Investigating the domestic cat's apparent predisposition to chronic kidney disease and hyperthyroidism

Chronic kidney disease (CKD) and hyperthyroidism are two age-related diseases that are especially prevalent in domestic cats, compared to other species. This thesis explored potential reasons for the relatively high prevalence of these diseases in domestic cats. In particular, consumption of high levels of fish by domestic cats, relative to other companion animal species, such as dogs, and their wildcat ancestors, was considered. Study 1 investigated whether pro-oxidant minerals, such as arsenic and mercury, that are abundant in fish and which may instigate or progress CKD via oxidative stress mechanisms, may accumulate in domestic cat kidneys and associate with the presence of chronic interstitial nephritis (CIN). Although domestic cats, compared to dogs and Scottish wildcats, have greater arsenic concentrations in their kidneys and urine, suggesting increased arsenic consumption, the predominant arsenic species in fish-containing cat foods with high total arsenic content is arsenobetaine and therefore, presents low risk of renal toxicity. Arsenic concentration did not associate with the presence of CIN and mercury and iron concentrations were lower in cat kidneys, than in dogs. Domestic cat kidneys appeared to have depleted protective and/or antioxidant trace elements, including copper, zinc, rubidium and strontium, relative to dog kidneys, which may contribute to the increased prevalence of CIN in aged domestic cats’ kidneys. In other species, CKD may result from renal accumulation of intracellular lipid, which has a lipotoxic effect on the cells. However, the renal proximal tubule epithelial cells of healthy cats naturally contain an abundance of cytoplasmic lipid droplets, of which the composition is unknown. Study 2 aimed to quantify and characterise the intracellular lipids within the domestic cat’s kidney, compared to kidneys of dogs and Scottish wildcats. Domestic cat and Scottish wildcat kidneys contained a similar amount of lipid and significantly more than dogs at all ages studied. However, domestic cat renal intracellular lipid droplets were found to contain an additional lipid molecular class, monoalkyldiacylglycerol (MADAG), which is comparatively reduced in Scottish wildcat kidneys and absent from dog kidneys. The branched-chain fatty acid composition of the identified MADAGs, which are unusual in mammalian tissues, implies that they may originate from plant oils or fish-based ingredients that are incorporated into commercial pet foods. The cat, as an obligate carnivore whose ancestors evolved in an arid environment, may not be physiologically well-adapted to metabolise such ingredients. These findings indicate a fundamental tendency for felines to accumulate certain renal lipids, which may be exacerbated by chronic consumption of a commercial diet and domesticity. The pathogenesis of feline hyperthyroidism is unknown, however, cats that eat canned, or fish-flavoured, foods may have increased risk of developing the condition. Such foods may have high iodine content. Due to the similarities between feline hyperthyroidism and human toxic nodular goitre (TNG), a similar aetiology of fluctuating dietary iodine intake was considered for feline hyperthyroidism. Study 3 explored whether domestic cats, consuming commercial pet foods and with relatively high intake of fish, are more likely than dogs to experience large fluctuations in their dietary iodine intake, which may underpin the high prevalence of feline hyperthyroidism. Although most complete diets that were analysed in this study complied with FEDIAF nutritional guidelines for iodine, a few had levels of iodine that exceeded the legal maximum, or were below the recommended minimum concentration. We established that even feeding identical foods over time would introduce significant flux in iodine intake, as the iodine content of subsequent batches varies considerably. Nonetheless, from a survey of cat owners, we found that most pet cats experience dietary changes, most commonly alternating between wet and dry foods and a variety of flavours on a daily basis. Iodine concentration did not associate with any particular flavour of food, including fish, or with wet foods packaged in cans versus other packaging types. This study highlights that cats may occasionally consume diets that are deficient or excessive in iodine content. However, urinary iodine analysis suggested that, on average, the daily iodine intakes of cats and dogs are not different. Nonetheless, hair iodine concentration, as a biomarker of long-term iodine intake, was different in euthyroid, versus hyperthyroid, cats. A causative implication of dietary iodine in feline hyperthyroidism remains to be established, however. These studies, which employed a series of histological, chromatographic and mass spectrometry methods, showed that domestic cats differ from dogs and Scottish wildcats with regard to the mineral and lipid composition of their kidneys, suggesting that a species and environmental interaction may be responsible for the high prevalence of CKD in domestic cats. Further studies are required to establish the origin and role of the unusual renal lipid in the domestic cat. Some ‘complete’ pet foods contain levels of certain minerals, which may be involved in CKD or hyperthyroidism development, that fall outside of the recommended range to ensure adequate nutrition. Thus, stricter regulation of pet food manufacture is required, to ensure that domestic cats receive an appropriate diet, which might include avoiding certain ingredients, which, in high levels that the cat is not evolutionarily adapted to consume, may promote disease