Glomerular Collagen V Codeposition and Hepatic Perisinusoidal Collagen III Accumulation in Canine Collagen Type III Glomerulopathy

Abstract

Collagen type III glomerulopathy, also known as collagenofibrotic glomerulopathy, is a rare renal disease of unknown pathogenesis. The disease occurs in humans and animals and is characterized by massive glomerular accumulations of collagen type III. In the present study, we describe a Drever dog litter affected by an early onset variant of this glomerular disease, where 4 of 9 puppies developed renal failure within 50 days of age. Necropsy specimens of kidney from the 4 affected cases were studied by light microscopy, electron microscopy, and immunohistochemistry, and characteristic lesions compatible with a diagnosis of collagen type III glomerulopathy were found. In addition, 2 cases showed atypical epithelium in the collecting ducts of the medulla, so-called adenomatoid change. Immunohistochemistry of renal specimens from collagen type III glomerulopathy-affected dogs (n ¼ 10) originating from two different dog strains, the Drever dogs and a mixed-breed strain, demonstrated that the deposited glomerular collagen is composed of a mixture of collagen III and collagen V. The distribution of the collagen V corresponded to the localization of collagen III; however, differences in staining intensity showed that collagen type III is the dominating component. Immunohistochemistry for collagen III (n ¼ 9) and a transmission electron microscopic study (n ¼ 1) showed hepatic perisinusoidal collagen type III deposition in affected cases from both dog strains. This is the first report documenting glomerular accumulations of collagen type V and perisinusoidal liver collagen III deposition in canine collagen type III glomerulopathy.

Diagnosis of Collagen Type III Glomerulopathy Using Picrosirius Red and PASH/Masson’s Trichrome Stain

“…5 In contrast, canine Col3GP is mainly reported in juvenile dogs with only one report of a dog living beyond 12 months of age. 8 –10,13 –15 Despite this difference, clinical signs, light microscopy, and ultrastructural findings from the puppies of the current report were strikingly similar to those in human cases. Urinalysis and serum chemistry values were available for one dog and resembled those in human cases in which proteinuria and eventual renal failure are common findings.…”

“…Collagen type III glomerulopathy (Col3GP), also known as collagenofibrotic glomerulopathy, is a rare renal disease described in humans and several animal species. 1,2,4 –6,8–10,12 –17 Individuals with Col3GP accumulate abundant type III collagen and, to a lesser extent, fibronectin and type V collagen in the mesangium and subendothelial space, adjacent to the glomerular basement membrane. This differs from the normal glomerular extracellular matrix, which contains type IV collagen, fibronectin, and other components, but lacks type III collagen.…”

Collagenofibrotic glomerulopathy in a young cat

“…In a litter of Newfoundland dogs, a fatal juvenile glomerulopathy with glomerulosclerosis and glomerulofibrosis has been reported 7. In mongrel dogs and in a drever dog litter, a collagen type III, known as collagenofibrotic glomerulopathy has been described as a juvenile hereditary glomerulopathy with an autosomal recessive inheritance mode 8 9. A local synthesis of the collagen type III was also detected in the mesangium of mongrel dogs by in situ hybridisation supporting the mesangial origin 8.…”

“…But since in affected drever dogs also the liver is affected, a systemic disease cannot be ruled out 6–9 13 14. The mesangial deposits have been identified as collagen using special stains like Van Gieson, Masson’s trichrome or immunohistochemistry against collagen III as well as TEM 1–3 6–11 13 14. In a litter of Newfoundland dogs, a fatal juvenile glomerulopathy with glomerulosclerosis and glomerulofibrosis has been reported 7.…”

“…In dogs, a collagen type III glomerulopathy has been described and is mostly inherited as an autosomal recessive trait 6–9. Moreover, this glomerulopathy type has also been reported in a cynomolgus macaque,10 in pigs4 and in a cat 11…”