Renal Disease and Screening Tests

Louise Lynch (May 2010)

Kidneys

Most dogs (and humans) are born with two kidneys which lie at the back of the upper abdomen on either side of the spine. They are close to other organs in the abdomen including bowel, liver, spleen and pancreas. The functioning unit of the kidney is called a nephron and each kidney will have hundreds of thousands of these. The basic job of the kidney is to clear the body of waste substances but they also regulate the volume of water in the body and the levels of various chemicals. They are essential for maintaining a healthy “status quo”.

Kidneys have a characteristic appearance on scans (ultrasound/CT/MRI) with an outer cortex, inner medulla and collecting system of tubes which take the urine formed by kidney processes to the bladder.

Renal dysplasia and polycystic kidney disease (PKD)

These are conditions well-known in humans and less well described in dogs including Skye terriers and bull terriers.

Renal Dysplasia (RD) means that the kidneys are structurally abnormal. It may affect one or both kidneys partially or totally. Structurally abnormal kidney is non-functional. The condition may be asymptomatic in a young dog.

Polycystic kidney disease (PKD) is a progressive disease involving the development of multiple cysts. As the cysts develop they lead to enlargement of the kidneys and this is often associated with pain and compression of normal kidney tissue, which impairs function and can lead to kidney failure. The rate of development of cysts is as yet unknown in Skye terriers, but in humans diagnosis can usually be made by ultrasound scanning at the age of 20 (in a small number of cases PKD is not evident in humans by age 20 and rescanning at age 30 is required). In bull terriers ultrasound scanning at 12 months is recommended to identify affected dogs. Impairment of kidney function starts well after structural changes are evident – often 20 – 30 years later in humans. The kidneys have a huge amount of functional reserve and impairment is not detectable until more than 75% of kidney tissue is destroyed / lost.

Kidney function declines normally with time and so neither condition may be apparent in a young dog but they may become evident when a critical point is reached (i.e. when 75% or more of the kidney tissue has been destroyed) or if the kidneys are stressed by dehydration during an illness. Infection or gastro-intestinal upsets are common causes of unmasking a hitherto unknown kidney problem, as is anaesthesia for an unrelated problem. The kidneys in a dehydrated dog normally respond to the situation by conserving salt and water and losing acid. If they can’t do this well enough, the dog will quickly become unwell.

It is worth pointing out that there may well be a discrepancy between humans and Skyes in the clinical course and natural history of PKD, BUT the majority of humans with adult PKD get past the age of 50 without reaching end-stage renal failure. Many humans never reach end-stage renal failure, dying of other causes in old age, and remain asymptomatic until the advanced stages of the disease.

Diagnosing renal dysplasia and polycystic kidney disease

Both conditions produce structural changes well in advance of functional changes.

Blood and urine tests are useful for monitoring and treating the conditions in affected dogs i.e. in management and prognosis, but have no value at all in the initial diagnosis. They will be normal in a dog with normal kidney function and give no insight at all into any structural changes.

Both conditions are inherited. The genetic abnormality responsible for renal dysplasia may be widespread in Skyes and only expressed in some of the puppies produced by mating a dog carrying the gene and a bitch carrying the gene. The genetic abnormality responsible for polycystic kidney disease is usually an autosomal dominant gene in humans – any person carrying the gene will have the condition and as genes come in pairs and a baby has a 50% chance of getting the abnormal gene, their offspring will have a 50% chance of both having the gene and the disease.

Renal dysplasia is congenital – present from birth.

Polycystic kidney disease is progressive and may or may not be structurally evident at birth or in puppyhood. In humans, ultrasound scanning at the age of 20 is normally diagnostic with a “late” scan at 30 as a very few people won’t have evident cysts at 20. The natural history of the disease in Skyes isn’t known – we don’t know how rapidly the cysts develop, although some dogs have had positive scans in puppyhood. It seems sensible to leave scanning as late as possible to pick up as many positives as possible in breeding stock prior to breeding. The English Bull Terrier Club recommends 12 months for their breeding stock.

Scanning tests available include ultrasound scanning, MRI and CT. Both MRI and CT give excellent images of kidneys. However, both need an anaesthetised dog and there is a finite risk of mortality even in a healthy dog. Cost is effectively prohibitive for a screening test. Ultrasound scanning is, therefore, the first-line investigation of choice in humans and similarly for dogs.

Ultrasound involves passing high frequency sound waves through body tissues and measuring the time taken and number of waves reflected back. If all the waves are reflected back, the image on the screen is white e.g. from bone and if all the waves are absorbed, the image is black e.g. water. Kidneys have a characteristic structure and are usually easily imaged. Cysts would usually appear with a grey outline and a central darkness.

Medical ultrasound uses frequencies of between 2 and more than 15 MHz. Audible sound is between 20 Hz and 20 kHz. A high frequency transducer (probe) will give excellent resolution i.e. good pictures with clear anatomy but not penetrate very deep into body tissue and vice versa. An ultrasound operator will use the highest frequency transducer available for tissues at an expected depth for good quality images. Lots of different transducers are available but a common one for dog kidneys would be a 38mm linear probe between 10 and 5 MHz.

The quality of ultrasound very much depends on the skill and experience of the operator. Not all vets (or doctors) are confident in diagnostic ultrasound scanning but would normally be able to recommend a colleague if not. Over the past couple of years ultrasound scanners have become cheaper and more user friendly / smaller / portable.

A good contact is required between skin and transducer to get a good image. Ultrasound doesn’t pass through air. Lots of gel required. Shaving the relevant area of skin is standard practice, although isn’t strictly necessary and could be avoided by negotiation with your vet.

Dogs can be scanned standing or prone (lying on their backs) with their tummy exposed. The position per se is not important as long as a good view of the whole of both kidneys can be obtained. The ultrasound probe is moved around the underlying kidney. Loops of gut will naturally fall forwards if the dog is standing, which might make the imaging easier as bowel gas can be an unwanted artefact.

False positives, false negatives, true positives

Every screening test has false positives (abnormality detected when none exists) and false negatives (normal scan when the dog has the condition). We don’t know what the incidence of this is for Skyes, but we do know that it will occur. We can only take the best evidence that we have at the current time to do the best for our breed.

Any positive / abnormal scan demands rescanning and further investigation and the dog should obviously not breed until a diagnosis has been obtained. As mentioned above, other abdominal viscera lie close to the kidneys and a condition of any of these e.g. tumour, may appear to originate from the kidneys, and bowel gas can create an artefact. Simple single renal cysts (not caused by PKD) exist and would need monitoring.

A single abnormal ultrasound scan would not be a reason to euthanase a healthy dog.

Even if the dog is diagnosed with PKD or renal dysplasia, it may be completely well for many years or even the rest of its life. The diagnosis on its own is not sufficient reason to euthanase an asymptomatic dog. The diagnosis is important in excluding the dog from breeding, but its future management should be decided between the owner and their vet.

False negatives are more unlikely and could occur if the dog has either only a very small dysplastic area in one kidney or if the multiple cysts of polycystic disease are either too small to detect or have not developed. (The further investigation and monitoring of an affected dog is outside the remit of this article)

The gold standard for the screening of any genetic condition is the identification of affected gene(s) and a DNA-based screening test. The only way to achieve this is through a comprehensive DNA database and identification and notification of affected dogs. Serious funding can then be applied for to do the science. In the interim we can submit DNA and screen breeding stock. We have to liaise with the international breed clubs. We are already getting samples from affected dogs abroad. We don’t have the answers now, but if we don’t try to the best of our ability using the best evidence available, we never will.

 

Louise Lynch

BSc(Hons) class I in chemical pathology
MB ChB
DA
FRCA
FFPMRCA

(Email: louiselynch@btinternet.com)

Louise is a medical doctor – consultant in chronic and cancer pain management currently – previously a consultant in anaesthesia and intensive care. She works for the Leeds Teaching Hospitals NHS Trust. She uses ultrasound as part of her pain management practice in imaging nerves of the brachial plexus and suprascapular nerves to do nerve blocks for human patients. She has experience of renal medicine after many years working on intensive care units and some research experience in dialysis for renal failure.

Louise has two Skye terriers, Oscar and Florence. Oscar had an MRI earlier this year – both kidneys incidentally normal and Florence had an ultrasound last month – standing, not shaved, all okay.