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Kidney: autosomal dominant polycystic disease

ISSN 2398-2950

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Introduction

  • An inherited disorder characterized by the presence of multiple fluid filled cysts within the renal cortex and medulla, and occasionally also within the hepatic parenchyma.
  • Autosomal dominant polycystic kidney disease (AD-PKD) is the most common inherited renal disease of cats and is a common condition in Persian and Exotic Shorthaired cats. In most cats it occurs due to an autosomal dominant mutation of the PKD1 gene.
  • Affected cats can be identified by a gene test (cats of any age) or ultrasound scanning of the kidneys (cats over 10 months of age).
  • The International Cat Care AD-PKD Negative Register International Cat Care AD-PKD negative register allows breeders and owners to find cats that have been gene tested and are negative, encouraging the development of controlled breeding plans aimed at eliminating the condition.
  • Cause: autosomal dominant inherited disorder causing multiple, congenital renal cysts which enlarge with age; acquired renal cysts occur rarely, usually in small numbers.
  • Signs: initially asymptomatic, progressing at an unpredictable rate to chronic renal failure.
  • Diagnosis: gene test, ultrasonography. 
  • Treatment: no specific treatment available.
  • Prognosis: poor.
Print off the owner factsheet Autosomal dominant polycystic kidney disease Autosomal dominant polycystic kidney disease to give to your client.

Presenting signs

  • Asymptomatic in early stages.
  • Advancing to chronic renal failure Kidney: chronic kidney disease with lethargy, anorexia, polyuria, polydipsia, constipation, weight loss, muscle wastage and possibly vomiting.
  • Cysts may result in hematuria and risk of urinary tract infections.
  • Enlarged, irregular kidney(s) on abdominal palpation. Cysts are often bilateral.

Geographic incidence

  • Worldwide.

Age predisposition

  • Cysts are congenital.
  • Cysts enlarge with age at an unpredictable rate, eventually causing kidney disease. Kidney disease may develop as young as 2 or 3 years of age, or may not occur until into old age. The mean age when cats develop signs of chronic kidney disease is 7 years.

Breed/Species predisposition

  • Very common in Persians Persian longhair and Exotic Shorthairs Exotic Shorthair; affects approximately one third of cats of these breeds in the UK, and around the world.
  • Other breeds which have used Persian crosses in the past may also have imported the gene, eg Burmilla, British Shorthair British shorthair, Asian Asian, Bombay Bombay, Cornish Rex Cornish Rex, Devon Rex Devon Rex, Ragdoll Ragdoll, Snowshoe Snowshoe, Tiffanie. In other breeds, prevalence may reach 16%.
  • Cystic renal disease occurs with a low prevalence in the Maine Coon Maine Coon and is unrelated to the PKD1 mutation seen in Persians and related breeds.

Pathogenesis

Etiology

  • Inherited:
    • Polycystin-1 is a renal tubule membrane glycoprotein required for epithelial cell proliferation and differentiation. It is encoded by the PKD1 gene. Insufficient polycystin-1 production causes remodelling of renal tubules and cyst formation.
    • AD-PKD is an autosomal dominant condition inherited on a single gene meaning that:
      • All cats with the abnormal gene have AD-PKD (healthy carriers do not exist).
      • Only one parent of an affected cat needs to be affected.
      • Every cat with AD-PKD will pass the disease to a proportion of its kittens (even if the other parent is unaffected).
  • Acquired:
    • Renal cysts may be due to microbes, drugs, toxins, etc. These diseases occur rarely in cats.

Pathophysiology

  • Autosomal dominant polycystic kidney disease is an inherited condition causing the development of multiple cysts in renal tissue.
  • Cysts are present from birth. Cats are initially asymptomatic, however the cysts gradually enlarge displacing normal renal parenchyma. Subsequently, substantial tubulointerstitial inflammation and/or fibrosis occurs in surrounding tissue resulting in chronic kidney disease and kidney failure.

Timecourse

  • Rate of progression from asymptomatic disease to kidney failure Kidney: chronic kidney disease is highly variable, and unpredictable.
  • Severely affected individuals may succumb at an early age, eg 2-3 years old, other cats maintain adequate renal failure into old age.
  • The "average" age quoted for development of renal failure is 7 years of age, but there is enormous variability between individuals.

Diagnosis

Presenting problems

  • Weight loss.
  • Reduced appetite.
  • Polyuria/polydipsia.

Client history

  • No clinical signs in early stage of disease.
  • Weight loss, poor appetite.
  • Polyuria/polydipsia.
  • Lethargy.
  • Some affected cats may develop abdominal enlargement.
  • Possibly constipation, vomiting.
  • Cysts may result in hematuria and risk of urinary tract infections.

Clinical signs

  • Renal enlargement, most commonly bilateral.
  • Irregular kidney surface (loss of normal bean shape).
  • Hematuria.
  • Rarely patients may present with signs associated with liver disease (6-68% of affected cats have hepatic cysts).

Diagnostic investigation

2-D Ultrasonography

  • Enlarged kidney with irregular surface, loss of normal bean shape.
  • Multiple round, well-demarcated, thin-walled anechoic to hypoechoic areas within the cortex or medulla of the kidney:
    • Ultrasonography can identify cysts >2 mm in diameter. Cysts may be very small, around 1 mm diameter, in the early stages of disease .
    • Affected kidneys may have reduced corticomedullary definition and may have mineralised foci.
  • Cysts maybe present in other abdominal organs, eg liver/biliary tree.
  • In advanced disease, cysts are large and diagnosis is relatively simple.
  • Ultrasound scanning by experienced sonographers, using a high definition ultrasound probe is more than 95% accurate for detection of disease in cats over 10 months of age.
  • Cats under 10 months of age or those that are to be used for breeding should be screened using the gene test.

Gene test

  • Identification of the gene (PKD1) that causes autosomal dominant AD-PKD has led to the development of a gene test. Developed initially by Veterinary Genetics Laboratory (VPL) in California, the gene test has shown excellent agreement with the results of ultrasound screening Internation Cat Care AD-PKD negative register.
  • The test is now available in the UK via Langford Veterinary Diagnostics and the Animal Health Trust, Newmarket.
  • The test can be run using cells collected from the mouth (buccal mucosal swab) or on a blood sample.
  • Animals can be tested at any age. Buccal swabs are not recommended for testing suckling kittens as they may be contaminated with maternal DNA.
All other tests are only able to detect disease once renal failure is present.

Cytopathology

  • Analysis of cystic fluid:
    • Aspiration of cystic fluid may cause iatrogenic infection of the renal cysts.
    • Clear, odorless fluid, without detection of hemorrhage or infection on sediment examination.
  • Urinalysis Urinalysis: centrifuged sediment:
    • Possible evidence of secondary infection on sediment examination, usually due to iatrogenic contamination.

Biochemistry and Hematology

Urinalysis

Radiography

  • Radiography is not useful in early stages.
  • Renal enlargement, irregular in outline.
  • Cysts fail to opacify on intravenous urography. Intravenous urography Radiography: intravenous urography is not without risk and may result in induction of dehydration, progression of kidney disease and rare anaphylactic shock.

Histopathology

  • Kidney biopsy Biopsy: kidney is rarely indicated, especially in affected Persian and Exotic Shorthaired cats. Histopathology may help to differentiate acquired and hereditary renal cysts.
    The possible complications of this biopsy should be seriously considered, because of the limited additional information gained by histopathology.

Confirmation of diagnosis

Discriminatory diagnostic features

  • Biochemistry.
  • Urinalysis.
  • Fluid/aspirate analysis.

Definitive diagnostic features

Gross autopsy findings

  • Multiple fluid-filled cysts in one or both kidneys   Kidney: polycystic 01 external surface - pathology    Kidney: polycystic 02 cut surface - pathology  .
  • Occasionally only a few cysts are present.
  • Kidney(s) enlarged and irregular in outline (usually bilaterally, but one kidney may be more severely affected than the other).
  • Cysts vary in size from 1 mm to greater than 1 cm in diameter.
  • Cysts contain clear fluid.
  • Cysts within other organs (biliary tree, liver, pancreas).

Histopathology findings

  • Fluid-filled cavities, lined by epithelium within the kidney. Cysts are focal dilations of the renal tubules.
  • Substantial tubulointerstitial inflammation and/or fibrosis may also be detected.
  • Mineralization of cyst wall in advanced disease.

Differential diagnosis

  • Renal neoplasia Kidney: neoplasia - usually irregular and hypoechoic on ultrasonography, eg lymphoma.
  • Hydronephrosis Hydronephrosis / hydroureter dilated anechoic renal pelvis on ultrasonography   Kidney: hydronephrosis - ultrasound  , surrounded by echogenic (renal) tissue.
  • Perirenal pseudocysts Kidney: perinephric/perirenal pseudocysts.
  • Renal hematoma is usually unilateral. May have a similar appearance on ultrasonography.
  • Renal abscess - irregular and hypoechoic on ultrasonography and usually has a thicker wall than a cyst. Usually unilateral.
  • Granulomatous nephritis due to FIP.
  • Acromegaly Acromegaly.

Treatment

Initial symptomatic treatment

Standard treatment

  • Management of chronic renal failure Kidney: chronic kidney disease when it develops:
    • If present, hypertension Hypertension should be treated with amlodipine Amlodipine.
    • If present, proteinuria Proteinuria should be managed with telmisartan Telmisartan or benazepril Benazepril.
    • A kidney diet may be considered after IRIS stage 3.
    • Phosphate binding agents should be considered if dietary therapy alone is not successful in managing hyperphosphatemia Hyperphosphatemia.
    • Appetite stimulants (eg mirtazapine) may be useful in cats with reduced appetite.
    • Erythropoeitin stimulating agents (eg darbopoeitin) may be useful in cats with moderate to severe anemia of renal disease.
  • Ultrasound guided drainage of cysts and/or alcoholization fails to slow disease progression but may reduce discomfort associated with capsular stretch.
  • Antibiosis if cysts have become infected - lipid soluble antibiotics, eg trimethoprim Trimethoprim, clindamycin Clindamycin, tetracycline Tetracycline because they penetrate the cyst. Antibiosis may also be required if evidence of urinary tract infection exists.

Monitoring

  • Monitor renal function.
  • Monitor for complications of chronic kidney disease:

Subsequent management

Treatment

Monitoring

Prevention

Control

  • Avoid breeding from lines producing affected individuals. The International Cat Care AD-PKD Negative Register allows breeders and owners to identify cats that have been tested and found to be negative.
  • Perform gene testing or ultrasound screening of all Persian and Exotic Shorthaired cats before they are used for breeding.
  • Consider ultrasound screening of breeding animals from other cat breeds that have used Persian blood-lines in their development, eg Burmilla, British Short-haired British shorthair, Maine Coone Maine Coon.

Outcomes

Prognosis

  • Poor: progressive disorder causing chronic kidney disease in the majority of affected animals however many cats remain asymptomatic for long periods and some cats may never show clinical disease. If signs of kidney disease are rapidly progressive, the prognosis is poor.
  • Good: in cases of acquired renal cysts if there is no underlying progressive kidney disorder.

Expected response to treatment

  • Improved quality of life.
  • No effect on rate of progression of disease; once cats with AD-PKD develop signs of chronic renal failure they often deteriorate relatively rapidly.

Reasons for treatment failure

  • Disease progression will result in deterioration of kidney function.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Bonazzi M, Volta A, Gnudi G et al (2009) Comparison between ultrasound and genetic testing for the early diagnosis of polycystic kidney disease in Persian and Exotic Shorthair cats. J Fel Med Surg 11 (6), 430-434 PubMed.
  • Helps C, Tasker S, Harley R (2007) Correlation of the feline PKD1 genetic mutation with cases of PKD diagnosed by pathological examination. Exp Mol Path 83 (2), 264-268 PubMed.
  • Zatelli A, D’Ippolito P, Bonfanti U et al (2007) Ultrasound-assisted drainage and alcoholization of hepatic and renal cysts: 22 cases. JAAHA 43 (2), 112-6 PubMed.
  • Grahn R A, Biller D S, Young A E et al (2004) Genetic testing for feline polycystic kidney disease. Anim Genet 35 (6), 503-504 PubMed.
  • Lyons L A, Biller D S, Erdman C A et al (2004) Feline polycystic kidney disease mutation identified in PKD1. J Am Soc Nephrol 15 (10), 2548-2555 PubMed.
  • Barthez P Y, Rivier P & Begon D (2003) Prevalence of polycystic kidney disease in Persian and Persian related cats in France. J Fel Med Surg (6), 345-347 PubMed.
  • Reichle J K, DiBartola S P & Léveillé R (2002) Renal ultrasonographic and computed tomographic appearance, volume, and function of cats with autosomal dominant polycystic kidney disease. Vet Radiol Ultrasound 43 (4), 368-373 PubMed.
  • Barrs V R, Gunew M, Foster S F et al (2001) Feline polycystic kidney disease in Persian cats and related breeds in Sydney and Brisbane. Aust Vet J 79 (4), 257-259 PubMed.
  • Beck C & Lavelle R B (2001) Feline polycystic kidney disease in Persian and other cats a prospective study using ultrasonography. Aust Vet J 79 (3), 181-184 PubMed.
  • Cannon M J (2001) Polycystic Kidney Disease in Persian Cats. UK Vet (1), 64-66.
  • Cannon M J, Mackay A D, Barr F J et al (2001) Prevalence of polycystic kidney disease in Persian cats in the UK. Vet Rec 149 (14), 409-411 PubMed.
  • Malik R (2001) Genetic diseases of cats. JFMS (2), 109-113 PubMed.
  • Biller D S, Chew D J, DiBartola S P (1990) Polycystic kidney disease in a family of Persian cats. JAVMA 196 (8), 1288-1290 PubMed.

Other sources of information

  • Biller D S (1994) Polycystic kidney disease.In:Consultations in Feline Medicine 2.Ed. J R August. W B Saunders. pp 325-330.