Renal Abnormalities Caused by Canine Distemper Virus Infection in Terminal Patients

Abstract

The aim of this study was to analyze the glomerular and tubular alterations in dogs with terminal distemper through light microscopy, immunofluorescence, and electron microscopy. Thirteen animals with a molecular diagnosis of distemper and neurological signs were selected. As a control group, 10 clinically healthy animals with no manifestations or signs of disease and with negative tests for Ehrlichia sp., Anaplasma sp., and Babesia sp. were included in this study. Renal tissue was evaluated by light microscopy, topochemistry for DNA/chromatin, and video image analysis to detect the nuclear phenotypes of the renal tubular epithelial cells (RTECs), immunofluorescence, and transmission electron microscopy. Results showed that dogs with distemper exhibited anemia, hypergammaglobulinemia, and proteinuria. Creatinine in the distemper group was lower compared to the control group (p = 0.0026), but there was no significant difference in relation to urea (p = 0.9876). Although this alteration may be due to the smaller muscle mass observed in animals with distemper, it probably is not of clinical importance. Glomerular and tubular lesions were confirmed by light microscopy in 84.6% of these animals. Additional findings in the animals with distemper included deposition of different classes of immunoglobulins, particularly IgM in 92.3% of the cases, fibrinogen deposition in 69.2% of the cases as assessed by immunofluorescence, alterations in the nuclear phenotypes of the RTEC characterized by condensation of chromatin, loss of DNA and reduction in the nuclear shape, and the presence of subendothelial and mesangial electron-dense deposits. These findings confirm the existence of renal alterations related to terminal distemper.

Keywords: Paramyxoviridae; glomerulonephritis; glomerulosclerosis; microscopy; proteinuria; tubular necrosis.

Figure 1

(A) Photomicrograph of a foamy glomerulus of a dog with distemper in a section stained with Masson's trichrome (400 ×); (B) Tubular necrosis in a section stained with Masson's trichrome (200 ×). White arrows indicate tubular cell detachment; (C) Photomicrograph of the renal medulla to characterize acute tubular necrosis. Tubular lumens are dilated and filled with necrotic cells (arrows). Some tubules have vacuolar degeneration (arrowhead). Hematoxylin and Eosin (100 ×); (D) Photomicrograph of glomerular congestion and endocapillary hypercellularity. There is increased numbers of intracapillary cells causing narrowing of glomerular capillary lumina; (E) Photomicrograph of ischemic changes in the glomerulus revealed by PAMS staining. Glomerular basement membrane duplication (arrows) and also wrinkling and irregularity of the loop (arrowhead); (F) Photomicrograph of the increased thickness of glomerular basement membranes without spikes and generalized expansion of the mesangial matrix revealed by PAMS staining.

Figure 2

(A) Immunofluorescence image showing strong staining for glomerular IgM in a granular pattern in the mesangium; (B) Immunofluorescence image showing moderate staining for glomerular C3 in a granular pattern in the mesangium—In detail it is possible to identify the granular pattern (top right); Surface plot graph charts representative of the degree of condensation of chromatin presented by the RTECs in control (C) and distemper (D) groups. The nuclei contain 2 sets of chromatin with different states of supraorganization. The first set (green pseudocolor) had unpacking chromatin (41–60 pixels); and the second (orange) had highly compacted chromatin (20–40 pixels).

Figure 3

(A) Electron microscopy image of renal fragments exhibiting mesangial deposits of electron-dense material (arrows); (B) Electron microscopy image of renal fragments showing fusion of pedicels (arrows); (C) Electron microscopy image of increased mesangial cellularity (arrows); (D) Electron microscopy image showing initial stage of vacuolar degeneration in tubular epithelial cells (arrows).