CKD Risk Factors

Risk factors in dogs and cats for development of chronic kidney disease (Updated 2019)

Xavier Roura Barcelona, Spain

The prevalence of chronic kidney disease (CKD) has been estimated to be 0.5-1.0% in dogs and 1.0-3.0% in cats, but it increases with age, especially in cats with reported prevalence of 80% in the geriatric cat population.

Unlike in human medicine (Johnson et al. 2004), the prevalence of dogs and cats at risk for CKD has not been adequately determined (Reynolds et al., 2013). However, the number of these at-risk patients is likely to far exceed the number of dogs and cats with CKD.

Epidemiological studies show an increased risk of CKD among dogs and cats with certain clinical and demographic characteristics, suggesting that risk factors for CKD exist in both species (Bartlett et al., 2010; Brown et al., 2016; Finch et al., 2016; Jepson, 2016; Conroy et al., 2019).

Nephron damage associated with CKD is usually irreversible and often progressive (Polzin et al., 2005; O'Neill et al., 2013; Brown et al., 2016; Conroy et al., 2019). Therefore, the aim is to identify and manage risk factors for CKD, which might prevent or slow the development of CKD, and reduce the chances of the morbidity and mortality expected at later stages of the disease (i.e., IRIS Stages 3 and 4) (Polzin et al., 2005).

A risk factor is defined as an attribute that is associated with increased risk of an outcome. However, the detection of risk factors for CKD is complicated by the fact that dogs and cats are often diagnosed when the disease in advanced (Bartlett et al., 2010; Jepson, 2016), when it is difficult to distinguish risk factors from concurrent disease processes (Brown et al., 2016; Finch et al., 2016; Conroy et al., 2019). It is also clear that multiple risk factors contribute to the gradual decline in kidney function over time and concurrent diseases could contribute to this process (Greene et al., 2014; Brown et al., 2016).

The association between a risk factor and the outcome may be either causal or non-causal (Bartlett et al., 2010; Brown et al., 2016; Finch et al., 2016). Causal risk factors are direct determinants of the outcome, and successful intervention to reduce exposure to them could improve outcomes (if the risk factor is modifiable). Non-causal risk factors may be associated with the outcome through confounding or reverse causation. Interventions to reduce exposure to non-causal risk factors might not necessarily improve outcomes.

Unfortunately, there are relatively few clinical studies evaluating phenotypic, environmental, or lifestyle risk factors for the development of canine or feline CKD. At this time, RISK FACTORS that have been identified are:

Breed

It has been suggested by some studies that certain breeds of dogs and cats could be predisposed to CKD (Table 1). These include Shar Pei, Bull Terrier, English Cocker Spaniel, Cavalier King Charles Spaniel, West Highland White Terrier, and Boxer (O'Neill et al., 2013; Cianciolo et al., 2016; Littman, 2017). Cat breeds that have been suggested to be predisposed to CKD include Persian, Abyssinian, Siamese, Ragdoll, Burmese, Russian Blue, and Maine Coon. Familial diseases have been related to specific breeds in both species (Littman, 2017).

Age

Dogs and cats may develop CKD at any age. Juvenile onset CKD is likely to be a consequence of familial renal diseases. With these exceptions, CKD is more frequent in older dogs and cats (White et al., 2006; O'Neill et al., 2013; Reynolds et al., 2013; Brown et al., 2016). However, older dogs and cats could also have other age-associated disease processes that might play a role in the development of CKD (Jepson et al., 2009; Brown et al., 2016).

Sex

No sex-based risk of CKD has been reported in the general population, although idiopathic membranous glomerulopathy has been reported to be more frequent in male cats, and male neutered cats may develop signs of CKD at a younger age than spayed females (White et al., 2006; Greene et al., 2014).

Comorbidities

Disorders that have been identified as potential risk factors for development of CKD in dogs and/or cats include among others (Tables 2 and 3): hypercalcemia, cardiac diseases, periodontal disease, cystitis, urolithiasis, hyperthyroidism, cardiac abnormalities detected on auscultation, diabetes and infectious pathogens (e.g., leishmaniosis) (Jepson et al., 2009; O'Neill et al., 2013; Greene et al., 2014; Brown et al., 2016; Cianciolo et al., 2016; Finch et al., 2016; Martinelli et al., 2016; Cohen, 2018; Stevens et al., 2018; Trevejo et al., 2018; van den Berg et al., 2018; Lamoureux et al., 2019).

Diet

Some dietary formulations have been associated with the development of CKD in cats. In particular, potassium-depleted or phosphorus-increased with high-protein diets were associated with the development of CKD in cats (Brown et al., 2016; Böswald et al., 2018). However, these diets may not have the same effect in dogs. Furthermore, no association was evident in senior cats between high-salt intake and increased risk of CKD; and changes in dietary sodium intake did not affect arterial blood pressure in dogs and cats. A case -control study evaluating risk factors for CKD in cats found a dry food diet was potentially protective (Piyarungsri 2018) although this finding has not been replicated in the few other published epidemiology studies from different parts of the world. Recent studies have suggested high inclusion rates of inorganic forms of phosphate in diets may lead to kidney damage in cats (Dobenecker et al., 2018a&b; Alexander et al., 2019). Further work is required to determine the mechanisms and the forms of phosphorus which give rise to these observations.

Drugs

Several therapeutic or diagnostic agents have been associated with the development of CKD in dogs and cats, for example NSAID, aminoglycosides, sulfonamides, polymyxins, amphotericin, vaccines or other chemotherapeutics (Polzin et al., 2005; Finch et al., 2016).

Acute kidney injury

Any glomerular or tubular-interstitial acute injury from primary or secondary diseases (Tables 1-3) could initiate the development of CKD in dogs and cats (Cowgill et al., 2016; Goic et al., 2016; Sugisawa et al., 2016; van den Berg et al., 2018). In people, prior acute kidney injury is associated with an increased risk of CKD and end stage renal disease (Chawla and Kimmel 2012, Coca et al 2012) and the same may apply to dogs and cats.

Identifying, monitoring and managing at RISK patients

A comprehensive history and good medical records are essential for identifying patients at risk of CKD.

Concluding that a dog or cat is 'at risk' of CKD is not based on blood biochemistry data from a routine health screen. Serum markers of renal function will be within the laboratory reference range and considering the dog and cat at risk is based purely on the history. Evidence of renal abnormality, such as abnormal renal imaging, persistent renal proteinuria or persistently reduced urinary concentrating ability (after excluding other medical conditions) confirm a diagnosis of kidney disease, even in the absence of any increase in sCr or serum SDMA. If indicated, the disease may be further characterized by obtaining a renal biopsy in order confirm a diagnosis of CKD. If a persistent renal abnormality is defined by these tests, the dog or cat is diagnosed as having CKD and should be staged (see article on IRIS Staging of CKD).

Dogs and cats that are 'at risk' of CKD based only on their history should be monitored on a regular basis for evidence of deteriorating kidney function or the appearance of further renal abnormalities. Thus, blood biochemistry, urinalysis, blood pressure, body weight, and body condition score should be monitored, initially every 3 months to ascertain potential disease progression. If stable, patients could then be monitored every 6 to 12 months Evidence of serial increases in serum creatinine and/or SDMA or urine protein within the laboratory reference ranges may then be sufficient to make a diagnosis of early CKD and to proceed to staging as discussed above.

Management of the 'at risk' patient should focus on ensuring that no additional risks for damaging the kidneys are introduced. For example, avoiding nephrotoxic drugs, prompt treatment of dehydration and careful management of anesthesia to avoid hypotension.

Table 1. Familial nephropathies in dogs and cats

DOGS
Breed associated familial renal diseases (including renal dysplasia )1 Alaskan Malamute, Beagle, Border Terrier, Boxer, Cairn Terrier, Chow-Chow, Doberman, Dutch Kooiker, Finnish Harrier, Golden Retriever, Gordon Setter, Keeshond, Lhasa Apso, Miniature Schnauzer, Norwich Terrier, Shih Tzu, Soft-Coated Wheaten Terrier, Standard Poodle
Primary glomerulopathies Basenji, Beagle, Bernese Mountain Dog, Brittany Spaniel, Bull Mastiff, Bull Terrier, Dalmatian Doberman, English Cocker Spaniel, English Springer Spaniel, French Mastiff, Navasota mixed-breed, Newfoundland, Pembroke Welsh Corgi, Rottweiler, Samoyed
Polycystic kidney diseases Bull Terrier, Cairn Terrier, West Highland White Terrier
Amyloidosis Beagle, English Foxhound, Shar Pei, bulldog
Immune-mediated glomerulonephritis Bernese Mountain Dog, Brittany Spaniel, Soft-Coated Wheaten Terrier
Miscellaneous Basenji (Fanconi syndrome), German Shepherd (multifocal cystoadenocarcinoma), Pembroke Welsh Corgi (telangiectasia), copper-induced Fanconi syndrome in Labrador retrievers
CATS
Polycystic kidney diseases British Longhaired, British Shorthaired, Burmilla, Exotic Shorthaired, Himalayan, Main Coon, Persian, Ragdoll, Scottish Fold, Selkirk Rex
Amyloidosis Abyssinian, Siamese, Oriental

Table 2. Diseases associated with renal disease in dogs

Infectious causes Canine adenovirus 1, parvovirus, bacterial endocarditis, brucellosis, borreliosis, dirofilariasis, erhlichiosis, leishmaniosis, leptospirosis, hepatozoonosis, Rocky mountain spotted fever, bartonellosis, babesiosis, blastomycosis, coccidioidomycosis, trypanosomiasis, toxin of Escherichia coli, chronic bacterial infections (chronic UTI, periodontal diseases, pyoderma, pyometra, septicemia, prostatitis)

Neoplasia Leukemia, lymphoma, mastocytosis, primary erythrocytosis, systemic histiocytosis, others

Inflammatory causes Pancreatitis, prostatitis, systemic lupus erythematous, other immune-mediated diseases

Other causes Hyperadrenocorticism, excessive crystalluria, urolithiasis, excessive corticosteroid administration, familial, diabetes mellitus, cyclic hematopoiesis (grey collies), intravenous iodinated contrast agent, trimethoprim-sulfonamide therapy, hyperlipidemia, idiopathic

Table 3. Diseases associated with renal disease in cats

Infectious causes Chronic bacterial infections, mycoplasma polyarthritis, feline immunodeficiency virus, feline infectious peritonitis, feline leukemia virus, leptospirosis, bartonellosis, periodontal disease

Neoplasia Leukemia, lymphoma, adenocarcinoma

Inflammatory causes Pancreatitis, cholangiohepatitis, systemic lupus erythematous, other immune-mediated diseases, chronic progressive polyarthritis

Miscellaneous Acromegaly, excessive crystalluria, urolithiasis, mercury toxicity, familial, acute kidney injury, idiopathic

¹ Renal dysplasia is a polymorphic disorder characterized at the microscopic level by abnormal differentiation of mesenchymal and epithelial elements, decreased nephron number, loss of the demarcating zone between the cortex and the medulla, and metaplastic transformation of mesenchyme to cartilage and bone (National Kidney Foundation definition). Not all of the breeds listed have been characterized to have such pathology and in veterinary medicine 'renal dysplasia' in sometimes used more broadly and applied to young dogs with familial/congenital kidney disease where the pathology has not been so precisely characterized.

References & Further Reading

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Bijsmans ES, Jepson RE, Chang YM, et al. Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease. J Vet Intern Med 2015; 29: 855-861.

Böswald LF, Kienzle E, Dobenecker B. Observation about phosphorus and protein supply in cats and dogs prior to the diagnosis of chronic kidney disease. J Anim Physiol Anim Nutr (Berl) 2018; 102 Suppl 1: 31-36.

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Chawla LS, Kimmel PL. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 2012; 82: 516-524.

Cianciolo RE, Mohr FC, Aresu L, et al. World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs. Vet Pathol 2016; 53: 113-35.

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