Objectives Chronic kidney disease (CKD) is a significant disease in cats. Identifying risk and protective factors may help to prevent this significant disease. Methods An age-matched case-control study was performed to determine the risk factors in cats with naturally occurring CKD. Twenty-nine clinically normal cats aged ⩾5 years and 101 cats with naturally occurring CKD were studied. Risk factors were determined by interviewing cat owners from the Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University, and veterinary hospitals in the Bangkok Metropolitan area, through questionnaires completed between June 2004 and November 2014. Univariable and multivariable analyses were performed using two independent proportional test methods and logistic regression analysis with backward elimination. Results Male sex (odd ratios [OR] 2.80, 95% confidence interval [CI] 1.02-8.87; P = 0.02), tap water (OR 3.43, 95% CI 1.08-11.45; P = 0.03) and an outdoor lifestyle (OR 3.77, 95% CI 1.03-17.99; P = 0.04) were associated with an increased risk for CKD. Commercial dry cat food (OR 0.06, 95% CI 0.02-0.17; P = 0.00), filtered water (OR 0.13, 95% CI 0.03-0.52; P = 0.01) and an indoor lifestyle (OR 0.28, 95% CI 0.07-0.98; P = 0.02) were associated with a decreased risk. Logistic regression analysis using backward elimination demonstrated that cats fed commercial dry cat food (OR 0.042, 95% CI 0.01-0.17; P = 0.00) had a decreased risk for CKD compared with cats on other types of diet. Conclusions and relevance Multivariable analysis found only feeding commercial dry cat food to be significant, suggesting that commercial dry cat food may be a potential protective factor for CKD in cats.