Long-term outcomes of peritoneal dialysis started in infants below 6 months of age: An experience from two tertiary centres.

peer reviewedBACKGROUND: 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

Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018–004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here. METHODS: Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7–20.5) months). RESULTS: Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)). CONCLUSIONS: Lumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1. GRAPHICAL ABSTRACT: A higher resolution version of the Graphical abstract is available as Supplementary information

Comparative pharmacokinetics of tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus to prolonged-release tacrolimus formulation.

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Front Pediatr

INTRODUCTION: Primary infection or reactivation of Epstein-Barr Virus (EBV) is a significant cause of morbidity and mortality in pediatric kidney transplantation. Valganciclovir (VGC) treatment is recommended for prophylaxis of cytomegalovirus infection, but its role for the prevention of EBV infection remains controversial. PATIENTS AND METHODS: All pediatric kidney transplant recipients aged 4.5 log/ml. Outcomes were compared between patients receiving VGC prophylaxis (group P+) and those not receiving VGC prophylaxis (group P-). RESULTS: A total of 79 patients were included, 57 (72%) in the P+ group and 22 (28%) in the P- group; 25 (31%) were at risk of primary infection and 54 (69%) at risk of reactivation. During the first year post-transplant, the occurrence of severe EBV infection was not different between the P+ group (n = 13, 22.8%) and the P- group (n = 5, 22.7%) (p = 0.99). Among patients at risk of primary infection, the rate of severe EBV infection was not different between the two groups (42.1% in P+ vs. 33.3% in P-). A higher frequency of neutropenia was found in the P+ group (66.6%) than in the P- group (33.4%) (p < 0.01). CONCLUSION: Our observational study suggests no effect of VGC for the prevention of EBV infection in pediatric kidney transplant recipients, irrespective of their EBV status. Adverse effects revealed an increased risk of neutropenia

Caractéristiques cliniques des syndromes hémolytiques et urémiques de l'enfant en fonction des mutations génétiques du système du complément

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The effect of lumasiran therapy for primary hyperoxaluria type 1 in small infants

BACKGROUND: Lumasiran, a sub-cutaneous RNA-interference therapy, has been recently approved for primary hyperoxaluria type 1 (PH1), with doses and intervals according to body weight. Little is known as to its use in infants; the aim of this study was to describe treatment outcome in 3 infants who received lumasiran therapy before 2 years of age. CASE-DIAGNOSIS/TREATMENT: Patient 1 was diagnosed antenatally and received lumasiran from day 9. According to the product information template (PIT), he received monthly lumasiran (3 times at 6 mg/kg, then 3 mg/kg), with hyperhydration and potassium citrate. Despite decreased plasma oxalate levels, persistent normal kidney function, and good tolerance, kidney ultrasound performed after 2 months found nephrocalcinosis, without normalization of urinary oxalate (UOx). The dose was increased back to 6 mg/kg, inducing a normalization in UOx. Nephrocalcinosis started to improve at month 10. Patient 2 was diagnosed at 2.5 months (acute kidney failure); nephrocalcinosis was present from diagnosis. She received monthly lumasiran (6 mg/kg), with progressive decrease in UOx and substantial improvement in kidney function but stable nephrocalcinosis after 9 injections. Patient 3 was diagnosed fortuitously (nephrocalcinosis) at 3.5 months and received lumasiran before genetic diagnosis, leading to decreased UOx and maintenance of normal kidney function. Nephrocalcinosis improved after 5 injections. CONCLUSIONS: This report presents the youngest children treated with lumasiran worldwide. Lumasiran seems effective without side effects in infants but does not completely prevent the onset of nephrocalcinosis in the most severe forms. Higher doses than those proposed in the PIT might be required because of hepatic immaturity

Rituximab efficiency in children with steroid-dependent nephrotic syndrome

International audienceAlthough most patients with idiopathic nephrotic syndrome (NS) respond to steroid treatment, development of steroid dependency may require a long-term multidrug therapy including steroid and calcineurin inhibitor. Rituximab was shown to allow a reduction of the doses of steroid and immunosuppressive drugs in those patients. In the present series, 22 patients with steroid-sensitive, but steroid-dependent nephrotic syndrome were treated with rituximab. Rituximab reduced B cell count down to an undetectable level in all patients. A second treatment was necessary in 18 patients in order to maintain B cell depletion for up to 18 months. B cell depletion lasted 4.9 to 26 months (mean 17.2 months). At last follow-up, 9 patients were in remission without oral steroid or calcineurin inhibitor, although B cell count had recovered for 2.9 to 17 months (mean 9.5 months). A remission under ongoing B cell depletion was observed in 10 other patients in the absence of oral steroid or calcineurin inhibitor. Rituximab failed in 2 patients and 1 refused any additional treatment, despite B cell recovery and relapse. Toxicity of rituximab was limited to reversible cytokine shock in 2 patients and reversible neutropenia in 1 patient. No severe infection was observed

Skin microvascular dysfunction as an early cardiovascular marker in primary hyperoxaluria type I

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Combined use of creatinine and cystatin C improves the detection of renal dysfunction in children undergoing home parenteral nutrition

International audienceBackground Renal dysfunction can complicate home parenteral nutrition (HPN). The aims were, in the context of pediatric HPN, to assess renal function using the measured glomerular filtration rate (mGFR), determine the most accurate formula(s) to estimate GFR, and identify possible underlying mechanisms of renal impairment.Methods A retrospective study was performed in 2 centers. Patients receiving HPN and aged 2-16 years without medical history of nephropathy were included. GFR was measured using iohexol clearance. Estimated GFR (eGFR) was calculated using creatinine, cystatin C-based, and combined (eGFR(cr+cyst)) Schwartz formulas.Results A total of 36 patients (18 females) were included; they received HPN for 8 (2-16) years. The primary digestive disease was short-bowel syndrome for 16 (44%) patients, gastrointestinal motility disorder for 10 (28%), or congenital diarrhea for 10 (28%). The median (range) mGFR was 99 (33-136) ml/min/1.73 m(2); 9 (25%) patients had mildly decreased mGFR (= 60 ml/min/1.73 m(2)), and 2 (6%) had mildly to severely decreased mGFR (<60 ml/min/1.73 m(2)). The eGFR(cr+cyst) formula was the most accurate and precise to estimate GFR. A significant negative correlation between mGFR and PN duration was found for patients receiving PN for 6-7/7 days (P = .008). Activation of the renin-angiotensin system was identified in 15 of 36 (42%) patients.Conclusion Renal dysfunction was frequent and correlated with the duration of PN only for patients with the most severe intestinal failure. The use of eGFR(cr+cyst) improves its detection in these patients. Chronic dehydration may be an underlying mechanism