The Importance of Feline Kidney Disease
Rosanne Jepson BVSc (Dist) MVetMed PhD DipACVIM MRCVS - 27/04/2014
The importance of Feline Kidney Disease
Rosanne Jepson BVSc (Dist) MVetMed PhD DipACVIM MRCVS
Cats with chronic kidney disease are seen every week in veterinary practices across the country. Over the next few years this caseload is only likely to increase due to the ageing cat population. To introduce a special focus on chronic disease in cats, Rosanne Jepson from the Royal Veterinary College reviews the aetiology and clinical presentation of this common disease.
Chronic kidney disease (CKD) is an important condition that is commonly recognised in feline practice. There is relatively little information telling us exactly how common CKD is in cats but early studies suggest a prevalence of 1.8-3 % of the feline population as a whole.1 As we start to recognise CKD at an earlier time point and with improvements in our diagnostic ability, CKD may be more prevalent than first suspected.
The kidney is a vital organ involved in many homeostatic processes including filtration and excretion of nitrogenous waste, maintenance of hydration and volume status, acid-base regulation, endocrine hormone production (e.g. erythropoietin and Vitamin D) and regulation of blood pressure. Loss of kidney function can therefore affect multiple body systems. CKD can impact greatly on a cat’s health and wellbeing and it is therefore important that we strive to recognise CKD so that we can start appropriate monitoring and treatment at the earliest opportunity. CKD means that there has been a structural or functional change in one or both kidneys that has been present for >2-3 months. The term chronic kidney disease is now used in favour of other previous terminology such as chronic renal failure or chronic renal insufficiency.
What types of kidney disease affect cats?
There are a number of disease conditions that can affect the feline kidney. The most common form of CKD in the geriatric cat is tubulointerstitial nephritis but in 20-40 % of cats diagnosed with CKD another underlying disease may be identified.2,3
Approximately 30 % of cats >15 years old will have evidence of tubulointerstitial nephritis. The average age at diagnosis of CKD due to tubulointerstitial nephritis is 12 years, with most cats typically being > 8 years old.4 However, cats of any age can be diagnosed with this condition and no sex or breed predispositions have been identified. Tubulointerstitial nephritis is a nonspecific pathological response of the kidney to an insult but this histopathological diagnosis does not tell us about the inciting cause and it is rare to ever find an underlying aetiology (Figure 1).
Figure 1: Histopathological appearance of tubulointerstitial nephritis in a cat. Tubulointerstitial inflammation (black arrow), glomerulus (blue arrow), proximal tubule (green arrow). Image courtesy of Dr. Simon Priestnall.
Some studies have investigated the role that vaccination and feline immunodeficiency virus may play in the development of tubulointersititial nephritis but these causal links have never been confirmed.5,6 It has also been hypothesized that tubulointerstitial nephritis is just part of the normal ageing process in the cat.7 In human medicine, CKD due to tubulointerstitial nephritis is also a disease of the ageing population and it is considered a complex disease influenced by many environmental and genetic factors. The same is likely to be true in cats where, in addition, secondary factors such as episodes of pyelonephritis, nephrolithiasis or ureterolithiasis, administration of nephrotoxic medications or toxic insults can impact on disease development and progression.
Other primary renal conditions can affect the feline kidney. Some of these conditions have breed predispositions or are congenital. For example, polycystic kidney disease (PKD) is an autosomal dominant condition that affects Persians, related breeds such as Exotic and British Shorthair, Chinchilla and has also been reported in Birmans, Snowshoes, Scottish Folds, Ragdolls and others. PKD results in the development of multiple variable sized cystic lesions throughout the kidney and also sometimes within the liver. The cysts tend to form early in life and have been reported in kittens as young as 6-8 weeks but become larger and more numerous with age. As cysts grow, the kidney can become enlarged and irregular and this may be noted on physical examination in otherwise healthy cats but ultimately cats with PKD may become azotaemic. The prevalence of PKD is reported to be about 38 % of Persians worldwide and is caused by a single mutation in the gene PKD1.8-12 A genetic test (PCR) is available to identify this mutation and means that PKD can be detected before cystic lesions might otherwise be found on ultrasound examination (Figure 2).
Figure 2: Polycystic kidney disease. a) An autosomal dominant polycystic kidney disease is identified in Persian cats. b) Ultrasound examination identifies multiple parenchymal cysts throughout both kidneys. Image courtesy of Dr Livia Benigni.
A familial form of amyloidosis is recognised in Abyssinian cats but reflects only about 2% of all feline kidney pathology.2,13 This condition is most likely to be autosomal dominant but with variable penetrance and results in deposition of amyloid within the kidney. The average age of Abyssinian cats diagnosed with amyloidosis is 3 years (range 1-5 years) but deposition of amyloid can begin in cats <1 year of age.14 Because the medullary interstitium is often more markedly affected than the glomeruli, about 25 % of Abyssinian cats with amyloidosis will not have proteinuria.14 However, depending on the degree of amyloid deposition cats will progress to become azotaemic. Other breeds can develop amyloidosis including Somali, Siamese and Oriental cats and it is possible for other body organs such as the liver, intestines, spleen, and pancreas to have amyloid deposits.15,16 This seems to be of greater consequence for Siamese and Oriental cats than for Abyssinians. Reactive amyloidosis, which is not a familial condition, can also occur secondary to inflammatory or infectious disease processes in the kidney.
Other primary feline renal diseases can have sex predispositions, for example membranous nephropathy which is identified in younger (mean 3.6 years, range 1-7 years) male cats with a male to female ratio of 6:1.17,18 Membranous nephropathy is a glomerular disease. Loss of function of the glomerular filtration barrier means that cats with this condition are markedly proteinuric with a urine protein to creatinine ratio >1.0 and often considerably higher. A proportion of these cats will also show clinical and biochemical signs of nephrotic syndrome (proteinuria, hypoalbuminaemia, hypercholesterolaemia, peripheral oedema). Cats with membranous nephropathy may not initially be azotaemic. This is because their total number of nephrons and therefore their total glomerular filtration rate is normal. However, as the disease progresses azotaemia may develop due to loss of nephrons.
Obstructive nephropathy is a condition where one or both ureters become obstructed by a urolith, often calcium oxalate, although other forms of obstruction, e.g. strictures or dried solidified blood ureteroliths, are possible (Figure 3).19-21 When obstruction is bilateral or, where unilateral ureteral obstruction occurs at the same time as other renal pathology, cats may present acutely with azotaemia.
Figure 3: Ultrasound examination of a kidney with ureterolithiasis. This image obtained from a 6 year old male neutered domestic shorthair shows kidney (red arrow), dilation of the left ureter and a hyperechoic stone (white arrow) causing obstruction within the ureteral lumen. Image courtesy of Dr Taizha Ciasca.
However, it is suspected that many cats that have episodes of unilateral ureteral obstruction go undetected providing the non-affected kidney has sufficient function. In this situation the obstructed kidney may become small and shrunken while the non-affected kidney can become hypertrophied in order to compensate. This has led to the colloquial term ‘big kidney little kidney syndrome’. Cats with this condition may present at an earlier age than would typically be expected for cats with ageing CKD due to tubulointerstitial nephritis.19
Pyelonephritis most often occurs due to an ascending urinary tract infection (UTI). However, UTI is uncommon in cats with normal kidney function as their high urine concentrating ability is hostile to bacteria. Pyelonephritis as a primary kidney disease in cats is therefore uncommon but is more often identified in conjunction with another underlying kidney disease, e.g. tubulointersitial nephritis, and may certainly contribute to disease progression. Other forms of inflammatory or infectious disease can also affect the feline kidney e.g. Feline infectious peritonitis.
Renal lymphoma is reported to account for approximately 10% of all feline kidney pathology with a median age at diagnosis of 9 years and the most common clinical finding being renomegaly.2,22 Other forms of renal neoplasia have been reported to affect the feline kidney including renal carcinoma, transitional cell carcinoma, nephroblastoma and haemangiosarcoma.23
Perinephric pseudocysts are a rare condition where serous fluid accumulates in a fibrous sac surrounding the kidney. In between 40-50% of cases the condition is bilateral. As suggested by the name these are not true cystic structures because they lack an epithelial lining. On physical examination the kidney will feel enlarged but smooth and non-painful.24,25
When should I be concerned about chronic kidney disease?
CKD is usually suspected based on a combination of historical inform
ation from the owner and findings on physical examination. It is always important to differentiate between acute kidney injury and CKD because treatment and prognosis can be very different (Box 1). Given that the most common form of CKD is tubulointerstitial nephritis, it is always important to consider the possibility of kidney disease in older cats and it is widely recommended that cats >8-9 years should be screened for CKD on an annual basis. As highlighted above, for other forms of CKD both history and signalment can be key.
The commonest clinical signs of CKD reported by owners are polydipsia, lethargy, weight loss and a variable appetite (Table 1). However, it is widely reported that up to 75 % of functioning nephrons must be lost before azotaemia can be detected. Therefore, in the early stages of CKD it is possible that no abnormalities will be reported by the owner and the cat may be asymptomatic. In this situation a diagnosis of CKD may only be made by identifying abnormalities on palpation of the kidneys and by assessment of kidney function.
Typical findings on physical examination in patients with established CKD can include poor body condition and abnormalities on kidney palpation among others (Table 2). Kidneys are usually small and irregular with tubulointerstitial nephritis but in other conditions the kidneys may be enlarged e.g. renal lymphoma, or painful e.g. pyelonephritis. Asymmetric kidneys may raise suspicion of obstructive nephropathy.
A suspicion of CKD of any aetiology should always be confirmed by assessing kidney function with a biochemistry profile and a simultaneous urinalysis, with culture where indicated, and urine protein to creatinineratio. In some instances, diagnostic imaging (ultrasound examination, plain and contrast radiography) or advanced diagnostics such as pyelocentesis, fine needle aspirates or renal biopsy can be invaluable. Having diagnosed CKD, the next step is to consider staging. The International Renal Interest Society (IRIS)*, an international group of key opinion leaders in veterinary nephrology and urology, has developed a staging system, which classifies cats, after diagnosis of CKD, according to their creatinine concentration (Table 3) and offers further substaging for both proteinuria (Table 4) and blood pressure (Table 5). This staging system can help with the management and monitoring of cats with CKD.
This article was kindly provided by Boehringer Ingelheim, makers of Semintra®:
Full references available on request from Boehringer Ingelheim Limited, Vetmedica Division, Bracknell, Berkshire, RG12 8YS:
* International Renal Interest Society (IRIS): www.iris-kidney.com* International Renal Interest Society (IRIS): www.iris-kidney.com
