redazione@vetpedia.it +39-0372-40-35-36/37/47

Polycystic kidney disease in the dog and cat

Details
Category: Schede
Hits: 10
  • Disciplina: Urologia
  • Specie: Cane e Gatto

The presence of renal and hepatic cysts was described for the first time in human medicine in 19561 and since then these cysts have been the object of clinical, genetic and pathological studies. Most authors agree in defining polycystic kidney disease (PKD) as an inherited disease and classify it into two main categories: a dominant type (autosomal dominant PKD), also known as the adult type, and a recessive type (autosomal recessive PKD), also known as the infantile type.2-5

This disease was described in the Persian cat more than 40 years ago6and since then has been documented in other cat breeds, such as the Himalayan, Exotic, Scottish Fold, Burmese, Domestic Shorthair, American Shorthair, British Shorthair, Ragdoll and Carthusian.7 It has also been reported in some dog breeds such as the Bull Terrier,8,9 Cairn Terrier,10 West Highland White Terrier11 and in a raccoon,12 a goat,13 rats,14 mice,15 pigs16 and rabbits.17

 

AETIOLOGY

Autosomal dominant PKD is most prevalent in Persian cats or Persian crossbreeds, and in related breeds, such as the Exotic Shorthair. The disease affects approximately 38% of Persian cats worldwide.18 An epidemiological study conducted in Italy by ultrasound examination19 found a 41% prevalence in all Persian and Exotic cats tested. The prevalence in other cat breeds is not known.7 Bull Terriers are also affected by this disease, with the estimated prevalence in this breed being 26% in one study.9

Recently, autosomal dominant PKD in cats has been attributed to a single mutation due to C>A transversion in exon 29 of the feline PKD1 gene, causing a stop codon in the mRNA.20The PKD1 gene encodes polycystin 1 which, in the normal kidney, controls cell proliferation and maintains the tubular cells in a state of terminal differentiation.21

In Bull Terriers the gene has not yet been identified, but the study of pedigrees has suggested an autosomal dominant type of transmission.9,18 In this case too, a mutation in the PKD1 locus is strongly suspected to be the cause of the disease.22

In humans, autosomal recessive PKD, which is much rarer than the autosomal dominant form, leads to severe renal and biliary disease that typically occurs during childhood.21,23 In veterinary medicine this form of kidney disease has been suspected in the Cairn Terrier,10the West Highland White Terrier11 and in six kittens from four litters which were engendered by cats related to each other and which died before 7 weeks of age.24 The gene responsible for this disease in the dog and cat has not yet been isolated. Human autosomal recessive PKD is caused by a series of mutations of the PKHD1 gene, which encodes a protein called fibrocystin/polyductin. Although the function of this gene in healthy tissues is not yet known, it seems to play a key role in maintaining the integrity of organs, including the kidneys and the liver, by modulating cellular functions such as proliferation, secretion, apoptosis and terminal differentiation.21

PKD must be distinguished from glomerulocystic kidney disease, a rare disease characterized by cystic dilatation of Bowman's space, glomerular atrophy and mild interstitial fibrosis. In humans it usually affects children, but some cases have been reported in adults. The pathogenesis remains unknown but possible causes are periglomerular fibrosis and obstruction of the proximal tubule due to ischaemic phenomena.25 In dogs sporadic cases have been reported in purebred Blue Merle Collies,26 Belgian Malinois27 and Shibas.25

PKD must also be differentiated from acquired cystic kidney disease, meaning the abnormal development of cysts in the renal parenchyma of patients with chronic renal failure. According to studies in human medicine these cysts appear to develop in response to alterations induced by the state of uraemia (release of growth factors, acidosis, increased production of ammonia), which seem to stimulate the proliferation of the epithelial cells of the nephrons that survived the underlying renal disease, regardless of the cause.23 These cysts are usually small.28 Single cysts may also be found and in this case the main differential diagnosis is a cystic tumour.28

 

PATHOPHYSIOLOGY

PKD is characterized by multiple cysts of various sizes which develop in both kidneys, originate from renal tubules and form in both the cortex and the medulla.29In cats, cysts may also develop in the liver and pancreas, albeit less commonly. Liver cysts have been also found in the Cairn Terrier10 and West Highland White Terrier,11 but not in the Bull Terrier.18 Renal cysts appear early in life and gradually become more numerous and voluminous with age. The growth of these cysts may cause renal enlargement which can be an incidental finding during the clinical examination of apparently healthy animals.18

In the autosomal dominant form, kidney failure usually occurs in old age (it has been reported in Persian cats from 3 to 10 years old, the mean age being 7 years) and is caused by compression of the normal renal parenchyma by the cysts.18,30

In contrast, in patients with the autosomal recessive form, the clinical signs usually appear before the age of 2 months.18

 

SIGNALMENT

Gender: there is no gender predisposition in either the dog or cat.31

Age: the cysts are detected early, at 8 weeks in the dog and 4-8 weeks in the cat; the onset of symptoms is delayed in cases of autosomal dominant PKD, which affects middle-aged or elderly subjects, while it occurs earlier in cases of autosomal recessive PKD, which is usually already symptomatic during the first months of life.

Breed predisposition: autosomal dominant PKD has been reported in Bull Terriers and in Persian cats, Persian crossbreeds, the Himalayan, Exotic, Scottish Fold, Burmese, Domestic Shorthair, American Shorthair, British Shorthair, Ragdoll and Carthusian breeds, whereas autosomal recessive PKD has been reported in Cairn Terriers and West Highland White Terriers and in cats crossbred with the Persian breed.24

       

SIGNS

The signs are those typical of chronic renal failure, such as polyuria, polydipsia, vomiting, dehydration, weight loss and sensorial depression. The symptoms of autosomal dominant PKD usually appear in advanced age (> 7 years). Some cats, however, remain clinically healthy for most of their lives.7,32 In sharp contrast, patients with the autosomal recessive form usually show clinical signs before the age of 2 months.18

When cysts enlarge and stretch the renal or hepatic capsule, they can cause symptoms related to pain, such as anorexia, asthenia and reluctance to move, and vomiting.33 In the case of infected cysts, pain with fever may occur.

       

CLINICAL EXAMINATION

At abdominal palpation patients with PKD can be found to have renal enlargement, lumpy  kidneys and, in some cases, tenderness.33 Other alterations are those typical of chronic renal failure, such as dehydration, pale mucous membranes, uraemic breath and mouth ulcers.31

Patients with PKD can also have arterial hypertension.34 In fact, this is one of the most common alterations secondary to autosomal dominant PKD in humans and often precedes renal failure.35In humans the incidence of hypertension increases with age36,37 and correlates with the degree of renal involvement.38 According to one theory, the expansion of cysts causes renal hypoperfusion and consequent activation of the renin-angiotensin-aldosterone system (RAAS).39-41 In feline medicine, studies on the activation of the RAAS in the course of autosomal dominant PKD34,42 have produced conflicting results.

 

BLOOD TESTS

Blood tests can remain normal for most of the patient's life, and then start to show the typical signs of renal failure, such as increased urea and creatinine, hyperphosphataemia, normocytic and normochromic anaemia and metabolic acidosis.31 In the case of hepatic involvement, it is possible to find alterations characteristic of liver failure such as increased levels of alanine transaminase, alkaline phosphatase and bile acids.11

 

URINALYSIS 

Hyposthenuria or isosthenuria is present in the course of chronic renal failure. There are also reports of haematuria, which probably occurs as a result of intrarenal bleeding, and pyuria in some patients with PKD.34 Proteinuria has also been reported,43 which is particularly common in Bull Terriers; in these dogs, however, PKD is often associated with hereditary nephritis and it is, therefore, difficult to determine which of the two diseases causes the proteinuria.9,12

In humans, proteinuria is found more frequently in the advanced stage of the disease and is usually associated with hypertension, more severe renal morphological and functional alterations and a more rapid and aggressive course than in renal failure.44

A urine culture is recommended, as cysts can become infected, thereby complicating the clinical picture.31

      

DIAGNOSTIC IMAGING

Radiographic examinations

Direct radiographsmay appear normal if cysts are small, but if they are numerous or large, the kidneys may appear enlarged and/or have an irregular surface.45

Excretory urographyshows spherical filling defects in the parenchyma and the pelvis can appear distorted.45

Ultrasound examination

Before the development of genetic testing, ultrasound examination was the only method to diagnose this disease. Unlike the genetic test, ultrasonography allows the clinician to evaluate the severity of the disease and monitor its progression.32 Abdominal ultrasound can also highlight the presence of hepatic (Fig. 1) and pancreatic cysts. A high-frequency probe (≥ 7 MHz) is needed in order to obtain a good resolution. Longitudinal, sagittal, and transverse scans are necessary in order not to miss any cysts.46 Nevertheless, small cysts (<2 mm) may go undetected.32

The cysts appear as rounded or oval cavities with an anechoic content; the wall is smooth, thin, conspicuous and with strong posterior acoustic enhancement. When particularly large, these cysts can distort the profile of the organ. The medulla is less echogenic than the cortex, hence cysts in this anatomical area are more difficult to identify.46

In the cat, the ultrasound identification of multiple cysts of various sizes in both kidneys is diagnostic (Fig. 2).46 In young cats, however, the presence of a single renal cyst may be considered diagnostic (Fig. 3), given the extremely low prevalence of cysts in cats without PKD.32,46 In some cases cysts are already visible in 6- to 8-week old kittens. This said, the sensitivity of ultrasound studies increases to 75% at 16 weeks, and rises further to 91% at 36 weeks, with a specificity at this age of 100%.18,46 To increase the sensitivity of ultrasound examination, some authors recommend repeating ultrasonography at least twice, performing the first ultrasound examination at 16 weeks and re-examining the negative subjects at 10 months of age.47 Ten months is the minimum age considered reliable for official certification by certain breed associations, though a good correlation has been demonstrated between the non-detection of cysts at the age of 3 months and the absence of PKD.48

In the dog, it is more common to find simple renal cysts, and this tendency increases with age so the diagnostic criteria are more stringent and require the presence of at least three cysts between the two kidneys.46 As for the Bull Terrier, in some cases cysts are visible in 8-week old puppies;22 however, guidelines on the age at which to perform an ultrasound for the first time have not yet been established. In the presence of fewer than three cysts, or if only one kidney is involved, some authors9 consider the result uncertain and examine the patient again after 6-12 months although the condition is considered likely in cases in which a first-degree relative is affected.

 

GENETIC TESTING

For Persian cats and related breeds a genetic test is now available that identifies the mutation of the PKD1 gene in the DNA isolated from blood samples or buccal swabs. The test can be performed by two different methods: polymerase chain reaction restriction fragment length polymorphism or real-time polymerase chain reaction.49,50 These methods are equally sensitive and specific, but the real-time polymerase chain reaction is faster and less prone to contamination during processing.50

Unlike ultrasound examination, genetic testing can be done at any age and the samples necessary for the analysis are very easy to collect and send to the laboratory. However, as previously mentioned, genetic testing does not allow the severity or the progression of the disease to be assessed. For these reasons ultrasound examination is still necessary.50 It should also be pointed out that genetic testing cannot diagnose polycystic kidney diseases that are not linked to a mutation of the PKD1 gene. A recent study51 identified a small percentage of cats negative for the genetic test but with post-mortem evidence of PKD, suggesting the existence of other mutations causing PKD or of other forms of PKD. No genetic test is yet available for autosomal dominant PKD in Bull Terriers or for canine and feline autosomal recessive PKD.

 

HISTOPATHOLOGY

Renal histopathology shows the presence of roundish or ovoid cysts, which are unilocular or multilocular, with a thin wall usually made up by a single layer of squamous or cuboidal epithelial cells, originating from nephrons and collecting ducts; in some cases, however, they are surrounded by stratified cuboidal cells. The cysts are filled with clear or haemorrhagic fluid and in some cases may contain degenerated epithelial cells, purulent, proteinaceous material or fibrin.9,29,30,51 Adult animals with advanced stage disease may also have alterations typical of chronic tubulo-interstitial nephritis, with varying degrees of lymphoplasmacytic infiltration, areas of neutrophilic infiltration and focal fibrosis.9,29

In the Bull Terrier the condition is often associated with the typical lesions of hereditary nephritis characteristic of this breed, such as microcystic glomeruli, cystic dilatation of Bowman’s capsule, persistence of foetal glomeruli in the adult and juxtamedullary ectopic glomeruli. A more severe clinical picture may be expected in the presence of both conditions.30

Hepatic cysts may be unilocular or multilocular, surrounded by cuboidal or columnar biliary epithelial cells and fibrous connective tissue rich in collagen, within a normal liver parenchyma.10,11

Pancreatic cysts may be surrounded by fibrotic tissue and signs of inflammation can also be present.31

 

TREATMENT

There is no specific treatment for PKD; when chronic renal failure treatment is present, therapy should be aimed at slowing its progression and treating the clinical symptoms associated with the uraemic syndrome. The key points of treatment are: dietary restriction of proteins and phosphorus; intravenous or subcutaneous fluid therapy to correct dehydration; anti-emetics and gastroprotectants to treat nausea, vomiting and uraemic gastritis; and control of any secondary alterations such as hyperphosphataemia, hypertension, proteinuria, fluid-electrolyte and acid-base disorders and anaemia.

With the increase in size of cysts there is a higher risk of a cyst rupturing following trauma or compression and extra caution is, therefore, required in the presence of large cysts. Bleeding secondary to a ruptured cyst is usually self-limiting but clots can form and cause urinary tract obstruction. In human medicine, it has been reported that blood transfusions can be needed in cases of severe bleeding and, if the bleeding cannot be stopped, nephrectomy may even be necessary is some cases.23

In case of pain-related symptoms other possible causes should first be excluded, such as infections or stones, and only then should pain treatment be started. Non-steroidal anti-inflammatory drugs should be used with caution as they can accelerate the progression of renal damage.

In the presence of infected or complicated cysts - or when the cysts are very large and cause distension of the renal capsule, leading to symptoms of pain or urinary flow obstruction - percutaneous drainage of the cysts may be necessary, using ultrasound-guided aspiration. Following analgesia with tramadol and anaesthesia with propofol, an ultrasound-guided spinal needle (22 or 23 G) is inserted into the cyst; the stylet is removed and the needle is connected to a syringe via an extension with a three-way valve; the syringe should not be too large in order to avoid creating an excessive negative pressure during the aspiration. At this point the liquid is aspirated slowly; it is advisable to collect specimens for bacteriological examination and for cytology. When the drainage of the cyst has been completed, the same needle is used to inject 95% ethanol into the evacuated cyst: the volume of ethanol injected should be about half the volume of the liquid aspirated. The ethanol is left in situ for 3 minutes and then aspirated slowly. The procedure is then repeated, this time adding 2% lidocaine to the ethanol in a 1 to 10 ratio. The second injection of ethanol increases its contact with the epithelial cells, thus increasing the sclerosing effect and reducing the frequency of relapses.33,51

The effect of this procedure is short-lived as fluid tends to accumulate again within the cysts. However, the instillation of sclerosing substances, such as ethanol, reduces this fluid accumulation and slows the expansion of the cysts. It is generally unnecessary to administer analgesics for more than 24 hours after the procedure. The most common complication is mild bleeding, which usually resolves spontaneously after discontinuation of the procedure. In some cases this is accompanied by pain and the analgesic treatment must be prolonged for a few days. Other possible complications are the spread of potentially infectious material contained within the cyst and rupture of the cyst; however, such complications do not usually occur if the procedure is performed correctly. In the case of  neoplastic cysts, there is a risk of metastatic spread along the needle tract, although this risk is greatly reduced by the use of ethanol.33,51

In most cases the clinical picture improves considerably following the procedure and the pain resolves. In humans, the drainage of large cysts is also accompanied by resolution of hypertension. In a retrospective study this effect also occurred in canine patients, but not in cats.33

Infected cysts can be extremely difficult to treat because antibiotics must penetrate the cysts in order to be effective. The choice of antibiotic should be based on an antibiogram, bearing in mind that bacterial cultures are not always reliable when performed on urine rather than on the intracystic fluid because the cysts do not communicate with the urinary space. In human medicine it has been reported that lipophilic antibiotics with an alkaline pH penetrate cysts more effectively. Among these, the use of trimethoprim, chloramphenicol, ciprofloxacin, vancomycin, clindamycin and erythromycin has been reported.23 A similar study would be useful in veterinary medicine. In some cases antibiotic therapy is ineffective and percutaneous or surgical drainage becomes indispensable.

In humans the use of ACE-inhibitors seems to slow the progression of renal failure associated with PKD, whereas in feline patients the results are mixed.31,34,42

In a murine model, rapamycin, an immunosuppressive and antiproliferative agent, has been shown to slow the progression of renal disease in the course of PKD, preventing the development of new cysts and causing the remission of existing ones. It was hypothesized that these effects depend on a combination of reduced cell proliferation and increased apoptosis of the epithelial cells of the cysts themselves.52Clinical trials in the cat and dog would be required to evaluate the effectiveness of this strategy, the optimal doses and the possible side effects in these species.

 

MONITORING

Serial controls of the renal function are necessary, including blood-chemistry tests, urinalysis, abdominal ultrasound and blood pressure measurements in order to monitor the progression of the disease and promptly treat any complication secondary to the disease itself.

The frequency of follow-up examinations depends on the severity of the clinical picture and on the values of azotaemia:31

  • in stage I (patients without azotaemia, with creatinine values ​​<1.6 mg/dl), if the patient is stable and asymptomatic, follow-up examinations every 6-12 months are sufficient;
  • in stage II (mild renal azotaemia, with creatinine between 1.6 and 2.8 mg/dl), follow-up examinations should be performed every 3-6 months;
  • in stage III (moderate renal azotaemia, with creatinine between 2.8 and 5 mg/dl), follow-up examinations should be performed every 2 months;
  • in stage IV (severe renal azotaemia, with creatinine > 5 mg/dl), follow-up examinations should be performed on a monthly basis.

It is also advisable to perform a urine culture at least twice a year, as renal cysts can become infected, thereby complicating the clinical picture.31

 

PROGNOSIS

The long-term prognosis is poor because of the gradual destruction of the renal parenchyma by the expanding cysts;44 however, life expectancy depends on the degree of involvement of the renal parenchyma and on the severity of the renal failure at diagnosis. Favourable prognostic factors are the presence of small cysts that do not alter the renal architecture and the absence of renal failure. Conversely, negative prognostic factors are the presence of multiple, large cysts in both kidneys which significantly alter the renal architecture, hyperazotaemia and proteinuria.31

 

ERADICATION

The disease can be eradicated through breeding by screening all subjects and excluding from reproduction all subjects testing positive.47

As previously mentioned, no genetic test is currently available for Bull Terriers. Therefore, in order to minimise transmission of the disease in this species, an ultrasound examination should be performed on all dogs at risk before allowing reproduction.18

 

References

  1. Al-Bhalal L., Akthar M. (2008)– Molecular basis of autosomal recessive polycystic kidney disease (ARPDK). Adv Anat Pathol; 15: 54-58.
  2. Appleman E., Berent A. (2006)-  Polycystic Kidney Disease. Standard of Care: Emergency and Critical Care Medicine; 8(10): 7-10.
  3. Barret B.J., Foley R. Morgan J., Hefferton D., Parfrey P. (1994)– Differences in hormonal and renal vascular responses between normotensive patients with autosomal dominant polycystic kidney disease and unaffected family members. Kidney Int; 46(4): 1118-1123.
  4. Barrs  V.R., Gunew M., Foster S.F., Beatty J.A., Malik R. (2001)– Prevalence of autosomal dominant polycystic kidney disease in Persian cats and related-breeds in Sidney and Brisbane. Australian Veterinary Journal; 79(4): 257-259.
  5. Beck C., Lavelle R.B. (2001)– Feline polycystic kidney disease in Persian and other cats: a prospective study using ultrasonography. Australian Veterinary Journal; 79(3): 181-184.
  6. Bernstein J. (1976)– A classification of renal cysts. In: Polycystic Diseases of the Kidney; John Wiley and Sons, New York; pp 7-30.
  7. Biller D.S., Chew D.J., DiBartola S.P. (1990)-  Polycystic kidney disease in a family of Persian cats. J Am Vet Med Assoc; 196: 1288-1290.
  8. Blyth H., Ockenden B.G. (1971)-  Polycystic diseases of kidney and liver presenting in childhood. J Med Genet; 8: 257-284.
  9. Bonazzi M., Volta A., Gnudi G., Bottarelli E., Gazzola M., Bertoni G. (2007) – Prevalence of the polycystic kidney disease and renal and urinary bladder ultrasonographic abnormalities in Persian and Exotic Shorthair cats in Italy. Journal of Feline Medicine and Surgery; 9: 387-391.
  10. Bonazzi M., Volta A., Gnudi G., Cozzi M.C., Strillacci M.G., Polli M., Longeri M., Manfredi S., Bertoni G. (2009) – Comparison between ultrasound and genetic testing for the early diagnosis of polycystic kidney disease in Persian and Exotic Shorthair cats. Journal of Feline Medicine and Surgery; 11: 430-434.
  11. Bristowe F. (1956)– Cystic disease of the liver associated with similar disease of the kidneys. Trans Pathol Soc London; 7: 235-237.
  12. Burrows A.K., Malik R., Hunt G.B. (1994)– Familial polycystic kidney disease in bull terrier. J Small Anim Pract; 35:364-369.
  13. Cerasola G., Li Vecchi M., Mulé G., Cottone S., Mangano M.T., Andronico G. Contomo A., Parrino I.A., Renda F., Pavone G., Scialabba A. (1997) – Role of renin-angiotensin-aldosterone system and of sympathetic activity in arterial hypertension associated with autosomal dominant polycystic kidney disease. Contrib Nephrol; 122: 22-27.
  14. Chalofoux A., Phaneuf J.B., Oliviero M., Gosselin Y. (1982) – Glomerular polycystic kidney disease in a dog (Blue merle collie). Canadian Veterinary Journal; 23: 365-368.
  15. Chapman A.B., Johnson A.M.,Gabow P.A., Schrier W. (1990)– The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. N Engl J Med; 323(16): 1091-1096.
  16. Chapman A.B., Johnson A.M.,Gabow P.A., Schrier R.W.(1994)– Overt proteinuria and microalbuminuria in autosomal dominant polycystic kidney disease. J Am Soc Nephrol; 5: 1349- 1354.
  17. Conte F., Serbelloni P., Milani S., Sessa A. (1995)– Clinical data of a cooperative Italian study of ADPKD. Contrib Nephrol; 115: 72-87.
  18. Cowley B.D., Gundapaty S., Kraybill A.L., Barash B.D., Harding M.A., Calvet J.P., Gattone V.H. 2nd (1993) – Autosomal-dominant polycystic kidney disease in the rat. Kidney Int; 43(3): 522-534.
  19. Crowell W.A., Hubbell J.J., Riley J.C. (1979)– Polycystic renal disease in related cats. J Am Vet Med Assoc; 175: 286-8.
  20. Dalgaard O.Z. (1957)– Bilateral polycystic disease of the kidneys: a follow-up of two-hundred and eighty-four patients and their families. Acta Med Scand; 328(suppl): 1-255.
  21. Dennis R., McConnell F. (2007)– Diagnostic imaging of the urinary tract. In: Elliott J., Grauer G.F. Eds: BSAVA Manual of Canine and Feline Nephrology and Urology. Second edition. BSAVA, Quedgeley, Gloucester: 125-58.
  22. Eaton K.A., Biller D.S., DiBartola S.P., Radin M.J., Wallerman M.L. (1997) – Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats. Veterinary Pathology; 34: 117-126.
  23. Fox R.R., Krinsky W.L., Cary D.D. (1971)– Hereditary cortical renal cysts in the rabbit. J Hered; 62: 105-109.
  24. Gabow P.A., Chapman A.B., Johnson A.M.,  Tangel D.J., Duley I.T., Kaehny W.D., Manco-Johnson M., Schrier R.W. (1990)– Renal structure and hypertension in autosomal dominant polycystic kidney disease. Kidney Int; 38(6): 1177-1180.
  25. Gabow P.A. (1993)– Autosomal dominant polycystic kidney disease. N Engl J Med; 329: 332-342.
  26. GardnerK.D. (1976)- Cystic Diseases of Kidney. John Wiley and Sons, New York.
  27. Hamir A.N., Klein L. (1996)-  Polycystic kidney disease in a raccoon (Procyon lotor). J Wildlife Dis; 32: 674-677.
  28. Helps C.R., Tasker S., Harley R. (2007)– Correlation of the feline PKD1 genetic mutation with cases of PKD diagnosed by pathological examination. Exp Mol Pathol; 83: 264-268.
  29. Helps1 C.R., Tasker S., Barr F.J., Wills S.J., Gruffydd-Jones T.J. (2007)– Detection of the single nucleotide polymorphism causing feline autosomal-dominant polycystic kidney disease in Persians fron the UK using a novel real-time PCR assay. Molecular and Cellular Probes; 21: 31-34.
  30. Krotec K., Smith Meyer B., Freeman W., Hamir A.N. (1996)– Congenital cystic disease of the liver, pancreas, and kidney in a Nubian goat (Capra hircus). Vet Pathol; 33: 708-710.
  31. Lees G.L. (2007) – Juvenile and familial nephropathies. In: Elliott J., Grauer G.F. Eds: BSAVA Manual of Canine and Feline Nephrology and Urology. Second edition. BSAVA, Quedgeley, Gloucester: 79-86.
  32. Lettow E., Dammrich K. (1967)– Congenital polycystic liver and kidney lesions in a cat. Kleinter-Prax; 12: 34-43.
  33. Lieberman E., Salinas-Madrigal L., Gwinn J.L., Brennan L.P., Fine R.N., Landing B.H. (1971)– Infantile  polycystic disease of the kidney and liver: Clinical, pathological and radiological correlations and comparison with congenital hepathic fibrosis. Medicine; 50: 277-318.
  34. Lulich J.P., Osborne C.A., Walter P.A., O'Brien T.D. (1988) – Feline idiopathic polycystic kidney disease. Compend Cont Ed Pract Vet: Small Anim Pract; 10: 1030-1040.
  35. Lyons L.A., Biller D.S., Erdman C.A., Lipinski M.J., Young A.E., Roe B.A., Qin B. Grahn R.A. (2004) – Feline Polycystic Kidney Disease Mutation Identified in PKD1. J Am Soc Nephrol; 15: 2548-55.
  36. MartinezJ.R., Grantham J.J. (1995)– Polycystic Kidney Disease: Etiology, Pathogenesis, and Treatment. Disease-a-Month; XLI(11): 693-765.
  37. McAloose D, Casal M., Patterson D.F., Dambach D.M. (1998) -  Polycystic kidney and liver disease in two related West Highland-White Terrier litters. Vet Pathol; 35: 77-81.
  38. Mckenna S.C., Carpenter J.L. (1980) – Polycystic disease of the kidney and liver in the Cairn Terrier. Vet Pathol; 17: 436-442.
  39. Miller R.H., Lehmkuhl L.B., Smeak D.D., DiBartola S.P., Radin J. (1999) – Effect of enalapril on blood pressure, renal function, and the renin-angiotensin-aldosterone system in cats with autosomal dominant polycystic kidney disease. Am J Vet Res; 60(12): 1516-25.
  40. Mylonakis M.E., Patsikas M.N., Koutinas A.F., Kaldrymidou H., Plevraki K. (1999)- Polycystic kidney  disease in a Persian cat. Aust Vet Pract; 29: 59-61.
  41. Nicolau C., Torra R., Badenas C., Vilana R., Bianchi L., Gilabert R., Darnell A., Brù C. (1999) - Autosomal dominant polycystic kidney disease types 1 e 2: assessment of US sensitivity for diagnosis. Radiology; 213: 273-276.
  42. O'Leary C.A., Mackay B.M., Malik R., Edmondston J.E., Robinson W.F., Huxtable C.R. (1999)– Polycystic kidney disease in Bull Terriers: an autosomal dominant inherited disorder. Aust Vet J; 6: 361-366.
  43. O'Leary C.A., Ghoddusi M., Huxtable C.R. (2002)– Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull Terriers. Aust Vet J; 80(6): 353-361.
  44. O'Leary C.A., Duffy D., Biros I., Corley S. (2009)– Linkage confirms canine pkd1 orthologue as a candidate for bull terrier polycystic kidney disease. Animal Genetics; 40: 543-546.
  45. Ottesen N. (2004)-  Polycystic Kidney  Disease in Persian cats: comparison of renal ultrasonography at the age of 3 and 12 months. Abstracts from the Annual Conference of the European Association of Veterinary Diagnostic Imaging. Veterinary Radiology & Ultrasound; 45(6): 586-613.
  46. Pedersen K.M., Pedersen H.D., Häggström J., Koch J., Ersbøll A.K. (2003) – Increased Mean Arterial Pressure and Aldosterone-to-Renin Ratio in Persian Cats with Polycystic Kidney Disease. J Vet Intern Med; 17:21-27.
  47. Ramos-Vara J.A., Miller M.A., Ojeda J.L., Reid R., Craft D., Watson G.L. (2004)- Glomerulocystic kidney  disease in a Belgian Malinois dog: an ultrastructural, immunohistochemical, and lectin-binding study. Ultastructural Pathology; 28: 33-42.
  48. Schieren G., Pey R., Bach J., Hafner M., Gretz N. (1996)– Murine models of polycystic kidney disease. Nephrol Dial Transplant; 11(suppl): 38-45.
  49. Shillingford J.M., Piontek K.B., Germino G.G., Weimbs T. (2010)– Rapamycin Ameliorate PKD Resulting from Conditionaò Inactivation of Pkd1.J Am Soc Nephrol; 21: 489-97.
  50. Takahashi M., Morita T., Sawada M., Uemura T., Haruna A., Shimada A. (2005)– Glomerulocystic Kidney in a Domestic Dog. J Comp Path; 133: 205-208.
  51. Volta A., Manfredi S., Gnudi G., Gelati A., Bertoni G. (2010) - Polycystic kidney disease in a Chartreux cat. Journal of Feline Medicine and Surgery; 12: 138-140.
  52. Walter P.A., Johnston G.R., Feeney D.A., O'Brien T.D. (1988)– Applications of ultrasonography in the diagnosis of parenchymal kidney disease in cats: 24 cases (1981-1986). JAVMA; 192(1): 92-98.
  53. Webster W.R., Summer P.M. (1978) – Congenital  polycystic kidney and liver syndrome in piglets. Aust Vet J; 54: 451.
  54. Wills S.J., Barrett E.L., Barr F.J., Bradley K.J., Helps C.R., Cannon M.J., Gruffydd-Jones T.J. (2009) – Evalutation of the repeatability of ultrasound scanning for detection of feline polycystic kidney disease. Journal of Feline Medicine and Surgery; 11: 993-996.
  55. Zatelli A., Bonfanti U., D'Ippolito P. (2005)– Obstructive Renal Cyst in a Dog: Ultrasonography-Guided Treatment Using Puncture Aspiration and Injection with 95% Ethanol. J Vet Intern Med; 19: 252-54.
  56. Zatelli A., D'Ippolito P., Bonfanti U., Zini E. (2007)– Ultrasound-Assisted Drainage and Alcoholization of Hepatic and Renal Cysts: 22 Cases. J Am Anim Hosp Assoc; 43: 112-16.