Renal dysplasia

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Renal dysplasia in a dog, showing characteristic a large, normally developed glomerulus, and a small fetal glomerulus with a dilated Bowman’s capsule (arrow)[1]

Renal dysplasia is an autosomal-dominant multifactorial genetic renal disease of dogs characterized by delayed maturation of renal and other parenchymal tissue, leading to progressive renal degeneration, protein-losing nephropathy and chronic renal disease.

This disease is usually an inherited syndrome but congenitally-acquired neonatal urinary tract infections, viruses and vitamin A deficiency may result in a phenotypically-identical presentation of arrested or delayed nephric development.

An autosomal-recessive genetic predisposition has been noted in the Soft Coated Wheaten Terrier[2].

Because of the typically adult-onset nature of this condition and the multi-organ involvement, it can be confused with non-hereditary causes, and has few consistent clinical signs.

The age of onset and clinical disease symptoms are highly variable, and kidney failure from this birth defect can occur at any age, even in dogs that are up to 10 years of age or beyond.

Clinically affected dogs are often middle-aged dogs of any breed which present with weight loss and extreme polyuria and polydipsia. The extreme polyuria and polydipsia seen in younger dogs (under 6 months of age), is thought to be caused by lack of response by immature renal tubules to antidiuretic hormone activity[3].

Renal biopsy confirms the histological presence of immature fetal glomeruli, persistent primitive mesenchyme and metanephric ducts, asynchronous differentiation of nephrons, and atypical tubular epithelium[4].

Blood tests usually reveal non-regenerative anemia, hyperammonemia, hypercreatinemia and hyperphosphatemia[5]. Urinalysis may reveal concurrent pyelonephritis[6]. Hyperfibrinogenemia is a consistent finding, and these dogs have a higher risk of thromboembolism[7].

Ultrasonography often features poor corticomedullary definition, multifocal hyperechoic speckles in the renal medulla or a diffusely hyperechoic medulla[1].

Diagnosis requires renal biopsy, as no mutation-based DNA test is available. A surgical wedge biopsy is the only reliable diagnostic method, as approximately 100 glomeruli have to be evaluated, and the architecture of the renal cortex has to be assessed[8]. Histopathology usually demonstrate abnormal or asynchronous differentiation of renal tissue, with the presence of immature or fetal glomeruli and mesenchymal tissue in the medulla[9]. Other histological features include mineralization of renal tubules and diffuse interstitial fibrosis in the cortex and medulla[10].

Concurrent genetic abnormalities have been reported in dogs with pre-existing renal dysplasia, including urolithiasis, ectopic ureter[11], renal agenesis, hepatic capsular fibrosis, lymphatic duplication of connective tissue, pulmonary calcification[12] and half-circular tracheal rings[13].

A differential diagnosis would include psychogenic polydipsia, diabetes insipidus, hyperadrenocorticism, hypoadrenocorticism, other causes of chronic renal disease disease such as polycystic kidney disease, chronic pyelonephritis, Leptospira spp, as well as congenital disorders such as renal agenesis or hypoplasia (Ask-Upmark kidney)[14].

There is no specific treatment for this disease, and in clinically affected dogs, renal degeneration continues to end-stage renal disease. Poor quality of life factors usually dictates renal transplantation or euthanasia.

Renal transplantation may be the only viable curative procedure for this condition[15].

References

  1. 1.0 1.1 Seiler GS et al (2010) Ultrasonographic findings in Cairn Terriers with preclinical renal dysplasia. Vet Radiol Ultrasound 51(4):453-457
  2. Littman MP et al (2013) Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs. Mamm Genome Jan 17
  3. Hoppe A & Karlstam E (2000) Renal dysplasia in boxers and Finnish harriers. J Small Anim Pract 41(9):422-426
  4. Bruder MC et al (2010) Renal dysplasia in Beagle dogs: four cases. Toxicol Pathol 38(7):1051-1057
  5. Morita T et al (2005) Renal dysplasia with unilateral renal agenesis in a dog. J Comp Pathol 133(1):64-67
  6. Abraham LA et al (2003) Renal dysplasia and urinary tract infection in a Bull Mastiff puppy. Aust Vet J 81(6):336-339
  7. Donahue SM et al (2011) Examination of hemostatic parameters to detect hypercoagulability in dogs with severe protein-losing nephropathy. J Vet Emerg Crit Care (San Antonio) 21(4):346-355
  8. Vaden SL (2005) Renal biopsy of dogs and cats. Clin Techn Small Anim Pract 20:11–22
  9. Khan KNM et al (2002) In: Haschek WM, Rousseaux CG, Wallig MA, editors. Handbook of toxicologic pathology. Vol. 2. San Diego: Elsevier Science. pp:255–330
  10. Bovee KC (2003) Proceedings of the 28th World Congress of the World Small Animal Veterinary Association; 2003. Renal Dysplasia in Shih Tzu Dogs
  11. Yoon HY et al (2010) Bilateral ureteral ectopia with renal dysplasia and urolithiasis in a dog. J Am Anim Hosp Assoc 46(3):209-214
  12. Walsh VP et al (2005) Suspected fatal venous air embolism during anaesthesia in a Pomeranian dog with pulmonary calcification. N Z Vet J 53(5):359-362
  13. Williams JH et al (2005) Lymphangiosarcoma in a 3.5-year-old Bullmastiff bitch with vaginal prolapse, primary lymph node fibrosis and other congenital defects. J S Afr Vet Assoc 76(3):165-171
  14. Kolbjørnsen O et al (2008) End-stage kidney disease probably due to reflux nephropathy with segmental hypoplasia (Ask-Upmark kidney) in young Boxer dogs in Norway. A retrospective study. Vet Pathol 45(4):467-474
  15. Phillips H & Aronson LR (2012) Use of end-to-side arterial and venous anastomosis techniques for renal transplantation in two dogs. J Am Vet Med Assoc 240(3):298-303