood nephrotic syndrome in the Netherlands, especially in the treatment of FRNS, SDNS, and SRNS.• The recommendation on the steroid treatment of a first episode of nephrotic syndrome in the KDIGO guideline leaves room for interpretation and is likely the cause of substantial differences in steroid-tapering practices among Dutch pediatricians and pediatric nephrologists.

The mean of GFR-estimates based on serum creatinine (eGFRcrea) and cystatin C (eGFRcys) has superior accuracy than each estimate alone. Recent studies have shown that agreement between eGFRcrea and eGFRcys is an indicator for the accuracy of the mean of the two estimates. As long as the difference between the two (|ΔeGFR|) is below 40%, a high P30 accuracy rate of more than 90% was documented in research settings using gold-standard GFR measurements. This was the case in approximately 80% of the measurements. The study was set out to explore |ΔeGFR| in a broader pediatric nephrological population and identify factors influencing the discrepancy between eGFRcrea and eGFRcys. We retrospectively analyzed 1596 simultaneous cystatin C and creatinine measurements in 649 unique patients at the pediatric nephrology outpatient clinic of VU university medical center. The FASage equation was used to calculate eGFRcrea, FAScys for eGFRcys. |ΔeGFR| was calculated as 100x(|eGFRcrea-eGFRcys|)/(0.5x(eGFRcrea+eGFRcys). ΔeGFR below 40% was considered high agreement. Patient characteristics like age, diagnosis, glucocorticosteroid use, eGFR, BMI and sex were analyzed for their effect on ΔeGFR below or above 40% using non-parametric tests and a potential explanation for measurements with low agreement was sought. Eighty-seven percent of the population had a |ΔeGFR| lower than 40%. Measurements with |ΔeGFR| above 40% were significantly more frequent from patients with neural tube defects. In 102 out of 208 measurements with low agreement, a potential explanation was found. In a broad pediatric nephrological population, |ΔeGFR| is below 40% in the vast majority of measurements. In this group, the mean of eGFRcrea and eGFRcys can be used as an accurate estimate of GFR.

Context A congenital solitary functioning kidney (cSFK) is a common developmental defect that predisposes to hypertension and chronic kidney disease (CKD) as a consequence of hyperfiltration. Every urologist takes care of patients with a cSFK, since some will need lifelong urological care or will come with clinical problems or questions to an adult urologist later in life. Objective We aim to provide clear recommendations for the initial clinical management and follow-up of children with a cSFK. Evidence acquisition PubMed and EMBASE were searched to identify relevant publications, which were combined with guidelines on related topics and expert opinion. Evidence synthesis Initially, cSFK diagnosis should be confirmed and risk factors for kidney injury should be identified using ultrasound. Although more research into early predictors of kidney injury is needed, additional congenital anomalies of the kidney or urinary tract and absence of compensatory kidney hypertrophy have repeatedly been associated with a worse prognosis. The role of voiding cystourethrography and antibiotic prophylaxis remains controversial, and is complicated by the exclusion of children with a cSFK from studies. A yearly follow-up for signs of kidney injury is recommended for children with a cSFK. As masked hypertension is prevalent, annual ambulatory blood pressure measurement should be considered. During puberty, an increasing incidence of kidney injury is seen, indicating that long-term follow-up is necessary. If signs of kidney injury are present, angiotensin converting enzyme inhibitors are the first-line drugs of choice. Conclusions This overview points to the urological and medical clinical aspects and long-term care guidance for children with a cSFK, who are at risk of hypertension and CKD. Monitoring for signs of kidney injury is therefore recommended throughout life. Large, prospective studies with long-term follow-up of clearly defined cohorts are still needed to facilitate more risk-based and individualized clinical management. Patient summary Many children are born with only one functioning kidney, which could lead to kidney injury later in life. Therefore, a kidney ultrasound is made soon after birth, and other investigations may be needed as well. Urologists taking care of patients with a solitary functioning kidney should realize the long-term clinical aspects, which might need medical management., Take Home Message Urologists should be aware of the clinical aspects and long-term risks for their patients with a congenital solitary functioning kidney, which predisposes to kidney injury and warrants long-term follow-up. Kidney ultrasound is the preferred tool to confirm diagnosis and screen for additional urogenital anomalies. Thereafter, a yearly blood pressure and urine albumin-creatinine measurement is indicated, and additional treatments can be recommended depending on the long-term individual outcome of these patients.

Background: Urinary tract infections (UTI) are among the most common infections in children. The primary tool to detect UTI is dipstick urinalysis, however, this has limited sensitivity and specificity. Therefore, urine culture has to be performed to confirm a UTI. Urinary volatile organic compounds (VOC) may serve as potential biomarker for diagnosing UTI. Previous studies on urinary VOCs focused on detection of UTI in a general population, therefore, this proof-of-principle study was set up in a clinical high-risk pediatric population. Methods: This study was performed at a tertiary nephro-urological clinic. Patients included were 0&ndash, 18 years, clinically suspected of a UTI, and had abnormal urinalysis. Urine samples were divided into four groups, i.e., urine without bacterial growth, contamination, colonization, and UTI. VOC analysis was performed using an electronic nose (eNose) (Cyranose 320&reg, ) and VOC profiles of subgroups were compared. Results: Urinary VOC analysis discriminated between UTI and non-UTI samples (AUC 0.70, p = 0.048, sensitivity 0.67, specificity 0.70). The diagnostic accuracy of VOCs improved when comparing urine without bacterial growth versus with UTI (AUC 0.80, p = 0.009, sensitivity 0.79, specificity 0.75). Conclusions: In an intention-to-diagnose high-risk pediatric population, UTI could be discriminated from non-UTI by VOC profiling, using an eNose. Since eNose can be used as bed-side test, these results suggest that urinary VOC analysis may serve as an adjuvant in the diagnostic work-up of UTI in children.

ispartof: PEDIATRIC NEPHROLOGY vol:35 issue:10 pages:1867-1870 ispartof: location:Germany status: published

Introduction Reporting estimated glomerular filtration rate (eGFR) instead of serum concentrations is advised in current guidelines. Most creatinine-based eGFR equations for children require height, a parameter not readily available to laboratories. Combining height-dependent creatinine- and cystatin C-based eGFR improves performance. Recently, a height-independent creatinine-based eGFR equation has been developed. Aim To compare the combination of height-independent creatinine- and cystatin C-based equations with a combination of equations using anthropometric data. Methods Retrospective analysis of 408 pediatric inulin clearance studies with simultaneous height, creatinine, cystatin C and urea measurements. eGFR calculation using the recalibrated Schwartzcrea (height-dependent), FASage (height-independent) and the Schwartzcys equation. The means (Schwartzcrea + Schwartzcys) / 2 and (FASage + Schwartzcys) / 2 were compared with the CKiD3 equation incorporating cystatin C, creatinine, urea, height and gender in terms of %prediction error and accuracy. Results All three single parameter equations performed similarly (P30 accuracy around 80%). (FASage + Schwartzcys) / 2 (P30 89.2%) and (Schwartzcrea + Schwartzcys) / 2 (P30 89.0%), performed comparably to CKiD3 (P30 90.0%). If the difference between the creatinine- and the cystatine C based eGFR was < 40%, P30 accuracy of the mean exceeded 90%. Conclusion Combining the height-independent FASage and SchwartzCys equations substantially improves accuracy and performs comparably to height-dependent equations. This allows laboratories to directly report eGFR in children.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2, 824 cases and 21, 498 controls. Affected individuals carried a significant burden of rare exonic (i.e. affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD- CNVs and novel deletions ; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs ; vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12, and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1- p16.3, and 22q11.2 were specific for KA ; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

IntroductionIdiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome).Methods and analysisAn international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2–16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores.Ethics and disseminationThe trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.Trial registration numberNL6826, 2017-001025-41

INTRODUCTION: Beta-trace protein (BTP) is a low molecular weight protein, produced mainly in the cerebrospinal fluid. It has been proposed as a marker for kidney function. Recently, a new method for GFR estimation using mean normal values to rescale GFR marker concentrations has been described for creatinine and cystatin C, two commonly used endogenous markers for kidney function. The aim of this study is to apply this approach to BTP in children. METHOD: We retrospectively analyzed serum concentrations of creatinine, cystatin C and BTP measured during inulin clearance tests in children. BTP was measured using a particle-enhanced immunonephelometric assay (Siemens Healthcare). A novel BTP-based eGFR equation was developed using published normal values for children: eGFRBTP[ml/min/1.73m2] = 107.3/BTP/QBTP with QBTP = 0.69. Performance of this equation was compared to the established creatinine-based full age spectrum equation FASage and the cystatin C-based FAScys equations as well as the BTP-based Benlamri equation in terms of bias, % prediction error and P30 and P10 accuracy rates. RESULTS: 322 inulin clearance tests were studied. Overall, our novel equation performed comparably to the creatinine-based FASage and the BTP-based Benlamri equations but was less accurate than FAScys (P30: 79.2 vs 86.3%, p = .008). Combining markers significantly enhanced performance compared to the single marker equations, with the exception of FAScys. CONCLUSION: Rescaled BTP concentrations are a simple method for estimating GFR in children. However, the additional value of BTP for the estimation of GFR compared to rescaled creatinine and cystatin C still remains to be demonstrated. ispartof: CLINICA CHIMICA ACTA vol:486 pages:259-264 ispartof: location:Netherlands status: published

Renal agenesis and hypodysplasia (RHD) are major causes of pediatric chronic kidney disease and are highly genetically heterogeneous. We conducted whole-exome sequencing in 202 case subjects with RHD and identified diagnostic mutations in genes known to be associated with RHD in 7/202 case subjects. In an additional affected individual with RHD and a congenital heart defect, we found a homozygous loss-of-function (LOF) variant in SLIT3, recapitulating phenotypes reported with Slit3 inactivation in the mouse. To identify genes associated with RHD, we performed an exome-wide association study with 195 unresolved case subjects and 6,905 control subjects. The top signal resided in GREB1L, a gene implicated previously in Hoxb1 and Shha signaling in zebrafish. The significance of the association, which was p = 2.0 × 10-5 for novel LOF, increased to p = 4.1 × 10-6 for LOF and deleterious missense variants combined, and augmented further after accounting for segregation and de novo inheritance of rare variants (joint p = 2.3 × 10-7). Finally, CRISPR/Cas9 disruption or knockdown of greb1l in zebrafish caused specific pronephric defects, which were rescued by wild-type human GREB1L mRNA, but not mRNA containing alleles identified in case subjects. Together, our study provides insight into the genetic landscape of kidney malformations in humans, presents multiple candidates, and identifies SLIT3 and GREB1L as genes implicated in the pathogenesis of RHD.

Background: While glucocorticosteroids (GCS) are widely used in patients with kidney disease, little is known about their effect on serum creatinine, the most commonly used endogenous marker of kidney function. Methods: We assessed the effect of GCS on the relationship between estimated GFR using the Schwartz equation (eGFR) and measured GFR using a single-injection inulin clearance (Cin) in children both in a paired analysis and a cross-sectional study. Primary outcome variable was the difference between eGFR and Cin (ΔGFR) in a paired analysis involving 22 patients during and off GCS treatment (mean GFR 103.8 ml/min/1.73 m2, mean prednisone dose 34.8 mg/m2/day). In a cross-sectional analysis in 42 patients receiving GCS (mean dose of 25.7 mg/m2/day), a dose-dependent effect was explored using univariate and multivariate linear regression of various variables including GCS dosage with serum creatinine as dependent variable. Results: The paired analysis showed no significant difference in ΔGFR with or without GCS [− 23 (SD 53) vs. − 9 (SD 41) ml/min/1.73 m2, p = 0.203]. Stepwise multivariate linear regression analysis showed a significant correlation between age and Cin, while GCS dose was not related to serum creatinine. Conclusion: GCS use had no significant effect on serum creatinine as a marker for kidney function in a mixed population of renal outpatient clinic children.

Background/Aims: The fractional excretion of sodium (FeNa) may be helpful in establishing the cause of acute renal failure. This study was performed to determine the influence of the glomerular filtration rate (GFR), sodium intake, and tubular function on FeNa in children without renal failure. Methods: In this single institute cross-sectional study, 24-h-urine collections from patients (4-18 years of age, GFR >60 mL/min/1.73 m2) were used when considered reliable, and analyzed to determine sodium excretion, creatinine clearance and FeNa. The influence of tubular function was studied in 5 patients with generalized tubular dysfunction. Results: Based on data from 761 patients, a multiple regression formula was designed based on GFR and sodium excretion that predicted over 80% of the variation in FeNa (R2 = 0.824, p < 0.001). Using this formula, the predicted FeNa was significantly lower than the measured FeNa in the children with tubular dysfunction. Conclusion: FeNa depends on GFR and sodium intake, and tubular function cannot be assessed without possessing adequate knowledge on all factors. Therefore, no normal range or cut-off value for FeNa to assess tubular function can be given, and doing so is a misapplication of this equation.

International audience; 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.).

In the version of this article initially published, affiliation 38 incorrectly read “ICNU-Nephrology and Urology Department, Barcelona, Spain”; “Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain” is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.

Contains fulltext : 186643.pdf (Publisher’s version ) (Closed access) BACKGROUND AND OBJECTIVE: Children with a solitary functioning kidney may develop CKD. Although widely used, equations to estimate GFR are not validated in these patients. This study sought to determine the precision of common estimating equations in the KIMONO (KIdney of MONofunctional Origin) cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Two creatinine-based (estimated GFR [eGFR]-Schwartz, urinary creatinine clearance), two cystatin C-based (eGFR-Zappitelli1, eGFR-CKiD [Chronic Kidney Disease in Children] 1), and two cystatin C/creatinine-based (eGFR-Zappitelli2, eGFR-CKiD2) estimates were compared with the gold standard GFR measured by inulin single injection (GFR-inulin) in 77 children with a solitary functioning kidney (time span of assembly, 2005-2012). Included patients were 1.5-19.8 years of age. Kidney Disease Outcomes Quality Initiative (K/DOQI) classification was compared between GFR-inulin and eGFR methods to analyze misclassification by estimating equations. RESULTS: The eGFR-CKiD2 equation performed best in children with a solitary functioning kidney (mean bias, -0.9 ml/min per 1.73 m(2); 95% and 54% of values within +/-30% and +/-10% of GFR-inulin, respectively). Mean bias for eGFR-Schwartz was 0.4 ml/min per 1.73 m(2), with 90% and 33% of values within +/-30% and +/-10% of GFR-inulin, respectively. For all estimates, misclassification in K/DOQI stage ranged from 22% (eGFR-Zappitelli1) to 44% (urinary creatinine clearance) of children. CONCLUSIONS: Use of a combined serum cystatin C/creatinine-based equation (eGFR-CKiD2) is recommended to monitor renal function in children with a solitary functioning kidney. When cystatin C is not routinely available, eGFR-Schwartz should be used. Misclassification in K/DOQI-stage remains a caveat for all equations. 01 mei 2013

Inleiding Kinderen met een mononier hebben mogelijk een verhoogd risico op het ontwikkelen van hypertensie, (micro)albuminurie en chronische nierinsufficientie.Twee oorzaken hiervoor zouden glomerulaire hyperfiltratie en de hoge incidentie van congenitale afwijkingen van nieren en urinewegen (CAKUT) kunnen zijn. De KIMONO-studie inventariseert het bestaan van tekenen van nierschade op de kinderleeftijd in een groot cohort van kinderen met een mononier.

OBJECTIVE: The present study was undertaken to evaluate the practicability of the proposed pediatric RIFLE (pRIFLE) criteria in a patient population at risk for acute kidney injury (AKI) and to analyze the prevalence and association of AKI as defined by pRIFLE with mortality.DESIGN: Retrospective, descriptive cohort study.SETTING: Single-center, 9-bed PICU facility.PATIENTS: Children with respiratory failure requiring mechanical ventilation for more than 4 days admitted between January 2002 and December 2006.INTERVENTIONS: None.MEASUREMENTS AND RESULTS: Data of 103 patients were studied. Median age was 4.5 years (range 1 month-17 years). Six patients received renal replacement therapy. Seventeen patients (17%) died. Sixty patients (58%) developed AKI by pRIFLE. Mean time to attainment of the first RIFLE stratum was 1.9 +/- 1.6 days. By pRIFLE, 34 of the 60 patients fulfilled the maximum AKI criteria on the first day after admission based on the estimated creatinine clearance criterion. Patients with AKI according to the pRIFLE scoring system had five times higher mortality than patients without AKI (25 vs. 5%, P < 0.05).CONCLUSIONS: We observed a high incidence of significant AKI in a PICU population at risk, which was associated with high mortality. Pediatric RIFLE criteria may guide in the early identification of patients at risk for AKI and in the initiation of therapy.

Objectives: The ratio of the urinary mass concentrations of cystatin C and creatinine (UcysC/Ucrea) ≥ 11.3 mg/mmol has recently been proposed as an accurate marker for the detection of GFR ≤ 60 mL/min/1.73 m 2 . Design and methods: We prospectively evaluated the diagnostic performance of UcysC/Ucrea ≥ 11.3 mg/mmol and factors associated with increased UcysC/Ucrea in 72 children and adults with a wide variety of renal disorders. UcysC/Ucrea was calculated, and GFR wad estimated from serum creatinine and cystatin C by equations. Results: UcysC/Ucrea ≥ 11.3 mg/mmol had a low diagnostic value to detect GFR values ≤ 60 mL/min/1.73 m 2 estimated by creatinine or cystatin-C-based equations with sensitivities of 72% and 63%, and specificities of 42% and 34%. ROC curves for UcysC/Ucrea to detect GFR ≤ 60 mL/min/1.73 m 2 confirmed this with AUCs of 0.59 for creatinine and 0.57 for cystatin-C-based equations. Multivariate analysis identified tubular proteinuria, tubulointerstitial disease and heavy proteinuria, but not GFR ≤ 60 mL/min/1.73 m 2 , as factors independently associated with increased UcysC/Ucrea. Conclusions: UcysC/Ucrea ≥ 11.3 mg/mmol is not an accurate marker to detect GFR ≤ 60 mL/min/1.73 m 2 , but reflects tubular dysfunction and proteinuria due to heavy proteinuria and tubulointerstitial disease.

Contains fulltext : 170897.pdf (Publisher’s version ) (Open Access) BACKGROUND: Children with unilateral Wilms tumor (WT) treated with chemotherapy and/or radiotherapy and nephrectomy have excellent survival rates. A solitary functioning kidney (SFK) is associated with progressive renal injury. This study aims to investigate the additional effect of Wilms tumor treatment on renal function compared with children with an SFK for non-oncological reasons. METHODS: A single-center retrospective cohort study on the renal injury markers of 79 survivors of unilateral WT was performed and compared with a matched group of children with an SFK for non-oncological reasons. Mean age at follow-up was 12.4 (SD 5.9) years. RESULTS: During follow-up, mean estimated glomerular filtration rate (eGFR) and blood pressure z-scores remained stable at an acceptable level. However, in the group of 31 WT patients with a follow-up of 15 years, 23 % showed signs of renal injury. This proportion was smaller than the 54 % in a group of SFK patients based on non-oncological causes (p = 0.004). CONCLUSIONS: A significant proportion of WT survivors develop renal injury during follow-up. Our data may be an underestimation of the true frequency of progressive renal injury, due to a lack of information on proteinuria. As with patients with a non-oncological SFK, long-term follow-up is essential to monitor WT survivors.

Item does not contain fulltext Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to be difficult. Here we studied the role of rare copy number variations in 80 patients from the KIMONO study cohort for which pathogenic mutations in three genes commonly implicated in CAKUT were excluded. In total, 13 known or novel genomic imbalances in 11 of 80 patients were absent or extremely rare in 23,362 population controls. To identify the most likely genetic drivers for the CAKUT phenotype underlying these rare copy number variations, we used a systematic in silico approach based on frequency in a large data set of controls, annotation with publicly available databases for developmental diseases, tolerance and haploinsufficiency scores, and gene expression profile in the developing kidney and urinary tract. Five novel candidate genes for CAKUT were identified that showed specific expression in the human and mouse developing urinary tract. Among these genes, DLG1 and KIF12 are likely novel susceptibility genes for CAKUT in humans. Thus, there is a significant role of genomic imbalance in the determination of kidney developmental phenotypes. Additionally, we defined a systematic strategy to identify genetic drivers underlying rare copy number variations.

A low nephron endowment may be associated with hypertension. Nephrogenesis is the process that leads to the formation of nephrons until week 36 of gestation in humans and may be inhibited by many factors like intrauterine growth restriction and premature birth. To study the consequences of a low glomerular number, animal models have been developed. We describe a model of postnatal food restriction in the rat in which litter size is increased to 20 pups, which leads to growth restriction. In the rat, active nephrogenesis continues until postnatal day 8, which coincides with the growth restriction in our model. Design-based stereological methods were used to estimate glomerular number and volume. Our results show an approximately 25% lower glomerular number in rats after postnatal food restriction (30,800 glomeruli/kidney) compared with control rats (39,600 glomeruli/kidney, P < 0.001). Mean glomerular volume was increased by 35% in the growth-restricted rats (P = 0.006). There was a significant negative correlation between glomerular volume and glomerular number (r = -0.76, P < 0.001). We conclude that postnatal food restriction in the rat leads to a low nephron endowment with compensatory enlargement. It is therefore a suitable model to study the effect of intrauterine growth restriction or prematurity on kidney development and the consequences of a reduced glomerular number in later life.

Intrauterine growth restriction (IUGR) is associated with a higher risk of hypertension in adulthood. In Western countries, IUGR is based on uteroplacental dysfunction. We hypothesize that aging augments the increased baseline blood pressure after IUGR and alters the cardiovascular response to acute stress.To evaluate blood pressure during aging in the rat, we used a model of uteroplacental dysfunction (bilateral uterine artery ligation). Blood pressure was measured in male offspring at the ages of 6, 9, and 12 months using telemetry, allowing for unstressed measurements in conscious animals. At 6 and 12 months of age, cardiovascular data were obtained during acute olfactory stress induced by ammonia and subsequent recovery.Rats born after IUGR had lower birth weights (4.6 versus 6.5 g, P0.001) and did not completely catch up in weight by 12 months of age (519 versus 567 g, P0.01). Systolic blood pressure was significantly higher in IUGR animals at all ages. Pulse pressure (PP) was identical in both groups at the age of 6 months. However, PP increased in the IUGR group with increasing age, unlike the control group, and was significantly higher at 9 and 12 months of age. At the age of 12 months, there was a highly significant negative correlation between birth weight and PP (r = -0.82, P0.001). IUGR rats reached a higher peak in systolic blood pressure during stress, and showed a longer period for the raised heart rate to recover after stress.IUGR is associated with raised baseline blood pressure, an increasing PP with age, and an altered stress response.

Low birth weight (LBW) due to intrauterine growth restriction (IUGR) in humans is associated with increased blood pressure (BP) in adulthood. In Western countries, IUGR is based on uteroplacental dysfunction. We used an animal model of uteroplacental dysfunction to evaluate this correlation. We hypothesize that IUGR increases baseline BP and alters the BP response to acute stress, which may explain BP differences in previous studies using stressful methods to obtain BP. IUGR was induced by bilateral uterine artery ligation in pregnant Wistar rats according to a modified method of Wigglesworth. BP was measured in the offspring using telemetry, allowing for unstressed measurements in conscious animals. Cardiovascular data were obtained at the age of 12 wk during baseline and acute olfactory stress induced by an ammonia gauze. Rats born after IUGR had a lower birth weight versus controls and did not completely catch up in weight. At baseline, systolic BP (SBP), mean arterial pressure (MAP), and pulse pressure (PP) were elevated in IUGR rats versus controls, by 8, 6, and 5 mm Hg, respectively. There was a strong negative correlation between birth weight and SBP and between birth weight and PP. During acute stress, there was a tendency to reach a higher peak in SBP and to need a longer period to recover in IUGR animals. We conclude that IUGR is associated with increased baseline BP.

Autosomal-recessive Schimke immuno-osseous dysplasia (SIOD) characterized by spondyloepiphyseal dysplasia, focal-segmental glomerulosclerosis (FSGS), T-cell immunodeficiency and facial dysmorphism is caused by defects in the SMARCAL1 gene. The gene product is involved in the transcriptional regulation of other genes. A 12-year-old boy of consanginous Turkish descent developed disproportionate short stature from spondyloepiphyseal dysplasia at the age of 6 and nephrotic syndrome at the age of 10 years. Renal biopsy revealed FSGS, the kidney function was normal, T-lymphocytes were diminished without infectious complications, and he has had no cerebral ischemia. Analysis of the patient's SMARCAL1 gene revealed a novel homozygous C1798T transition leading to a R561C substitution. The parents and two healthy sisters were found to be heterozygous. A younger brother, who is also homozygous for the mutation, is clinically asymptomatic and has no proteinuria at the age of 18 months. Still, his CD4 cells are diminished. For SMARCAL1 mutations a clear genotype-phenotype correlation has been reported: severe SIOD with in utero or early-childhood onset leading to end-stage renal disease within a few years is caused by nonsense, frame shift or splice mutations. Many patients die from infections and cerebrovascular insults during childhood. Mild SIOD manifests later and progresses more slowly without infectious or cerebral vascular complications--the underlying defect being missense mutations in all three patients reported so far. The novel R561C missense mutation in our patient with mild SIOD is additional evidence for the genotype-phenotype correlation reported for SMARCAL1 mutations.

Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n =18) or in remission (n =23) (after treatment with prednisolone) for presence or activity of Hx. For comparison, plasma or urine from proteinuric subjects with focal and segmental glomerulosclerosis (FSGS, n =11), membranoproliferative glomerulonephritis (MPGN, n =9), IgA nephropathy (n =5) or healthy control donors (n =10), were incorporated into the study. Electrophoresis and Western blotting methods were used for evaluation of the Hx status, whereas protease activity of Hx was tested upon kidney tissue in vitro according to standard methods. The results show (1) a decreased mean titer of plasma Hx exclusively in MCD relapse subjects as compared with MCD in remission (0.21 +/- 0.14 mg/ml vs 0.44 +/- 0.06 mg/ml; p

Renal involvement is regularly encountered in neonates with invasive candidiasis, especially when risk factors like congenital malformations of the renal tract or poor bladder emptying and preterm birth are present. However, complete obstruction of the renal collecting system by fungal balls is rare. Although conservative management has been advocated for partial obstruction, complete obstruction is considered an indication for surgical drainage. We report a patient with anuria and Candida albicans bezoars in a solitary kidney, suggesting post-renal acute kidney injury. The patient was treated with systemic fluconazole and peritoneal dialysis for 4 days. The fungus balls disappeared and renal function recovered. Conclusion: Systemic antifungal therapy leads to clearance of obstructing fungus balls, and nephrostomy should be reserved for anuria due to bilateral complete obstruction with severe hydronephrosis. In these cases, temporary dialysis is a potential alternative.

Background Patients suffering from an H1N1 infection mainly suffer from respiratory symptoms but may also develop symptoms in other organ systems, such as the kidneys. Case-diagnosis/treatment A 4 ½ year-old boy was admitted with relatively mild respiratory symptoms of H1N1 infection, but developed severe generalized proximal tubular dysfunction with sterile leucocyturia and a reversible rise in serum creatinine. He made a full recovery with supportive therapy. Conclusion Influenza H1N1 may be associated with acute tubulointerstitial nephritis.

Cystatin C, a cationic low-molecular-weight protein ( M r 13 300) (1), has been described as a promising endogenous marker of glomerular filtration rate (GFR) in both adults (2)(3) and children (4). The correlation of serum cystatin C concentrations with the results of inulin and 51Cr-EDTA clearance examinations was superior to the correlation obtained with serum creatinine (2)(3)(4). The gene for cystatin C is expressed in all nucleated cells (5) and bears the characteristics of a housekeeping gene (6). Therefore, the cystatin C production rate is assumed to remain constant (3). This is supported by clinical evidence from several studies (7)(8). In renal transplant recipients, however, increases in serum cystatin C concentrations out of proportion to renal function impairment have been reported (9)(10)(11)(12)(13). Although serum cystatin C decreases before serum creatinine falls after successful transplantation, serum cystatin C concentrations increase by almost 30% between days 2 and 6 despite stable allograft function (14)(15). The pathogenesis of this observation is as yet unexplained. Because patients receive high doses of corticosteroids after transplantation, a potential role of concomitant steroid therapy has been discussed (9)(12). In patients with severe asthma, Cimerman et al. (16) observed an increase in serum cystatin C with high-dose corticosteroid therapy. In vitro, dexamethasone produces a significant and dose-dependent increase in cystatin C production in HeLa cells (17). To investigate the effect of systemic steroid therapy on serum cystatin C concentrations in patients with normal excretory renal function, the present study analyzed cystatin C, β2-microglobulin ( M r 11 800), and …

Item does not contain fulltext Congenital anomalies of the kidney and urinary tract are the major cause of ESRD in childhood. Children with a solitary functioning kidney form an important subgroup of congenital anomalies of the kidney and urinary tract patients, and a significant fraction of these children is at risk for progression to CKD. However, challenges remain in distinguishing patients with a high risk for disease progression from those patients without a high risk of disease progression. Although it is hypothesized that glomerular hyperfiltration in the lowered number of nephrons underlies the impaired renal prognosis in the solitary functioning kidney, the high proportion of ipsilateral congenital anomalies of the kidney and urinary tract in these patients may further influence clinical outcome. Pathogenic genetic and environmental factors in renal development have increasingly been identified and may play a crucial role in establishing a correct diagnosis and prognosis for these patients. With fetal ultrasound now enabling prenatal identification of individuals with a solitary functioning kidney, an early evaluation of risk factors for renal injury would allow for differentiation between patients with and without an increased risk for CKD. This review describes the underlying causes and consequences of the solitary functioning kidney from childhood together with its clinical implications. Finally, guidelines for follow-up of solitary functioning kidney patients are recommended.

Item does not contain fulltext BACKGROUND: Children with a solitary functioning kidney are at increased risk of developing chronic kidney disease. Hypertension may be an early indicator of renal dysfunction in these patients. We determined blood pressure (BP) profiles of children with a solitary functioning kidney by using ambulatory BP monitoring (ABPM). METHODS: To assess the occurrence with (pre)hypertension, we compared ABPM to office BP measurement in 47 children with a solitary functioning kidney. None of the subjects used antihypertensive agents or had been hypertensive during previous clinical visits. RESULTS: Mean age of study subjects was 12.7 (+/-3.3) years. Hypertension was identified in ten (21 %) subjects with ABPM, whereas only two (4 %) children were hypertensive during office BP measurement (p < 0.01). Fifteen (32 %) children had an ABPM standard deviation (SD) value >/=90th percentile versus six (13 %) subjects based on office BP measurement (p = 0.051). Although 24-h ABPM SD scores were higher in the congenital type than in the acquired type of solitary functioning kidney (p

We assessed whether the GFR marker cystatin C can be measured reliably in capillary blood samples in children with renal disease. Cystatin C was measured in venous and capillary blood samples obtained simultaneously from 48 children, and GFR was estimated using the Filler equation. Estimated GFR based on capillary cystatin C concentrations was higher than the venous cystatin C based GFR. The limits of agreement between estimated GFR based on capillary and venous measurements exceeded ± 20% at the upper reference concentration, which hampers the clinical usefulness of capillary sampling.

Serum cystatin C, β2-microglobulin, and β-trace protein are endogenous markers of glomerular filtration rate (GFR). Cystatin C, in particular, is a promising alternative to creatinine for the detection of incipient renal failure. However, corticosteroids affect the extrarenal metabolism of cystatin C, which limits the use of cystatin C as a marker of GFR in a variety of clinical settings. Low-molecular–weight (LMW) β-trace protein might be a useful alternative in this respect. The present study set out to compare the effect of corticosteroid therapy on the serum concentrations of cystatin C, β2-microglobulin, and β-trace protein. We studied a group of 108 children being treated or followed for malignancy (n = 41) or renal disease (n = 67). In the former group 14 patients (34%) were treated with glucocorticoids, in the latter 18 (27%). We compared single-injection inulin clearance studies in 76 patients not receiving steroids with 32 in patients receiving corticosteroid treatment (median dose 33.0 mg prednisone-equivalent per m2 body surface area per day, range 1.2–70.4). Mean (SD) age was 9.7 (5.8) years, mean (SD) GFR 92.8 (34.6) mL · min−1 · (1.73 m2)−1. Patients included in the …

Item does not contain fulltext Nephronophthisis is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. Most NPHP gene products form molecular networks. Here we identify ANKS6 as a new NPHP family member that connects NEK8 (NPHP9) to INVS (NPHP2) and NPHP3. We show that ANKS6 localizes to the proximal cilium and confirm its role in renal development through knockdown experiments in zebrafish and Xenopus laevis. We also identify six families with ANKS6 mutations affected by nephronophthisis, including severe cardiovascular abnormalities, liver fibrosis and situs inversus. The oxygen sensor HIF1AN hydroxylates ANKS6 and INVS and alters the composition of the ANKS6-INVS-NPHP3 module. Knockdown of Hif1an in Xenopus results in a phenotype that resembles loss of other NPHP proteins. Network analyses uncovered additional putative NPHP proteins and placed ANKS6 at the center of this NPHP module, explaining the overlapping disease manifestation caused by mutation in ANKS6, NEK8, INVS or NPHP3. 6 p.

Item does not contain fulltext BACKGROUND: Unilateral renal agenesis (URA) is associated with other congenital anomalies of the kidney and urinary tract (CAKUT) and extra-renal anomalies. However, the reported prevalences of these anomalies are highly variable. We estimated the prevalence of associated CAKUT and extra-renal anomalies in patients with URA. Furthermore, we determined the prevalence of renal injury in URA patients. METHODS: We conducted a systematic review of English and non-English articles using PubMed and Embase.com. Included studies reported at least one of the following items: incidence of URA, gender, side of URA, prenatal diagnosis, performance of micturating cystourethrogram, associated CAKUT, urinary tract infection or extra-renal anomalies. Studies that described a mean/median glomerular filtration rate (GFR) and proportions of patients with hypertension, micro-albuminuria or a decreased GFR were also included. RESULTS: Analyses were based on 43 included studies (total number of patients: 2684, 63% male). The general incidence of URA was 1 in approximately 2000. Associated CAKUT were identified in 32% of patients, of which vesicoureteral reflux was most frequently identified (24% of patients). Extra-renal anomalies were found in 31% of patients. Hypertension could be identified in 16% of patients, whereas 21% of patients had micro-albuminuria. Ten per cent of patients had a GFR

Item does not contain fulltext 01 juni 2012

Background Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (αFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (ΔCFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). Methods Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. Results In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xαFH, of which five had ΔCFHR1/3); four patients carried combined genetic defects or a mutation, together with αFH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant. Conclusions Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options. © 2011 IPNA., SCOPUS: ar.j, info:eu-repo/semantics/published

Nephrotic syndrome (NS) is a clinical diagnosis with proteinuria, hypoalbuminaemia and oedema. NS is rare in children, and its incidence in The Netherlands is unknown. The aim of this study was to estimate the incidence of idiopathic NS in the Netherlands. All paediatric patients (age 0-18 years) with a newly diagnosed NS in the Netherlands were registered by the Dutch Pediatric Surveillance Unit during the years 2003 until 2006, secondary NS was excluded. All paediatricians filled out questionnaires about the first clinical findings of the patients and incidences were calculated. A literature review on incidences of childhood NS was conducted. The incidence of NS in children in the Netherlands in the years 2003 until 2006 was 1.52/ 100, 000 children/ year. The median age at diagnosis was 3.88 years with a mean age of 5.08 years. A significant male:female ratio of 2.04:1 was found. This prospective study of NS in the Netherlands revealed an incidence of 1.52:100, 000 children/year, and is similar to the incidences found all over the world.

Background Monitoring of renal function is crucial in pediatric oncology. The use of creatinine to estimate glomerular filtration rate (GFR) is hampered by its dependency on muscle mass. Muscle wasting is common in children with cancer, leading to overestimation of GFR. Data on cystatin C are sparse in pediatric oncology, although this marker could be particularly useful in this population. Procedure Inulin clearance, estimated GFR using serum cystatin C according to Filler (eGFRcys) and serum creatinine according to Schwartz (eGFRcrea) were measured in 68 children with malignancy and 121 controls. We analyzed the difference between measured and estimated GFR and performance, bias and accuracy. Results Multiple linear regression analysis showed overestimation of GFR by eGFRcrea in females (B = −21.18; P = 0.001), and in patients with malignancy (B = −21.77; P = 0.014). eGFRcys overestimated GFR in females (B = −10.47; P = 0.001), but was independent of treatment for malignancy. Agreement with gold standard in detecting GFR below 90 ml/min/1.73 m2 is better for eGFRcys (AUC 0.854) than for eGFRcrea (AUC 0.675) in the group with cancer. They performed comparably in the control group. Bland–Altman analysis showed considerable bias for eGFRcrea compared to eGFRcys (−14.3 ml/min/1.73 m2 vs. −7.3 ml/min/1.73 m2). The proportion of estimates within 30% of true GFR for eGFRcrea (72.1%) was lower than for eGFRcys (82.4%) in the group with cancer. In the control group eGFRcrea (84.3%) outperformed eGFRcys (76.0%). When using the 50% limits of agreement, eGFRcys outperformed eGFRcrea in both groups. Conclusion Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy. Pediatr Blood Cancer 2011; 57: 262–267. © 2011 Wiley-Liss, Inc.

Item does not contain fulltext BACKGROUND: Children with a solitary functioning kidney (SFK) have an increased risk of developing hypertension, albuminuria and chronic kidney disease in later life. This renal injury is hypothesized to be caused by glomerular hyperfiltration that follows renal mass reduction in animal studies. Furthermore, children with an SFK show a high incidence of congenital anomalies of the kidney and urinary tract (CAKUT), which could further compromise renal function. METHODS: A retrospective study of renal injury markers was performed in 206 children, divided into groups based on the origin of SFK [primary (congenital) SFK (n = 116) and secondary SFK (n = 90)]. Data on ipsilateral CAKUT were stratified separately. For blood pressure, albuminuria and glomerular filtration rate, longitudinal models were additionally developed using generalized estimated equation analysis. RESULTS: Renal injury, defined as the presence of hypertension and/or albuminuria and/or the use of renoprotective medication, was present in 32% of all children with an SFK at a mean age of 9.5 (SD 5.6) years. Children with ipsilateral CAKUT had higher proportions of renal injury (48.3 versus 24.6%, P < 0.05). Furthermore, longitudinal models showed a decrease in glomerular filtration rate in both groups from the beginning of puberty onwards. CONCLUSIONS: This large cohort study demonstrates that renal injury is present in children with an SFK at a young age, whereas our longitudinal models show an increased risk for chronic kidney disease in adulthood. Renal injury is even more pronounced in the presence of ipsilateral CAKUT. Therefore, we underline that clinical follow-up of all children with an SFK is needed.

Incomplete or aberrant glycosylation leading to Tn antigen (GalNAcα1-Ser/Thr) expression on human glycoproteins is strongly associated with human pathological conditions, including tumors, certain autoimmune diseases, such as the idiopathic IgA nephropathy, and may modulate immune homeostasis. In addition, the Tn antigen is highly expressed by certain pathogens and plays a role in host–pathogen interactions. To enable experimental approaches to study interactions of the Tn antigen with the immune system and analyze anti-Tn antibody responses in infection or disorders, we generated a Tn-expressing resource that can be used for high-throughput screening. In consideration of IgA nephropathy in which the hinge region is incompletely glycosylated, we used this hinge sequence that encodes five potential glycosylation sites as the ideal template for the synthesis of a Tn antigen-expressing glycopeptide. Inclusion of an N-terminal biotin in the peptide enabled binding to streptavidin-coated ELISA plates as monitored using Helix pomatia agglutinin or anti-Tn monoclonal antibody. We also found that the biotinylated IgA-Tn peptide is a functional acceptor for β1-3-galactosylation using recombinant T-synthase (β1-3-galactosyltransferase). Besides its immunochemical functionality as a possible diagnostic tool for IgA nephropathy, the peptide is an excellent substrate for glycan elongation and represents a novel template applicable for glycan–antigen-associated diseases.

Contains fulltext : 87541.pdf (Publisher’s version ) (Closed access) PURPOSE: Urological characteristics of renal ectopia have been addressed previously but little is known about the functional consequences. We sought to study renal function, blood pressure, proteinuria and urological abnormalities in children with renal ectopia. As a secondary objective, we compared these parameters between simple and crossed ectopia. MATERIALS AND METHODS: For this retrospective, single center, observational study we reviewed case documents and radiological records. We also analyzed longitudinal data on blood pressure, proteinuria and kidney function. RESULTS: Renal ectopia was diagnosed in 41 cases, of which 26 (63%) were simple renal ectopia, ie unilateral pelvic kidney. In 32% of patients the diagnosis was made during prenatal screening. Median patient age was 0.24 years at diagnosis and 7.7 years at the most recent control visit. Associated urological abnormalities were found in 66% of patients. Voiding cystourethrography was performed in all patients, with vesicoureteral reflux shown in 13. In 8 of 10 cases with unilateral reflux the condition manifested in the orthotopic kidney. The relative function of the ectopic kidney on dimercapto-succinic acid scan was 38%, and in 22% of patients glomerular filtration rate was less than 90 ml per minute per 1.73 m(2). Albuminuria and proteinuria were absent in most cases. Longitudinal analysis of blood pressure, glomerular filtration rate and albuminuria revealed a stable course for all parameters. No substantial difference was observed between simple and crossed renal ectopia. CONCLUSIONS: Our data suggest no adverse effects on blood pressure or kidney function in children with renal ectopia. However, periodic followup seems warranted, at least until young adulthood. 01 april 2010

Patients with atypical haemolytic uremic syndrome (aHUS) with a mutation in the gene encoding membrane cofactor protein (CD46) are known to have a better prognosis than those with mutations in factor H (CFH) or factor I (CFI), but a small number of the former still proceed to end-stage renal failure. Plasma therapy (PE) is the recommended approach to treat both acute episodes and prevent recurrences in aHUS, but studies have yet to show PE efficacy in aHUS associated with a CD46 mutation. The factors determining failure to treatment are not clear and may be related to the mutation involved or to insufficient treatment. Our experience of PE in a family of three sisters with CFH-associated aHUS suggests that intensive and prophylactic PE allows renal function to be maintained in both native kidneys and allografts. The success of this strategy has led us to use it in all cases of aHUS. Here, we describe the effect of this strategy in a child with aHUS and a CD46 mutation. The initial episode was treated with daily PE, resulting in the recovery of renal function. However, over the next 4 years, there was a progressive decline in renal function to end-stage renal failure, with evidence of an on-going thrombotic microangiopathy despite continuous prophylactic PE. Prophylactic PE does not influence the natural course of aHUS and CD46 mutation.

Contains fulltext : 69925.pdf (Publisher’s version ) (Closed access) AIM: According to the hyperfiltration hypothesis, a low nephron endowment will lead to hyperfiltration in the remaining glomeruli and is associated with systemic hypertension, proteinuria and glomerulosclerosis. Being born with one functioning kidney instead of two, for instance because of unilateral renal agenesis or multicystic dysplastic kidney, is a cause of congenital renal mass reduction. METHODS: In order to study the effect of congenital renal mass reduction on renal function and blood pressure, a retrospective chart review of 66 patients at the Pediatric Renal Center of the VU University Medical Center was performed. As intrauterine growth restriction is associated with a low nephron endowment, the additional effect of birthweight was also studied. RESULTS: A total of 50% of patients with congenital renal mass reduction is found to be hypertensive, using anti-hypertensive drugs, and/or having microalbuminuria (>20 mug/min). Patients born small for gestational age have significantly smaller kidneys and lower estimated glomerular filtration rate than patients with a normal birthweight. CONCLUSIONS: We conclude that microalbuminuria and/or hypertension is present in 50% of patients with congenital solitary kidneys, which warrants a systematic follow-up of blood pressure, proteinuria and renal function in all patients with congenital solitary functioning kidneys, especially in patients with a low birthweight.

Objectives Comparison of the effect of corticosteroid therapy on the diagnostic performance of cystatin C (Cys) and β-trace protein (bTP), two endogenous markers of GFR. Design and methods Out of a total of 193 pediatric inulin clearance studies, a random sample of 85 steroid-free studies served to establish GFR prediction equations (eGFR), which were used to compare the remaining 76 steroid-free and 32 steroid-positive studies (median prednisone dose 33.0 mg m− 2 day− 1). Results We found a positive relationship between prednisone dose and eGFRβTP (b = 0.414, p = 0.0002) and a negative relationship with eGFRcys (b = −0.208, p = 0.0091). Only Cys independently predicted GFR below 90 mL min− 1 1.73 m− 2, both in steroid-positives (b = 6.260, p = 0.010) and steroid-negatives (b = 6.845, p = 0.012). Glucocorticoid therapy did not affect the accuracy in estimating GFR within 30% of measured GFR for Cys, while accuracy was lower with bTP (65.6% vs. 81.6%, p = 0.08). Conclusion Glucocorticoids have less impact on the diagnostic accuracy of Cys than bTP.

Contains fulltext : 71405.pdf (Publisher’s version ) (Closed access) BACKGROUND: Posterior urethral valves (PUVs), the most common congenital cause of lower urinary tract obstruction, have been described to occur in families. Until now, reports have been published on 10 cases of PUVs in two siblings and 13 cases of PUVs in identical and nonidentical twins, of which we provide an overview. CASES: We report for the first time on three siblings with PUVs, with a different presentation and course in the three brothers. This within-family variability is well noted and is even present in identical twins. CONCLUSIONS: This finding suggests that both genetic and environmental factors play a role in the presence and severity of PUVs. As brothers of patients with PUVs seem to be at increased risk of having PUVs, we suggest antenatal ultrasound screening in brothers of patients with PUVs in order to guide early and optimal care.