CKD Risk Factors

Risk factors in dogs and cats for development of chronic kidney disease (2016)

Xavier Roura Barcelona, Spain

Chronic kidney disease (CKD) is a major cause of morbidity and mortality in dogs and cats. The prevalence of 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. It has been estimated that as many as 30-50% of cats 15 years of age or older have CKD. Nephron damage associated with CKD is usually irreversible and often progressive.

The prevalence of dogs and cats at risk for CKD has not been determined. 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. Chronic kidney disease can be attributed to multiple etiologies including congenital disorders (e.g., polycystic kidney disease, renal dysplasia), glomerulopathies, which can be secondary to acquired systemic conditions (e.g., neoplasia or infection, or by an unidentified process) and others (see below).

In principle, the aim is to identify and manage risk factors for CKD which might prevent or slow the development of CKD, reducing the chances of the animal suffering the associated morbidity and mortality seen at the later stages (IRIS Stages 3 and 4).

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 presented for medical care when the disease in advanced, and because it is difficult to distinguish risk factors from concurrent disease processes associated with aging. 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.

The association between a risk factor and the outcome may be either causal or non-causal. Causal risk factors are determinants of the outcome, and successful intervention to reduce exposure to them could improve outcomes. 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, with evidence from some studies but not others, that certain breeds of dogs could be predisposed to CKD including Chinese Shar Pei, Bull Terrier, English Cocker Spaniel, Cavalier King Charles Spaniel, West Highland White Terrier and Boxer. 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 reported to be related to specific breeds in both species (Table 1).

Age
Dogs and cats may develop CKD at any age. Juvenile onset CKD is the most common consequence of familial renal diseases. With these exceptions, CKD is more frequent in older dogs and cats. However, older dogs and cats could also have other age-associated disease processes that might play a role in the development of CKD

Gender
No gender-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.

Comorbidities
Disorders that have been identified as potential risk factors for development of CKD in both dogs and cats include hypercalcemia, cardiac diseases, periodontal or infectious diseases (Table 2). Cystitis, urolithiasis, hyperthyroidism and diabetes have been identified as risk factors for CKD only in cats.

Diet
Some dietary formulations have been associated with the development of CKD in cats. In particular, a potassium-depleted, high-protein diet was associated with the development of CKD. However, no association was evident in old cats between high-salt intake and increased risk of CKD.

Drugs
Several therapeutic agents have been associated with the development of CKD in dogs and cats, for example aminoglycosides, sulfonamides, polymyxins, amphotericin or other chemotherapeutics.

Acute kidney injury
Any glomerular or tubulointerstitial acute injuries from primary or secondary diseases (Table 2 and 3) could initiate CKD.

Table 1. Familial nephropathies in dogs and cats3

DOGS

Renal dysplasia

Lhasa Apso, Shih Tzu, Standard Poodle, Soft-Coated Wheaten Terrier, Chow-Chow, Alaskan Malamute, Miniature Schnauzer, Dutch Kooiker, Golden Retriever

Primary glomerulopathies

Samoyed (X linked), English Cocker Spaniel (autosomal recessive), Bull Terrier (autosomal dominant), Dalmatian (autosomal dominant), Doberman, Bull Mastiff, Newfoundland, Rottweiler, Pembroke Welsh Corgi, Beagle

Polycystic kidney diseases

Bull Terrier (autosomal dominant), Cairn Terrier and West Highland White Terrier (autosomal recessive)

Amyloidosis

Shar Pei, English Foxhound, Beagle

Immune-mediated glomerulonephritis

Soft-Coated Wheaten Terrier, Bernese Mountain Dog (autosomal recessive suspected), Brittany Spaniel (autosomal recessive)

Miscellaneous

Basenji - Fanconi syndrome; German Shepherd - multifocal cystoadenocarcinoma (autosomal dominant); Pembroke Welsh Corgi - telangiectasia

CATS

Polycystic kidney diseases

Persian (autosomal dominant)

Amyloidosis

Abyssinian (autosomal dominant with incomplete penetrance suspected), Siamese, Oriental

Table 2. Diseases associated with renal disease in dogs

Infectious causes

Canine adenovirus 1, bacterial endocarditis, brucellosis, borreliosis, dirofilariasis, erhlichiosis, leishmaniosis, leptospirosis, hepatozoonosis, Rocky mountain spotted fever, bartonellosis, babesiosis, blastomycosis, coccidioidomycosis, trypanosomiasis, chronic bacterial infections (periodontal diseases, pyoderma, pyometra, septicaemia, prostatitis)

Neoplasia

Leukaemia, lymphosarcoma, mastocytosis, primary erythrocytosis, systemic hisitiocytosis, others

Inflammatory causes

Pancreatitis, prostatitis, systemic lupus erythematosus, other immune-mediated diseases

Other causes

Idiopathic, hyperadrenocorticism, excessive corticosteroid administration, familial, diabetes mellitus, cyclic hematopoiesis (grey collies), trimethoprim-sulfonamide therapy, hyperlipidemia

Table 3. Diseases associated with renal disease in cats

Infectious causes

Chronic bacterial infections, mycoplasmal polyarthritis, feline immunodeficiency virus, feline infectious peritonitis, feline leukaemia virus, leptospirosis, bartonellosis

Neoplasia

Leukaemia, lymphoma, adenocarcinoma

Inflammatory causes

Pancreatitis, cholangiohepatitis, systemic lupus erythematosus, other immune-mediated diseases, chronic progressive polyarthritis

Miscellaneous

Acromegaly, mercury toxicity, familial, idiopathic

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.

Brown CA, Elliott J, Schmiedt CW, Brown SA. Chronic Kidney Disease in Aged Cats: Clinical Features, Morphology, and Proposed Pathogeneses. Vet Pathol 2016; 53: 309-326.

Cowgill LD, Polzin DJ, Elliott J, et al. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury? Vet Clin North Am Small Anim Pract 2016; 46: 995-1013.

Finch NC, Syme HM, Elliott J. Risk Factors for Development of Chronic Kidney Disease in Cats. J Vet Intern Med 2016; 30: 602-610.

Grauer GF. Management of glomerulonephritis. In: Elliott J, Grauer F (eds). BSAVA Manual of canine and feline nephrology and urology. 2nd edn, BSAVA 2007: 231-238.

Greene JP, Lefebvre SL, Wang M, et al. Risk factors associated with the development of chronic kidney disease in cats evaluated at primary care veterinary hospitals. J Am Vet Med Assoc 2014; 244: 320-327.

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