Prevalence of chronic kidney disease in France: methodological considerations and pitfalls with the use of Health claims databases.

Background: Health policy-making require careful assessment of chronic kidney disease (CKD) epidemiology to develop efficient and cost-effective care strategies. The aim of the present study was to use the RENALGO-EXPERT algorithm to estimate the global prevalence of CKD in France. Methods: An expert group developed the RENALGO-EXPERT algorithm based on healthcare consumption. This algorithm has been applied to the French National Health claims database (SNDS), where no biological test findings are available to estimate a national CKD prevalence for the years 2018-2021. The CONSTANCES cohort (+219 000 adults aged 18-69 with one CKD-EPI eGFR) was used to discuss the limit of using health claims data. Results: Between 2018 and 2021, the estimated prevalence in the SNDS increased from 8.1% to 10.5%. The RENALGO-EXPERT algorithm identified 4.5% of the volunteers in the CONSTANCES as CKD. The RENALGO-EXPERT algorithm had a positive predictive value of 6.2% and negative predictive value of 99.1% to detect an eGFR<60 ml/min/1.73 m². Half of 252 false positive cases (ALGO+, eGFR > 90) had been diagnosed with kidney disease during hospitalization, and the other half based on healthcare consumption suggestive of a 'high-risk' profile; 95% of the 1661 false negatives (ALGO-, eGFR < 60) had an eGFR between 45 and 60 ml/min, half had medication and two-thirds had biological exams possibly linked to CKD. Half of them had a hospital stay during the period but none had a diagnosis of kidney disease. Conclusions: Our result is in accordance with other estimations of CKD prevalence in the general population. Analysis of diverging cases (FP and FN) suggests using health claims data have inherent limitations. Such an algorithm can identify patients whose care pathway is close to the usual and specific CKD pathways. It does not identify patients who have not been diagnosed or whose care is inappropriate or at early stage with stable GFR.

Juvenile neuropsychiatric systemic lupus erythematosus: A specific clinical phenotype and proposal of a probability score.

OBJECTIVE: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic auto-immune disease involving several organs. Neuropsychiatric (NP) SLE (NPSLE) is frequent in j-SLE and associated with increased morbidity/mortality. Although NPSLE classification criteria exist, attributing NP features to j-SLE remains a major challenge. The study objective is to thoroughly describe j-NPSLE patients and assist in their diagnosis. METHODS: This is a 4-year retrospective monocentric study of j-SLE patients. NP events were attributed to j-SLE using standardised diagnostic criteria and multidisciplinary paediatric clinical expertise. Clinical features, brain magnetic resonance imaging (MRI)s and samples analysis including cerebrospinal fluid were assessed. A risk of j-NPSLE score was developed based on multivariable logistic regression analysis. RESULTS: Of 39 patients included, 44% were identified as having j-NPSLE. J-NPSLE diagnosis was established at the onset of j-SLE in 59% of patients. In addition to frequent kidney involvement (76%) and chilblains (65%), all j-NPSLE patients displayed psychiatric features: cognitive symptoms (82%), hallucinations (76%), depressed mood (35%), acute confused state (18%) and catatonia (12%). Neurological involvement was often mild and nonspecific, with headache (53%) in about half of the patients. The main features reported on brain MRI were nonspecific T2/FLAIR white matter hyperintensities (65%), and cerebral atrophy (88%). Upon immunosuppressive treatment, clinical improvement of NP features was observed in all j-NPSLE patients. The score developed to attribute j-NPSLE probability, guide further investigations and appropriate treatments is based on hallucinations, memory, sleep and renal involvement (Sensitivity: 0.95 Specificity: 0.85). Cerebrospinal fluid (CSF) neopterin assessment increases the score sensitivity and specificity. CONCLUSION: Physicians should carefully and systematically assess the presence of NP features at diagnosis and early stages of j-SLE. For j-NPSLE patients with predominant psychiatric features, a multidisciplinary collaboration, including psychiatrists, is essential for the diagnosis, management and follow-up.

REIN: a tool at the service of the paediatric patients / REIN : un outil au service des patients pédiatriques

On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of paediatric CKD patients, the following key messages were retained. Paediatric stage 5 chronic kidney disease (CKD) has particularities that require to be analysed and taken into account because the mortality of these patients remains 30 times higher than that of children of the same age. The REIN registry enables illustrating the specificities of stage 5 CKD in the paediatric age-group in France and providing a set of indicators making it possible to describe the future of these patients as well as the choices made concerning the modalities of replacement therapy. As compared to other European countries, the incidence and prevalence of stage 5 CKD in France is in the middle range for children under 15 and 20 years old. Renal transplant is by far the leading treatment for stage 5 CKD in children and adolescents under 18 years of age in France, allowing to offer these patients the best possible life expectancy. Owing to the small volume of patients, only a nationwide registry can provide an unbiased view and enables analysing this population requiring a hyperspecialised treatment. The participation of French paediatric nephrologists in the REIN French registry also enables providing input to the European registry (ESPN/ERA www.espn-reg.org/index.jsp) and the international registry (IPNA https://ipna-registry.org) (Consulted on September 15th 2022) and thus the possibility of international studies, which are vital to be in line with an approach to improving practices.

À l'occasion des 20 ans du REIN (Réseau Epidémiologie et Information en Néphrologie), un travail de synthèse sur les apports du registre a été mené. Sur la question des patients pédiatriques, les messages clés suivants ont été retenus. La maladie rénale chronique (MRC) stade 5 pédiatrique a des particularités qui nécessitent d'être analysées et prises en compte car la mortalité de ces patients reste 30 fois supérieure à celle des enfants du même âge. Le registre REIN permet d'illustrer les spécificités de la MRC stade 5 à l'âge pédiatrique en France et de fournir un ensemble d'indicateurs permettant de décrire le devenir de ces patients ainsi que les choix faits concernant les modalités de traitement de suppléance. En comparaison à d'autres pays européens, l'incidence et la prévalence de la MRC stade 5 en France se situent dans les valeurs moyennes chez les enfants de moins de 15 et 20 ans. La transplantation rénale est de loin le premier traitement de la MRC stade 5 parmi les enfants et les adolescents de moins de 18 ans en France, permettant d'offrir à ces patients la meilleure espérance de vie possible. En raison du petit volume de patients, seul un registre à l'échelon national permet d'avoir une vision non biaisée et d'analyser cette population nécessitant une prise en charge hyperspécialisée. La participation des néphropédiatres français au registre français REIN permet aussi d'alimenter le registre européen (ESPN/ ERA www.espn-reg.org/index.jsp) et le registre international (IPNA https://ipna-registry.org) (Consulté le 15 septembre 2022) et ainsi la possibilité d'études internationales, indispensables pour s'inscrire dans une démarche d'amélioration des pratiques.

Successful global anti-B-cell strategy with daratumumab in a patient with post-transplant nephrotic syndrome recurrence unresponsive to immunoadsorption and obinutuzumab.

BACKGROUND: Steroid-resistant nephrotic syndrome recurrence post-transplant unresponsive to immunoadsorption is a dilemma, and no reliable treatment strategy has been identified to induce remission so far. CASE PRESENTATION: A 2-year-old girl presented first with idiopathic nephrotic syndrome. She did not reach remission after 30 days of oral steroids and remained resistant to steroid pulses, oral tacrolimus, IV cyclosporine, and to 30 sessions of plasma exchange. Bilateral nephrectomy was performed because of extrarenal complications. Two years later, she received an allograft from a deceased donor and idiopathic nephrotic syndrome relapsed immediately post-transplantation. She did not reach remission after immunosuppressive therapy including tacrolimus, mycophenolate mofetil, methylprednisolone pulses, daily immunoadsorption, and B-cell depletion. She received obinutuzumab 1 g/1.73 m2 injections weekly for 3 weeks and then daratumumab 1 g/1.73 m2 weekly for 4 weeks. One week after the last daratumumab infusion, urine protein/creatinine ratio began to decrease. Proteinuria was negative for the first time at Day 99. Immunoadsorption was stopped 147 days after, and she remained relapse-free at last follow-up (18 months post-transplantation). The treatment was complicated by a pneumocystis jirovecii pneumonia with a favorable outcome and persistent hypogammaglobulinemia. CONCLUSION: A obinutuzumab and daratumumab combination seems to be a promising strategy in post-transplantation SRNS recurrence without response to standard treatment options.

Optimizing COVID-19 Vaccination Strategy in Pediatric Kidney Transplant Recipients: Humoral and Cellular Response to SARS-CoV-2 mRNA Vaccination.

In this retrospective cohort study, we analyze the early humoral and cellular response in 64 adolescents KTx recipients, after two or three doses of mRNA vaccine BNT162b2 against different variants of COVID-19. After 2 doses, 77.8% % of children with no history of infection had a positive humoral response with a median anti-S IgG level of 1107 (IQR, 593-2,658) BAU/mL. All the patients with a history of infection responded with a higher median IgG level (3,265 (IQR, 1,492-8,178) BAU/mL). In non-responders after 2 doses, 75% responded after a third dose with a median Ab titer at 355 (IQR, 140-3,865 BAU/mL). Neutralizing activity was significantly lower against the delta and the omicron variants compared to the wild-type strain and did not improve after a 3rd dose, while infection did provide higher levels of neutralizations against the variants. T cell specific response correlated with humoral response and no patient displayed a cellular response without a humoral response. Adolescent KTx recipients exhibit a high seroconversion rate after only two doses. A third injection, induces a response in the majority of the non-responders patients but did not counterbalance the strong decrease in neutralizing antibody activities against variants highlighting the need for boosters with specific vaccines.

Outcome of children with IgA vasculitis with nephritis treated with steroids: a matched controlled study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%) patients received oral steroids alone, 207 (51%) patients received three methylprednisolone pulses followed by oral steroids, and 44 patients (12.5%) did not receive steroids. Thirty-two children treated with oral steroids alone were compared with 32 matched control patients who did not receive steroids. One year after disease onset, IgAVN remission proportion was not different between these two groups: 62% versus 68%, respectively. Ninety-three children treated with oral steroids alone were compared with 93 matched patients treated with three methylprednisolone pulses followed by oral corticosteroids. IgAVN remission proportion was not different between these two groups: 77% versus 73%, respectively. CONCLUSION: The benefit of oral steroids alone and methylprednisolone pulses could not be established based on this observational study. Randomized controlled trials are thus required to determine the efficacy of steroids in IgAVN. A higher resolution version of the Graphical abstract is available as Supplementary information.

Benefits of BNP/NT-proBNP serum level evaluation for dry weight adjustment in pediatric hemodialysis patients.

BACKGROUND: Dry weight (DW) adjustment in children on hemodialysis (HD) can be challenging. It relies on clinical evaluation and additional supports. Our aim was to study the benefits of cardiac biomarker assessment, in addition to the more commonly used technique, bioimpedance spectroscopy (BIS), and clinical signs for DW prescription in pediatric HD patients. METHOD: Observational study including 41 children on HD in three pediatric HD centers in the Paris region. During one session, BIS was performed before the session and serum levels of BNP and NT-proBNP were analyzed before and after the session. RESULTS: Median pre-dialysis level of BNP was 87 ng/L [24-192] and NT-proBNP 968 ng/L [442-4828]. Cardiac biomarker levels showed positive correlation with the BIS hydration status evaluation (p = 0.004). The most appropriate cutoff for pre-dialysis BNP to detect significant overhydration (OH) was 165 ng/L (sensitivity 0.67, specificity 0.84). Based on the BIS evaluation, only 32% of patients with high blood pressure (BP) had OH, whereas in the normal BP group, 33% had significant OH. CONCLUSIONS: DW prescription for children on HD should not only rely on clinical evaluation, particularly BP, but should also include additional helpful parameters. BIS is well-validated in children, but it has limitations in non-cooperative patients, and its cost can limit its use in some settings. Cardiac biomarkers, especially BNP, were well-correlated to hydration status evaluated by BIS, and thus could add valuable information for individual patient management and DW assessment. A higher resolution version of the Graphical abstract is available as Supplementary information.

Juvenile Neuropsychiatric Systemic Lupus Erythematosus: Identification of Novel Central Neuroinflammation Biomarkers.

INTRODUCTION: Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains difficult, especially in pediatrics, with no specific biomarker of the disease yet validated. OBJECTIVES: To identify central nervous system (CNS) disease biomarkers of j-NPSLE. METHODS: A 5-year retrospective tertiary reference monocentric j-SLE study. A combination of standardized diagnostic criteria and multidisciplinary pediatric clinical expertise was combined to attribute NP involvement in the context of j-SLE. Neopterin and interferon-alpha (IFN-α) protein levels in cerebrospinal fluid (CSF) were assessed, together with routine biological and radiological investigations. RESULTS: Among 51 patients with j-SLE included, 39% presented with j-NPSLE. J-NPSLE was diagnosed at onset of j-SLE in 65% of patients. No specific routine biological or radiological marker of j-NPSLE was identified. However, CSF neopterin levels were significantly higher in active j-NPSLE with CNS involvement than in j-SLE alone (p = 0.0008). Neopterin and IFN-α protein levels in CSF were significantly higher at diagnosis of j-NPSLE with CNS involvement than after resolution of NP features (respectively p = 0.0015 and p = 0.0010) upon immunosuppressive treatment in all patients tested (n = 10). Both biomarkers correlated strongly with each other (Rs = 0.832, p < 0.0001, n = 23 paired samples). CONCLUSION: CSF IFN-α and neopterin constitute promising biomarkers useful in the diagnosis and monitoring of activity in j-NPSLE.

Predictive factors for survival in patients with oligohydramnios secondary to antenatal kidney disease.

BACKGROUND: Renal oligohydramnios (ROH) is caused by bilateral congenital abnormalities, either of renal parenchymal or obstructive origin. ROH is a poor prognostic factor of neonatal survival; lung hypoplasia is reported to be the main cause of mortality. We aimed to describe the fetal morbidity and pre- and postnatal mortality in case of ROH due to renal congenital pathologies and to find predictive risk factors for morbidity and mortality. METHODS: All data were collected in Trousseau Hospital in the obstetric, neonatology, and pediatric nephrology units, from 2008 to 2020. RESULTS: We included 66 fetuses with renal parenchymal pathologies posterior urethral valves (PUV) (N = 25), bilateral kidney agenesis (N = 10), hypodysplasia (N = 16), and polycystic kidney disease (N = 10) causing oligohydramnios identified on antenatal ultrasound. Total pre- and postnatal mortality was 76% (50/66). Mortality, excepting termination of pregnancy (TOP), was 65%. The presence of pneumomediastinum and pneumothorax was not different in survivors and non-survivors. Fetuses with kidneys having features of hypodysplasia on ultrasound at T2 and those with oligohydramnios before 32 weeks GA had a higher risk of death. There was a significant difference in plasma creatinine of the surviving patients compared to the deceased patients, from day 3 onwards (183 µmol/L [88; 255] vs. 295 µmol/L [247; 326]; p = 0.038). CONCLUSIONS: The main differences between survivors and non-survivors among patients with "renal oligohydramnios" were oligohydramnios detection before 32 weeks GA, dysplasia detection on the second trimester ultrasound, and increase of serum creatinine from day 3 onwards. A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Impact of nephrology care trajectories pre-CKD stage 5 on initiation of kidney replacement therapy in children.

BACKGROUND: To improve pre-emptive kidney transplantation (PKT) in children and limit starting dialysis in an emergency, we aimed to describe nephrology care trajectories pre-CKD stage 5. METHODS: We included all children in France who, between 2010 and 2016, started kidney replacement therapy (KRT): standard dialysis (reference group) and emergency dialysis or PKT. We identified four pre-CKD stage 5 nephrology care trajectories before KRT that were extracted from the national exhaustive medical-administrative database and used logistic regression to explore associations between patient characteristics, care trajectories, and KRT initiation. RESULTS: Six hundred forty-three pediatric patients started KRT in France; 406 started dialysis and 30.5% emergency dialysis. The "optimal" care trajectory encompassed 179 patients, 82.7% with at least 18 months nephrology follow-up. Conversely, the "no care" trajectory encompassed 118 patients with no nephrology follow-up before KRT. The "severe" trajectory encompassed 128 patients; 93% hospitalized more than once a year and 18% in an intensive care unit. Finally, the "irregular" trajectory encompassed 127 patients, 77% and 46% with irregular laboratory monitoring and CKD drug delivery, respectively. With the "optimal" trajectory as the reference, probability of emergency dialysis was higher with the "irregular" and "no care" trajectories (odds ratio 3.02 [95% confidence interval 1.18-7.66] and 26.5 [10.8-64.8], respectively), and PKT was reduced with the "severe" trajectory (0.43 [0.23-0.82]). CONCLUSION: We identified a group of patients with irregular follow-up who may benefit the most from interventions aiming at improving adherence to treatment and earlier diagnosis of their CKD to improve access to PKT. A higher resolution version of the Graphical abstract is available as Supplementary information.

Management of IgA Vasculitis with Nephritis.

Immunoglobulin A (IgA) vasculitis (IgAV), previously called Henoch-Schönlein purpura, is characterized by IgA-dominant immune deposits affecting small vessels and often involves the skin, gastrointestinal tract, joints, and kidneys. IgAV is the most common cause of systemic vasculitis in children. The long-term prognosis is dependent on renal involvement: IgAV with nephritis (IgAVN) can progress to renal failure. IgAVN is an inflammatory disease, providing a rationale for the use of corticosteroids. However, data supporting the use of corticosteroids in patients with established IgAVN of any severity remain limited, although most clinicians use them. Even in patients with severe forms of IgAVN, methylprednisolone pulses added to oral corticosteroids appears to improve renal outcomes. Considering the multihit hypothesis for the pathogenesis of IgAVN, involving many other immune agents, there is a strong rationale for the use of other immunosuppressive drugs in patients with IgAVN, including mycophenolic acid, cyclophosphamide, rituximab, calcineurin inhibitors, and complement inhibitors. Thus, these immunosuppressive treatments have also been evaluated in IgAVN, usually in corticosteroid-dependent or corticosteroid-resistant forms and in small retrospective studies. However, their efficacy has not been proven. Thus, the risk of progression to renal failure and the ongoing debate about the best management of IgAVN justifies the interest in investigating and identifying treatments that can potentially preserve renal function in patients with IgAVN. This review reports on the efficacy of the different drugs currently used for the treatment of IgAVN in adults and children.

Procalcitonin serum levels in stage 5 chronic kidney disease children on hemodialysis.

BACKGROUND: Infections are responsible for morbidity and mortality in children on hemodialysis (HD). Procalcitonin (PCT) is rarely used in this population, even though it is an efficient biomarker of infection and sepsis. Our aim was to study PCT baseline level in uninfected children with stage 5 chronic kidney disease (CKD 5) on HD, and determine how to use it in this population. METHODS: Prospective observational study including 40 uninfected children on classical HD or hemodiafiltration (HDF) in three pediatric HD centers in the Paris region. PCT was monitored before and after three consecutive sessions within 1 week. RESULTS: Median pre-dialysis PCT was 0.60 ng/mL [0.36-1.15], median post-dialysis PCT was 0.23 ng/mL [0.10-0.47], PCT reduction rate was 59.8% [37.5-75.8]. Seventy percent of pre-dialysis PCT were <1 ng/mL. Anuric patients had higher pre-dialysis PCT than those with residual urine output (0.70 [0.42-1.30] vs. 0.48 [0.30-0.93] ng/mL, p=0.01). HDF was more efficient than HD to clear PCT during sessions (reduction rate 75% [67-80] vs. 37 [31-50]), p<0.001). CONCLUSION: PCT levels in pediatric HD patients without infection are higher than normal, but this increase is relatively moderate compared to massive increases of PCT in children with bacterial infections on HD. If PCT is measured after dialysis sessions, the specific technique-dependent reduction rates should be taken into consideration. Moderately increased PCT levels around 2 ng/ml should be interpreted with caution; however, higher PCT serum levels can be used to motivate rapid start of antibiotic treatment in pediatric HD patients.

Dynamic prediction models for graft failure in paediatric kidney transplantation.

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 a first kidney transplantation before the age of 21 years in France in 2002-13 and survived >90 days with a functioning graft. We used a Cox model including baseline predictors only (sex, age at transplant, primary kidney disease, dialysis duration, donor type and age, human leucocyte antigen matching, cytomegalovirus serostatus, cold ischaemia time and delayed graft function) and two joint models also accounting for post-transplant estimated glomerular filtration rate (eGFR) trajectory. Predictive performances were evaluated using a cross-validated area under the curve (AUC) and R2 curves. RESULTS: When predicting the risk of graft failure from any time within the first 7 years after paediatric kidney transplantation, the predictions for the following 3 or 5 years were accurate and much better with the joint models than with the Cox model (AUC ranged from 0.83 to 0.91 for the joint models versus 0.56 to 0.64 for the Cox model). CONCLUSION: Accounting for post-transplant eGFR trajectory strongly increased the accuracy of graft failure prediction in young kidney transplant recipients.

Setting reasonable objectives for improving preemptive kidney transplantation rates in children.

BACKGROUND: This study aims to develop a method to estimate the potential of preemptive kidney transplantation (PKT) by identifying patients who were transplanted after a dialysis period (non-preemptive kidney transplantation (NPKT)) despite being medically suitable for PKT. METHODS: All children (< 18 years old) starting kidney replacement therapy (KRT) in France, between 2010 and 2016 and transplanted before December 31, 2017, were included. A propensity score (PS) of receiving PKT was estimated by multivariate logistic regression based on recipient medical characteristics. Healthcare use during the 24 months prior to KRT initiation was extracted from the French National Health Insurance database, and a pre-KRT follow-up of more than 18 months was considered sufficient to allow preemptive transplantation. RESULTS: Among 643 patients who started KRT, 149 (23.2%) were preemptively transplanted. Using PS stratification, among 391 NPKT patients, we identified 145 patients (37%) suitable for PKT, according to clinical characteristics. Mean age was 12.3 years, 67% were males, and 56% had urological abnormalities. Among those 145 patients, we identified 79 NPKT patients who started on dialysis despite early referral to a nephrologist (more than 18 months prior to KRT initiation). CONCLUSIONS: This method estimates a potential of 228 (149 + 79) PKT (35%) among pediatric patients in France. A similar method could be used in adults or in other countries. Estimation of the rate of patients with CKD stage 5 medically suitable for PKT will be of interest for health policy makers when setting up objectives for improvement in preemptive kidney transplant access.

Tolvaptan therapy to treat severe hyponatremia in pediatric nephrotic syndrome.

BACKGROUND: Tolvaptan is a selective oral vasopressin V2-receptor antagonist. Some data have implicated stimulation of arginine vasopressin (AVP) as an important factor in oedema formation in a rodent model of nephrotic syndrome (NS) and adult NS patients. We report case of pediatric NS with severe hyponatremia efficiently treated by tolvaptan. CASE/DIAGNOSIS - TREATMENT: A 22-month-old girl presented first with NS. She remained nephrotic after a 30-day course of oral steroids. Tacrolimus was inefficient and there was no response to plasma exchanges (15 sessions on a daily basis). She had severe oedema and ascites. Thus, in addition to immunosuppressive therapy, she received diuretics, furosemide 5 mg/kg/day, and amiloride 1 mg/kg/day, and required water restriction. She was hypertensive and was treated with a full dose of calcium inhibitor (amlodipine 0.5 mg/kg/day). After2 months of treatment, serum sodium reached 116 mmol/L and urinary osmolarity 547 mosmol/L, suggesting an inappropriate AVP secretion. Tolvaptan was introduced at 0.3 mg/kg/day and progressively increased to 3 mg/kg/day on day 4, leading to a partial correction of serum sodium (130 mmol/l) and a urinary osmolarity decrease to 90 mosmol/L. Tolvaptan was then continued at the dose of 3 mg/kg/day with unchanged serum sodium, without hypernatremia or dehydration. Her weight decreased from 14.8 k to 14 k, but oedema still persisted. CONCLUSION: Tolvaptan was very efficient in this case of hyponatremia associated with steroid-resistant NS. Tolvaptan should be considered in the management of therapy-resistant hyponatremia in patients with NS.

Immunoglobulin serum levels in rituximab-treated patients with steroid-dependent nephrotic syndrome.

BACKGROUND: Rituximab (RTX) is efficient in steroid-dependent nephrotic syndrome (SDNS) in pediatric and adult patients. The aim of this study is to describe hypogammaglobulinemia as a side effect of RTX treatment. METHODS: All pediatric patients (< 18 years old) of four French pediatric nephrology centers who received RTX for SDNS between 2010 and 2015 have been included. Clinical and biological data have been analyzed retrospectively before, during, and after RTX treatment. Hypogammaglobulinemia was defined as an IgG level < - 2 standard deviations for patient age. RESULTS: A total of 107 pediatric patients have been included, 65.9% were boys, median age at nephrotic syndrome diagnosis was 3.1 interquartile range [IQ 2.24-5.45] years and age at RTX introduction was 11.7 [IQ 8.6-14.2] years. Twenty-one patients had hypogammaglobulinemia before the initiation of RTX. Of the patients, 25/86 had at least one hypogammaglobulinemia during B cell depletion or after B cell recovery while IgG levels at initiation were normal with a persisting hypogammaglobulinemia for 13 patients 1 year after B cell recovery. Patients who developed hypogammaglobulinemia were younger at RTX initiation with a median age of 8.2 years [IQ 6.3-12.4]. Among all the 46 patients with hypogammaglobulinemia during follow-up, 13 had a concomitant infection. CONCLUSIONS: Hypogammaglobulinemia is a frequent complication of RTX treatment in younger children treated for SDNS. The use of RTX in children has to be carefully evaluated and their clinical and biological follow-up should be adapted to the age-dependent risk profile for hypogammaglobulinemia.

Histological prognostic factors in children with Henoch-Schönlein purpura nephritis.

BACKGROUND: The management of IgA vasculitis with nephritis (IgAVN) remains controversial because of the difficulty to identify prognostic factors. This study reports the prognosis of children with IgAVN in relation to histological parameters. METHODS: All children with IgAVN diagnosed between 2000 and 2015 in three pediatric nephrology centers were included. The following histological parameters were analyzed: mesangial proliferation (MP), endocapillary proliferation (EP), crescents, active, or chronic tubular and interstitial lesions (TIa lesions/TIc lesions), and segmental glomerulosclerosis (GS). Clinical and biological data were collected at the time of renal biopsy. The primary endpoint was IgAVN remission defined as a proteinuria < 200 mg/l without renal failure. RESULTS: One hundred fifty-nine children were included with a median age of 7.6 years. Acute glomerular or TI lesions including MP, EP, crescents, and TIa lesions were observed, respectively, in 81%, 86%, 49%, and 21% of patients. Chronic glomerular lesions including GS and TIc lesions were observed in 6 and 7% of patients. Median initial proteinuria was 330 mg/mmol, albuminemia 32 g/l, and eGFR 110 ml/min/1.73 m2. One hundred twelve (70%) patients were in remission at the end of a median follow-up of 37.4 months. Chronic lesions were significantly associated with the absence of remission in multivariate analysis, whereas EP, crescents and TIa were not associated with a poor prognosis. CONCLUSIONS: Of children with IgAVN, 30% present a persistent renal disease at the end of a 3-year follow-up. Chronic histological lesions, but not EP or crescents, are associated with a bad prognosis and must be evaluated in IgAVN histological classification.