Finch, N., Syme, H. M., & Elliott, J. (2016). Risk Factors for Development of Chronic Kidney Disease in Cats. Journal of Veterinary Internal Medicine, 30(2), 602-610. https://doi.org/10.1111/jvim.13917 Publisher's PDF, also known as Version of record License (if available): CC BY Link to published version (if available): 10.1111/jvim.13917 Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Wiley Online at DOI: 10.1111/jvim.13917. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ J Vet Intern Med 2016;30:602–610 Risk Factors for Development of Chronic Kidney Disease in Cats N.C. Finch, H.M. Syme, and J. Elliott Background: Identification of risk factors for development of chronic kidney disease (CKD) in cats may aid in its earlier detection. Hypothesis/objectives: Evaluation of clinical and questionnaire data will identify risk factors for development of azotemic CKD in cats. Animals: One hundred and forty-eight client-owned geriatric (>9 years) cats. Methods: Cats were recruited into the study and followed longitudinally for a variable time. Owners were asked to com- plete a questionnaire regarding their pet at enrollment. Additional data regarding dental disease were obtained when available by development of a dental categorization system. Variables were explored in univariable and multivariable Cox regression models. Results: In the final multivariable Cox regression model, annual/frequent vaccination (P value, .003; hazard ratio, 5.68; 95% confidence interval, 1.83–17.64), moderate dental disease (P value, .008; hazard ratio, 13.83; 95% confidence interval, 2.01–94.99), and severe dental disease (P value, .001; hazard ratio, 35.35; 95% confidence interval, 4.31–289.73) predicted development of azotemic CKD. Conclusion: Our study suggests independent associations between both vaccination frequency and severity of dental disease and development of CKD. Further studies to explore the pathophysiological mechanism of renal injury for these risk factors are warranted. Key words: Feline; Predictors; Renal. hronic kidney disease (CKD) has a high prevalence Cin both humans and domestic cats. In human Abbreviations: patients across Europe, Asia, and North America the BAH Beaumont Sainsbury Animals’ Hospital 1 prevalence is reported to be 2.5–11.2%. The figure is CKD chronic kidney disease similar in cats with approximately 10% of cats CRFK Crandell-Rees feline kidney >10 years of age reported to be affected although the DSH domestic short hair 2 etiopathogenesis may have some differences. Chronic DLH domestic long hair kidney disease is defined as a sustained decrease in FIV feline immunodeficiency virus renal function over at least 3 months. It is not a single GIS geospatial information system entity but a heterogeneous syndrome resulting in loss GFR glomerular filtration rate of functioning renal mass. In veterinary patients, con- LTF lost to follow-up genital or acquired disorders can lead to development KEEP National Kidney Foundation’s Kidney Early of CKD. Acute kidney damage (single or repeated epi- Evaluation Program sodes) secondary to urinary obstruction, nephrotoxins, PDSA People’s Dispensary for Sick Animals pyelonephritis, or ischemic injury also can progress to USG urine specific gravity CKD. The disease syndrome is an important cause of morbidity and mortality in cats and as a result, there is much interest in identifying risk factors for disease. These risk factors may not only aid in early detection, but also may help in understanding disease pathogenesis and development of new treatments. From the Bristol Renal, School of Clinical Sciences, University of Few studies have explored risk factors and predictors Bristol, Bristol, UK (Finch); Department of Clinical Science and of CKD in cats. Biochemical variables that predict Services, Royal Veterinary College, Hatfield, Herts UK (Syme); development of azotemic CKD within 12 months have and the Department of Comparative Biomedical Sciences, Royal 3 Veterinary College, London, UK (Elliott). This work was performed been reported. A recent retrospective study reported an at the Royal Veterinary College, London, NW1 0TU. increased odds of diagnosis of CKD in cats with weight This work was presented as part of the International Renal Inter- loss, thin body condition, dehydration, a recent history est Society Award at ECVIM congress, Liverpool, September 2013 of general anesthesia, prior diagnosis of periodontal dis- and ACVIM forum, Nashville, June 2014. ease or cystitis and being male.4 A case–control study Corresponding author: N.C. Finch, Bristol Renal, School of Clini- reported hyperthyroidism, lower urinary tract disease, cal Sciences, University of Bristol, Bristol BS1 3NY, UK; e-mail: frequent vomiting, altered appetite, and weight loss to natalie.fi[email protected]. 5 Submitted September 22, 2015; Revised December 21, 2015; be risk factors for CKD in cats. However, many of Accepted February 2, 2016. these risk factors may have resulted from CKD rather Copyright © 2016 The Authors. Journal of Veterinary Internal than leading to its development. An earlier case–control Medicine published by Wiley Periodicals, Inc. on behalf of the Ameri- study identified ad libitum feeding, low dietary fiber, can College of Veterinary Internal Medicine. various nutritional factors, and low body weight to be This is an open access article under the terms of the Creative associated with increased odds of CKD.6 Other studies Commons Attribution License, which permits use, distribution and have suggested certain breeds of cat, particularly the reproduction in any medium, provided the original work is properly cited. Maine coon, Abyssinian, Siamese, Russian blue, and 2 DOI: 10.1111/jvim.13917 Burmese and also cats infected with feline immunodefi- Risk Factors for CKD in Cats 603 ciency virus (FIV)7 to have increased risk of CKD from cats that died or were LTF also were censored. At the compared to control cats. Certain breeds such as the initial and all subsequent visits, a full medical history was Birman normally may have higher serum creatinine obtained and physical examination performed. At the study concentrations which could lead to misclassification in end-point cats were categorized according to their renal status these studies.8 Results of these previous studies should (azotemic or nonazotemic). Cats were classified as having azote- – mic CKD if they had a plasma creatinine concentration above the be interpreted with caution because they were of case laboratory reference range (>2.0 mg/dL [177 lmol/L]) in associa- control design, having potential to introduce bias and tion with decreased urine concentrating ability (USG < 1.035) or 9 confounders. A further limitation was collection of demonstrated persistently increased plasma creatinine concentra- data retrospectively, which can introduce additional tion at 2 visits typically 6–8 weeks apart. Renal biopsies were not bias. performed. Dietary factors have been suggested to contribute to development of CKD in cats.10–13 Feeding a commer- Questionnaire data cially available high protein, acidifying diet which was potassium depleted led to hypokalemia and development At the initial visit, cat owners were asked to complete a ques- of CKD in healthy cats, although the formulation of this tionnaire regarding their pet’s lifestyle, dietary habits, and vaccina- diet is unlikely to represent typical commercial diets fed tion status. This questionnaire has been presented in a previous to cats.10 An earlier study found cats fed an acidifying study evaluating risk factors for hyperthyroidism in cats.17 When diet developed both hypokalemia and azotemia, but was questionnaires were not completed fully or further information limited by the low number of cats included.11 was required owners were contacted retrospectively by telephone Previous studies found cats given commercially avail- and additional information obtained. Information was collected regarding breed, sex, diet, environment, cigarette smoke exposure, able vaccines by SC injection developed anti-Crandell- vaccination, and history of dental disease. Because of the low Rees feline kidney (CRFK) proteins and antirenal tissue numbers in each breed group, cats were classified as domestic 14,15 antibodies. Furthermore, interstitial nephritis was short hair (DSH)/domestic long hair (DLH) or pedigree for statis- identified in renal biopsy tissue collected after SC vacci- tical analysis. Dietary variables evaluated included type of food nation.16 A large proportion of the feline population fed (wet versus dry) and feeding of urinary or senior diets. Infor- receives regular vaccinations and, based on findings mation regarding the environment the cat lived in included from previous studies described above, this practice whether the cat lived predominantly indoors or outdoors and may be considered a potential risk factor for CKD in whether the household was situated in an urban or semirural/rural cats. No epidemiological studies have evaluated the environment. Vaccination status was categorized as (1) never vac- effects of vaccination on kidney function in cats. cinated, (2) primary vaccination only, (3) occasional vaccination (>2-year interval),