A clinical study of canine collagen type III glomerulopathy

Abstract

BackgroundCollagen type III glomerulopathy (Col3GP), also known as collagenofibrotic glomerulonephropathy, is a rare renal disease with unknown pathogenesis that occurs in animals and humans. We recently described a naturally occurring canine autosomal recessive model of Col3GP, and the aim of the present work was to study the clinical features of canine Col3GP and compare with the human phenotype. In humans two different clinical syndromes with different age at onset (child- or adulthood) have been observed. In children a more aggressive course with familial occurrence is described, characterized by progressively increasing proteinuria, nephrotic syndrome, hypertension and chronic renal failure. A markedly increased serum level of the aminoterminal propeptide of type III procollagen (PIIINP) is considered a useful marker for the disease. Since Col3GP and concurrent hypocomplementemia have been observed in humans, we also aimed to investigate if hypocomplementemia was present in Col3GP affected dogs. A litter consisting of seven puppies, four Col3GP affected and three healthy unaffected, was observed from the day of birth until the affected puppies developed a mild or moderate renal azotemia.ResultsDuring the period of observation growth retardation, increasing blood pressure, progressive proteinuria, azotemia, hypoalbuminemia, hypercholesterolemia and increased serum PIIINP were observed in all the affected dogs. Hypocomplementemia was not detected. Affected dogs were euthanized between 109 and 144 days of age, and pathological examinations revealed ascites and massive glomerular accumulations of collagen type III, consistent with Col3GP.ConclusionsDogs with Col3GP develop juvenile chronic renal failure, preceded by nephrotic syndrome, elevated serum PIIINP and hypertension, thus have similar clinical features as the juvenile Col3GP in humans. Further studies of this naturally occurring canine phenotype may provide more information on the pathogenesis and genetics of Col3GP in both animals and humans.

Telmisartan alleviates collagen type III glomerulopathy: A case report with literature review

“…The clinical manifestations of CG are not sufficiently specific for diagnosis uninformed by pathological findings. The major clinical manifestations of CG are proteinuria, hypertension and subsequent slowly progressive chronic kidney disease (1,4,5). Electron microscopic examination of glomerular basement membrane (GBM) biopsy specimens has revealed massive deposition of banded type III collagen fibrils (diameter, 50-60 nM) (2).…”

Role of advanced glycation end products in the onset of diabetic kidney disease complications

“…The four pathways described are the result of persistent hyperglycemia and converge in the formation of AGEs, with formation of ROS, mainly superoxide anion, contributing to altering intracellular redox status, leading to oxidative stress 29,30,33 . Therefore, the increased ROS in DM, together with the reduction of antioxidant defenses are related to the onset of diabetic complication 31,33,34 . ROS increase leads to DNA breaking, which activates poly ADP-ribose polymerase (PARP), reducing the Role of AGEs in diabetic kidney disease activity of glyceraldehyde-3-phosphate (GAPDH), a key enzyme in the glycolytic pathway, which, in turn, activates the polyol pathway, increases the formation of AGEs, PKC activation, and increases the flow of hexosamines 35 .…”

“…Increased intracellular glucose is related to pathophysiological mechanisms that trigger DM chronic complications 31 . These mechanisms include: 1) Stimulation of the polyol pathway: in the persistent hyperglycemia, part of the glucose is converted to sorbitol, which increases ROS production, leading to cell dysfunction 29 .…”

“…These mechanisms include: 1) Stimulation of the polyol pathway: in the persistent hyperglycemia, part of the glucose is converted to sorbitol, which increases ROS production, leading to cell dysfunction 29 . 2) Activation of protein kinase C (PKC) isoforms, which induce the synthesis of diacylglycerol, fibronectin, collagen type IV, contractile proteins, and extracellular matrix protein genes in endothelial cells and neurons 29,31 . 3) Activation of hexosamine pathway, which may interfere with the glycosylation of proteins, changing their final structure and also altering gene expression.…”

Emerging perspectives on hereditary glomerulopathies in canines

“…62,63 Test matings indicated an autosomal mode of inheritance. As in humans, increased serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) may be used as a marker of this defect.…”