Background The megalin/cubilin/amnionless complex is essential for albumin and low molecular weight (LMW) protein reabsorption by renal proximal tubules (PT). Mutations of the LRP2 gene encoding megalin cause autosomal recessive Donnai-Barrow/facio-oculo-acoustico-renal syndrome (DB/ FOAR), which is characterized by LMW proteinuria. The pathophysiology of DB/FOAR-associated PT dysfunction remains unclear. Clinical case A 3-year-old girl presented with growth retardation and proteinuria. Clinical examination was unremarkable, except for a still-opened anterior fontanel and myopia. Psychomotor development was delayed. At 6, she developed sensorineural hearing loss. Hypertelorism was noted when she turned 12. Blood analyses, including renal function parameters, were normal. Urine sediment was bland. Proteinuria was significant and included albumin and LMW proteins. Immunoblotting analyses detected cubilin and type 3 carbonic anhydrase (CA3) in the urine. Renal ultrasound was unremarkable. Optical examination of a renal biopsy did not disclose any tubular or glomerular abnormality. Electron microscopy revealed that PT apical endocytic apparatus was significantly less developed. Immunostaining for megalin showed a faint signal in PT cytosol contrasting with the distribution of cubilin at the apical membrane. The diagnostic procedure led to identifying two mutations of the LRP2 gene. Conclusions The functional loss of megalin in DB/FOAR causes PT dysfunction characterized by increased urinary shedding of CA3 and cubilin.

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) À1.3 (À5.7;1.6) and weight-SDS À1.4 (À3.6;0.6). Peritoneal dialysis duration was 12 (2;32) months, and at peritoneal dialysis discontinuation height-SDS was À1.0 (À4.3;0.7) weight-SDS À0.7 (À3.2;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.

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