Introduction

Feline LUTD includes cystic calculi, infectious and sterile cystitis, neoplasia, anatomic defects, behavioural problems, and feline idiopathic/interstitial cystitis (FIC). Urolithiasis comprises 15–23% of cases, urethral plugs 10–21%, anatomic defects up to 11%, bacterial infections 1–8% and neoplasia up to 2%1. In cats over 10 years old bacterial infections account for 20–50 % of LUTD cases; urine culture should be performed rather than assuming the urine is sterile.^1,2 Signs of LUTD in cats under 10 years old without urethral obstruction is caused by FIC in 55–73% of cases.¹

Clinical Signs

Dysuria, stranguria and pollakiuria localise the disease to the LUT, and along with haematuria, are the common signs associated with LUTD. Urinating outside the litter box (periuria) can be a manifestation of cystitis. LUTDs may not affect the patient’s general health, and do not cause polyuria, polydipsia or azotaemia.

Obesity, Stress and LUTD

In humans, stress is associated with obesity, though it can be difficult to differentiate cause and effect. About half of adult cats are overweight or obese and they have a higher prevalence of LUTD, including FIC and urolithiasis, compared to normal weight cats.³

Pathogenesis of FIC, a Highly Complex Disorder

Cats with FIC have a variable disease course with signs usually resolving in 5 to 7 days, then recurring. This waxing and waning is likely associated with events activating the central stress response system.⁴ Many affected cats show signs from other organ systems; e.g., the gastrointestinal tract, skin, lung, cardiovascular, central nervous, endocrine, and immune systems. The disease aetiology likely has a neuropathic aspect as well as a local bladder wall disorder.

The bladder smooth and striated muscles and the neurovascular supporting tissues engage in complex neuroendocrine communications between the body and brain to coordinate urination. Bladder neural connections include sensory afferent, central, and somatic, sympathetic, and parasympathetic efferent neurons interacting between the urothelium and the cerebral cortex.⁴

Cats with FIC show a denuded uroepithelium with increased permeability and a decreased total glycosaminoglycans layer in the bladder.⁴ Urine protein concentration was four times and urine protein to creatinine ratio five times higher in cats with FIC than in normal cats.⁵ Increased serum concentrations of pro-inflammatory cytokines and chemokines are also present in FIC cats.⁶

In addition to uroepithelial bladder abnormalities, urinary changes, and altered serum cytokines in FIC, there are alterations in components of acetylcholine synthesis and release. Changes in the nonneuronal cholinergic system may contribute to alterations in cell-to-cell contacts and communication with underlying cells that contributes to changes in sensory function and visceral (bladder) hyperalgesia. Differences in sensory neuron anatomy and physiology are present in FIC cats, suggesting a more widespread abnormality of sensory neuron function. The acoustic startle response, a brainstem reflex motor response to a perceived threat from unexpected auditory stimuli, is increased in FIC cats. Differences in sympathetic nervous system function identified in FIC cats include changes in the brain stem region associated with an important source of noradrenaline. This area is involved in brain functions such as vigilance, arousal, and analgesia and mediates the visceral response to stress. Changes in brainstem help explain the waxing and waning of sign and the aggravation of signs by environment stressors.⁴

Some cats with FIC have abnormalities in the hypothalamic-pituitary-adrenal axis, with decreased serum cortisol secretion and smaller adrenal glands compared with healthy cats. Thus, some of these cats have an excessive sympathetic response to stress with decreased cortisol response, in addition to pathology within the bladder.⁴

Risk Factors for FIC

Risk factors for FIC include being an indoor cat, young middle age (4–7 years), neutered, and overweight. Other factors may include low activity, using a litter tray, eating a high proportion of dry food, and living with more than one other cat, especially with conflict between the cats. Compared to normal cats, cats with FIC have been described as being more fearful, nervous, having less hunting behaviours, hiding when unknown visitors are in the house and drinking less water.⁷ Episodes are often triggered by stress, e.g., moving house, new cats in the house or neighbourhood, new people in the house, or car rides to the clinic. A case-control study on indoor cats in South Korea showed increased FIC odds ratios for males cv females (odds ratio 2.34), cats not having vantage points to see out (odds ratio 4.64), cats living in an apartment (cv in a house) (odds ratio 2.53), and cohabiting with other cats compared to living alone (odds ratio 3.16)8. Cats using non-clumping litter had 2.62 times the odds compared with those using clumping litter.

Treatment for FIC

FIC generally cannot be cured, though it is often possible to decrease the frequency and severity of episodes. The initial treatment should include analgesics (e.g., buprenorphine) as these episodes are painful. Addressing stress management and diet are among the most important treatments.

Environmental Enrichment

A thorough history about feeding and management should be obtained. Resources can be found online (http://indoorpet.ocu.edu/veterinarians/research/ondex.cfm [VIN editor: URL was inaccessible as of 9-24-2020]). Multimodal environmental modification (MEMO) should be adopted to reduce stress, although only one or two changes should be made at a time. Each cat should have his own food bowl, separate from the water bowl, and both should be away from the litter box. It is recommended that the number of litter boxes equal the number of cats plus one, although this can be challenging to place around a house. As non-clumping litter is identified as a risk factor, using a non-scented clumping litter and/or meticulous cleaning of the litter box may help.

The cat should be able to access all resources without competing with other cats. When cats are not compatible, microchip-operated cat flaps in internal doors can offer a means for separate and private access to feeding and litter boxes9. Environmental enrichment should also include resting and hiding places, provision of normal cat behaviours (e.g., scratching, hunting or play-hunting) and a set routine with familiar people. Pheromone use can be helpful.

Moisture/Water

If possible, a wet diet should be fed and water intake increased. Water intake may be encouraged by daily fresh water and multiple full bowls placed away from food and litter boxes. Some cats prefer running water, e.g. a water fountain. Many FIC cats present with a urine specific gravity (SG) of around 1.050; decreasing the urine SG to <1.035 decreases frequency of the episodes.¹⁰

Diet and Supplements

Weight Loss

Weight loss is important for the overweight or obese cat for many health concerns. While overweight body condition is more common in FIC cats than in normal cats, no studies have been done which show that weight loss results in fewer episodes of FIC. Obesity is associated with a chronic state of inflammation which could exacerbate the urinary signs.

Glycosaminoglycans and Glucosamine

The urinary bladder glycosaminoglycans (GAGs) layer of cats with FIC is thought to be reduced or damaged, and oral provision of glucosamine, the precursor of GAGs, may have some benefit. Studies have not confirmed this in cats, although the studies may have been underpowered.¹⁰

Antioxidants

A struvite prevention diet with lower calcium, phosphorus and added antioxidants (vitamin E and carotene) and omega-3 fatty acids resulted in fewer recurrent episodes of clinical FIC signs compared to cats fed a control diet.¹¹

Stress and Anxiety Modification with Nutrients and Dietary Ingredients

The two currently used anti-anxiety ingredients for FIC are L-tryptophan and milk protein hydrolysate (MPH). L-tryptophan is an essential amino acid and the precursor of brain serotonin. Increased serotonin is associated with increased sedation, and decreased aggression, fearfulness, insomnia and pain sensitivity. In a double-blinded controlled cat study, added L-tryptophan decreased anxiety, stress-related behaviours and house soiling.¹² Milk protein hydrolysates, e.g., alpha-casozepin, have a similar structure to gamma aminobutyric acid (GABA), an inhibitory neurotransmitter which decreases anxiety and stress related disorders. Oral MPH given to cats decreases fearful behaviours and increases contact with people.¹³ A study showed beneficial effects of an alpha-casozepine and L-tryptophan supplemented diet on fear and anxiety in cats placed in an unfamiliar location although fear in the presence of an unfamiliar person was not decreased.¹⁴ A urinary food supplemented with milk protein hydrolysate and L-tryptophan fed for eight weeks to eighteen FIC cats improved FLUTD signs, and emotional and quality of life scores.¹⁵

Summary for Treatment of FIC

In summary, feeding a wet food and a food or ingredient to decrease stress have good evidence for decreasing the signs of FIC. Antioxidant therapy also appears to help and glucosamine may have some benefit. Overweight cats are more at risk and although weight loss has not been studied as a therapy it is recommended due to the risk of co-morbidities of obesity.

References

References are available upon request.