Serial evaluations of nutritional status are a key part of CKD patient management and a nutritional plan should be performed for every patient. Awareness of these parameters and tools for assessment have been made available by the WSAVA global nutritional initiative. A nutritional assessment should include body weight, body condition score, muscle mass score, adequacy of caloric intake (including open-ended questions about how the pet is eating), and a complete dietary history (including pet food, treats, supplements and items used to give medications). In obese patients with inadequate muscle mass, body condition score often does not adequately describe muscle loss. Assessment of muscle mass is particularly important in CKD patients as it can have a profound effect on serum creatinine and affect the interpretation of the severity of disease, as well as have notable implications for the nutritional status of the patient. Minimally a score of adequate muscle mass, or mild, moderate or severe muscle loss should be determined based on epaxial, skull, scapular and iliac musculature and documented in the medical record at each visit.

Several anti-emetic/anti-nausea therapies are available that may be helpful in amelioration of nausea and vomiting associated with CKD. These include the 5HT₃ receptor antagonists, ondansetron and dolasetron, and the NK₁ receptor antagonist maropitant citrate. These drugs work at the chemoreceptor trigger zone and vomiting center in the brain where uremic toxins are sensed, as well as at receptors in gastrointestinal tract. Maropitant is commonly used for acute vomiting; however, a pharmacokinetic and toxicity study in cats indicated that longer-term usage appears safe and anecdotally it is typically used for long-term therapy in chronically ill patients.¹ A recent study assessed the efficacy of maropitant for management of chronic vomiting and inappetence in cats with CKD.² When given daily for two weeks, maropitant was demonstrated to palliate vomiting associated with chronic kidney disease, however did not appear to significantly improve appetite or result in weight gain in cats with Stage II and III CKD within the timeframe of the study.²

Ondansetron has been documented to be twice as effective as metoclopramide in palliating uremic nausea and vomiting in human CKD patients.² Pharmacokinetic studies in cats have demonstrated that oral bioavailability of ondansetron is poor in this species (∼35%) and the half-life is very short (approximately 1 hour), making it most appropriately a q 8 h medication.³ Subcutaneous ondansetron had a slightly longer half-life of 3 hours. A pharmacokinetic study in dogs revealed that the oral bioavailability of ondansetron was very poor (<10%), indicating this may not be an appropriate route of administration.⁴ Ondansetron is also not appropriate as a transdermal medication, as a recent abstract assessing transdermal absorption in cats demonstrated no detectable blood levels after administration. Dolasetron has traditionally been recommended as a once-daily medication at doses of 0.5–1 mg/kg.

Although more commonly used as an appetite stimulant, mirtazapine also demonstrates anti-emetic properties, acting at the 5HT₃ receptor similar to ondansetron. Several studies have described successful palliation of nausea and vomiting in human patients; particularly cancer patients undergoing chemotherapy. In cats, mirtazapine has been shown to significantly reduce vomiting associated with CKD.⁵

In addition to addressing uremic nausea and vomiting, appetite stimulants can also be used to encourage food intake, particularly in late-stage patients and in patients where a feeding tube is not desirable to the owner. Cyproheptadine has been used for some time as an appetite stimulant and has anecdotal efficacy in many patients; however, its efficacy has never been scientifically evaluated. Mirtazapine has become more commonly used and recent exploration of its pharmacodynamics and pharmacokinetics has provided information for more effective use in animals.^6-8 Pharmacodynamic studies in cats have illustrated that it can be a potent appetite stimulant, but higher doses are more commonly associated with side effects (hyperexcitability, vocalization, tremors).⁹ Smaller, more frequent doses are recommended. Pharmacokinetic studies have demonstrated that the half-life is short enough that it could be administered daily in normal cats. Dose recommendations are 1.88 mg every 24 hours in cats without liver or kidney disease and 0.6–1 mg/kg once to twice daily in dogs without liver or kidney disease. In dogs, twice-daily dosing may be required due to relatively short half-life compared to other species.⁶ Renal disease delays clearance in CKD cats and thus every-other-day administration is recommended.⁷ The effect of liver disease on the metabolism of the drug in cats and dogs is currently unknown. In humans, liver disease delays elimination by 30% and reduced dosing intervals are recommended. A placebo-controlled, double-masked crossover clinical trial demonstrated mirtazapine was an effective appetite stimulant in cats with CKD and resulted in significantly increased appetite and weight.⁵ Mirtazapine also is amenable to transdermal administration and has been demonstrated to achieve both appropriate serum levels and appetite stimulation in healthy cats. Although clinical studies in cats with CKD are forthcoming, starting doses for transdermal application in CKD are anecdotally successful at 1.89 to 3.75 mg every other day. Owners should be aware mirtazapine and cyproheptadine cannot be administered concurrently; cyproheptadine is used as an antidote for the serotonin effects of mirtazapine overdose and thus negates the efficacy of the latter.

Future availability of the ghrelin agonist capromorelin may also provide additional opportunities to address appetite in dogs and cats with CKD by targeting the pathophysiology of appetite regulation. In both human and rodent studies, administration of ghrelin has resulted in increased appetite and energy intake in patients with CKD. In recent abstracts, administration of capromorelin resulted in increased appetite, food intake and weight in normal and inappetent dogs and increased food intake and weight in laboratory cats.

The exact role of hypergastrinemia in contributing to gastric hyperacidity and/or gastric lesions in cats and dogs with CKD is still unclear. Limiting gastric acidity with the use of H₂ blockers like famotidine or proton pump inhibitors such as omeprazole anecdotally appears to palliate inappetence in some CKD patients; however, as previously mentioned, both the degree of hyperacidity present in CKD and the efficacy of these medications for management of patients with CKD remain unproven.

Recent studies of the effect of omeprazole on the gastric pH in normal cats indicates that at 1 mg/kg twice daily it is superior to famotidine in its ability to inhibit acid production.¹⁰ Twice-daily administration appears to be superior to once-daily administration. However proton pump inhibitors have recently been linked to an increased risk of kidney disease in humans. The applicability of this finding to veterinary patients is currently unknown.

Common medications used in medical management of appetite

References

1.  Hickman MA, Cox SR, Mahabir S, et al. Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats. J Vet Pharmacol Ther. 2008;31:220–229.

2.  Quimby JM, Brock WT, Moses K, et al. Chronic use of maropitant for the management of vomiting and inappetence in cats with chronic kidney disease: a blinded, placebo-controlled clinical trial. J Feline Med Surg. 2015;17:692–697.

3.  Quimby JM, Lake RC, Hansen RJ, et al. Oral, subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats. J Vet Pharmacol Ther. 2014;37:348–353.

4.  Saynor DA, Dixon CM. The metabolism of ondansetron. Eur J Cancer Clin Oncol. 1989;25(Suppl 1):S75–77.

5.  Quimby JM, Lunn KF. Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: A masked placebo-controlled crossover clinical trial. Vet J. 2013;197:651–655.

6.  Giorgi M, Yun H. Pharmacokinetics of mirtazapine and its main metabolites in Beagle dogs: a pilot study. Vet J. 2012;192:239–241.

7.  Quimby JM, Gustafson DL, Lunn KF. The pharmacokinetics of mirtazapine in cats with chronic kidney disease and in age-matched control cats. J Vet Intern Med. 2011;25:985–989.

8.  Quimby JM, Gustafson DL, Samber BJ, et al. Studies on the pharmacokinetics and pharmacodynamics of mirtazapine in healthy young cats. J Vet Pharmacol Ther. 2011;34:388–396.

9.  Ferguson LE, McLean MK, Bates JA, et al. Mirtazapine toxicity in cats: retrospective study of 84 cases (2006–2011). J Feline Med Surg. 2015.

10. Parkinson S, Tolbert K, Messenger K, et al. Evaluation of the effect of orally administered acid suppressants on intragastric pH in cats. J Vet Intern Med. 2015;29:104–112.