Idiopathic nephrotic syndrome (INS) in children is the most common glomerular disease and is characterized by recurrent relapses. There is no community consensus on the treatment of relapsing forms of nephrotic syndrome in children, unlike that for the initial presentation. To date, available treatments only enable relapsing patients to be maintained in remission, rather than modifying the course of the disease; therefore, more therapeutic trials are needed. The Société de Néphrologie Pédiatrique (SNP) decided to implement within its French centers a national coordinated long-term clinical research program for children treated for INS based on a Trials within Cohorts (TwiCs) model. The aim of this paper is to describe the PIN’SNP cohort and research program as well as the TwiCs design adapted to INS research in the French regulatory system. This retrospective-prospective, multicenter research program will rely on a dynamic prospective cohort of children followed for an INS, known as the PIN’SNP cohort (i) to identify cases treated within SNP centers, (ii) to describe their clinical and epidemiological characteristics, and (iii) to provide a platform to nest prospective trials, and thus facilitate inclusion of patients in these future trials. The PIN’SNP cohort is the first French national pediatric platform dedicated to the implementation of randomized nested trials along with longitudinal and observational studies on INS in children. The adaptation of the TwiCs design to inform all eligible patients/parents to each nested trial will facilitate methodological robustness and ethical acceptability and reinforce communication between investigators and participants. number NCT04207580.

OBJECTIVE:The aim of this study was to describe the quality of life (QoL) of children with a chronic illness treated in a tertiary multidisciplinary pediatric department in comparison with the general population. STUDY DESIGN:A cross-sectional study was conducted in the tertiary multidisciplinary (nephrology, hepatogastroenterology, endocrinology, diabetology, transplantation) pediatric department of Timone Hospital in Marseille, France. Patients 8-17 years of age with a chronic disease were included during regular follow-up appointments. Medical and sociodemographic variables were obtained from medical records. Self-reported QoL was assessed using the VSPA (Vécu et Santé Perçu de l'Adolescent) questionnaire and parent-reported QoL was assessed using the VSPA questionnaire for parents. RESULTS:A total of 244 patients were included. Overall QoL did not differ significantly from that of the general population. Adolescent patients' self-reported QoL scores were lower than those of the general population in the domains of physical health and leisure, and parents reported QoL scores for adolescent patients lower than those of the general population for self-esteem and physical health. Adolescents' self-reported QoL scores were higher than in the general population for relationships with parents, healthcare professionals, and teachers as well as for school achievement. Parents also reported higher QoL scores in these areas for their children. CONCLUSION:Children and adolescents with a variety of chronic diseases had similar overall QoL scores to the general population but with different QoL profiles; their scores in some domains were higher than those of the general population.

Lumasiran and Kidney Transplantation for Primary Hyperoxaluria Type 1 Although lumasiran targets glycolate oxidase and decreases hepatic oxalate synthesis, systemic oxalate release continues after single-organ kidney transplantation, requiring close follow-up with rigorous hyperhydration.

Although lumasiran targets glycolate oxidase and decreases hepatic oxalate synthesis, systemic oxalate release continues after single-organ kidney transplantation, requiring close follow-up with rigorous hyperhydration.

IgA vasculitis (IgAV) is the most common vasculitis in children. IgAV long-term prognosis depends on kidney involvement or IgA vasculitis with nephritis (IgAVN). To date, steroid treatment (oral steroids or methylprednisolone pulses) has not proven to be formally efficient. This study aimed to assess the role of steroids on IgAVN outcome. All children with IgAVN diagnosed 2000–2019 in 14 French pediatric nephrology units with minimal follow-up of 6 months were retrospectively included. Outcomes of patients treated with steroids were compared with those of a control group of untreated patients matched for age, sex, proteinuria, eGFR, and histological features. The primary endpoint was IgAVN remission defined as urine protein-to-creatinine ratio < 20 mg/mmol without impaired eGFR one year after disease onset. A total of 359 patients with IgAVN were included with a median follow-up time of 249 days (range 43–809). One hundred eight (30

Primary hyperoxaluria type 1 (PH1) is caused by a mutation in the AGXT gene, encoding the hepatic peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT). Defects in AGT increase glyoxylate and oxalate production, the latter inducing kidney stones and nephrocalcinosis [1, 2]. Symptoms vary from recurrent bilateral kidney stones with moderate chronic kidney disease (CKD) to early kidney failure in infancy [1, 3, 4]. Until recently, the treatment of PH1 was only symptomatic [2], consisting of standard of care (SOC) with intensive hyperhydration, urine alkalinization and conservative CKD management, with the use of pyridoxine in patients with peculiar mutations [5]. Among patients who reach kidney failure, intensive hemodialysis should be performed; however, systemic oxalosis worsens despite intensive dialysis, and bone is the main compartment for oxalate storage. Combined or sequential double liver/kidney transplantation (CLKT) has been traditionally recommended, as kidney transplant (KTx) alone leads to graft loss due to oxalate deposits, except in B6-sensitive forms [6–8]. With such challenging technical procedures and long-term complications of immunosuppressive therapies, patients’ quality of life (QoL) and survival may be significantly impaired [6].

ABSTRACTBackgroundCOVID-19 is a complex multisystem disease, frequently associated with kidney injury. Since the beginning of the COVID-19 pandemic, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children. This prompted us to examine whether SARS-CoV-2 might be the underlying trigger.MethodsWe conducted a French nationwide retrospective cohort study. We included all consecutive children diagnosed with aTIN or TINUs of undetermined cause between April-2020 and March-2021. SARS-CoV-2 antibody responses were tested by a luciferase immunoprecipitation system and compared to age-matched controls. Immunohistochemistry, immunofluorescence and molecular microbiology analyses were performed on kidney biopsies.ResultsForty-eight children were included with a median age at diagnosis of 14.7 years (9.4-17.6). aTIN and TINUs incidence rates increased 3-fold and 12-fold, respectively, compared to pre-pandemic years. All patients had impaired kidney function with a median eGFR of 31.9 ml/min/1.73m² at diagnosis. Kidney biopsies showed lesions of acute tubulointerstitial nephritis and 25% of patients had fibrosis. No patient had concomitant acute COVID-19. All 16 children tested had high anti-N IgG titers and one had anti-S IgGs. Next-generation sequencing failed to detect any infectious agents in kidney biopsies. However, SARS-CoV-2 RNA was detected by PCR in two kidney samples supporting a potential direct link between SARS-CoV-2 and aTIN/TINUs.ConclusionsWe describe a novel form of post-acute COVID-19 syndrome in children, unique in its exclusive kidney and eye involvement, and its distinctive anti-SARS-CoV-2 N+/S-serological profile. Our results support a causal association linking SARS-CoV-2 infection to this newly-reported burst of renal/eye inflammation.

Background: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic ure-mic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Sante publique France in connection with microbiological investigations at the national reference center for STEC promptly identi-fied a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month. Method: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Sante publique France. Clinical data were analyzed from the patients' hospital records obtained from the treating physicians. Results: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5-60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/ 1.73m(2) and four had hypertension. One patient had neurological sequelae. Conclusion: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients' young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at -risk foods by young children as key preventive measures against STEC infections. (C) 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Primary Coenzyme Q10 (CoQ10) deficiency is an ultra-rare disorder caused by defects in genes involved in CoQ10 biosynthesis leading to multidrug-resistant nephrotic syndrome as the hallmark kidney manifestation. Promising early results have been reported anecdotally with oral CoQ10 supplementation. However, the long-term efficacy and optimal prescription remain to be established. In a global effort, we collected and analyzed information from 116 patients who received CoQ10 supplements for primary CoQ10 deficiency due to biallelic pathogenic variants in either the COQ2, COQ6 or COQ8B genes. Median duration of follow up on treatment was two years. The effect of treatment on proteinuria was assessed, and kidney survival was analyzed in 41 patients younger than 18 years with chronic kidney disease stage 1-4 at the start of treatment compared with that of an untreated cohort matched by genotype, age, kidney function, and proteinuria. CoQ10 supplementation was associated with a substantial and significant sustained reduction of proteinuria by 88% at 12 months. Complete remission of proteinuria was more frequently observed in COQ6 disease. CoQ10 supplementation led to significantly better preservation of kidney function (5-year kidney failure-free survival 62% vs. 19%) with an improvement in general condition and neurological manifestations. Side effects of treatment were uncommon and mild. Thus, our findings indicate that all patients diagnosed with primary CoQ10 deficiency should receive early and life-long CoQ10 supplementation to decelerate the progression of kidney disease and prevent further damage to other organs.

Background Hemolytic uremic syndrome (HUS) is the most common cause of acute kidney failure in children younger than five years. Central nervous system involvement occurs in 15% of patients, with clinical manifestations including confusion, coma, seizures, stroke, and cortical blindness. Ocular involvement in children with HUS is rare, but retinal and choroidal hemorrhages as well as ischemic retinopathy due to thrombotic microangiopathic lesions have been documented. Patient Description We describe a 26-month-old girl with typical HUS who experienced severe visual loss likely resulting from cytotoxic injury of both lateral geniculate nuclei with bilateral damage to optic pathways coupled with macular thrombotic microangiopathic lesions. Her vision recovered completely within a month in conjunction with the normalization of her imaging studies. Conclusions Although this child's vision was severely impaired, the prognosis for this mixed visual impairment of peripheral and central origin was excellent with a full recovery.

Assessing the initial severity of immunoglobulin A vasculitis nephritis (IgAV-N) is important due to its determining effect on kidney management and outcomes. This paper describes a multicentre paediatric cohort of IgAV-N patients and discusses relationships among clinical presentation, histological features, and kidney outcome. We retrospectively studied a cohort of 170 children with biopsy-proven IgAV-N, diagnosed between 2007 and 2017. One-quarter of the cohort (27%) presented with initial nephrotic syndrome (NS). Kidney biopsy revealed International Study of Kidney Disease (ISKDC) grade II or grade III in 83% of cases. Endocapillary proliferation was observed in 73% of patients, and chronic lesions were observed in 25%. Data analysis showed a significant association between NS at onset and endocapillary proliferation and cellular crescents. After a median follow-up of 21 months (IQR 12–39), 30% of patients had persistent proteinuria or decreased eGFR. At the end of follow-up, kidney impairment was more often observed in patients with NS at onset and those with cellular crescents and chronic lesions on initial kidney biopsy. Conclusion: This study highlights the relationship between the clinical and histological presentation of IgAV-N and the factors that affect kidney outcome. The ISKDC classification may be improved by including lesions that are more discriminating for disease severity and prognosis.

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.

BACKGROUND:Acute tubulointerstitial nephritis (ATIN) is a rare condition in children. The etiology, treatment, and outcome of childhood ATIN remain poorly understood. The long-term prognosis seems to be favorable; however, chronic kidney disease has been reported. This article describes clinical outcomes in a series of children with biopsy-proven ATIN. METHODS:All medical records with biopsy-proven ATIN between January 2006 and 2016 were retrospectively analyzed. The incidence, clinical features, etiology, treatment, and outcome were recorded for each patient. RESULTS:Over 10 years, ATIN was diagnosed in 25 cases (8%) based on 306 renal needle biopsies. The most frequent clinical signs were abdominal pain, asthenia/weight loss, and fever. A median glomerular filtration rate estimated at 30.1mL/min/1.73 m2 (16.5; 45.5). Drug-induced toxicity was the main etiology (eight patients). Other causes were TINU syndrome (tubulointerstitial nephritis and uveitis) (seven patients), infection (two patients), and toxic agents other than medication (one patient). No etiology was found in seven patients (idiopathic cases). Eighteen patients (72%) were treated with steroids. At the end of follow-up, eight patients presented chronic kidney disease, three hypertension, and three tubular dysfunction. Overall, renal function was highest in the idiopathic ATIN group and in children treated without delay. CONCLUSIONS:In a single-center 10-year series of biopsy-confirmed ATIN in children, drugs and TINU syndrome were the main etiologies of ATIN. This study suggests that children with idiopathic ATIN and prompt treatment have a better prognosis. In this series, occurrence of chronic kidney disease justified long-term follow-up.

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. 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. 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. 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.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are often used as analgesic and antipyretic drugs. Nephrotoxicity is a common side effect and leads in 1–5% of pediatric cases to acute kidney injury (AKI). The nephrotoxic effects of NSAIDs arise mainly from two pathological mechanisms: (1) acute tubulo-interstitial nephritis (ATIN) following immune reaction and (2) prerenal failure because of reduced renal plasma flow. Histological examinations are required to confirm the pathomechanism of AKI after NSAID exposure. The aim of this study was to illustrate the risk of ATIN in children with AKI after NSAID exposure. Results: The medical records of all 100 pediatric patients with biopsy-proven AKI treated between January 2006 and 2016 at La Timone Hospital, Marseille, France, were analyzed retrospectively. Twenty-five of these patients had ATIN, four of which were healthy children who had been treated with NSAIDs. In other words, NSAID side effects accounted for 4% of all cases of biopsy-proven AKI and 16% of all cases of ATIN. None of the patients had hypovolemia when they received NSAIDs. Clinical symptoms were non-specific. All patients had abdominal pain and vomiting but normal urine volume output. Maximum serum creatinine levels ranged from 300 to 512 μmol/l, with estimated minimum creatinine clearances of 12–26 ml/min/1.73 m2. None of the patients had significant proteinuria. One child had hyperechogenic enlarged kidneys. Three patients were treated with steroids, one of whom also received intravenous methylprednisolone. Renal function improved gradually in all patients, but the patient who received methylprednisolone developed moderate chronic kidney disease (CKD). Conclusions: Biopsy proven-AKI secondary to NSAID use can be severe and be associated with ATIN. Since NSAID-induced ATIN can lead to CKD, clinicians using NSAIDs should focus on preventing AKI.