Background: Renal amyloidosis is characterized by the pathologic deposition within glomeruli and/or interstitium of congophilic fibrils, most often composed of either immunoglobulin light chains or serum amyloid A-related protein and, less commonly, mutated forms of apolipoproteins AI or AII, lysozyme, fibrinogen, gelsolin, or transthyretin.
Study design: Case series.
Setting & participants: 10 patients with renal amyloidosis who had an amyloidogenic protein that was not identified using routine immunohistochemistry.
Outcomes: Clinical, pathologic, biochemical, and genetic characteristics.
Measurements: Tandem mass spectrometry was used to analyze fibrils extracted from sections of formalin-fixed paraffin-embedded amyloid-containing kidney biopsy specimen blocks.
Results: Chemical analyses showed peptides corresponding to the carboxy-terminal portion of the leukocyte chemotactic factor 2 (LECT2) molecule. In addition, deposits were immunostained using an anti-human LECT2 monoclonal antibody. Plasma specimens were available from 2 individuals for whom LECT2 concentration in these samples was within the reference range. Additionally, in 4 of the cases analyzed at the molecular level, isolation of genomic DNA and polymerase chain reaction amplification of LECT2-encoding exons showed no mutations. However, all were homozygous for the G allele encoding valine at position 40 in the mature protein, a finding confirmed using restriction enzyme analysis of the polymorphic site.
Limitations: Causality is not addressed.
Conclusions: Based on our studies, we posit that LECT2-associated renal amyloidosis represents a unique and perhaps not uncommon disease, especially in Mexican Americans. The pathogenesis, extent, and prognosis remain to be determined.
Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.