Pierre Cochat

• Professor at Claude Bernard University Lyon 1

Introduction The 2021 reform of early access (EA) for medicinal products in France includes a mandatory data collection for each patient. The objective of this work was to perform a two-year review of the protocols for therapeutic use and data collection (PUT-RD) validated by the health technology assessment body (Haute Autorité de Santé [HAS]) in...

Antimicrobial resistance (AMR) has become a worldwide growing concern over the past decades. Thus, encouraging manufacturers to develop new antibiotics is needed. We hypothesised that transparency on the regulatory appraisals of antibiotics would provide an incentive to pharmaceutical development. We thus aimed at reporting the French health techno...

Introduction Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G>A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. Methods In t...

Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified diseas...

Background Primary hyperoxalurias (PHs) constitute rare disorders resulting in abnormal glyoxalate metabolism. PH-associated phenotypes range from progressive nephrocalcinosis and/or recurrent urolithiasis to early kidney failure. Methods A retrospective study was conducted for patients with confirmed PH diagnoses from three tertiary centers in Sa...

Nedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double‐blind, placebo‐controlled study, we randomly a...

Introduction Infantile oxalosis is the most severe form of primary hyperoxaluria type 1 (PH1), with onset of end-stage kidney disease (ESKD) during infancy. We aimed to analyze the outcome of these patients as our current understanding is limited due to a paucity of reports. Methods A retrospective registry study was conducted using data from the...

Purpose Primary hyperoxaluria type 1 (PH1) is a rare, progressive, genetic disease with limited treatment options. We report the efficacy and safety of lumasiran, an RNA interference therapeutic, in infants and young children with PH1. Methods This single-arm, open-label, phase 3 study evaluated lumasiran in patients aged <6 years with PH1 and an...

Introduction: In primary hyperoxaluria type 1 (PH1), oxalate overproduction frequently causes kidney stones, nephrocalcinosis, and kidney failure. As PH1 is caused by a congenital liver enzyme defect, combined liver-kidney transplantation (CLKT) has been recommended in patients with kidney failure. Nevertheless, systematic analyses on long-term tr...

Primary hyperoxaluria (PH) is a group of diseases due to mutations in genes coding for enzymes involved in oxalate metabolism. Three types of PH are identified depending on the gene mutated. Type 1 is the most frequent with 80% of the cases, while PH2 and PH3 are rarer. The severity of renal involvement varies between the three types. Indeed, betwe...

During the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histolog...

Primary hyperoxaluria (PH) is a family of ultra-rare autosomal recessive inherited disorders of hepatic glyoxylate metabolism characterized by oxalate overproduction. Nedosiran is an RNA interference agent that inhibits hepatic lactate dehydrogenase, the enzyme responsible for the common, final step of oxalate production in all three genetic subtyp...

Background and objectives In the rare disease primary hyperoxaluria type 1, overproduction of oxalate by the liver causes kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing hepatic oxalate production. The objective of this first-in-human, randomi...

Background Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase. Methods...

Résumé Les hyperoxaluries primitives sont transmises sur le mode autosomique récessif ; il s’agit d’affections rares, engageant souvent le pronostic rénal et parfois le pronostic vital, notamment dans les formes à début précoce. Il existe trois types, répondant à des déficits enzymatiques distincts. Le type 1 représente 85 % des cas et résulte d’un...

In this chapter we have attempted to briefly review selected high points in the development of dialysis therapy for children, focusing on the ingenuity and resourcefulness of some of the early pioneers. It is an exciting story. We have left to the chapters that follow a detailed description of these innovations. Our goal is to place them in histori...

Résumé Des recommandations spécifiques à la néphrologie ont été rédigées sous l’égide de l’Association internationale de néphrologie pédiatrique en 2011. Ces recommandations préconisent une transition individualisée, débutant entre 12 et 14 ans, avec des informations sur la maladie et les traitements du patient adaptées à l’âge et au niveau intelle...

Background In patients with primary hyperoxaluria (PH), endogenous oxalate overproduction increases urinary oxalate excretion, leading to compromised kidney function and often kidney failure. Highly elevated plasma oxalate (Pox) is associated with systemic oxalate deposition in patients with PH and severe chronic kidney disease (CKD). The relations...

Background: Cystinosis is a rare autosomal recessive disorder caused by intracellular cystine accumulation. Proximal tubulopathy (Fanconi syndrome) is one of the first signs, leading to end-stage renal disease between the age of 12 and 16. Other symptoms occur later and encompass endocrinopathies, distal myopathy and deterioration of the central n...

Background Little data are available for infants who started renal replacement therapy before 6 months of age. Because of extra-renal comorbidities and uncertain outcomes, whether renal replacement therapy in neonates is justified remains debatable. Methods We performed a retrospective analysis of all patients who began chronic peritoneal dialysis...

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by the functional defect of alanine-glyoxylate aminotransferase that results in the overproduction of oxalate. It can be devastating especially for kidneys, leading to end-stage renal disease (ESRD) during the first 2 to 3 decades of life in most patients. Consequently, man...

Objectives The one-compartment iohexol plasma clearance has been proposed as a reliable alternative to renal inulin clearance. However, this method’s performance depends on the formula used to calculate glomerular filtration rate (GFR). This study reports on performance comparisons between various mathematical formulas proposed for iohexol plasma c...

Background: Several models have been proposed to predict kidney graft failure in adult recipients but none in younger recipients. Our objective was to propose a dynamic prediction model for graft failure in young kidney transplant recipients. Methods: We included 793 kidney transplant recipients waitlisted before the age of 18 years who received...

Introduction: In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems. Methods: Patients with...

Background and Aims Distal renal tubular acidosis (dRTA) is a rare disorder leading to impaired net acid excretion by the kidney inducing hyperchloremic metabolic acidosis and hypokalemia. The therapeutic effect of the standard of care is of short duration and requires multiple day and night administrations; it is also often accompanied by gastroin...

Background and Aims PH1 is a rare genetic disorder characterized by hepatic oxalate overproduction, leading to recurrent kidney stones, nephrocalcinosis, progressive kidney failure, and multiorgan damage from systemic oxalosis. There are no approved pharmacologic therapies for PH1. Lumasiran is a subcutaneously-administered investigational RNAi the...

Eplet incompatibility appears to be a better predictor of the de novo appearance of DSA post‐Tx than HLA antigen matching in adults. We evaluated the HLA Matchmaker® software (version 2.1) in our pediatric cohort to predict the appearance of DSA post‐Tx. We included 70 pediatric patients (26 girls, 10 living donors, mean age 11.2 ± 3.9 years) after...

Rare diseases usually concern small and disseminated population. Implementing clinical research with the right design, outcomes measures and the recruitment of patients are challenges. Collaborations, training and multidisciplinary approach are often required. In this article, we provide an overview of a successful collaboration in nephropathic cys...

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....

Primary hyperoxaluria type 2 is a rare inherited disorder of glyoxylate metabolism causing nephrocalcinosis, renal stone formation and ultimately kidney failure. Previously, primary hyperoxaluria type 2 was considered to have a more favorable prognosis than primary hyperoxaluria type 1, but earlier reports are limited by low patient numbers and sho...

Background Insufficient elastin synthesis leads to vascular complications and arterial hypertension in children with Williams-Beuren syndrome. Restoring sufficient quantity of elastin should then result in prevention or inhibition of vascular malformations and improvement in arterial blood pressure. Methods The aim of this study was to assess the...

Objective To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria. Patients and Methods Data from 442 patients with cystinuria were recorded retrospectively. Crystalluria was studied in 89 patients. A mixed‐effects logistic regression model was used to estimate how urine...

Whether to initiate or to withhold Renal Replacement Therapy (RRT) in children with severe developmental disability (DD) remains a topic of intense debate. The present study investigated the opinion of professionals on this difficult issue and proposed a checklist with guiding questions for decision-making. Clinicians affiliated to different organi...

Around 1/1000 people have a solitary kidney. Congenital conditions mainly include multicystic dysplastic kidney and unilateral renal aplasia/agenesis; acquired conditions are secondary to nephrectomy performed because of urologic structural abnormalities, severe parenchymal infection, renal trauma, and renal or pararenal tumors. Children born with...

Background Primary hyperoxaluria type 1 (PH1) is an orphan inborn error of oxalate metabolism leading to hyperoxaluria, progressive renal failure, oxalate deposition, and increased cardiovascular complications. As endothelial dysfunction and arterial stiffness are early markers of cardiovascular risk, we investigated early endothelial and vascular...

Cytomegalovirus is common in adult recipients (prevalence of 40-90%). Children are typically seronegative but immunosuppression may prone to primary-infection or viral reactivation, with potentially severe consequences. CMV infection incidence in pediatric kidney transplant recipients has seldom been investigated. The aim of our study was to evalua...

Introduction: Secondary hyperoxalemia is a multifactorial disease that affects several organs and tissues in patients with native or transplanted kidneys. Plasma oxalate may increase during renal failure because it is cleared from the body by the kidneys. However, there is scarce evidence about the association between glomerular filtration rate and...

Objectives: ARPKD is a recessive rare disease due to PKHD1 mutation. The main objective of the study was to characterize the phenotypic variability according to the different types of PKHD1 mutations. Methods: This study was performed in 308 ARPKD patients with a genetic diagnosis from our genetic center. Related physicians provided minimal clin...

Background: Bone impairment appears to be a novel complication of nephropathic cystinosis despite cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study was to evaluate bone status among patients included in the French Crystobs study. Methods: In addition to clinical data, bone status was ev...

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Paediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports...

Background: Bone impairment is a poorly described complication of nephropathic cystinosis (NC). The objectives of this study were to evaluate in vitro effects of cystinosin (CTNS) mutations on bone resorption and of cysteamine treatment on bone cells [namely human osteoclasts (OCs) and murine osteoblasts]. Methods: Human OCs were differentiated...

RTx remains challenging in children under 3 years of age. This single-center study reviewed the medical records of children <3 years transplanted since 1987 (N = 32, Group 1). They were matched for donor type and RTx period with children aged 3-13 years (N = 32, Group 2) and 13-18 years (N = 32, Group 3). There were no between-group significant dif...

Background: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. Methods: Clinical data were analyzed in 59 SSNS families. EMP2...

In nephrology, some diseases begin specifically during childhood; however, they must be known by adult nephrologists so that to ensure continuity and homogeneity for their management. The aim of this review is therefore to propose a brief overview of the main pediatric diseases, for which a specific knowledge is warranted, and notably pediatric idi...

Context Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary kidney disease. Hypophosphatemia was demonstrated in adult patients with preserved renal function, together with high fibroblast growth factor 23 (FGF23) and low soluble Klotho levels. The latter explained the relative FGF23 hyporesponsiveness in this cohort....

Abstract for poster in ESPN 2017

This chapter presents two cases of children with primary hyperoxaluria type 1 (PH1) and oxalate (Ox) tissue deposition (oxalosis) awaiting combined liver and kidney transplantation (LKT), one treated with hemodialysis (HD) and one with HD and peritoneal dialysis (PD). Ox kinetics during HD and PD are calculated. Results show that neither HD nor com...

Background: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess...

To promote the standardization of nephro-uroradiological terms used in children, the European Society of Pediatric Radiology uroradiology taskforce wrote a detailed glossary. This work has been subsequently submitted to European experts in pediatric urology and nephrology for discussion and acceptance to improve the quality of radiological reports...

Background: Childhood-onset systemic lupus erythematosus (cSLE) is rare, and considered more severe than its adult-onset counterpart. Lupus nephritis (LN) occurs more frequently in children, accounting for higher long-term morbidity and mortality compared with adults. Thus, reliable biological markers are needed to predict disease course. This stu...

Background: The survival rates of renal transplant children are indeed on the rise, but it is still important to ensure that there is optimal renal function in these children in all their future growing years. The number of functioning nephrons and the graft ability to adapt to an increasing demand during body growth seem to be the most important...

Background Primary hyperoxaluria (PH) is a rare, genetic disorder which involves the overproduction of endogenous oxalate, leading to hyperoxaluria, recurrent urolithiasis and/or progressive nephrocalcinosis and eventually resulting in kidney failure and systemic oxalosis. The aim of this trial was to investigate whether treatment involving an oxal...

The number of serum 25-hydroxyvitamin D (25OHD) assays has increased tenfold in France in less than 10 years, sometimes for invalidated reasons. In 2013, the French National Authority for Health (Haute autorité de santé, or HAS) limited the indications for serum 25OHD measurements to rickets/osteomalacia, older adults with recurrent falls, monitori...

Since its founding in 1971, the International Pediatric Nephrology Association (IPNA; www. ipna-online. org) has played a critical role in promoting knowledge and communication among pediatric nephrologists as well as aligned practitioners and other health professionals who share the interest in pediatric kidney disease and improving the diagnosis,...

Hyperoxaluria may be either a secondary or a primary disease. Three distinct autosomal recessive inherited enzyme defects of metabolism have been related to type 1, type 2, and type 3 primary hyperoxalurias (PH), i.e., alanine: glyoxylate aminotransferase (AGT), glyoxylate reductase/hydroxypyruvate reductase (GRHPR), and 4-hydroxy-2-oxoglutarate al...

Hypophosphatemic rickets and short stature are observed in nephropathic cystinosis, an orphan autosomal recessive lysosomal storage disease due to a deficiency of cystinosin (CTNS gene). Although bone impairment is not common, it nevertheless appears to be more and more discussed by experts, even though the exact underlying pathophysiology is uncle...

Background: The risk of graft failure in young kidney transplant recipients has been found to increase during adolescence and early adulthood. However, this question has not been addressed outside the USA so far. Our objective was to investigate whether the hazard of graft failure also increases during this age period in France irrespective of age...

Background: The global pediatric nephrology workforce is poorly characterized. The objectives of our study were to assess pediatric nephrologists' perceptions of the adequacy of the pediatric nephrology workforce, and understand regional challenges to fellow recruitment and job acquisition. Perceptions regarding optimal length of training and rese...

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or wh...

Background: Estimating kidney glomerular filtration rate (GFR) is of utmost importance in many clinical conditions. However, very few studies have evaluated the performance of GFR estimating equations over all ages and degrees of kidney impairment. We evaluated the reliability of two major equations for GFR estimation, the CKD-EPI and Schwartz equ...

Statistical analysis plan. (DOC)

STARD checklist. (DOC)

Background Experience in combined liver-kidney transplantation (CLKT) in children is limited. Methods We conducted a retrospective study of all pediatric CLKTs performed at our medical institution between 1992 and 2013.

Background: Experience in combined liver-kidney transplantation (CLKT) in children is limited. Methods: We conducted a retrospective study of all pediatric CLKTs performed at our medical institution between 1992 and 2013. Results: We identified 18 pediatric patients (9 girls) who had undergone CLKT at our institution during the study period. T...

Purpose of review To provide transplant physicians with a summary of the pathogenesis and diagnosis of adenine phosphoribosyl transferase (APRT) deficiency and primary hyperoxaluria and, focussed on kidney transplantation, and to discuss interventions aimed at preventing and treating the recurrence of crystalline nephropathy in renal transplant rec...

Background: To determine the prevalence of microalbuminuria and associated factors among Congolese human immunodeficiency virus (HIV)-infected children. Methods: This was a cross-sectional study in which 77 HIV-infected antiretroviral therapy-naive children and 89 uninfected controls were enrolled. Microalbuminuria was assessed using the immune-...

This position statement brings up guidance on pre-emptive kidney transplantation from living donors. The provided guidance is based on a systematic review of the literature.

Smith-Magenis syndrome is a complex neurodevelopmental disorder that includes intellectual deficiency, speech delay, behavioral disturbance and typical sleep disorders. Ninety percent of the cases are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases are linked to mutations of the same gene. Behavioral disorders often include outbur...