Risk Factors for Chronic Kidney Disease in Pets

Adapted from the IRIS education article "Risk factors in dogs and cats for development of chronic kidney disease" by Xavier Roura (Barcelona, Spain), updated 2019.

How Common Is CKD?

The prevalence of chronic kidney disease (CKD) has been estimated at 0.5% to 1.0% in dogs and 1.0% to 3.0% in cats, but it increases with age, especially in cats. Estimates for cats aged 15 years and older range from about 30% to as high as 80%, depending on the study.

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

The nephron damage associated with CKD is usually irreversible and often progressive (Polzin, 2005; O'Neill et al., 2013; Brown et al., 2016; Conroy et al., 2019). The aim is therefore to identify and manage risk factors for CKD, which might prevent or slow its development and reduce the illness and death expected in the later stages of the disease, IRIS Stages 3 and 4 (Polzin, 2005).

What Is a Risk Factor?

A risk factor is an attribute associated with an increased risk of an outcome. Identifying risk factors for CKD is complicated by the fact that dogs and cats are often diagnosed when the disease is already advanced (Bartlett et al., 2010; Jepson, 2016), when it is difficult to distinguish risk factors from other disease processes happening at the same time (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 that other diseases may contribute to this process (Greene et al., 2014; Brown et al., 2016).

The association between a risk factor and the outcome may be causal or non-causal (Bartlett et al., 2010; Brown et al., 2016; Finch et al., 2016). Causal risk factors directly determine the outcome, and successfully reducing exposure to them could improve outcomes, if the risk factor can be modified. Non-causal risk factors may be associated with the outcome through confounding or reverse causation, and reducing exposure to them may not improve outcomes.

Unfortunately, relatively few clinical studies have evaluated physical, environmental, or lifestyle risk factors for the development of CKD in dogs or cats. The risk factors identified so far are described below.

Breed

Some studies suggest that certain dog and cat breeds may be predisposed to CKD (see the familial kidney diseases listed below). Dog breeds include the 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 suggested to be predisposed to CKD include the Persian, Abyssinian, Siamese, Ragdoll, Burmese, Russian Blue, and Maine Coon. Familial kidney diseases have been linked to specific breeds in both species (Littman, 2017).

Age

Dogs and cats can develop CKD at any age. CKD in young animals is likely to be the result of a familial kidney disease. Apart from these cases, CKD is more common 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 may also have other age-related diseases that could play a role in the development of CKD (Jepson et al., 2009; Brown et al., 2016).

Sex

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

Other Diseases

Conditions identified as potential risk factors for the development of CKD in dogs or cats include, among others, hypercalcemia, heart disease, heart abnormalities detected on auscultation, periodontal disease, cystitis, urinary stones (urolithiasis), hyperthyroidism, diabetes, and infections such as 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). Fuller lists of the diseases associated with kidney disease in dogs and in cats appear below.

Diet

Some diets have been associated with the development of CKD in cats. In particular, diets depleted of potassium, and diets high in phosphorus combined with high protein, were associated with the development of CKD in cats (Brown et al., 2016; Böswald et al., 2018). These diets may not have the same effect in dogs. No association was found in senior cats between a high salt intake and an increased risk of CKD, and changes in dietary sodium did not affect arterial blood pressure in dogs and cats.

A case-control study of risk factors for CKD in cats found that a dry food diet was potentially protective (Piyarungsri and Pusoonthornthum, 2017), although this finding has not been replicated in the few other epidemiological studies published from other parts of the world. Recent studies have suggested that diets containing high levels of inorganic forms of phosphate may lead to kidney damage in cats (Dobenecker et al., 2018a and 2018b; Alexander et al., 2019). Further work is needed to determine the mechanisms involved and which forms of phosphorus are responsible.

Drugs

Several therapeutic and diagnostic agents have been associated with the development of CKD in dogs and cats, for example nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides, sulfonamides, polymyxins, amphotericin, vaccines, and some chemotherapy drugs (Polzin, 2005; Finch et al., 2016).

Acute Kidney Injury

Any acute injury to the glomeruli or to the tubules and interstitium, from a primary or secondary disease, could start 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, a previous acute kidney injury is associated with an increased risk of CKD and end-stage kidney 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 thorough history and good medical records are essential for identifying patients at risk of CKD.

A dog or cat is considered "at risk" of CKD based purely on its history, not on routine blood test results, because in these patients serum markers of kidney function are within the laboratory reference range. Evidence of a kidney abnormality, such as abnormal kidney imaging, persistent proteinuria of renal origin, or a persistently reduced ability to concentrate urine (after other medical conditions have been excluded), confirms a diagnosis of kidney disease even without any increase in serum creatinine or SDMA. If indicated, a kidney biopsy can further characterize the disease and confirm a diagnosis of CKD. If these tests show a persistent kidney abnormality, the dog or cat is diagnosed with CKD and should be staged (see our article on the IRIS staging system for CKD).

Dogs and cats that are at risk of CKD based only on their history should be monitored regularly for evidence of declining kidney function or new kidney abnormalities. Blood biochemistry, urinalysis, blood pressure, body weight, and body condition score should be checked, initially every 3 months, to detect possible progression. If the patient is stable, monitoring can then be reduced to every 6 to 12 months. Serial increases in serum creatinine, SDMA, or urine protein, even within the laboratory reference ranges, may then be enough to diagnose early CKD and proceed to staging.

Management of the at-risk patient should focus on not introducing any additional risks to the kidneys, for example by avoiding drugs that can damage the kidneys, treating dehydration promptly, and managing anesthesia carefully to avoid low blood pressure.

Familial Kidney Diseases in Dogs and Cats

Dogs

  • Breed-associated familial kidney diseases, including renal dysplasia (see note below): 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, Bullmastiff, Bull Terrier, Dalmatian, Doberman, English Cocker Spaniel, English Springer Spaniel, French Mastiff, Navasota mixed breed, Newfoundland, Pembroke Welsh Corgi, Rottweiler, Samoyed
  • Polycystic kidney disease: 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 cystadenocarcinoma), Pembroke Welsh Corgi (telangiectasia), Labrador Retriever (copper-associated Fanconi syndrome)

Cats

  • Polycystic kidney disease: British Longhair, British Shorthair, Burmilla, Exotic Shorthair, Himalayan, Maine Coon, Persian, Ragdoll, Scottish Fold, Selkirk Rex
  • Amyloidosis: Abyssinian, Siamese, Oriental

Note on renal dysplasia: renal dysplasia is a variable disorder characterized at the microscopic level by abnormal differentiation of mesenchymal and epithelial tissue, a reduced number of nephrons, loss of the boundary between the cortex and the medulla, and transformation of mesenchyme into cartilage and bone (National Kidney Foundation definition). Not all of the breeds listed have been shown to have this pathology, and in veterinary medicine the term "renal dysplasia" is sometimes used more broadly for young dogs with familial or congenital kidney disease whose pathology has not been precisely characterized.

Diseases Associated With Kidney Disease in Dogs

  • Infectious causes: canine adenovirus 1, parvovirus, bacterial endocarditis, brucellosis, borreliosis (Lyme disease), dirofilariasis (heartworm), ehrlichiosis, leishmaniosis, leptospirosis, hepatozoonosis, Rocky Mountain spotted fever, bartonellosis, babesiosis, blastomycosis, coccidioidomycosis, trypanosomiasis, Escherichia coli toxins, and chronic bacterial infections (chronic urinary tract infection, periodontal disease, pyoderma, pyometra, septicemia, prostatitis)
  • Neoplasia: leukemia, lymphoma, mastocytosis, primary erythrocytosis, systemic histiocytosis, and others
  • Inflammatory causes: pancreatitis, prostatitis, systemic lupus erythematosus, and other immune-mediated diseases
  • Other causes: hyperadrenocorticism, excessive crystalluria, urolithiasis, excessive corticosteroid administration, familial disease, diabetes mellitus, cyclic hematopoiesis (gray collies), intravenous iodinated contrast agents, trimethoprim-sulfonamide treatment, hyperlipidemia, and idiopathic disease

Diseases Associated With Kidney 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 erythematosus, other immune-mediated diseases, chronic progressive polyarthritis
  • Miscellaneous: acromegaly, excessive crystalluria, urolithiasis, mercury toxicity, familial disease, acute kidney injury, idiopathic disease

References and Further Reading

  • Alexander J, Stockman J, Atwal J, et al. Effects of the long-term feeding of diets enriched with inorganic phosphorus on the adult feline kidney and phosphorus metabolism. British Journal of Nutrition 2019;121:249–269.
  • Bartlett PC, Van Buren JW, Bartlett AD, et al. Case-control study of risk factors associated with feline and canine chronic kidney disease. Veterinary Medicine International 2010; Article ID 957570.
  • Bijsmans ES, Jepson RE, Chang YM, et al. Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease. Journal of Veterinary Internal Medicine 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. Journal of Animal Physiology and Animal Nutrition 2018;102 Suppl 1:31–36.
  • Brown CA, Elliott J, Schmiedt CW, Brown SA. Chronic kidney disease in aged cats: clinical features, morphology, and proposed pathogeneses. Veterinary Pathology 2016;53:309–326.
  • Chawla LS, Kimmel PL. Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney International 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. Veterinary Pathology 2016;53:113–135.
  • Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney International 2012;81:442–448.
  • Cohen SM. Crystalluria and chronic kidney disease. Toxicologic Pathology 2018;46:949–955.
  • Conroy M, Brodbelt DC, O'Neill D, et al. Chronic kidney disease in cats attending primary care practice in the UK: a VetCompass study. Veterinary Record 2019;184:526.
  • Cowgill LD, Polzin DJ, Elliott J, et al. Is progressive chronic kidney disease a slow acute kidney injury? Veterinary Clinics of North America: Small Animal Practice 2016;46:995–1013.
  • Dobenecker B, Hertel-Böhnke P, Webel A, et al. Renal phosphorus excretion in adult healthy cats after the intake of high phosphorus diets with either calcium monophosphate or sodium monophosphate. Journal of Animal Physiology and Animal Nutrition 2018a;102:1759–1765.
  • Dobenecker B, Webel A, Reese S, et al. Effect of a high phosphorus diet on indicators of renal health in cats. Journal of Feline Medicine and Surgery 2018b;20:339–343.
  • Finch NC, Syme HM, Elliott J. Risk factors for development of chronic kidney disease in cats. Journal of Veterinary Internal Medicine 2016;30:602–610.
  • 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. Journal of the American Veterinary Medical Association 2014;244:320–327.
  • Goic JB, Koenigshof AM, McGuire LD, et al. A retrospective evaluation of contrast-induced kidney injury in dogs (2006–2012). Journal of Veterinary Emergency and Critical Care 2016;26:713–719.
  • Jepson RE, Brodbelt D, Vallance C, et al. Evaluation of predictors of the development of azotemia in cats. Journal of Veterinary Internal Medicine 2009;23:806–813.
  • Jepson RE. Current understanding of the pathogenesis of progressive chronic kidney disease in cats. Veterinary Clinics of North America: Small Animal Practice 2016;46:1015–1048.
  • Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults: Part I. Definition, disease stages, evaluation, treatment, and risk factors. American Family Physician 2004;70:869–876.
  • Lamoureux A, Da Riz F, Cappelle J, et al. Frequency of bacteriuria in dogs with chronic kidney disease: a retrospective study of 201 cases. Journal of Veterinary Internal Medicine 2019;33:640–647.
  • Littman MP. Genetic basis for urinary tract diseases. In: Elliott J, Grauer GF, Westropp JL, eds. BSAVA Manual of Canine and Feline Nephrology and Urology, 3rd edition. BSAVA, 2017:172–184.
  • Martinelli E, Locatelli C, Bassis S, et al. Preliminary investigation of cardiovascular-renal disorders in dogs with chronic mitral valve disease. Journal of Veterinary Internal Medicine 2016;30:1612–1618.
  • O'Neill DG, Elliott J, Church DB, et al. Chronic kidney disease in dogs in UK veterinary practices: prevalence, risk factors, and survival. Journal of Veterinary Internal Medicine 2013;27:814–821.
  • Polzin D. Chronic kidney disease. In: Ettinger S, Feldman EC, eds. Textbook of Veterinary Internal Medicine, 6th edition. Elsevier Saunders, St Louis, 2005:1756–1785.
  • Piyarungsri K, Pusoonthornthum R. Risk and protective factors for cats with naturally occurring chronic kidney disease. Journal of Feline Medicine and Surgery 2017;19:358–363.
  • Reynolds BS, Lefebvre HP. Feline CKD: pathophysiology and risk factors — what do we know? Journal of Feline Medicine and Surgery 2013;15 Suppl 1:3–14.
  • Stevens KB, O'Neill D, Jepson R, et al. Signalment risk factors for cutaneous and renal glomerular vasculopathy (Alabama rot) in dogs in the UK. Veterinary Record 2018;183:448.
  • Sugisawa R, Hiramoto E, Matsuoka S, et al. Impact of feline AIM on the susceptibility of cats to renal disease. Scientific Reports 2016;6:35251.
  • Trevejo RT, Lefebvre SL, Yang M, et al. Survival analysis to evaluate associations between periodontal disease and the risk of development of chronic azotemic kidney disease in cats evaluated at primary care veterinary hospitals. Journal of the American Veterinary Medical Association 2018;252:710–720.
  • van den Berg MF, Schoeman JP, Defauw P, et al. Assessment of acute kidney injury in canine parvovirus infection: comparison of kidney injury biomarkers with routine renal functional parameters. The Veterinary Journal 2018;242:8–14.
  • White JD, Norris JM, Baral RM, et al. Naturally-occurring chronic renal disease in Australian cats: a prospective study of 184 cases. Australian Veterinary Journal 2006;84:188–194.