[Management of genetic renal disorders: local experience and importance of the network]. / Prise en charge des maladies rénales génétiques : expérience locale et importance du réseau.

In nephrology, rare disorders are frequently encountered. In children, about 60% of the renal disorders are rare, with congenital abnormalities of the kidney and urinary tract disorders (CAKUT), being highly prevalent. In adults, about 22% of the disorders leading to renal replacement therapies are rare and include glomerulonephritis and genetic disorders. Rarity may preclude the rapid and extensive access to care for patients suffering of renal disorders, especially in Switzerland, which is small and fragmented. Only collaborative network and access to databases, shared resources and to specific competence may help patient management. Lausanne and Geneva University Hospitals have started specialized outpatient clinics for rare renal disorders several years ago and are part of national and international networks.

Dans le domaine des maladies rénales, la rareté est fréquente. Chez l'enfant, 60 % des maladies touchant les reins sont rares et les malformations de l'axe urinaire sont prépondérantes. Chez l'adulte, près de 22 % des pathologies qui mènent à la maladie rénale terminale sont rares et incluent les glomérulonéphrites et les maladies génétiques. La rareté de ces pathologies fait que les compétences médicales peuvent être difficiles à trouver et l'expérience locale insuffisante. Ainsi, seule la mise en réseau des données, des ressources et des compétences peut permettre d'améliorer la prise en charge de ces patients. Le CHUV et les HUG ont mis en place des consultations spécialisées pour les maladies rénales rares. Elles s'inscrivent dans un réseau national et international.

[Rare causes of Hypophosphatemia: diagnostic approach]. / Hypophosphatémies de causes rares : approche diagnostique.

Hypophosphatemia is common and may be overlooked due to its asymptomatic nature or non-specific symptoms. Two main mechanisms are at its origin: a shift towards the intracellular sector and an increase in urinary phosphate excretion. A measurement of the urinary phosphate reabsorption threshold allows a diagnostic orientation. Alongside common forms of parathyroid hormone-dependent hypophosphatemia, one should not ignore rare FGF23-mediated forms, in particular X-linked hypophosphatemic rickets. The treatment, above all etiological, also includes the administration of phosphate and, in the event of an excess of FGF23, supplementation with calcitriol. In cases of oncogenic osteomalacia and X-linked hypophosphatemic rickets, the use of burosumab, an anti-FGF23 antibody, must be considered.

L'hypophosphatémie est fréquente. Pourtant, elle peut parfois être méconnue de par son caractère asymptomatique ou ses symptômes non spécifiques. Deux grands mécanismes sont à son origine : un shift vers le secteur intracellulaire et une augmentation de l'excrétion urinaire de phosphate. Une mesure du seuil de réabsorption urinaire de phosphate permet une orientation diagnostique. À côté de formes communes d'hypophosphatémies parathormone-dépendantes, il ne faut pas méconnaître des formes rares FGF23 médiées, en particulier le rachitisme hypophosphatémique lié à l'X. Le traitement, avant tout étiologique comporte aussi l'administration de phosphate et lors d'un excès de FGF23, une supplémentation en calcitriol. En cas d'ostéomalacie oncogénique et de rachitisme hypophosphatémique lié à l'X, l'emploi de burosumab, anticorps anti-FGF23, doit être considéré.

Early urine output monitoring in very preterm infants to predict in-hospital neonatal outcomes: a bicentric retrospective cohort study.

OBJECTIVE: To evaluate whether urine output (UO), rarely assessed in the literature, is associated with relevant neonatal outcomes in very preterm infants, and which UO threshold may be the most clinically relevant. DESIGN: Retrospective cohort study. SETTING: Two Level IV neonatal intensive care units. PATIENTS: Very preterm infants born between 240/7 and 296/7 weeks of gestation documented with eight UO measurements per day between postnatal day 1 and day 7. MAIN OUTCOME MEASURES: Composite outcome defined as death before discharge, or moderate to severe bronchopulmonary dysplasia, or severe brain lesions. The association between this outcome and UO was studied using several UO thresholds. RESULTS: Among 532 infants studied, UO <1.0 mL/kg/hour for at least 24 consecutive hours was measured in 55/532 (10%) infants and the primary outcome was recorded in 25 patients. The association between a UO threshold <1.0 mL/kg/hour and the primary outcome was found marginally significant (crude OR 1.80, 95% CI 1.02 to 3.16, p=0.04). The primary outcome was recorded in 112/242 (46%) patients with a UO <2.0 mL/kg/hour and only 64/290 (22%) patients with a UO ≥2.0 mL/kg/hour (p<0.001). This UO threshold was found significantly associated with the primary outcome (crude OR 3.1, 95% CI 2.1 to 4.7, p<0.001), an association confirmed using a multivariate logistic regression model including baseline covariates (adjusted OR 3.7, 95% CI 2.2 to 6.4, p<0.001). CONCLUSION: A UO <2 mL/kg/hour over 24 hours between postnatal day 1 and day 7 strongly predicts neonatal mortality or severe morbidities in very preterm infants.

Urine Output Monitoring for the Diagnosis of Early-Onset Acute Kidney Injury in Very Preterm Infants.

BACKGROUND AND OBJECTIVES: The current threshold used for oliguria in the definition of neonatal AKI has been empirically defined as 1 ml/kg per hour. Urine output criteria are generally poorly documented, resulting in uncertainty in the most accurate threshold to identify AKI in very preterm infants with known tubular immaturity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a bicentric study including 473 very preterm infants (240/7-296/7 weeks of gestation) born between January 2014 and December 2018 with urine output measurements every 3 hours during the first 7 days of life and two serum creatinine measurements during the first 10 days of life. AKI was defined using the neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition. We tested whether higher urine output thresholds (1.5 or 2 ml/kg per hour) in modified AKI definitions may better discriminate neonatal mortality compared with the current definition. RESULTS: Early-onset AKI was developed by 101 of 473 (21%) very preterm infants. AKI was diagnosed on the basis of urine output criteria alone (no rise in creatinine) for 27 of 101 (27%) participants. Early-onset AKI was associated with higher risk of death before discharge (adjusted odds ratio, 3.9; 95% confidence interval, 1.9 to 7.8), and the AKI neonatal KDIGO score showed good discriminative performance for neonatal mortality, with an area under the receiver operating characteristic (ROC) curve of 0.68 (95% confidence interval, 0.61 to 0.75). Modified AKI definitions that included higher urine output thresholds showed significantly improved discriminative performance, with areas under the ROC curve of 0.73 (95% confidence interval, 0.66 to 0.80) for the 1.5-ml/kg per hour threshold and 0.75 (95% confidence interval, 0.68 to 0.81) for the 2-ml/kg per hour threshold. CONCLUSIONS: Early-onset AKI was diagnosed on the basis of urine output exclusively for a quarter of the cases. Furthermore, modified AKI definitions that included higher urine output improved the discriminative performance for predicting mortality.

Antibody-mediated rejection after kidney transplantation in children; therapy challenges and future potential treatments.

Antibody-mediated rejection (AMR) remains one of the most critical problems in renal transplantation, with a significant impact on patient and graft survival. In the United States, no treatment has received FDA approval jet. Studies about treatments of AMR remain controversial, limited by the absence of a gold standard and the difficulty in creating large, multi-center studies. These limitations emerge even more in pediatric transplantation because of the limited number of pediatric studies and the occasional use of some therapies with unknown and poorly documented side effects. The lack of recommendations and the unsharp definition of different forms of AMR contribute to the challenging management of the therapy by pediatric nephrologists. In an attempt to help clinicians involved in the care of renal transplanted children affected by an AMR, we rely on the latest recommendations of the Transplantation Society (TTS) for the classification and treatment of AMR to describe treatments available today and potential new treatments with a particular focus on the pediatric population.

Neutrophil gelatinase-associated lipocalin distribution in preterm newborns without acute kidney injury as defined by a reference method.

INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) has been proposed as an early acute kidney injury (AKI) biomarker in the neonatal population. Our goal is to describe this biomarker behavior in this high-risk population, in absence of AKI as confirmed by inulin clearance. MATERIALS AND METHODS: Prospective study including 42 preterm newborns (mean gestational age: 30.7 ± 2.3 weeks) with a urinary NGAL collection between day 1 and 6 of life. RESULTS: Median urinary neutrophil gelatinase-associated lipocalin (uNGAL) value is 122.8 ng/ml (7-1981.5 ng/ml). Statistically significant higher uNGAL values are found in female. uNGAL median values are decreasing when comparing extremely, very, and late preterm groups (812.2 ng/ml [75.8-1453.9] vs. 124.4 ng/ml [31.4-1981.5] vs. 65.3 ng/ml [7.1-1091]). There is a statistically significant inverse correlation between gestational age and uNGAL values (Pearson's coefficient r= -0.37). uNGAL median values are higher in groups exposed to gentamicin, neonatal asphyxia, early onset sepsis, or patent ductus arteriosus. Median inulin clearance is 18.8 ml/min/1.73 m2 [14.8-25.5 ml/min/1.73 m2]. There is no correlation between uNGAL values and inulin clearance results (Pearson's coefficient r=-0. 29, p: .06). CONCLUSIONS: In this preterm newborn's series without AKI, the median uNGAL and its high variability are in accordance with published reference ranges. Correlation between uNGAL and gestational age exists, as well as gender impact. Newborns exposed to different renal insults present higher uNGAL values, suggesting potential undetected tubular toxicity or reflecting NGAL production in case of inflammatory or ischemic processes.

Serum NGAL, BNP, PTH, and albumin do not improve glomerular filtration rate estimating formulas in children.

Glomerular filtration rate (GFR) is difficult to measure, and estimating formulas are notorious for lacking precision. This study aims to assess if the inclusion of additional biomarkers improves the performance of eGFR formulas. A hundred and sixteen children with renal diseases were enrolled. Data for age, weight, height, inulin clearance (iGFR), serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) were collected. These variables were added to the revised and combined (serum creatinine and cystatin C) Schwartz formulas, and the quadratic and combined quadratic formulas. We calculated the adjusted r-square (r2) in relation to iGFR and tested the improvement in variance explained by means of the likelihood ratio test. The combined Schwartz and the combined quadratic formulas yielded best results with an r2 of 0.676 and 0.730, respectively. The addition of BNP and PTH to the combined Schwartz and quadratic formulas improved the variance slightly. NGAL and albumin failed to improve the prediction of GFR further. These study results also confirm that the addition of cystatin C improves the performance of estimating GFR formulas, in particular the Schwartz formula.Conclusion: The addition of serum NGAL, BNP, PTH, and albumin to the combined Schwartz and quadratic formulas for estimating GFR did not improve GFR prediction in our population. What is Known: • Estimating glomerular filtration rate (GFR) formulas include serum creatinine and/or cystatin C but lack precision when compared to measured GFR. • The serum concentrations of some biological parameters such as neutrophil gelatinase-associated lipocalin (NGAL), parathyroid hormone (PTH), albumin, and brain natriuretic peptide (BNP) vary with the level of renal function. What is New: • The addition of BNP and PTH to the combined quadratic formula improved its performance only slightly. NGAL and albumin failed to improve the prediction of GFR further.

SARS-CoV-2 / COVID-19 in patients on the Swiss national transplant waiting list.

AIMS OF THE STUDY: The impact of coronavirus disease 2019 (COVID-19) on patients listed for solid organ transplantation has not been systematically investigated to date. Thus, we assessed occurrence and effects of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients on the Swiss national waiting list for solid organ transplantation. METHODS: Patient data were retrospectively extracted from the Swiss Organ Allocation System (SOAS). From 16 March to 31 May 2020, we included all patients listed for solid organ transplantation on the Swiss national waiting list who were tested positive for SARS-CoV-2. Severity of COVID-19 was categorised as follows: stage I, mild symptoms; stage II, moderate to severe symptoms; stage III, critical symptoms; stage IV, death. We compared the incidence rate (laboratory-confirmed cases of SARS-CoV-2), the hospital admission rate (number of admissions of SARS-CoV-2-positive individuals), and the case fatality rate (number of deaths of SARS-CoV-2-positive individuals) in our study population with the general Swiss population during the study period, calculating age-adjusted standardised incidence ratios and standardised mortality ratios, with 95% confidence intervals (CIs). RESULTS: A total of 1439 patients were registered on the Swiss national solid organ transplantation waiting list on 31 May 31 2020. Twenty-four (1.7%) waiting list patients were reported to test positive for SARS-CoV-2 in the study period. The median age was 56 years (interquartile range 45.3–65.8), and 14 (58%) were male. Of all patients tested positive for SARS-CoV-2, two patients were asymptomatic, 14 (58%) presented in COVID-19 stage I, 3 (13%) in stage II, and 5 (21%) in stage III. Eight patients (33%) were admitted to hospital, four (17%) required intensive care, and three (13%) mechanical ventilation. Twenty-two patients (92%) of all those infected recovered, but two male patients aged >65 years with multiple comorbidities died in hospital from respiratory failure. Comparing our study population with the general Swiss population, the age-adjusted standardised incidence ratio was 4.1 (95% CI 2.7–6.0). CONCLUSION: The overall rate of SARS-CoV-2 infections in candidates awaiting solid organ transplantation was four times higher than in the Swiss general population; however, the frequency of testing likely played a role. Given the small sample size of affected patients, conclusions have to be drawn cautiously and results need verification in larger cohorts.

Results in the ESPN/ERA-EDTA Registry suggest disparities in access to kidney transplantation but little variation in graft survival of children across Europe.

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 67% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low-, medium-, and high-risk) graft recipients from high-income countries.

The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design.

BACKGROUND: Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. METHODS: Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1-ß = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. RESULTS: In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. CONCLUSIONS: Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.

Renal follow-up in pediatrician practice after discharge from neonatology units: about a survey.

There is growing evidences of long-term renal and cardiovascular consequences of prematurity, intra-uterine growth restriction, and neonatal acute kidney injury (AKI). We performed an online survey to describe current pediatric management in this population, sent to 148 ambulatory pediatricians in Geneva. Among the 40% of pediatricians who completed the survey, 43% modify their blood pressure measurement practice in case of neonatal acute kidney injury, 24% and 19% in a context of prematurity or intra-uterine growth restriction, respectively. Twenty-five percent provide information about cardiovascular risk factors or catch up growth. In case of prematurity or intra-uterine growth restriction, renal tests (ultrasound, serum creatinine, micro albuminuria) or referral to nephrologist were realized by less than 5% of the pediatricians. For neonatal acute kidney injury, renal tests, and referral to specialists are performed by 30 and 60% of pediatricians, respectively. When prematurity or intra-uterine growth restriction was associated with abnormal blood pressure or abnormal renal tests, the referral to the specialist reached 80%.Conclusion: Ambulatory renal and cardio-vascular follow-up in case of neonatal medical history can be enhanced, with necessity to raise awareness and to edict guidelines available to pediatricians. What is Known: • There is a compelling evidence of long-term renal and cardiovascular consequences of prematurity and low birth weight. • Specific cardiovascular and renal follow-up guidelines, coming from professional organizations, are currently not available for these patients. What is New: • Pediatricians in ambulatory setting do not adapt their renal and cardiovascular follow-up in case of neonatal medical history. • There is a necessity to raise awareness about these long-term consequences among pediatricians and to edict guidelines available to them.

Spot urine samples to estimate 24-hour urinary calcium excretion in school-age children.

Urinary calcium/creatinine ratio (UCa/Cr) on a single spot urine sample is frequently used in children to evaluate calciuria, but its accuracy to estimate 24-h urinary calcium excretion (24hUCa) has not been properly assessed. We analyzed the correlation between UCa/Cr in various spot samples and 24hUCa among healthy children. A 24-h urine specimen and three spot urine samples (evening, first, and second morning) were collected in a convenience sample of children aged 6 to 16 years (n = 101). Measured 24hUCa was compared with UCa/Cr in each of the three spot samples. The ability of UCa/Cr to discriminate between children with and without hypercalciuria (calciuria > 4 mg/kg/24 h, 1 mmol/kg/24 h) and optimal timing of the spot sample were determined. Eighty-five children completed an adequate 24-h urine collection. Pearson correlation coefficients between the UCa/Cr on the spot sample and 24hUCa were 0.64, 0.71, and 0.52 for the evening, first, and second morning spot samples, respectively. Areas under the ROC curve were 0.90, 0.82, and 0.75, respectively, for the corresponding spot samples.Conclusion: The relatively strong correlation between 24hUCa and UCa/Cr in evening and first morning spot urine samples suggests that these spots could be preferred in clinical practice.Trial registration: ClinicalTrials.gov , NCT02900261, date of trial registration 14 September 2016. What is Known: •Urinary calcium/creatinine ratio on a single spot urine sample is frequently used as a proxy for 24-h urinary calcium excretion. •Correlation of these indicators, including the best timing for spot urine sampling, has not been properly assessed. What is New: •Relatively strong correlations were found between the calcium/creatinine ratio on a single spot urine sample and 24-h urinary calcium excretion in healthy children. •Evening and first morning spot samples had the highest correlation.

Variables of interest to predict glomerular filtration rate in preterm newborns in the first days of life.

BACKGROUND: Measurement of neonatal renal function is challenging, and accurate, easy-to-use markers to estimate glomerular filtration rate (eGFR) are lacking. This study aimed to evaluate principal determinants of GFR in neonates and develop a predictive equation. METHODS: GFR was measured, using single injection inulin clearance, at median day 3 of life in 48 newborns. Associations of clearance with height, gestational age, weight, creatinine, and cystatin C were explored and a multivariable model to estimate GFR developed. We also evaluated preexisting GFR equations (Schwartz, Zappitelli, combined Zappitelli). RESULTS: Forty-four clearances were measured, 36 very preterm neonates (28-32 weeks); 5 extremely preterm (< 28 weeks), and 3 term newborns. No patient presented acute renal insufficiency. Median inulin clearance in preterm infants was 18.83 ml/min/1.73 m2 (IQ 15.29; 24.99). Inulin clearance correlated with weight (ρ 0.74), gestational age (ρ 0.72), height (ρ 0.49), and creatinine (ρ - 0.42), but not cystatin C. In the multivariable model, predicted GFR equation was 2.32* (weight (g))0.64/(creatinine (mcmol/l))0.62. Mean error in predicting clearance was - 0.8 ml/min/1.73 m2 (- 3.0-1.4) ranging from - 14.9 to 13.3 ml/min/1.73 m2. Mean prediction error with Zappitelli and combined Zappitelli equations were 28.5 ml/min/1.73 m2 (95% CI 24.6-32.3) and 28.3 ml/min/1.73 m2 (95% CI 24.9-31.7), respectively, and 2 ml/min/1.73 m2 (95% CI - 0.6-4.6) for Schwartz equation. CONCLUSIONS: Weight and gestational age are crucial determinants of GFR in neonates. The Zappitelli models were not validated in our population. Our predictive model and Schwartz models performed better. Our model should be evaluated in another preterm population, particularly in those presenting renal insufficiency.

Immunosuppressant therapeutic drug monitoring and trough level stabilisation after paediatric liver or kidney transplantation.

BACKGROUND: Immunosuppressive therapy must be guided by therapeutic drug monitoring (TDM) in paediatric liver (LT) and kidney transplantation (KT) patients to prevent under- and overdosing, which have clinical consequences. AIM: The purpose of our study was to analyse TDM results in our institutions and evaluate factors associated with blood level stabilisation after LT and KT. METHODS: Blood levels of immunosuppressants were measured by immunoassay analysis. We compared blood level stabilisation between LT and KT, and evaluated associated factors in a retrospective study in two Swiss university hospitals. RESULTS: Forty-six patients (27 LT [median age 1.0 y], 19 KT [15.1 y]) were included. During the first month after transplantation, 32.8% (LT) and 41.2% (KT) of tacrolimus, and 22.1% (KT) of ciclosporin trough levels (measured before the next dose) were within target. In KT, trough levels stabilised earlier for tacrolimus than for ciclosporin (p = 0.02). Intensive care and hospital discharge occurred earlier in KT patients (p <0.001). Living-donor LT was associated with an earlier intensive care discharge compared with deceased donor (5.5 vs 11 days, p = 0.02). Primary metabolic disease and graft/recipient weight-ratio ≥0.03 was associated with earlier tacrolimus level stabilisation (14 vs 18 days, p = 0.01 and 15 vs 22 days, p = 0.05, respectively). In KT, recipient age (≥15.1 years) and weight (≥39.4 kg) were associated with an earlier trough level stabilisation (both 13 days vs not reached, p <0.001), and age with earlier hospital discharge (10 vs 14 days, p = 0.02). CONCLUSION: Immunosuppressant trough levels were often outside the target range in the first month after LT and KT. Organ-specific factors were associated with trough stabilisation.

Management of delivery of a fetus with autosomal recessive polycystic kidney disease: a case report of abdominal dystocia and review of the literature.

BACKGROUND: Autosomal recessive renal polycystic kidney disease occurs in 1 in 20,000 live births. It is caused by mutations in both alleles of the PKHD1 gene. Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease is rarely discussed, and literature concerning abdominal dystocia is extremely scarce. We present a case of a patient with autosomal recessive renal polycystic kidney disease whose delivery was complicated by abdominal dystocia, and we discuss the factors that determined the route and timing of delivery. CASE PRESENTATION: A 23-year-old Caucasian woman, G2 P0, with a prior unremarkable pregnancy was referred to our tertiary center at 31 weeks of gestation because of severe oligoamnios (amniotic fluid index = 2) and hyperechogenic, dedifferentiated, and enlarged fetal kidneys. She had no other genitourinary anomaly. Fetal magnetic resonance imaging showed enlarged, hypersignal kidneys and severe pulmonary hypoplasia. We had a high suspicion of autosomal recessive renal polycystic kidney disease, and after discussion with our multidisciplinary team, the parents opted for conservative care. Ultrasound performed at 35 weeks of gestation showed a fetal estimated weight of 3550 g and an abdominal circumference of 377 mm, both above the 90th percentile. Because of the very rapid kidney growth and suspected risk of abdominal dystocia, we proposed induction of labor at 36 weeks of gestation after corticosteroid administration for fetal lung maturation. Vaginal delivery was complicated by abdominal dystocia, which resolved by continuing expulsive efforts and gentle fetal traction. A 3300-g (P50-90) male infant was born with Apgar scores of 1-7-7 at 1, 5, and 10 minutes, respectively, and arterial and venous umbilical cord pH values of 7.23-7.33. Continuous peritoneal dialysis was started at day 2 of life because of anuria. Currently, the infant is 1 year old and is waiting for kidney transplant that should be performed once he reaches 10 kg. Molecular analysis of PKHD1 performed on deoxyribonucleic acid (DNA) from the umbilical cord confirmed autosomal recessive renal polycystic kidney disease. CONCLUSIONS: Management of delivery in cases of suspected autosomal recessive renal polycystic kidney disease needs to be discussed because of the risk of abdominal dystocia. The route and timing of delivery depend on the size of the fetal abdominal circumference and the gestational age. The rate of kidney growth must also be taken into account.

Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL).

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is increasingly diagnosed during childhood by the presence of renal cysts in patients with a positive familial history. No curative treatment is available and early detection and diagnosis confronts pediatricians with the lack of early markers to decide whether to introduce renal-protective agents and prevent the progression of renal failure. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a tubular protein that has been recently proposed as an early biomarker of renal impairment in the ADPKD adult population. Methods: Urinary NGAL (uNGAL) levels were measured in 15 ADPKD children and compared with 15 age and gender matched controls using parametric, non-parametric, and Bayesian statistics. We also tested the association of uNGAL levels with markers of disease progression, such as proteinuria, albuminuria, blood pressure, and Total Kidney Volume (TKV) using correlation analysis. TKV was calculated by ultrasound, using the ellipsoid method. Results: No difference in mean uNGAL levels was observed between groups (ADPKD: 26.36 ng/ml; Controls: 27.24 ng/ml; P = 0.96). Moreover, no correlation was found between uNGAL and proteinuria (P = 0.51), albuminuria (P = 0.69), TKV (P = 0.68), or mean arterial pressure (P = 0.90). By contrast, TKV was positively correlated with proteinuria (P = 0.04), albuminuria (P = 0.001), and mean arterial pressure (P = 0.03). Conclusion: uNGAL did not confirm its superiority as a marker of disease progression in a pediatric ADPKD population. In the contrary, TKV appears to be an easy measurable variable and may be promising as a surrogate marker to follow ADPKD progression in children.

[Vitamin D deficiency and rickets : screening and treatment, practical aspects for clinicians]. / Carence en vitamine D et rachitisme : dépistage et traitement, aspects pratiques pour le clinicien.

Vitamin D deficiency is increasing in Switzerland. If cases of rickets are scarce, pediatricians are often dealing with patients presenting vitamin D deficiency. The increase in vitamin D deficiency is certainly due to modification of life habits in recent decades. Clinical presentation varies according to age and severity of deficit. Treatments differ based on the level of vitamin D deficiency and symptoms. Vitamin D deficiency rickets is the most common cause of rickets and is predominantly seen in patients with risks factors They are other types of rickets like pseudo-vitamin D deficiency and hypophosphatemic rickets that the clinician needs to recognize. In which situation should the clinician suspect vitamin D deficiency or rickets ? Different types of rickets and practical aspects of treatment are reviewed in this article.

Le déficit en vitamine D est en augmentation en Suisse. Si les cas de rachitisme restent peu fréquents, les pédiatres sont souvent confrontés à un déficit en vitamine D. Cette augmentation est en lien avec les changements des habitudes de vie sur les dernières décennies. Le déficit en vitamine D se présente sous plusieurs formes et le traitement varie en fonction du degré du déficit et des symptômes. Le rachitisme carentiel est la forme la plus fréquente de rachitisme et concerne principalement les populations avec des facteurs de risque. Le diagnostic différentiel comprend le rachitisme pseudo-carentiel et le rachitisme hypophosphatémique. Quand et chez qui le praticien doit-il suspecter un déficit en vitamine D ou un rachitisme ? Le diagnostic différentiel et les aspects pratiques du traitement sont présentés dans cet article.

Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.

BACKGROUND: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. METHODS: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort. RESULTS: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing. CONCLUSIONS: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance.

Balancing competing needs in kidney transplantation: does an allocation system prioritizing children affect the renal transplant function?

Children often merit priority in access to deceased donor kidneys by organ-sharing organizations. We report the impact of the new Swiss Organ Allocation System (SOAS) introduced in 2007, offering all kidney allografts from deceased donors <60 years preferentially to children. The retrospective cohort study included all paediatric transplant patients (<20 years of age) before (n = 19) and after (n = 32) the new SOAS (from 2001 to 2014). Estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio (UPC), need for antihypertensive medication, waiting times to kidney transplantation (KTX), number of pre-emptive transplantations and rejections, and the proportion of living donor transplants were considered as outcome parameters. Patients after the new SOAS had significantly better eGFRs 2 years after KTX (Mean Difference, MD = 25.7 ml/min/1.73 m2 , P = 0.025), lower UPC ratios (Median Difference, MeD = -14.5 g/mol, P = 0.004), decreased waiting times to KTX (MeD = -97 days, P = 0.021) and a higher proportion of pre-emptive transplantations (Odds Ratio = 9.4, 95% CI = 1.1-80.3, P = 0.018), while the need for antihypertensive medication, number of rejections and living donor transplantations remained stable. The new SOAS is associated with improved short-term clinical outcomes and more rapid access to KTX. Despite lacking long-term research, the study results should encourage other policy makers to adopt the SOAS approach.