Renal and Extrarenal Phenotypes in Patients With HNF1B Variants and Chromosome 17q12 Microdeletions.

Introduction: Hepatocyte nuclear factor 1-beta (HNF1B) gene variants or the chromosome 17q12 deletion (17q12del) represent the most common monogenic cause of developmental kidney disease. Although neurodevelopmental disorders have been associated with the 17q12del, specific genotype-phenotype associations with respect to kidney function evolution have not yet been fully defined. Here, we aimed to determine whether 17q12del or specific HNF1B variants were associated with kidney survival in a large patient population with HNF1B disease. Methods: This was a retrospective observational study involving 521 patients with HNF1B disease from 14 countries using the European Reference Network for rare kidney diseases with detailed information on the HNF1B genotype (HNF1B variants or the 17q12del). Median follow-up time was 11 years with 6 visits per patient. The primary end point was progression to chronic kidney disease (CKD) stage 3 (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m2). Secondary end points were the development of hypomagnesemia or extrarenal disorders, including hyperuricemia and hyperglycemia. Results: Progression toward CKD stage 3 was significantly delayed in patients with the 17q12del compared to patients with HNF1B variants (hazard ratio [HR]: 0.29, 95% confidence interval [CI]: 0.19-0.44, P < 0.001). Progression toward CKD stage 3 was also significantly delayed when HNF1B variants involved the HNF1B Pit-1, Oct-1, and Unc-86 homeodomain (POUh) DNA-binding and transactivation domains rather than the POU-specific domain (POUs) DNA-binding domain (HR: 0.15 [95% CI: 0.06-0.37), P < 0.001 and HR: 0.25 (95% CI: 0.11-0.57), P = 0.001, respectively). Finally, the 17q12del was positively associated with hypomagnesemia and negatively associated with hyperuricemia, but not with hyperglycemia. Conclusion: Patients with the 17q12del display a significantly better kidney survival than patients with other HNF1B variants; and for the latter, variants in the POUs DNA-binding domain lead to the poorest kidney survival. These are clinically relevant HNF1B kidney genotype-phenotype correlations that inform genetic counseling.

The EKFC equation outperforms the CKD-EPI and CKiD equations for GFR estimation in adolescent and young adult kidney transplant patients.

AIM: This study evaluated the bias and accuracy of the CKD-EPI/CKiD and EKFC equations compared with the reference exogenous tracer-based assessment of glomerular filtration rate (GFR) in adult and pediatric patients according to their renal transplant status. METHODS: We assessed the bias and P30 accuracy of the CKD-EPI/CKiD and EKFC equations compared with iohexol-based GFR measurement. RESULTS: In the overall population (n = 59), the median age was 29 years (IQR, 16.0-46.0) and the median measured GFR was 73.9 mL/min/1.73m2 (IQR, 57.3-84.6). Among non-kidney transplant patients, the median was 77.7 mL/min/1.73m2 (IQR, 59.3-86.5), while among kidney transplant patients, it was 60.5 mL/min/1.73m2 (IQR, 54.2-66.8). The bias associated with the EKFC and CKD-EPI/CKiD equations was significantly higher among kidney transplant patients than among non-kidney transplant patients, with a difference between medians (Hodges-Lehmann) of +10.4 mL/min/1.73m2 (95% CI, 2.2-18.9; p = .02) for the EKFC and +12.1 mL/min/1.73m2 (95% CI, 4.2-21.4; p = .006) for the CKD-EPI/CKiD equations. In multivariable analysis, kidney transplant status emerged as an independent factor associated with a bias of >3.4 mL/min/1.73m2 (odds ratio, 7.7; 95% CI, 1.4-43.3; p = .02) for the EKFC equation and a bias of >13.4 mL/min/1.73m2 (odds ratio, 15.0; 95% CI, 2.6-85.7; p = .002) for the CKD-EPI/CKiD equations. CONCLUSION: In our study, which included adolescent and young adult kidney transplant patients, both the CKD-EPI/CKiD and EKFC equations tended to overestimate the measured glomerular filtration rate, with the EKFC equation exhibiting less bias. Renal transplant status significantly influenced the degree of estimation bias.

Multiparametric renal function assessment in cirrhotic patients shows high prevalence of medically actionable changes in multiple modules.

AIM: Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers. METHODS: We conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43-multiparametric renal function assessment between January 1, 2021, and June 30, 2023. RESULTS: All patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte-free water clearance <0.4 mL/min, or tubular maximum phosphate reabsorption capacity <0.8 mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14 mL/min/1.73 m2 (95% CI 6-29) and +9 mL/min/1.73 m2 (95% CI 2-15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease - Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate- and measured creatinine clearance-based assessments. CONCLUSIONS: This study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute-free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.

Campylobacter Colitis as a Trigger for Atypical Hemolytic Uremic Syndrome: About One Case.

We present the case of a 17-year-old Caucasian male whose condition featured acute renal failure, anemia, and deep thrombocytopenia after five consecutive days of diarrhea. Campylobacter coli was identified in stool cultures and, although the direct role of this germ in the pathogenesis of hemolytic uremic syndrome (HUS) remains uncertain to this day, initial presentation was considered broadly consistent with typical HUS. However, the patient showed no signs of spontaneous recovery over time. While secondary investigations showed no abnormalities in ADAMTS13 activity or in the alternate pathway of complement, patient's condition deteriorated. Worsening kidney failure required emergency renal replacement therapy and was followed by cardiac involvement in the form of acute heart failure. Given this unfavorable development, blood samples were drawn to look for mutations in the alternate complement pathway, and eculizumab therapy was initiated without further delay, allowing prompt improvement of cardiac function and recovery of diuresis. Upon discharge, the patient still had to undergo intermittent dialysis, which would later be withdrawn. Genetic analysis ultimately confirmed the presence of a complement factor H mutation associated with a high risk of disease recurrence, indicating long-term continuation of eculizumab therapy.

Social Deprivation Is Associated With Lower Access to Pre-emptive Kidney Transplantation and More Urgent-Start Dialysis in the Pediatric Population.

Introduction: Socioeconomic status (SES) is recognized as an important determinant of kidney health. We aimed to evaluate the association of social deprivation with different indicators at kidney replacement therapy (KRT) initiation in the French pediatric metropolitan population. Methods: All patients with end-stage kidney disease (ESKD) who started KRT before 20 years old in France between 2002 and 2015 were included. We investigated different indicators at KRT initiation, which are as follows: KRT modality (dialysis vs. pre-emptive transplantation), late referral to a nephrologist, and dialysis modality (hemodialysis [HD] vs. peritoneal dialysis [PD], urgent vs. planned start of dialysis, use of catheter vs. use of fistula for HD vascular access). An ecological index (European Deprivation Index [EDI]) was used as a proxy for social deprivation. Results: A total of 1115 patients were included (males 59%, median age at dialysis 14.4 years, glomerular/vascular diseases 36.8%). The most deprived group represented 38.7% of the patients, suggesting pediatric patients with ESKD come from a more socially deprived background. The most deprived group was more likely to initiate KRT with dialysis versus kidney transplantation. Among patients on HD, the odds of starting treatment in emergency with a catheter was >2-fold higher for the most deprived compared with the least deprived children (adjusted odds ratio [aOR] 2.35, 95% CI 1.16-4.78). Conclusion: Children from the most deprived area have lower access to pre-emptive transplantation, have lower access to PD, tend to be late referred to a nephrologist, and have more urgent initiation of HD with a catheter.

National survey of prevention and management of CMV infection in pediatric kidney transplantation in comparison to clinical practice guidelines.

Background: Cytomegalovirus (CMV) is one of the most frequent opportunistic infections in kidney transplant (KT) recipients and is a risk factor for patient and graft survival after KT. Center-to-center variation, optimal prevention and treatment strategies in pediatric KT are currently unknown. This survey aimed to assess current CMV prevention and treatment strategies used among French pediatric KT centers. Methods: A web-based survey was sent to all 13 French pediatric kidney transplantation centers. Results: Twelve (92%) centers responded to the survey. All centers used prophylaxis for the donor-positive/recipient-negative (D+/R-) group. For R + patients, 54% used prophylaxis, 37% used a pre-emptive strategy. In the low-risk group, D-/R-, 50% used a pre-emptive approach and 50% had no specific prevention strategy. The antiviral used by all centers for prophylaxis was valganciclovir (VGCV). The duration of prophylaxis varied from 3 to 7 months and the duration of viral load monitoring varied from 6 months to indefinitely. No center used a hybrid/sequential approach. For the treatment of CMV DNAemia, VGCV or intravenous GCV were used. Therapeutic drug monitoring of VGCV was performed in 5 centers (42%). Five centers reported drug resistance. Eight centers (67%) administered VGCV during the treatment of acute graft rejection. Conclusions: There is uniformity in CMV management in some areas among pediatric KT centers in France but not in others which remain diverse and are not up to date with current guidelines, suggesting unnecessary variation which could be reduced with better evidence to inform practice.

Renal Prognosis in Children With Tubulointerstitial Nephritis and Uveitis Syndrome.

INTRODUCTION: Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome. METHODS: We performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018. RESULTS: A total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m2 (4.9-62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (-4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m2 (60.3-152.7) and <90 ml/min per 1.73 m2 in 20 patients. CONCLUSION: In our study, nearly half of the patients had renal sequelae at last follow-up. Given the possible progression to chronic kidney disease, long-term monitoring of children with TINU syndrome is mandatory. Approximately a quarter of the children had asymptomatic uveitis suggesting all children presenting with TIN should undergo systematic ophthalmologic screening even in the absence of ocular signs.

Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation.

Bone complications of cystinosis have been recently described. The main objectives of this paper were to determine in vitro the impact of CTNS mutations and cysteamine therapy on human osteoclasts and to carry out a genotype-phenotype analysis related to osteoclastic differentiation. Human osteoclasts were differentiated from peripheral blood mononuclear cells (PBMCs) and were treated with increasing doses of cysteamine (0, 50, 200 µM) and then assessed for osteoclastic differentiation. Results are presented as median (min-max). A total of 17 patients (mainly pediatric) were included, at a median age of 14 (2-61) years, and a eGFR of 64 (23-149) mL/min/1.73 m2. Most patients (71%) were under conservative kidney management (CKM). The others were kidney transplant recipients. Three functional groups were distinguished for CTNS mutations: cystinosin variant with residual cystin efflux activity (RA, residual activity), inactive cystinosin variant (IP, inactive protein), and absent protein (AP). PBMCs from patients with residual cystinosin activity generate significantly less osteoclasts than those obtained from patients of the other groups. In all groups, cysteamine exerts an inhibitory effect on osteoclastic differentiation at high doses. This study highlights a link between genotype and osteoclastic differentiation, as well as a significant impact of cysteamine therapy on this process in humans.

Efficacy and safety of intravenous immunoglobulin with rituximab versus rituximab alone in childhood-onset steroid-dependent and frequently relapsing nephrotic syndrome: protocol for a multicentre randomised controlled trial.

INTRODUCTION: Guidelines for the treatment of steroid-dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS) are lacking. Given the substantial impact of SDNS/FRNS on quality of life, strategies aiming to provide long-term remission while minimising treatment side effects are needed. Several studies confirm that rituximab is effective in preventing early relapses in SDNS/FRNS; however, the long-term relapse rate remains high (~70% at 2 years). This trial will assess the association of intravenous immunoglobulins (IVIgs) to rituximab in patients with SDNS/FRNS and inform clinicians on whether IVIg's immunomodulatory properties can alter the course of the disease and reduce the use of immunosuppressive drugs and their side effects. METHODS AND ANALYSIS: We conduct an open-label multicentre, randomised, parallel group in a 1:1 ratio, controlled, superiority trial to assess the safety and efficacy of a single infusion of rituximab followed by IVIg compared with rituximab alone in childhood-onset FRNS/SDNS. The primary outcome is the occurrence of first relapse within 24 months. Patients are allocated to receive either rituximab alone (375 mg/m²) or rituximab followed by IVIg, which includes an initial Ig dose of 2 g/kg, followed by 1.5 g/kg injections once a month for the following 5 months (maximum dose: 100 g). ETHICS AND DISSEMINATION: The study has been approved by the ethics committee (Comité de Protection des Personnes) of Ouest I and authorised by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé). Results of the primary study and the secondary aims will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03560011.

Temocillin dosage adjustment in a preterm infant with severe renal disease: a case report.

BACKGROUND: Temocillin is a carboxypenicillin antibiotic indicated in complicated urinary tract infections due to susceptible ESBL-producing Enterobacteriaceae. While temocillin therapeutic schemes for adult patients with normal or impaired renal function are evidence based, little is known in paediatric populations. OBJECTIVES: We report herein the management of temocillin treatment in a preterm infant with end-stage renal disease. PATIENTS AND METHODS: The patient was a 7-month-old preterm infant born at 35 weeks gestation and treated by temocillin for 10 days for a bacteraemic urinary tract infection due to a susceptible ESBL-producing Enterobacter cloacae complex strain. Temocillin was administered by continuous infusion using a loading dose of 25 mg followed by a maintenance dose of 70 mg daily. Determination of MIC and temocillin plasma and urinary concentration was performed. RESULTS: Clinical improvement was observed 24 h after the initiation of temocillin treatment. Temocillin concentrations ranged between 21.6 and 35.5 mg/L in urine between the first and the sixth day of treatment and between 47.0 and 61.8 mg/L in plasma after 6 and 10 days of treatment, respectively. Temocillin concentrations were found to be above the determined MIC of 6 mg/L. From the measured concentrations, we can postulate that 100%fT>MIC was achieved in urine and at least equal to 40% in plasma. CONCLUSIONS: Temocillin dosing adjustment performed in the present reported case allowed safe and effective treatment. The strategy described herein could be used as a basis for further clinical studies relative to temocillin use in a paediatric population with renal impairment.

Comparison between citrate and acetate dialysate in chronic online hemodiafiltration: A short-term prospective study in pediatric settings.

BACKGROUND: The use of citrate in chronic hemodialysis to acidify dialysis solutions, in replacement of acetate, began in the 2000's. The purpose of the following study is to determine whether this change represents a better alternative regarding short-term tolerance, efficiency and biocompatibility of chronic renal replacement therapy (RRT) in pediatric patients. METHODS: A monocentric prospective observational study was conducted in the pediatric dialysis department of Nancy (France) between December 1st, 2014 and January 25, 2015 on a cohort of pediatric patients under predilution on-line hemodiafiltration (olHDF). Sessions were analysed during two study periods of 14 days: a first period during which dialysis solutions were acidified using acetate and a second during which solutes were acidified using citrate. These periods were separated by a washout period of 28 days on citrate solution. Each patient served as his own control. RESULTS: Dialysis clinical tolerance seems better under citrate regimen, with no statistical significance. No benefit was brought out regarding the prevention of coagulation accidents in the extracorporeal circuit under citrate regimen. The efficiency of olHDF sessions was similar between periods, both in terms of uremic toxins clearance and medium-molecular-weight molecules (MMWM) removal. The evolution of several biological parameters seemed favourable over the citrate period: increase in pre-dialysis serum bicarbonate, stability of plasma hemoglobin and decrease in erythropoietin resistance index (ERI). However, differences in the variation of these parameters between the two periods were not significant. No severe and/or symptomatic hypocalcemia occurred. CONCLUSION: The use of citrate instead of acetate in dialysis and substitution solutions appears in the short term as a safe alternative for chronic online hemodiafiltration in children.

[Vaccine recommendations for children with idiopathic nephrotic syndrome]. / Recommandations vaccinales pour les enfants avec un syndrome néphrotique idiopathique.

The specific treatment of idiopathic nephrotic syndrome is based on corticosteroid therapy and/or steroid-sparing immunosuppressive agents in children who are steroid-dependant or frequent relapsers (60-70 %). Patients have an increased infectious risk not only related to the disease during relapses (hypogammaglobulinemia and urinary leakage of opsonins) but also to treatments (corticosteroids or immunosuppressive agents) in period of remission. Vaccination is therefore particularly recommended in these patients. Potential vaccine risks are ineffectiveness, induction of vaccine disease and relapse of idiopathic nephrotic syndrome. Only live vaccines expose to the risk of vaccine disease: they are in general contra-indicated under immunosuppressive treatment. The immunogenicity of inactivated vaccines is reduced but persists. The immunogenic stimulus of vaccination may in theory trigger a relapse of the nephrotic syndrome. Nevertheless, this risk is low in the literature, and even absent in some studies. The benefit-risk ratio is therefore in favor of vaccination with respect to the vaccination schedule for inactivated vaccines, with wide vaccination against pneumococcus and influenza annually. Depending on the context and after expert advice, immunization with live vaccines could be discussed if residual doses/levels of immunosuppressive treatments are moderate and immunity preserved.

School level of children carrying a HNF1B variant or a deletion.

The prevalence of neurological involvement in patients with a deletion of or a variant in the HNF1B gene remains discussed. The aim of this study was to investigate the neuropsychological outcomes in a large cohort of children carrying either a HNF1B whole-gene deletion or a disease-associated variant, revealed by the presence of kidney anomalies. The neuropsychological development-based on school level-of 223 children included in this prospective cohort was studied. Data from 180 children were available for analysis. Patients mean age was 9.6 years, with 39.9% of girls. Among these patients, 119 carried a HNF1B deletion and 61 a disease-associated variant. In the school-aged population, 12.7 and 3.6% of patients carrying a HNF1B deletion and a disease-associated variant had special educational needs, respectively. Therefore, the presence of a HNF1B deletion increases the risk to present with a neuropsychiatric involvement when compared with the general population. On the other hand, almost 90% of patients carrying a HNF1B disease-associated variant or deletion have a normal schooling in a general educational environment. Even if these findings do not predict the risk of neuropsychiatric disease at adulthood, most patients diagnosed secondary to kidney anomalies do not show a neurological outcome severe enough to impede standard schooling at elementary school. These results should be taken into account in prenatal counseling.

Quality of life in adolescents with chronic kidney disease who initiate haemodialysis treatment.

BACKGROUND: To describe the quality of life of adolescents initiating haemodialysis, to determine the factors associated with quality of life, and to assess coping strategies and their impact on quality of life. METHODS: All adolescents initiating haemodialysis between September 2013 and July 2015 in French paediatric haemodialysis centres were included. Quality of life data were collected using the "Vécu et Santé Perçue de l'Adolescent et l'Enfant" questionnaire, and coping data were collected using the Kidcope questionnaire. Adolescent's quality of life was compared with age- and sex-matched French control. RESULTS: Thirty-two adolescents were included. Their mean age was 13.9 ± 2.0 years. The quality of life score was lowest in leisure activities and highest in relationships with medical staff. Compared with the French control, index, energy-vitality, relationships with friends, leisure activities and physical well-being scores were significantly lower in haemodialysis population. In multivariate analyses, active coping was positively associated with quality of life and especially with energy-vitality, relationships with parents and teachers, and school performance. In contrast, avoidant and negative coping were negatively associated with energy-vitality, psychological well-being and body image for avoidant coping, and body image and relationships with medical staff for negative coping. CONCLUSIONS: The quality of life of haemodialysis adolescents, and mainly the dimensions of leisure activities, physical well-being, relationships with friends and energy-vitality, were significantly altered compared to that of the French population. The impact of coping strategies on quality of life seems to be important. Given the importance of quality of life and coping strategies in adolescents with chronic disease, health care professionals should integrate these aspects into care management.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.

Patient and transplant outcome in infants starting renal replacement therapy before 2 years of age.

Background: Despite major technical improvements in the care of children requiring renal replacement therapy (RRT) before 2 years of age, the management of those patients remains challenging and transplantation is generally delayed until the child weighs 10 kg or is 2 years old. In this national cohort study, we studied patient and graft survival in children starting RRT before 2 years of age to help clinicians and parents when deciding on RRT initiation and transplantation management. Methods: All children starting RRT before 24 months of age between 1992 and 2012 in France were included through the national Renal Epidemiology and Information Network (REIN) registry. The primary endpoints were patient survival on dialysis and 10-year graft survival. Results: A total of 224 patients were included {62% boys, median age 10.5 months [interquartile range (IQR) 5.8-15.6]}. The 10-year survival rate was 84% (IQR 77-89). Suffering from extrarenal comorbidities was the only factor significantly associated with both an increased risk of death on dialysis [hazard ratio 5.9 (95% confidence interval 1.8-19.3)] and a decreased probability of being transplanted. During follow-up, 174 renal transplantations were performed in 171 patients [median age at first transplantation 30.2 (IQR 21.8-40.7) months]. The 10-year graft survival was 74% (IQR 67-81). Factors associated with graft loss in multivariate analysis were the time spent on dialysis before transplantation, donor/recipient height ratio with an increased risk for both small and tall donors and presenting two human leucocyte antigen-antigen D-related mismatches. Conclusions: This study confirms the good outcome of children starting RRT before 2 years of age. The main question remains when and how to transplant those children. Our study provides data on the optimal morphological and immunological matching in order to help clinicians in their decisions.

Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome.

BACKGROUND AND OBJECTIVES: Mutations in the MAGED2 gene, located on the X chromosome, have been recently detected in males with a transient form of antenatal Bartter syndrome or with idiopathic polyhydramnios. The aim of this study is to analyze the proportion of the population with mutations in this gene in a French cohort of patients with antenatal Bartter syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The French cohort of patients with antenatal Bartter syndrome encompasses 171 families. Mutations in genes responsible for types 1-4 have been detected in 75% of cases. In patients without identified genetic cause (n=42), transient antenatal Bartter syndrome was reported in 12 cases. We analyzed the MAGED2 gene in the entire cohort of negative cases by Sanger sequencing and retrospectively collected clinical data regarding pregnancy as well as the postnatal outcome for positive cases. RESULTS: We detected mutations in MAGED2 in 17 patients, including the 12 with transient antenatal Bartter syndrome, from 16 families. Fifteen different mutations were detected (one whole deletion, three frameshift, three splicing, three nonsense, two inframe deletions, and three missense); 13 of these mutations had not been previously described. Interestingly, two patients are females; in one of these patients our data are consistent with selective inactivation of chromosome X explaining the severity. The phenotypic presentation in our patients was variable and less severe than that of the originally described cases. CONCLUSIONS: MAGED2 mutations explained 9% of cases of antenatal Bartter syndrome in a French cohort, and accounted for 38% of patients without other characterized mutations and for 44% of male probands of negative cases. Our study confirmed previously published data and showed that females can be affected. As a result, this gene must be included in the screening of the most severe clinical form of Bartter syndrome.

Clinical and Genetic Spectrum of Bartter Syndrome Type 3.

Bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel Kb gene (CLCNKB), which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. To study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with CLCNKB mutations. Functional analyses were performed in Xenopus laevis oocytes for eight missense and two nonsense mutations. We detected 60 mutations, including 27 previously unreported mutations. Among patients, 29.5% had a phenotype of ante/neonatal Bartter syndrome (polyhydramnios or diagnosis in the first month of life), 44.5% had classic Bartter syndrome (diagnosis during childhood, hypercalciuria, and/or polyuria), and 26.0% had Gitelman-like syndrome (fortuitous discovery of hypokalemia with hypomagnesemia and/or hypocalciuria in childhood or adulthood). Nine of the ten mutations expressed in vitro decreased or abolished chloride conductance. Severe (large deletions, frameshift, nonsense, and essential splicing) and missense mutations resulting in poor residual conductance were associated with younger age at diagnosis. Electrolyte supplements and indomethacin were used frequently to induce catch-up growth, with few adverse effects. After a median follow-up of 8 (range, 1-41) years in 77 patients, chronic renal failure was detected in 19 patients (25%): one required hemodialysis and four underwent renal transplant. In summary, we report a genotype/phenotype correlation for Bartter syndrome type 3: complete loss-of-function mutations associated with younger age at diagnosis, and CKD was observed in all phenotypes.

Effect of center practices on the choice of the first dialysis modality for children and young adults.

BACKGROUND: Peritoneal dialysis (PD) remains the modality of choice in children, but there is no clear evidence to support a better outcome in children treated with PD. We aimed to assess factors that have an impact on the choice of dialysis modality in children and young adults in France and sought to determine the roles of medical factors and center practices. METHODS: We included all patients aged <20 years at the start of renal replacement therapy (RRT), recorded in the French RRT Registry between 2002 and 2013. Hierarchical logistic regression models were used to study the association between the patient/center characteristics and the probability of receiving PD as the first dialysis modality. RESULTS: We included 806 patients starting RRT in 177 centers, 23 of which were specialized pediatric centers. Six hundred and one patients (74.6 %) started with hemodialysis (HD), whereas 205 (25.4 %) started with PD. A greater probability of PD was found in younger children, whereas starting the treatment in an emergency setting was associated with a low use of PD. We found a significant variability among centers that accounted for 43 % of the total variability. The probability of PD was higher in adult centers and was proportional to the rate of PD in the center. CONCLUSIONS: Center practices are a major factor in the choice of dialysis modality. This raises concerns about patient and family choices and to what extent doctors may influence the final decision. Further pediatric studies focusing on children's and parents' wishes are needed to provide care as close as possible to patients' and families' expectations.