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Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers

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Abstract
Background: Proteinuria is a feature of pyometra-associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. Objectives: To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. Animals: Forty-seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. Methods: Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C-reactive protein, urinary thromboxane B(2)) and tubular function (urinary retinol-binding protein, urinary N-acetyl-beta-D-glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 21 or 31 were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. Results: UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05-8.69) compared with healthy bitches (0.08, 0.02-0.16) (P < .01). Twenty-two of 47 dogs with pyometra had UPC>0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. Conclusion: Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra-associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.
Keywords
Dog, Chronic kidney disease, Endometritis, Focal segmental glomerulosclerosis, BLOOD CONTAMINATION, DISEASE, ULTRASONOGRAPHY, IMMUNOGLOBULINS, PATHOGENESIS, DYSFUNCTION, COMPLEMENT, MANAGEMENT, LESIONS, SIGNS

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Chicago
Maddens, Bert, R Heiene, Pascale Smets, M Svensson, L Aresu, J van der Lugt, Sylvie Daminet, and Evelyne Meyer. 2011. “Evaluation of Kidney Injury in Dogs with Pyometra Based on Proteinuria, Renal Histomorphology, and Urinary Biomarkers.” Journal of Veterinary Internal Medicine 25 (5): 1075–1083.
APA
Maddens, Bert, Heiene, R., Smets, P., Svensson, M., Aresu, L., van der Lugt, J., Daminet, S., et al. (2011). Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers. JOURNAL OF VETERINARY INTERNAL MEDICINE, 25(5), 1075–1083.
Vancouver
1.
Maddens B, Heiene R, Smets P, Svensson M, Aresu L, van der Lugt J, et al. Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers. JOURNAL OF VETERINARY INTERNAL MEDICINE. 2011;25(5):1075–83.
MLA
Maddens, Bert, R Heiene, Pascale Smets, et al. “Evaluation of Kidney Injury in Dogs with Pyometra Based on Proteinuria, Renal Histomorphology, and Urinary Biomarkers.” JOURNAL OF VETERINARY INTERNAL MEDICINE 25.5 (2011): 1075–1083. Print.
@article{2134571,
  abstract     = {Background: Proteinuria is a feature of pyometra-associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. 
Objectives: To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. 
Animals: Forty-seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. 
Methods: Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C-reactive protein, urinary thromboxane B(2)) and tubular function (urinary retinol-binding protein, urinary N-acetyl-beta-D-glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 21 or 31 were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. 
Results: UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05-8.69) compared with healthy bitches (0.08, 0.02-0.16) (P {\textlangle} .01). Twenty-two of 47 dogs with pyometra had UPC{\textrangle}0.5, 12 had UPC{\textrangle}1.0, and 7 had UPC{\textrangle}2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC{\textrangle}1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. 
Conclusion: Dogs with pyometra and UPC{\textrangle}1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra-associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.},
  author       = {Maddens, Bert and Heiene, R and Smets, Pascale and Svensson, M and Aresu, L and van der Lugt, J and Daminet, Sylvie and Meyer, Evelyne},
  issn         = {0891-6640},
  journal      = {JOURNAL OF VETERINARY INTERNAL MEDICINE},
  keyword      = {Dog,Chronic kidney disease,Endometritis,Focal segmental glomerulosclerosis,BLOOD CONTAMINATION,DISEASE,ULTRASONOGRAPHY,IMMUNOGLOBULINS,PATHOGENESIS,DYSFUNCTION,COMPLEMENT,MANAGEMENT,LESIONS,SIGNS},
  language     = {eng},
  number       = {5},
  pages        = {1075--1083},
  title        = {Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers},
  url          = {http://dx.doi.org/10.1111/j.1939-1676.2011.00772.x},
  volume       = {25},
  year         = {2011},
}

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