[Solitary kidney: a risk factor for hypertension]. / Rein unique : un facteur de risque pour une hypertension artérielle ?

In patients with solitary kidney, either congenital or acquired, compensatory mechanisms come into play to maintain renal function, such as glomerular hyperfiltration and hypertrophy and renin-angiotensin-aldosterone system activation. In the long term, these mechanisms lead to arterial hypertension and then chronic kidney disease. The risk of arterial hypertension is greater in cases of congenital single kidney or of nephrectomy in childhood than in adulthood. Having a single kidney increases the risk of gestational hypertension and pre-eclampsia. Antihypertensive treatment is based on Angiotensin-converting enzyme inhibitors and sartans for their anti-proteinuric effect but otherwise does not differ from that of the general population.

Chez les patients avec un rein unique, qu'il soit d'origine congénitale ou acquise, des mécanismes compensatoires se mettent en place pour le maintien de la fonction rénale, comme une hyperfiltration et hypertrophie glomérulaires et une activation du système rénine-angiotensine-aldostérone. À terme, ces mécanismes mènent à une hypertension artérielle (HTA), puis à une insuffisance rénale chronique (IRC). Le risque d'HTA est plus important en cas de rein unique congénital ou de néphrectomie dans l'enfance qu'à l'âge adulte. Avoir un rein unique augmente les risques d'HTA gestationnelle et de prééclampsie. Le traitement antihypertenseur se base sur les inhibiteurs de l'enzyme de conversion (IEC) et les sartans pour leur effet antiprotéinurique, mais ne diffère pas sinon de celui de la population générale.

Hypovitaminosis D in migrant children in Switzerland: a retrospective study.

Cholecalciferol (vitamin D3) is essentially known for its role in the phosphocalcic metabolism and its associated pathologies, such as rickets. In Switzerland, 35 to 50% of children are vitamin D deficient. Due to skin colour, poor nutrition, living conditions and cultural practices, migrant population is particularly at risk. Our aim is to attest the prevalence of hypovitaminosis D in children arriving in Switzerland. We retrospectively assessed 528 children's vitamin D status and parathyroid hormone, phosphate and calcium levels between 2015 and 2018 by electrochemiluminescence and spectrophotometry. Cholecalciferol was considered insufficient under 50 nmol/L and severely deficient below 25 nmol/L. Seventy-three percent of children showed hypovitaminosis D and 28% had a severe deficiency. Highest prevalence of deficiency was found in children from Eastern Mediterranean (80%) and African regions (75%). Severe deficiency was more prevalent in the South East Asian (39%) and Eastern Mediterranean regions (33%) and more frequent in females. Deficiency was more frequent and more severe in winter. Hypovitaminosis D increased with age. Two children presented with all three biological manifestations associated to severe hypovitaminosis D (hyperparathyroidism, hypocalcaemia and hypophosphatemia).Conclusion: A majority of migrant children presented with hypovitaminosis D. They should be supplemented to prevent complications. A strategy could be to supplement all children at arrival and during wintertime without regular vitamin D level checks. What is Known: Hypovitaminosis D is frequent in children and can lead to bone-related complications. Migrant children are particularly at risk of deficiency. What is New: Three-quarters of migrant children evaluated at our migrant clinic in Geneva's children hospital are deficient in vitamin D, one third severely. A strategy to correct the deficiency would be to supplement all migrant children at arrival and in winter.

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.

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.

[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.

Proteinuria Increases Plasma Phosphate by Altering Its Tubular Handling.

Proteinuria and hyperphosphatemia are cardiovascular risk factors independent of GFR. We hypothesized that proteinuria induces relative phosphate retention via increased proximal tubule phosphate reabsorption. To test the clinical relevance of this hypothesis, we studied phosphate handling in nephrotic children and patients with CKD. Plasma fibroblast growth factor 23 (FGF-23) concentration, plasma phosphate concentration, and tubular reabsorption of phosphate increased during the proteinuric phase compared with the remission phase in nephrotic children. Cross-sectional analysis of a cohort of 1738 patients with CKD showed that albuminuria≥300 mg/24 hours is predictive of higher phosphate levels, independent of GFR and other confounding factors. Albuminuric patients also displayed higher plasma FGF-23 and parathyroid hormone levels. To understand the molecular mechanisms underlying these observations, we induced glomerular proteinuria in two animal models. Rats with puromycin-aminonucleoside-induced nephrotic proteinuria displayed higher renal protein expression of the sodium-phosphate co-transporter NaPi-IIa, lower renal Klotho protein expression, and decreased phosphorylation of FGF receptor substrate 2α, a major FGF-23 receptor substrate. These findings were confirmed in transgenic mice that develop nephrotic-range proteinuria resulting from podocyte depletion. In vitro, albumin did not directly alter phosphate uptake in cultured proximal tubule OK cells. In conclusion, we show that proteinuria increases plasma phosphate concentration independent of GFR. This effect relies on increased proximal tubule NaPi-IIa expression secondary to decreased FGF-23 biologic activity. Proteinuria induces elevation of both plasma phosphate and FGF-23 concentrations, potentially contributing to cardiovascular disease.

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.

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.

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.

[Henoch-Schönlein Purpura a dual follow up between pediatrician and pediatric nephrologist]. / Purpura de Henoch-Schönlein: une prise en charge entre pédiatre et néphrologue pédiatre.

Henoch-Schönlein purpura is a well known paediatric disease characterized by the classic triad: purpura, arthritis and abdominal pain. Short term prognosis is excellent and is mostly dependant on abdominal complications. Long term morbidity depends essentially on the severity of renal involvement which occurs in 35% of cases. Microhematuria and light proteinuria are the only signs in 80% of cases. The remaining 20% presents with nephrotic or nephritic syndrome and acute renal insufficiency. Among patients with Henoch-Schönlein nephritis the risk of developing renal insufficiency varies between 11-30% of cases. Currently, the follow up guidelines are multiple and the optimal treatment of nephritis is controversial; this is what this article proposes to discuss.

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.

On the relationship between proteinuria and plasma phosphate.

Albuminuria is strongly associated with renal and cardiovascular outcomes independently of renal function level. However, the pathophysiology of these associations is debated. In chronic kidney disease (CKD), phosphate retention participates in cardiovascular events and increased cardiovascular mortality. We hypothesised that albuminuria may modulate tubular phosphate handling by the kidney. To verify this hypothesis, we first studied the association between phosphataemia and albuminuria in children with nephrotic syndrome and in adults with CKD. In both cases, higher albuminuria was associated with higher phosphate level, independently of glomerular filtration rate. We further tried to decipher the molecular mechanisms of these observations. Using animal models of nephrotic proteinuria, we could show that albuminuric rats and mice had abnormally elevated sodium-phosphate apical co-transporter expression, despite elevated fibroblast growth factor 23 (FGF23). The FGF23 downstream pathway was inhibited despite elevated FGF23 levels. Klotho protein expression was also lower in proteinuric animals compared to controls. Finally, albumin had no direct effects on phosphate transport in cells. Altogether, we show that albuminuria induces alteration of phosphate tubular handling, independently of glomerular filtration rate. The mechanisms involved appear to include Klotho down-regulation and resistance to FGF23. This observation may link albuminuria to increased cardiovascular disease via altered phosphate handling. Finally, this observation opens up further opportunities to better understand the link between albuminuria, Klotho, FGF23 and phosphate handling.

Optimizing seroprotection against pneumococcus in children with nephrotic syndrome using the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Infections are among the main life-threatening complications in patients with nephrotic syndrome (NS), in particular with Streptococcus pneumoniae, the first cause of bacterial peritonitis and sepsis in these patients. This study aims to evaluate the baseline seroprotection of NS patients against S. pneumoniae, and immunize them with the 13-valent pneumococcal conjugate vaccine (PCV13) regardless of disease activity and previous immunization history, in order to evaluate the immunogenicity, safety profile, and effect of NS treatment on vaccine responses. METHODS: This multicentre prospective interventional study enrolled 42 children with NS at disease onset or during a regular follow-up appointment. PCV13 was administered at inclusion. Serotype-specific S. pneumoniae IgG titer were assessed at baseline, after immunization, and at 1year follow-up. Vaccine safety was evaluated clinically and by urinary tests. RESULTS: PCV13 induced high serotype-specific IgG titers that were maintained at high levels one year after vaccination, even in children previously immunized. No serious adverse event occurred and relapse frequency was unchanged. CONCLUSION: Given that high IgG titers were achieved and maintained after PCV13 vaccination, and considering the high morbidity related to S. pneumoniae, we propose PCV13 (re-)vaccination for all NS patients, irrespective of their previous immunization history, treatment and disease activity.

Successful use of bisphosphonate and calcimimetic in neonatal severe primary hyperparathyroidism.

Neonatal primary hyperparathyroidism (NPHT) is associated with an inactivating homozygous mutation of the calcium sensing receptor (CaSR). The CaSR is expressed most abundantly in the parathyroid glands and the kidney and regulates calcium homeostasis through its ability to modulate parathormone secretion and renal calcium reabsorption. NPHT leads to life threatening hypercalcemia, nephrocalcinosis, bone demineralization, and neurologic disabilities. Surgery is the treatment of choice. While waiting for surgery, bisphosphonates offer a good alternative to deal with hypercalcemia. Cinacalcet is a class II calcimimetic that increases CaSR affinity for calcium, leading to parathormone suppression and increased calcium renal excretion. At present, there is little evidence as to whether cinacalcet could improve the function of mutant CaSR in NPHT. We report a case of NPHT, treated successfully with bisphosphonates and cinacalcet after surgery failure. To our knowledge, it is the first time cinacalcet has been used for NPHT.

Encephalitis associated with glutamic acid decarboxylase autoantibodies in a child: a treatable condition?

OBJECTIVE: To increase the recognition of glutamic acid decarboxylase autoantibodies-related encephalitis in childhood. DESIGN: Case report and review of the literature. PATIENT: A 6-year-old girl who had developed refractory seizures, developmental regression, and type 1 diabetes mellitus at age 25 months. INTERVENTIONS: Blood analysis, electroencephalogram, cerebral magnetic resonance imaging, positron emission tomography scan, lumbar puncture, and measurement of glutamic acid decarboxylase activity were performed. Treatment with repeated plasmapheresis and rituximab, with concomitant antiepileptic drugs, was administered. RESULTS: Highly elevated titers of glutamic acid decarboxylase autoantibodies were found in the serum, as well as in the cerebrospinal fluid. Major clinical improvement in parallel with a decrease in the levels of serum and cerebrospinal fluid antibodies was observed with treatment. CONCLUSIONS: Encephalitis associated with glutamic acid decarboxylase autoantibodies is a severe epileptic disorder that occurs in young children as well as adults. It may be partially reversible with aggressive immunomodulatory treatment, including plasmapheresis and rituximab. Studies are warranted to determine whether early treatment leads to complete remission.