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: Emmanuel Estève, Pauline Krug, Aurélie Hummel, Jean-Baptiste Arnoux, Olivia Boyer, Anais Brassier, Pascale de Lonlay, Vincent Vuiblet, Stéphanie Gobin, Rémi Salomon, Christine Piètrement, Jean-Paul Bonnefont, Aude Servais, Louise Galmiche
• Journal: Human pathology (Hum Pathol) Vol. 62 Pg. 160-169 (Apr 2017) ISSN: 1532-8392 [Electronic] United States
• PMID: 28087478 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Amino Acid Transport System y+L
• Fusion Regulatory Protein 1, Light Chains
• SLC7A7 protein, human

Topics

• Adolescent
• Adult
• Amino Acid Metabolism, Inborn Errors (complications, genetics, pathology, therapy)
• Amino Acid Transport System y+L
• Amyloidosis (etiology, pathology)
• Biopsy
• Child
• Disease Progression
• Female
• Fluorescent Antibody Technique
• Fusion Regulatory Protein 1, Light Chains (genetics)
• Genetic Predisposition to Disease
• Glomerulonephritis, Membranoproliferative (etiology, pathology)
• Humans
• Infant
• Kidney (pathology)
• Male
• Mutation
• Nephrocalcinosis (etiology, pathology)
• Nephrotic Syndrome (etiology, pathology)
• Paris
• Phenotype
• Proteinuria (etiology, pathology)
• Renal Insufficiency, Chronic (etiology, pathology)
• Time Factors