Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis): Severity and Risk Factors

P M Gaffney; C Witte; D L Clifford; D M Imai; T D O'Brien; M Trejo; F Liberta; K Annamalai; M Fändrich; E Masliah; L Munson; C J Sigurdson

doi:10.1177/0300985815604725

Systemic Amyloid A Amyloidosis in Island Foxes (Urocyon littoralis): Severity and Risk Factors

Vet Pathol. 2016 May;53(3):637-47. doi: 10.1177/0300985815604725. Epub 2015 Sep 29.

Authors

P M Gaffney¹, C Witte², D L Clifford³, D M Imai⁴, T D O'Brien⁵, M Trejo⁶, F Liberta⁷, K Annamalai⁷, M Fändrich⁷, E Masliah⁶, L Munson⁸, C J Sigurdson⁹

Affiliations

¹ Departments of Pathology and Medicine, University of California-San Diego, La Jolla, CA, USA Department of Pathology, Immunology, and Microbiology, University of California-Davis, Davis, CA, USA.
² Wildlife Disease Laboratories, Institute for Conservation Research, San Diego Zoo Global, Escondido, CA, USA.
³ Wildlife Investigations Laboratory, California Department of Fish and Wildlife, Rancho Cordova, CA, USA Department of Veterinary Medicine and Epidemiology, University of California-Davis, Davis, CA, USA.
⁴ Department of Pathology, Immunology, and Microbiology, University of California-Davis, Davis, CA, USA.
⁵ Veterinary Population Medicine Department, Veterinary Diagnostic Laboratory, University of Minnesota, St Paul, MN, USA.
⁶ Departments of Pathology and Neuroscience, University of California-San Diego, La Jolla, CA, USA.
⁷ Institute for Pharmaceutical Biotechnology, Ulm University, Helmholtzstrasse, Ulm, Germany.
⁸ Department of Pathology, Immunology, and Microbiology, University of California-Davis, Davis, CA, USA Deceased Supplemental material for this article is available on the Veterinary Pathology website at http://vet.sagepub.com/supplemental.
⁹ Departments of Pathology and Medicine, University of California-San Diego, La Jolla, CA, USA Department of Pathology, Immunology, and Microbiology, University of California-Davis, Davis, CA, USA csigurdson@ucsd.edu.

Abstract

Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum AA (SAA) from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli (98% [n= 78 of 80] vs 56% [n= 45], respectively;P< .0001), and medullary deposition was more commonly severe (19% [n= 20 of 105]) as compared with glomeruli (7% [n= 7];P= .01). Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes as compared with free-ranging foxes (ORs = 3.2, 3.7, respectively; overall P= .05) and for females as compared with males (OR = 2.9;P= .05). Multivariable logistic regression revealed that independent risk factors for amyloid development were increasing age class (OR = 3.8;P< .0001), San Clemente Island subspecies versus San Nicolas Island subspecies (OR = 5.3;P= .0003), captivity (OR = 5.1;P= .0001), and nephritis (OR = 2.3;P= .01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis.

Keywords: Urocyon littoralis; amyloid A; amyloidosis; endangered species; island fox; logistic regression; nephritis; serum amyloid A.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloidosis / epidemiology
Amyloidosis / metabolism
Amyloidosis / pathology
Amyloidosis / veterinary*
Animals
Endangered Species
Female
Foxes*
Inflammation / veterinary
Kidney / metabolism
Logistic Models
Male
Nephritis / epidemiology
Nephritis / metabolism
Nephritis / pathology
Nephritis / veterinary*
Risk Factors
Serum Amyloid A Protein / metabolism*
Severity of Illness Index

Substances

Serum Amyloid A Protein

Grants and funding

T32 OD017863/OD/NIH HHS/United States