Search

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 transplantation outcomes are scarce. The merits of a sequential over combined procedure regarding kidney graft survival remain unclear as is the place of isolated kidney transplantation (KT) for patients with vitamin B6-responsive genotypes.Methods: We used the OxalEurope registry for retrospective analyses of patients with PH1 who underwent transplantation. Analyses of crude Kaplan–Meier survival curves and adjusted relative hazards from the Cox proportional hazards model were performed.Results: A total of 267 patients with PH1 underwent transplantation between 1978 and 2019. Data of 244 patients (159 CLKTs, 48 isolated KTs, 37 sequential liver–KTs [SLKTs]) were eligible for comparative analyses. Comparing CLKTs with isolated KTs, adjusted mortality was similar in patients with B6-unresponsive genotypes but lower after isolated KT in patients with B6-responsive genotypes (adjusted hazard ratio 0.07, 95% CI: 0.01–0.75, P = 0.028). CLKT yielded higher adjusted event-free survival and death-censored kidney graft survival in patients with B6-unresponsive genotypes (P = 0.025, P < 0.001) but not in patients with B6-responsive genotypes (P = 0.145, P = 0.421). Outcomes for 159 combined procedures versus 37 sequential procedures were comparable. There were 12 patients who underwent pre-emptive liver transplantation (PLT) with poor outcomes.Conclusion: The CLKT or SLKT remains the preferred transplantation modality in patients with PH1 with B6-unresponsive genotypes, but isolated KT could be an alternative approach in patients with B6-responsive genotypes.

Summary 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 histology) granted on the basis of basket trials. Basket trials in oncology offer the advantage of simultaneously evaluating treatments for multiple tumours, even rare cancers, in a single clinical trial. To address the novel challenges introduced by these trials, an interdisciplinary panel was convened on behalf of the Transparency Committee of the French National Authority for Health to clarify an approach designed to guarantee a transparent, reproducible, and fair assessment of histology-agnostic treatments for reimbursement by the French National Health Insurance Fund. The requirements of this approach include the need for randomisation, clinically relevant endpoints, appropriate correction for multiple significance testing, characterisation of subgroup heterogeneity, and validation of underlying biomarker assays. A prospectively designated external control is encouraged when the implementation of a direct comparison is deemed infeasible. We also underline the importance of recording outcomes from basket trials in a registry for use as future external controls.

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: In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with PH1 who were 6 years of age or older to receive subcutaneous lumasiran or placebo for 6 months (with doses given at baseline and at months 1, 2, 3, and 6). The primary end point was the percent change in 24-hour urinary oxalate excretion from baseline to month 6 (mean percent change across months 3 through 6). Secondary end points included the percent change in the plasma oxalate level from baseline to month 6 (mean percent change across months 3 through 6) and the percentage of patients with 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at month 6. Results: A total of 39 patients underwent randomization; 26 were assigned to the lumasiran group and 13 to the placebo group. The least-squares mean difference in the change in 24-hour urinary oxalate excretion (lumasiran minus placebo) was -53.5 percentage points (P

Primary hyperoxalurias are rare disease with autosomal recessive inheritance; they often lead to kidney failure and can lead to life-threatening conditions, especially in early onset forms. There are three types, responding to distinct enzyme deficits. Type 1 represents 85% of cases and results from an enzyme deficiency (alanine-glyoxylate aminotransferase) in the peroxisomes of the liver, causing hyperoxaluria leading to urolithiasis with or without nephrocalcinosis. As glomerular filtration decreases, a systemic overload appears and spares no organ. Treatment has hitherto been based on combined liver and kidney transplantation, with significant mortality and morbidity. The recent introduction of interfering RNA treatments opens up new perspectives. By blocking an enzymatic synthesis (glycolate oxidase or lacticodehydrogenase a) upstream of the deficit that causes the disease, oxaluria normalizes and the tolerance of the drug (administered by injection every 1 to 3 months) is good. This strategy will help prevent kidney failure in patients treated early and avoid liver transplantation in those who are diagnosed at an advanced stage of kidney failure.

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, between 60% and 80% of PH1 but only 20% of PH2 patients will reach end‐stage kidney disease. In PH3 patients, dialysis is uncommon. Because oxalate clearance is impaired in CKD patients, oxalate can precipitate in various organs leading to systemic oxalosis. We report an uncommon presentation of bone oxalosis associated with hypercalcemia in a dialyzed patient. This report emphasizes the difficulties to diagnose primary hyperoxaluria and the challenge of treating dialyzed patients.

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, many PH1 patients need kidney transplantation. However, because PH1 is caused by a liver enzyme deficiency, the only cure of the metabolic defect is liver transplantation. Thus, current transplant strategies to treat PH1 patients with ESRD include dual liver–kidney transplantation. However, the morbidity and mortality associated with liver transplantation make these strategies far from optimal. Fortunately, a therapeutic revolution is looming. Indeed, innovative drugs are being currently tested in clinical trials, and preliminary data show impressive efficacy to reduce the hepatic overproduction of oxalate. Hopefully, with these therapies, liver transplantation will no longer be necessary. However, some patients with progressing renal disease or those who will be diagnosed with PH1 at an advanced stage of chronic kidney disease will ultimately need kidney transplantation. Here we review the current knowledge on this subject and discuss the future of kidney transplant management in PH1 patients in the era of novel therapies.

Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology—Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.

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.

International audience; 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, randomized, placebo-controlled trial was to evaluate the safety, pharmacokinetic, and pharmacodynamic profiles of lumasiran in healthy participants and patients with primary hyperoxaluria type 1. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This phase 1/2 study was conducted in two parts. In part A, healthy adults randomized 3:1 received a single subcutaneous dose of lumasiran or placebo in ascending dose groups (0.3-6 mg/kg). In part B, patients with primary hyperoxaluria type 1 randomized 3:1 received up to three doses of lumasiran or placebo in cohorts of 1 or 3 mg/kg monthly or 3 mg/kg quarterly. Patients initially assigned to placebo crossed over to lumasiran on day 85. The primary outcome was incidence of adverse events. Secondary outcomes included pharmacokinetic and pharmacodynamic parameters, including measures of oxalate in patients with primary hyperoxaluria type 1. Data were analyzed using descriptive statistics. RESULTS: Thirty-two healthy participants and 20 adult and pediatric patients with primary hyperoxaluria type 1 were enrolled. Lumasiran had an acceptable safety profile, with no serious adverse events or study discontinuations attributed to treatment. In part A, increases in mean plasma glycolate concentration, a measure of target engagement, were observed in healthy participants. In part B, patients with primary hyperoxaluria type 1 had a mean maximal reduction from baseline of 75% across dosing cohorts in 24-hour urinary oxalate excretion. All patients achieved urinary oxalate levels ≤1.5 times the upper limit of normal. CONCLUSIONS: Lumasiran had an acceptable safety profile and reduced urinary oxalate excretion in all patients with primary hyperoxaluria type 1 to near-normal levels. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Study of Lumasiran in Healthy Adults and Patients with Primary Hyperoxaluria Type 1, NCT02706886.

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 relationship between Pox and estimated glomerular filtration rate (eGFR) in patients with preserved kidney function, however, is not well established. Our analysis aimed to investigate a potential correlation between these parameters in PH patients from three randomized, placebo-controlled trials (studies OC3-DB-01, OC3-DB-02, and OC5-DB-01). Methods Baseline data from patients with a PH diagnosis (type 1, 2, or 3) and eGFR > 40 mL/min/1.73 m2 were analyzed for a correlation between eGFR and Pox using Spearman’s rank and Pearson’s correlation coefficients. Data were analyzed by individual study and additionally were pooled for Studies OC3-DB-02 and OC5-DB-01 in which the same Pox assay was used. Results A total of 106 patients were analyzed. A statistically significant inverse Spearman’s correlation between eGFR and Pox was observed across all analyses; correlation coefficients were − 0.44 in study OC3-DB-01, − 0.55 in study OC3-DB-02, − 0.51 in study OC5-DB-01, and − 0.49 in the pooled studies (p Conclusions Baseline evaluations showed a moderate and statistically significant inverse correlation between eGFR and Pox in patients with PH already at early stages of CKD (stages 1–3b), demonstrating that a correlation is present before substantial loss in kidney function occurs. Graphical abstract

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 subtypes of PH. Here, we assessed in a two-part, randomized, single-ascending-dose, phase 1 study (PHYOX1) the safety, pharmacokinetics, pharmacodynamics, and exposure-response of subcutaneous nedosiran in 25 healthy participants (Group A) and 18 patients with PH1 or PH2 (Group B). Group A received nedosiran (0.3, 1.5, 3.0, 6.0, then 12.0 mg/kg) or placebo, and Group B received open-label nedosiran (1.5, 3.0, or 6.0 mg/kg). No significant safety concerns were identified. Injection site reactions (four or more hours post dose) occurred in 13.3% of participants in Group A and 27.8% of participants in Group B. Mean maximum reduction in 24-hour urinary oxalate excretion from baseline to day 57 (end of study) across Group B dose cohorts was 55% (range: 22%-100%) after single-dose nedosiran, with 33% participants reaching normal 24-hour urinary oxalate excretion. Based on the available modeling and simulation data, a fixed monthly dose of nedosiran 160 mg (free acid; equivalent to 170 mg sodium salt) in adults was associated with the highest proportion of simulated individuals achieving normal or near-normal 24-hour urinary oxalate excretion and fewest fluctuations in urinary oxalate response. Thus, single-dose nedosiran demonstrated acceptable safety and evidence of a pharmacodynamic effect in both PH1 and PH2 subpopulations consistent with its mechanism of action.

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 below 6 months between 2007 and 2017 in two tertiary centres. Results are presented as median (min;max). Results Seventeen patients (10 boys) were included (8 prenatal diagnoses, 6 premies), with the following diagnoses: congenital anomalies of kidney and urinary tract (n = 9), oxalosis (n = 5), congenital nephrotic syndrome (n = 2) and renal vein thrombosis (n = 1). Five patients had associated comorbidities. At peritoneal dialysis initiation, age was 2.6 (0.1;5.9) months, height-standard deviation score (SDS) −1.3 (−5.7;1.6) and weight-SDS −1.4 (−3.6;0.6). Peritoneal dialysis duration was 12 (2;32) months, and at peritoneal dialysis discontinuation height-SDS was −1.0 (−4.3;0.7) weight-SDS −0.7 (−3.2;0.2), parathyroid hormone 123 (44;1540) ng/L, and hemoglobin 110 (73;174) g/L. During the first 6 months of peritoneal dialysis, the median time of hospitalisation stay was 69 (15;182) days. Ten patients presented a total of 27 peritonitis episodes. Reasons for peritoneal dialysis discontinuation were switch to hemodialysis (n = 6), transplantation (n = 6), recovery of renal function (n = 2) and death (n = 1). After a follow-up of 4.3 (1.7;10.3) years, 12 patients were transplanted, 2 patients were still on peritoneal dialysis, 2 patients were dialysis free with severe chronic kidney disease and 1 patient had died. Seven patients displayed neurodevelopmental delay, of whom five needed special schooling. Conclusion We confirm that most infants starting peritoneal dialysis before 6 months of age will be successfully transplanted and will have a favourable growth outcome. Their quality of life will be impacted by recurrent hospitalisations and neurodevelopmental delay is frequent.

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 gastrointestinal discomfort and poor palatability impacting medication adherence. ADV7103, the first advanced therapy for dRTA, consists of a combination of prolonged-release potassium citrate and prolonged-release potassium bicarbonate granules providing round-the-clock alkali and potassium coverage with twice daily administration. Long-term adherence with ADV7103 is reported, along with acceptability of the product. Method B22CS is a multicentre, open-label long-term extension study, evaluating safety, tolerability, acceptability and efficacy of ADV7103 in adult and paediatric patients with dRTA. Adherence was assessed at each study visit up to 24 months, based on accountability of study drug retrieval, laboratory results, and interview of the patients in a diary and expressed as the proportion of patients that presented adherence lower than 50%, between 50% and 74%, between 75 and 90%, and higher than to 90%. Treatment acceptability as well as quality of life of the patients and their parents were assessed using a 100-mm visual analogue scales (VAS). Results Table 1 shows the evolution of compliance between Month 6 and Month 24. Overall, of the 29 patients remaining in the study after 24 months, 18 (62%) had adherence rates >90%, 5 (17%) had adherence rates of 75-90%, 6 (21%) had adherence rates of 50-74%, and there were no patients with adherence Compared to the alkalising treatments they had before the study, more than 80% of the patients perceived both the improvement of the formulation and of the number of daily doses at scores ≥ 75 mm. The overall improvement of quality of life reported by the patients was of 89 ± 19 mm and that reported by their parents was of 90 ± 14 mm after 24 months of treatment. Conclusion Adherence to treatment was maintained at a high level throughout the 24 months of the study confirming the good acceptance of ADV7103 therapy.

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 clearance vs. inulin urinary clearance. Methods GFR was simultaneously determined by inulin and iohexol clearance in 144 participants (age: 10–84 years; glomerular filtration rate: 15–169 mL/min/1.73 m2). A retrospective cross-sectional study evaluated the performance of four formulas proposed to calculate plasma iohexol clearance (Brøchner–Mortensen, Fleming et al., Jødal–Brøchner–Mortensen, and Ng–Schwartz–Munoz). The performance of each formula was assessed using bias, precision (standard deviation of the bias), accuracy (percentage iohexol within 5, 10, and 15%), root mean square error, and concordance correlation coefficient vs. renal inulin clearance as reference. Results Regarding accuracy, there was no difference in root mean square error (RMSE), P5, P10, or P15 between the four formulas. The four concordance correlation coefficients (CCC) between the value from each formula and in-GFR were high and not significantly different. At in-GFR ≥90 mL/min/1.73 m2, Ng–Schwartz–Munoz formula performed slightly better than other formulas regarding median bias (−0.5; 95% CI [−3.0 to 2.0] and accuracy P15 (95.0; 95% CI [88.0–100.0]). Conclusions The studied formulas were found equivalent in terms of precision and accuracy, but the Ng–Schwartz–Munoz formula improved the accuracy at higher levels of in-GFR.

International audience; 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 confirmed NC, aged \textgreater 4 years and receiving oral cysteamine (short acting or delayed release formulation as standard of care) from 3 French reference centers, were included. Adherence to treatment was primarily assessed as the percentage of days with a good adherence score, adherence score rating from 0 (poor) to 2 (good). A descriptive analysis was performed after 1-year follow-up. RESULTS: Seventeen patients (10 girls, median age: 13.9 (5.4-33.0) years) were included. Median age at diagnosis was 17.0 (3.0-76.9) months and age at start of cysteamine was 21.0 (15.5-116.3) months. Median daily dose of cysteamine was 1.05 (0.55-1.63) g/m(2)/day. Over the year, the median percentage of days with a good adherence score was 80 (1-99)% decreasing to 68 (1-99)% in patients \textgreater 11 years old. The median of average number of hours covered by treatment in a day was 22.5 (6.1-23.9) versus 14.9 (9.2-20.5) hours for delayed release versus short acting cysteamine. CONCLUSION: Our data are the first describing a rather good adherence to cysteamine, decreasing in adolescents and adults. We described a potential interest of the delayed release formulation. Our data highlight the need for a multidisciplinary approach including therapeutic education and individualized approaches in NC patients transitioning to adulthood. Graphical abstract.

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 a first R-Tx (January 2010-August 2016), without prior immunization, having complete HLA typing (A, B, C, DRB1 and DQB1) and DSA follow-up for at least one year. The mean of HLA and eplet incompatibilities was 4.7 ± 1.3 and 15.5 ± 6.1, respectively, with a correlation coefficient r2 between these two variables of 0.34 (P < .001). The eplet load was 12.8 ± 5.0 in living donors vs 15.9 ± 6.2 in deceased donors (P = NS), 12.6 ± 6.1 in preemptive R-Tx (n = 14) vs 16.3 ± 5.9 for non-preemptive R-Tx (P = .04). Seven patients (10%) developed DSA during the 3.5 ± 1.2 years post-Tx. The eplet load was 13.7 ± 5.5 for those who developed DSA vs 15.7 ± 6.1 for the others (P = NS). In our single-center series of pediatric R-Tx with good HLA matching and lower eplet load than previously published series, eplet incompatibilities do not predict the development of DSA. The question of the HLA matching requirement and the daily interest of the HLA Matchmaker® software to help select the grafts remain open.

Resume Objectif La polykystose renale recessive (PKR) est due a des mutations du gene PKHD1. L’objectif de l’etude est de caracteriser la variabilite phenotypique en fonction des differentes mutations de PKHD1. Methodes L’etude a ete realisee chez 308 patients atteints de PKR, diagnostiques dans notre laboratoire de genetique. Les medecins prescripteurs des analyses genetiques avaient fourni des donnees cliniques et biologiques minimales. Resultats Les patients ont ete divises en trois groupes genotypiques : le premier groupe (G1 ; n = 65) concernait les patients ayant deux mutations tronquantes, le second groupe (G2 ; n = 117) des patients avec une mutation tronquante et une mutation non tronquante, et le troisieme groupe (G3 ; n = 126) etait constitue des patients ayant deux mutations non tronquantes. Au total, 31 % des grossesses ont fait l’objet d’une interruption medicale de grossesse, 18 % des enfants sont decedes en periode neonatale, et 51 % des patients ont survecu apres la periode neonatale ; la proportion des patients ayant un phenotype severe (defini par une interruption medicale de grossesse ou un deces neonatal) etait significativement plus elevee dans le groupe G1 : 94 %, par rapport aux groupes G2 (47 %) et G3 (27 % ; p Conclusion La presence de deux mutations tronquantes du gene PKHD1 est associee a un phenotype perinatal et post-natal severe. Toutefois, la variabilite phenotypique des autres groupes genotypiques necessite une discussion au cas par cas lors du diagnostic antenatal.

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. In addition to clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local reference cohorts. At a median age of 22.5 (10.2–34.6) years, 10 patients with nephropathic cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations, and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HR-pQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520–1100) versus 1225 (480–1680) μm; p

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 idiopathic nephrotic syndrome, cystinosis, primary hyperoxaluria and hereditaries tubulopathies.

We report three pediatric cases of concomitant congenital Horner and Harlequin syndromes. This association suggests a lesion at the superior cervical ganglion or just inferior. Often, no underlying lesion is documented.

To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria.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 pH, specific gravity and cysteine-binding thiols (CBT) correlate with risk of cystine crystalluria.Alkalizing agents and CBT agents were given to 88.8% (n = 381) and 55.3% (n = 238) of patients, respectively. Gastrointestinal AEs were reported in 12.3%, 10.4% and 2.6% of patients treated with potassium bicarbonate, potassium citrate and sodium bicarbonate, respectively (P = 0.008). The percentages of patients who experienced at least one AE with tiopronin (24.6%) and with D-penicillamine (29.5%) were similar (P = 0.45). Increasing urine pH and decreasing urine specific gravity significantly reduced the risk of cystine crystalluria, whereas D-penicillamine and tiopronin treatments did not reduce this risk (odds ratio [OR] 1 for pH ≤6.5; OR 0.52 [95% confidence interval {95% CI} 0.28-0.95] for 7.0pH ≤7.5, P = 0.03; OR 0.26 [95% CI 0.13-0.53] for 7.5pH ≤8.0, P0.001; OR 1 for specific gravity ≤1.005 OR 5.76 [95% CI 1.45-22.85] for 1.006 ≤ specific gravity ≤1.010, P = 0.01; and OR 11.06 [95% CI 2.76-44.26] for 1.011 ≤ specific gravity ≤ 1.014, P0.001). Increased urine pH significantly increased the risk of calcium phosphate crystalluria (OR 1 for pH≤ 6.5; OR 6.09 [95% CI 2.15-17.25] for pH8.0, P0.001).Adverse events were frequent with D-penicillamine and tiopronin. Alkaline hyperdiuresis was well tolerated and reduced cystine crystalluria. Urine specific gravity ≤1.005 and urine pH7.5, while warning about calcium-phosphate crystallization, should be the goals of medical therapy.

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 oxalate-metabolising bacterium (Oxalobacter formigenes) could reduce urinary oxalate excretion in PH patients. The efficacy and safety of O. formigenes (Oxabact® OC5; OxThera AB, Stockholm, Sweden) was evaluated in a randomised, placebo-controlled, double-blind study for 8 weeks. The primary objective was reduction in urinary oxalate excretion (Uox). Secondary objectives included faecal O. formigenes count and decrease in plasma oxalate concentration (Pox). Twenty-eight patients randomised 1:1 to the treatment group (OC5) or the placebo group completed the study. After 8 weeks of treatment, there was no significant difference in the change in Uox (mmol/24 h/1.73 m2) between the groups (OC5: +0.042, placebo: −0.140). Post-hoc analysis showed a statistically significant increase in Uox per urinary creatinine excretion in the OC5 group (OC5: +5.41, placebo: −15.96; p = 0.030). Change in Pox from baseline was not significantly different between groups (p = 0.438). The O. formigenes cell count was significantly increased in OC5-treated patients (p

Munchausen syndrome by proxy is a persistent fabrication of illness done by a person to another. Renal and urologic forms of this syndrome are not as uncommon as can be thought; a review of all the cases of Munchausen-by-proxy syndrome reveals that 25% of the children had renal or urologic issues. This syndrome can result in a serious diagnostic dilemma for the physicians; knowing this entity can allow early recognition of falsification and limit the physical and psychological damages caused in the victim. In this study, we reviewed the pediatric nephrology cases of Munchausen syndrome by proxy, grouping them through the principal signs of presentation.

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 short follow up periods. Here we report on the clinical, genetic, and biochemical findings from the largest cohort of patients with primary hyperoxaluria type 2, obtained by a retrospective record review of genetically confirmed cases in the OxalEurope registry, a dataset containing 101 patients from eleven countries. Median follow up was 12.4 years. Median ages at first symptom and diagnosis for index cases were 3.2 years and 8.0 years, respectively. Urolithiasis was the most common presenting feature (82.8% of patients). Genetic analysis revealed 18 novel mutations in the GRHPR gene. Of 238 spot-urine analyses, 23 (9.7%) were within the normal range for oxalate as compared to less than 4% of 24-hour urine collections. Median intra-individual variation of 24-hour oxalate excretion was substantial (34.1%). At time of review, 12 patients were lost to follow-up; 45 of the remaining 89 patients experienced chronic kidney disease stage 2 or greater and 22 patients had reached stage 5. Median renal survival was 43.3 years, including 15 kidney transplantations in 11 patients (1 combined with liver transplantation). Renal outcome did not correlate with genotype, biochemical parameters or initially present nephrocalcinosis. Thus, primary hyperoxaluria type 2 is a disease with significant morbidity. Accurate diagnosis by 24-hour urine analysis and genetic testing are required with careful follow-up., SCOPUS: ar.j, info:eu-repo/semantics/published

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 congenital solitary kidney have a better long-term glomerular filtration rate than those with solitary kidney secondary to nephrectomy later in life. Acute and chronic adaptation processes lead to hyperfiltration followed by fibrosis in the remnant kidney, with further risk of albuminuria, arterial hypertension, and impaired renal function. Protective measures rely on non-pharmacological renoprotection (controlled protein and sodium intake, avoidance/limitation of nephrotoxic agents, keeping normal body mass index, and limitation of tobacco exposure). Lifelong monitoring should include blood pressure and albuminuria assessment, completed by glomerular filtration rate (GFR) estimation in case of abnormal values. In the absence of additional risk factors to solitary kidney, such assessment can be proposed every 5 years. There is no current consensus for indication and timing of pharmacological intervention.

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 plasma oxalate, especially in the early stages of chronic kidney disease (CKD). Methods: A case series focuses on the description of variations in clinical presentation. A pilot study was conducted using a cross-sectional analysis with 72 subjects. The glomerular filtration rate (GFR) and plasma oxalate levels were measured for all patients. Results: Median (IQR) GFR was 70.50 [39.0; 91.0] mL/min/1.73 m2. Plasma oxalate was < 5.0 µmol/L in all patients with a GFR > 30 mL/min/1.73m2. Among the 14 patients with severe CKD (GFR < 30 mL/min/1.73 m2) only 4 patients showed a slightly increased plasma oxalate level (between 6 and 12 µmol/L). Conclusion: In non-primary hyperoxaluria, plasma oxalate concentration increases when GFR < 30mL/min/1.73 m2 and, in our opinion, values greater than 5 µmol/L with a GFR > 30 mL/min/1.73 m2 are suggestive of primary hyperoxaluria. Further studies are necessary to confirm plasma oxalate increase in patients with low GFR levels (< 30mL/min/1.73 m2). RESUMO Introdução: A hiperoxalemia secundária é uma doença multifatorial que afeta vários órgãos e tecidos em pacientes com rins nativos ou transplantados. O oxalato plasmático pode aumentar durante a insuficiência renal porque é eliminado do corpo pelos rins. No entanto, há evidências escassas sobre a associação entre taxa de filtração glomerular e oxalato plasmático, especialmente nos estágios iniciais da doença renal crônica (DRC). Métodos: uma casuística centrada na descrição das variações na apresentação clínica. Foi realizado um estudo piloto a partir da análise transversal com 72 indivíduos. As taxas de filtração glomerular (TFG) e os níveis plasmáticos de oxalato foram medidos para todos os pacientes. Resultados: A TFG mediana (IIQ) foi de 70,50 [39,0; 91,0] mL/min/1,73 m2. O nível plasmático de oxalato foi < 5,0 µmol/L em todos os pacientes com TFG > 30 mL/min/1,73 m2. Entre os 14 pacientes com DRC grave (TFG < 30 mL/min/1,73 m2), apenas quatro apresentaram ligeiro aumento do nível plasmático de oxalato (entre 6 e 12 µmol/L). Conclusão: Na hiperoxalúria não primária, a concentração plasmática de oxalato aumenta quando TFG < 30 mL/min/1,73 m2 e, em nossa opinião, valores superiores a 5 µmol/L com TFG > 30 mL/min/1,73 m2 sugerem presença de hiperoxalúria primária. Estudos adicionais são necessários para confirmar o aumento do oxalato plasmático em pacientes com níveis baixos de TFG (< 30 mL/min/1,73 m2).

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 whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease.

Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of systemic oxalosis. Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains and specific oxalate osteopathy on plain X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction due to an invasion of bone surface by macrophages. We present data obtained in 10 samples from 8 patients with oxalosis (16-68 years) who underwent iliac crest bone biopsy and bone quality analysis using modern methods (microradiography, microindentation, Fourier Transform InfraRed Microspectroscopy, transmission electron microscopy) in addition to histomorphometry. Disseminated calcium oxalate deposits (whewellite) were found in the bone marrow space (with a granulomatous reaction) but not in the bone matrix. Calcium oxalate deposits were totally surrounded by macrophages and multinucleated giant cells, and a phagocytosis activity was sometimes observed. Very few calcium oxalate crystals were directly in close contact with the mineral substance of the bone. Bone mineralization was not modified by the presence of calcium oxalate even in close vicinity. Bone quality analysis also revealed a harder bone than normal, perhaps in relationship with decreased carbonate content in the mineral. This increase in bone hardness could explain a more "brittle" bone. In patients with oxalosis, the formation and growth of calcium oxalate crystals in the bone appeared independent of apatite. The mechanisms leading to nucleation and growth of oxalate deposits are still unclear and deserve further studies.

Background Online hemodiafiltration (oHDF) is increasingly used in children; we treated 28 children since 2009, adapting this technique to pediatric patients. Methods In this service evaluation audit, we assessed plasma electrolytes to evaluate the evolution of total (tCa) and ionized (iCa) during a session, as well as dialysate calcium (dCa) concentrations. Results Using a 1.25 mmol Ca/L-dialysate, both tCa and iCa decreased during the session, with iCa falling below 1.1 mmol/L in 4/5 patients. In contrast, using a 1.5 mmol Ca/L-dialysate, iCa remained normal in all patients. Major discrepancies were observed between the expected and the measured dCa: 1.25 vs. 1.01 (0.83–1.04), and 1.5 vs. 1.47 (0.85–1.75) mmol/L, respectively (results presented as median [range]). These differences were explained by the modality of reconstituting dialysate: increasing bicarbonates and/or decreasing sodium requested in the dialysate decreases calcium extraction from the acid preparation. Proof of concept was given when requesting in an “ex-vivo” setting modifications in the requested sodium and bicarbonate in dialysate directly on the Fresenius machine. Conclusion Nephrologists should be aware that “high bicarbonate and/or low sodium” requirements in oHDF decrease calcium in the dialysate.

Resume Le deficit en vitamine D est frequent dans la population generale et encore plus chez les patients souffrant de maladies chroniques. La prevention du rachitisme par la supplementation en vitamine D est l’une des mesures prophylactiques efficaces les plus anciennes connues en medecine. Elle a pratiquement eradique le rachitisme dans les pays developpes. Nous rapportons le cas de deux enfants, l’un ayant developpe un rachitisme mixte (carentiel et iatrogene lie aux antiepileptiques) et l’autre ayant presente un tableau d’hypercalcemie severe symptomatique secondaire a une intoxication a la vitamine D. Nous rappelons l’importance de la supplementation en vitamine D qui doit obeir a des regles precises : ni excessive, ni insuffisante. Par ailleurs, en dehors des exceptionnels surdosages en vitamine D, il doit etre tenu compte du risque d’hypercalcemie par mutation de la 24-hydroxylase ( CYP24A1 ).

Smith-Magenis syndrome (SMS) is a genetic disorder characterized by the association of facial dysmorphism, oral speech delay, as well as behavioral and sleep/wake circadian rhythm disorders. Most SMS cases (90%) are due to a 17p11.2 deletion encompassing the RAI1 gene; other cases stem from mutations of the RAI1 gene. Behavioral issues may include frequent outbursts, attention deficit/hyperactivity disorders, self-injuries with onychotillomania and polyembolokoilamania (insertion of objects into bodily orifices), etc. It is noteworthy that the longer the speech delay and the more severe the sleep disorders, the more severe the behavioral issues are. Typical sleep/wake circadian rhythm disorders associate excessive daytime sleepiness with nocturnal agitation. They are related to an inversion of the physiological melatonin secretion cycle. Yet, with an adapted therapeutic strategy, circadian rhythm disorders can radically improve. Usually an association of beta-blockers in the morning (stops daily melatonin secretion) and melatonin in the evening (mimics the evening deficient peak) is used. Once the sleep disorders are controlled, effective treatment of the remaining psychiatric features is needed. Unfortunately, as for many orphan diseases, objective guidelines have not been drawn up. However, efforts should be focused on improving communication skills. In the same vein, attention deficit/hyperactivity disorders, aggressiveness, and anxiety should be identified and specifically treated. This whole appropriate medical management is underpinned by the diagnosis of SMS. Diagnostic strategies include fluorescent in situ hybridization (FISH) or array comparative genomic hybridization (array CGH) when a microdeletion is sought and Sanger sequencing when a point mutation is suspected. Thus, the diagnosis of SMS can be made from a simple blood sample and should be questioned in subjects of any age presenting with an association of facial dysmorphism, speech delay with behavioral and sleep/wake circadian rhythm disorders, and other anomalies including short stature and mild dysmorphic features.

BACKGROUND Primary hyperoxaluria type 3 (PH3) is characterized by mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 patients are believed to present with a less severe phenotype than those with PH1 and PH2, but the clinical characteristics of PH3 patients have yet to be defined in sufficient detail. The aim of this study was to report our experience with PH3. METHODS Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after the presence of mutations in the alanine-glyoxylate aminotransferase gene had been ruled out. Clinical, biochemical and genetic data of the seven patients identified with HOGA1 mutations were subsequently retrospectively reviewed. RESULTS Among the seven patients identified with HOGA1 mutations the median onset of clinical symptoms was 1.8 (range 0.4-9.8) years. Five patients initially presented with urolithiasis, and two other patients presented with urinary tract infection. All patients experienced persistent hyperoxaluria. Seven mutations were found in HOGA1, including two previously unreported ones, c.834 + 1G > T and c.3G > A. At last follow-up, two patients had impaired renal function based on estimated glomerular filtration rates (GFRs) of 77 and 83 mL/min per 1.73 m(2), respectively. CONCLUSIONS We found that the GFR was significantly impaired in two of our seven patients with PH3 diagnosed during childhood. This finding is in contrast to the early-impaired renal function in PH1 and PH2 and appears to refute to preliminary reassuring data on renal function in PH3.

Primary disease recurrence after renal transplantation is mainly diagnosed by examination of biopsy samples, but can also be associated with clinical symptoms. In some patients, recurrence can lead to graft loss (7-8% of all graft losses). Primary disease recurrence is generally associated with a high risk of graft loss in patients with focal segmental glomerulosclerosis, membranous proliferative glomerulonephritis, primary hyperoxaluria or atypical haemolytic uraemic syndrome. By contrast, disease recurrence is associated with a limited risk of graft loss in patients with IgA nephropathy, renal involvement associated with Henoch-Schönlein purpura, antineutrophil cytoplasmic antibody-associated glomerulonephritis or lupus nephritis. The presence of systemic diseases that affect the kidneys, such as sickle cell anaemia and diabetes mellitus, also increases the risk of delayed graft loss. This Review provides an overview of the epidemiology, pathophysiology and management of primary disease recurrence in paediatric renal graft recipients, and describes the overall effect on graft survival of each of the primary diseases listed above. With appropriate management, few paediatric patients should be excluded from renal transplantation programmes because of an increased risk of recurrence.

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 from peripheral blood mononuclear cells (PBMCs) of patients and healthy donors (HDs). Cells were treated with increasing doses of cysteamine in PBMCs or on mature OCs to evaluate its impact on differentiation and resorption, respectively. Similarly, cysteamine-treated osteoblasts derived from murine mesenchymal stem cells were assessed for differentiation and activity with toxicity and proliferation assays. Results CTNS was expressed in human OCs derived from HDs; its expression was regulated during monocyte colony-stimulating factor- and receptor activator of nuclear factor-κB-dependent osteoclastogenesis and required for efficient bone resorption. Cysteamine had no impact on osteoclastogenesis but inhibited in vitro HD osteoclastic resorption; however, NC OC-mediated bone resorption was impaired only at high doses. Only low concentrations of cysteamine (50 μM) stimulated osteoblastic differentiation and maturation, while this effect was no longer observed at higher concentrations (200 µM). Conclusion CTNS is required for proper osteoclastic activity. In vitro low doses of cysteamine have beneficial antiresorptive effects on healthy human-derived OCs and may partly correct the CTNS-induced osteoclastic dysfunction in patients with NC. Moreover, in vitro low doses of cysteamine also stimulate osteoblastic differentiation and mineralization, with an inhibitory effect at higher doses, likely explaining, at least partly, the bone toxicity observed in patients receiving high doses of cysteamine.

International audience; Pediatric R-Tx patients are at high risk of developing EBV primary infection. Although high DNA replication is a risk factor for PTLD, some patients develop PTLD with low viral load. In this retrospective single-center study including all pediatric patients having received R-Tx (2003-2012 period), we aimed to identify risk factors for uncontrolled reactions to EBV (defined as the presence of a viral load \textgreater10~000~copies/mL or PTLD). A Cox proportional hazard model was performed. A total of 117 patients underwent R-Tx at a mean age of 9.7~\textpm~5.3~years, 46 of them being seronegative for EBV at the time of R-Tx. During follow-up, 54 patients displayed positive EBV viral load, 22 of whom presenting with primary infection. An uncontrolled reaction to EBV was observed in 24 patients, whilst 4 patients developed PTLD. Univariate and multivariate analyses suggested the following risk factors for an uncontrolled reaction: age below 5~years, graft from a deceased donor, >=5 HLA mismatches, EBV-seronegative status at the time of R-Tx, and a secondary post-Tx loss of anti-EBNA. Monitoring anti-EBNA after R-Tx may contribute to the early identification of patients at risk for uncontrolled reaction.

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 and communication between different clinicians involved in pediatric urology and nephrology.

International audience; 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 evaluate the incidence and timing of CMV infection during the first year after renal transplantation. We assembled a retrospective cohort of 136 children who had received a kidney transplant between 2003 and 2014 with a year follow-up. The patients were classified regarding CMV infection as high risk (D+/R-), intermediate risk (R+) or low risk (D-/R-). CMV infection was defined by the viral replication remaining asymptomatic whereas CMV disease concerned viral replication with clinical and/or biological symptoms. Oral valganciclovir was used as prophylaxis for high-risk recipients. A total of 38 patients (27.9%) developed CMV infection, 13 (40.6%) of the 32 D+/R-, 24 (45.3%) of the 53 R+ and 1 (2.0%) of the 51 D-/R-. Of these 38 infected patients, 10 developed tissue-invasive disease. During the first year after kidney transplantation, 27.9% of recipients developed CMV infection. This study confirms the influence of donor and recipient CMV status on infection propensity and highlights the importance of adequate follow-up for intermediate risk patients.

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. Objective: Evaluating phosphate and bone mineral metabolism in children with ADPKD compared with what is known in adult ADPKD patients. Design: Observational cross-sectional study. Setting: Multicenter study via ambulatory care in tertiary centers. Participants: Ninety-two children with ADPKD (52 males; mean 6 standard deviation age, 10.2 +/- 5.0 years) and 22 healthy controls (HCs, 10 males; mean 6 standard deviation age, 10.3 +/- 4.1 years). Main Outcome Measures: The predictor was early ADPKD stage. Bone mineral metabolism and renal phosphate handling were the main outcome measures. Performed measurements were serum phosphate, tubular maximum phosphorus reabsorption per glomerular filtration rate, FGF23, soluble Klotho, sclerostin, and bone alkaline phosphatase. Results: ADPKD children had significantly lower serum phosphate levels compared with HC. Low tubular maximum phosphorus reabsorption per glomerular filtration rate was observed in 24% of patients, although not significantly different from HC. Serum FGF23 and soluble Klotho levels were comparable between patients and HC. In addition, we showed decreased bone alkaline phosphatase levels in ADPKD children, suggesting suppressed bone formation. Conclusions: This report demonstrates hypophosphatemia and suppressed bone formation in a pediatric ADPKD cohort, with preserved renal function, compared with HC. Although FGF23 levels were not different from controls, they should be considered inappropriate, given the concomitant hypophosphatemia. Further studies are required to elucidate underlying pathophysiology and potential clinical consequences.

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines.The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a 'We recommend' statement, and 2 being a 'We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care.All together, the work group issued 112 statements. There were 51 (45%) recommendations graded '1', 18 (16%) were graded '2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.html.

La mesure de la concentration serique de 25-hydroxy vitamines D (25OHD) permet d’evaluer le statut vitaminique D d’un individu. Ceci ne signifie pas qu’il faille doser ce parametre biologique chez tous les patients. Le nombre de prescriptions de dosages de 25OHD a pourtant decuple en France entre 2005 et 2013 generant un cout important de remboursement pour la Caisse nationale de l’assurance-maladie des travailleurs salaries (CNAMTS) ce qui l’a conduit, logiquement, a la saisine [...]

The management of tubulopathies after renal transplantation (RTx) may require high doses of sodium and bicarbonate, reducing the quality of life and therapeutic compliance of the patient. Some studies on adult patients have highlighted the benefits of fludrocortisone (fludro) in the treatment of severe tubulopathies. This study was a retrospective review of the medical charts of 15 children, aged 12.4 (range 3.6–17.4) years who received fludro after RTx. With the administration of fludro, both sodium bicarbonate and chloride supplementation decreased, from 10 (range 0–14) to 0 (0–5) g/day, and from 9 (0–20) to 0 (0–3) g/day, respectively (both p

Resume Introduction L’hemodiafiltration (HDF) est encore peu utilisee en pediatrie en raison des exigences techniques, de son cout et des adaptations rendues necessaires par les differences de poids et de taille des enfants. Depuis 2009, nous utilisons l’HDF online (oHDF) et avons observe des concentrations plasmatiques basses d’hormone parathyroidienne (PTH) malgre une gestion des anomalies minerales et osseuses suivant les recommandations internationales. Methodes Les dossiers de 6 enfants suivis en oHDF dans notre centre ont ete repris retrospectivement, avec une evaluation prospective de leurs principaux parametres phosphocalciques sur un mode avant/apres session. Resultats Nous avons observe des concentrations basses de PTH ( Conclusion Il semble que l’oHDF en pediatrie puisse induire des modifications phosphocalciques specifiques, que des essais cliniques en cross-over hemodialyse conventionnelle/oHDF pourraient permettre de mieux comprendre. En attendant, l’utilisation en premiere intention des bains a 1,25 mmol/L de calcium, de meme qu’un suivi regulier de la PTH semblent necessaires.

Resume Introduction Les concentrations plasmatiques de la parathormone (PTH) et de l’acide urique (AU) s’elevent des que le debit de filtration glomerulaire (DFG) commence a diminuer au cours de la maladie renale chronique (MRC). L’objectif de cette etude etait d’evaluer l’association entre le DFG et l’augmentation de ces 2 parametres chez l’enfant. Patients et methodes Etude retrospective de 100 enfants âges de 5 a 18 ans ayant realise une exploration fonctionnelle renale (EFR), et qui presentaient une augmentation de la PTH ou de l’AU. Le DFG a ete mesure par la clairance de l’inuline (C In). Resultats Le DFG etait normal (> 90 mL/min/1,73 m2) chez 39 % des enfants, l’AU etait augmente chez 44 % et la PTH chez 75 % ; 29 % des enfants ayant une PTH elevee avaient un DFG normal. Une correlation inverse a ete observee entre l’AU et le DFG (r = −0,452, p ≤ 0,0001), et entre la PTH et le DFG (r = −0,226, p = 0,024). La meme relation negative a ete observee entre l’AU et la PTH (r = −0,266, p = 0,007), ainsi qu’entre l’AU et le taux de reabsorption du phosphore (TRPhosph) (r = −0,415, p Discussion L’hyperuricemie s’observait a tous les stades de la MRC, faisant discuter une atteinte tubulaire precoce infraclinique. L’augmentation precoce de la PTH dans cette cohorte semble en contradiction avec certaines etudes nord-americaines decrivant des concentrations de PTH normales en phase precoce de la MRC. Des etudes prospectives sont necessaires pour confirmer ces donnees et evaluer le role de l’AU dans la genese des anomalies minerales et osseuses de la MRC.

Primary hyperoxaluria type 1 (PH1) is a rare inborn error of glyoxylate metabolism of autosomal recessive inheritance, leading to progressive systemic oxalate storage (named 'oxalosis') with a high rate of morbidity and mortality, as well as an unacceptable quality of life for most patients. The adverse outcome, however, is partly due to issues that can be overcome. First, the diagnosis of PH is often delayed due to a general lack of knowledge of the disease among physicians. This accounts specifically for patients with pyridoxine sensitive PH, a group that is paradoxically most easy to treat. Second, lack of adherence to a strict conduction of conservative treatment and optimal urological management may enhance an adverse outcome of the disease. Third, specific techniques to establish PH1 and specific therapies are currently often not available in several low-resources countries with a high prevalence of PH. The management of patients with advanced disease is extremely difficult and warrants a tailor-made approach in most cases. Comprehensive programs for education of local physicians, installation of national centers of expertise, European support of low-resources countries for the management of PH patients and intensified international collaboration on the management of current patients, as well as on conduction of clinical studies, may further improve outcome of PH.

The risk of disease recurrence (DR) after renal transplantation (Tx) is relatively high in children and may lead to graft loss (GL), representing 7–8 % of all graft failures. Recurrence of the full disease may be associated with either a high risk of GL (focal and segmental glomerulosclerosis, membranoproliferative glomerulonephritis, oxalosis, atypical hemolytic uremic syndrome) or with a low risk of GL (IgA nephropathy, lupus, ANCA-associated glomerulonephritis). Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus and sickle cell disease. Adequate strategies should therefore be added to kidney Tx, such as pre-Tx genotyping, adequate donor selection, specific immunosuppression and/or biotherapy, associated liver Tx, etc. Under such conditions, very few patients would be excluded from kidney Tx only because of a major risk of DR. In the future, the issue of DR after kidney Tx may benefit from alternatives to organ Tx.

International audience; 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, monitoring of kidney transplant in adults, and surgical treatment of obesity in adults. Our aim here was to note that other indications for serum 25OHD measurements are supported by previous literature and by a number of national and international recommendations, in particular the following: any situation of bone fragility, any chronic renal failure

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 study aimed to investigate the capacity of anti-C1q autoantibodies (Abs) to predict renal flare and global disease activity in cSLE patients, and association with disease activity and kidney involvement. Twenty-eight patients with cSLE including 19 patients (68%) with a history of LN were included retrospectively. Anti-C1q Abs were analysed by ELISA at renal flare-up or in the quiescent phase of disease and compared with Farr dsDNA assay. Thirty-one flares occurred during follow-up: anti-C1q Abs were positive in 26 (84%), strongly associated with active disease status (p