title: Renal involvement in lysinuric protein intolerance: contribution of pathology to assessment of heterogeneity of renal lesions.
abstract: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disease caused by mutations in the SLC7A7 gene encoding the light subunit of a cationic amino acid transporter. Symptoms mimic primary urea cycle defects but dysimmune symptoms are also described. Renal involvement in LPI was first described in the 1980s. In 2007, it appeared that it could concern as much as 75% of LPI patients and could lead to end-stage renal disease. The most common feature is proximal tubular dysfunction and nephrocalcinosis but glomerular lesions are also reported. However, very little is known regarding histological lesions associated with LPI. We gathered every kidney biopsy of LPI-proven patients in our highly specialized pediatric and adult institution. Clinical, biological, and histological information was analyzed. Five LPI patients underwent kidney biopsy in our institution between 1986 and 2015. Clinically, 4/5 presented with proximal tubular dysfunction and 3/5 with nephrotic range proteinuria. Histology showed unspecific tubulointerstitial lesions and nephrocalcinosis in 3/5 biopsies and marked peritubular capillaritis in one child. Glomerular lesions were heterogeneous: lupus-like-full house membranoproliferative glomerulonephritis (MPGN) in one child evolved towards monotypic IgG1κ MPGN sensitive to immunomodulators. One patient presented with glomerular non-AA non-AL amyloidosis. Renal biopsy is particularly relevant in LPI presenting with glomerular symptoms for which variable histological lesions can be responsible, implying specific treatment and follow-up.
authors.affiliation: Pathology Department Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: esteve.emmanuel@gmail.com.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Estève
authors.affiliation: Pediatric Nephrology Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: pauline.krug@aphp.fr.
authors.forename: Pauline
authors.initials: P
authors.lastname: Krug
authors.affiliation: Nephrology Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: aurelie.hummel@aphp.fr.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Hummel
authors.affiliation: Metabolic Diseases Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: jean-baptiste.arnoux@aphp.fr.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Arnoux
authors.affiliation: Pediatric Nephrology Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: olivia.boyer@aphp.fr.
authors.forename: Olivia
authors.initials: O
authors.lastname: Boyer
authors.affiliation: Metabolic Diseases Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: anais.brassier@aphp.fr.
authors.forename: Anais
authors.initials: A
authors.lastname: Brassier
authors.affiliation: Metabolic Diseases Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: pascale.delonlay@aphp.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.affiliation: Nephrology and Renal Transplantation Department and Pathology Department, Centre Hospitalier et Universitaire de Reims, Reims, France. Electronic address: vvuiblet@chu-reims.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Vuiblet
authors.affiliation: Molecular Genetics Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gobin
authors.affiliation: Pediatric Nephrology Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: remi.salomon@aphp.fr.
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.affiliation: Department of Paediatrics, Nephrology Paediatric Unit, Centre Hospitalier et Universitaire de Reims, Reims, France. Electronic address: cpietrement@chu-reims.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Piètrement
authors.affiliation: Molecular Genetics Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.affiliation: Nephrology Department, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: aude.servais@aphp.fr.
authors.forename: Aude
authors.initials: A
authors.lastname: Servais
authors.affiliation: Pathology Department Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Sorbonne Paris Cité, 75015, Paris, France. Electronic address: louise.galmiche-rolland@aphp.fr.
authors.forename: Louise
authors.initials: L
authors.lastname: Galmiche
mesh_terms: D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D027241:Amino Acid Transport System y+L; D000686:Amyloidosis / Q000209:etiology / Q000473:pathology; D001706:Biopsy; D002648:Child; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology / Q000473:pathology; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology*; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000209:etiology / Q000473:pathology; D009404:Nephrotic Syndrome / Q000209:etiology / Q000473:pathology; D010297:Paris; D010641:Phenotype; D011507:Proteinuria / Q000209:etiology / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000473:pathology; D013997:Time Factors
chemical_list: D027241:Amino Acid Transport System y+L; D027301:Fusion Regulatory Protein 1, Light Chains; C421261:SLC7A7 protein, human
keywords: Amyloidosis; Kidney biopsy; Lysinuric protein intolerance; Membranoproliferative glomerulonephritis; Nephrocalcinosis