THIS is the second article on feline chronic kidney disease (CKD). Part I covered the approach to the cat with CKD and this article will focus on the long-term management of these patients. Before commencing treatment, it is important to obtain baseline clinical, haematological and biochemical information about the patient (see part 1) to enable the development of an individualised treatment plan. As discussed in part 1, determining the underlying cause of CKD can be difficult in these cats; however, treatment of the underlying cause, if found, may slow further progression of the disease. The specific treatment will depend on the diagnosed disease (e.g. renal lymphoma, pyelonephritis, nephrolithiasis) and is beyond the scope of this article; however, the importance of specific treatment cannot be overemphasised. Once any active renal disease has been recognised and treated appropriately, the goals of CKD management are to: prevent and/or treat the complications of decreased kidney function, thereby improving the clinical signs, slow progression of the disease and treat any concomitant unrelated conditions. As CKD is almost invariably a progressive disease, it is important to monitor the patient over time and make treatment changes as the disease progresses. Dehydration is common in cats with CKD and can result in reduced appetite, lethargy, weakness and constipation, as well as predisposing to acute kidney injury which can lead to disease progression. Increasing oral water intake by feeding moist foods, adding water to the food, providing a water fountain and offering broths made from poaching fish or chicken (avoid salty broths and milk) can help improve hydration. If these measures are insufficient, some owners are prepared to administer 75-100ml of a balanced electrolyte solution subcutaneously 2-3 times a week. This is relatively inexpensive, is well tolerated by many cats and can be a successful way of maintaining hydration. Nausea and vomiting are not uncommon in cats with CKD and contribute to dehydration, inappetance and weight loss. H2 antagonists such as famotidine, ranitidine or cimetidine can be used to treat hypergastrinaemia which contributes to uremic gastritis. Anti-emetics such as metoclopramide (Emeprid, Ceva; Vomend, Eurovet), chlorpromazine and maropitant may also be used.
Anorexia
Anorexia can be a major problem in cats with CKD and is often multifactorial. Feeding warmed food, hand-feeding, offering foods of different textures and adding flavour enhancers such as tuna juice or brewer’s yeast can all help. In some cases appetite stimulants such as cyproheptidine, mirtazapine or anabolic steroids are needed. Placement of an oesophagostomy or gastrotomy tube may be considered to deliver additional food, water and medications in some cases, although this will not be suitable for all cats or their owners. Hyperphosphataemia affects about 60% of cats with CKD and although it is unlikely to cause clinical signs, it has been shown to significantly reduce survival time (Boyd et al, 2008). Target serum phosphorus concentrations have been suggested for different International Renal Interest Society (IRIS) stages of CKD (see Table 1). It should be noted that these targets fall below the upper limit of the reference ranges of many laboratories. Hyperphosphataemia is treated initially by dietary phosphate restriction (i.e. feeding a prescription renal diet) and if this is insufficient after 4-8 weeks, by adding an intestinal phosphate binder. Feline maintenance diets are high in phosphate due to their high protein content and the administration of a phosphate binder to a maintenance diet is rarely adequate to achieve the target serum phosphate concentrations. Several phosphate binders are available on the veterinary market including lanthanum (Renalzin, Bayer) and calcium carbonate containing agents (Ipakitine, Vétoquinol). Phosphate binders must be administered with every meal as they act by binding dietary phosphate and reducing its absorption in the intestines. Calcium containing phosphate binders should be avoided in patients with hypercalcaemia and those receiving vitamin D. As hyperphosphataemic cats have increased total body phosphate, blood phosphate levels take time to normalise after the institution of treatment and serum levels should therefore be monitored no more often than monthly. Hypokalaemia is relatively common in stage II and III CKD and can contribute to lethargy, weakness, inappetance, weight loss and polyuria/polydipsia as well as causing the more classic signs of generalised muscle weakness and cervical ventroflexion in severe cases. Hypokalaemia can also adversely affect renal function. Feeding prescription renal diets which are nonacidifying and supplemented with potassium can be sufficient to prevent or correct hypokalaemia in mild cases. In cats in which this is insufficient and/or those with generalised muscle weakness, supplementation with oral potassium gluconate/citrate or supplementation of subcutaneous/intravenous fluids with potassium chloride may be necessary. Patients on intravenous potassium supplementation should undergo monitoring of their serum electrolytes at least daily. Initially, patients started on oral potassium supplements will need serum potassium measurement every 1-2 weeks, to enable appropriate dose adjustment. Metabolic acidosis is common particularly late in the course of CKD. Maintaining normal hydration and feeding feline prescription renal diets (which are non-acidifying) will help prevent acidosis. Oral potassium citrate or sodium bicarbonate can be administered if additional treatment is needed; however, this is not often necessary.
Proteinuria
Proteinuria (urine protein-to-creatinine ratio >0.4) can lead to progression of renal disease as filtered proteins are renotoxic. This has been identified as a risk factor for mortality in feline CKD patients (Syme et al, 2006). Treatment of cats with IRIS stage 2-4 CKD and proteinuria is therefore advised and involves: avoiding excessive dietary protein, the administration of angiotensin converting enzyme inhibitors (ACEi) and controlling hypertension.
The administration of ACEi to cats with CKD has been shown to significantly reduce proteinuria and reduce the number of cats progressing from IRIS stage II/III disease to stage IV disease (Mizutani et al, 2006). Systemic hypertension (present in about 20% of cats with CKD) can result in ocular, cerebral and cardiovascular pathology as well as progression of renal disease. ACEi alone are not very effective antihypertensive agents in cats; however, amlodipine is usually effective. In some cases, both drugs are necessary. Although the optimal endpoint for antihypertensive therapy has not been established in cats, blood pressure monitoring of hypertensive cats should initially be performed every 1-2 weeks with a suggested goal of <150/95mmHg generally advised. Anaemia can contribute to lethargy and inappetance as well as potentially causing disease progression due to renal
hypoxia. Anaemia in cats with CKD can be due to a variety of underlying causes and more than one cause likely exists in many cases. Treatments to consider in these patients include gastro-protectants (to treat gastrointestinal blood loss due to uraemic gastritis), B vitamin supplementation, ferrous sulphate (to treat iron deficiency caused by decreased intake and increased loss) and recombinant erythropoietin therapy (to treat relative erythropoietin deficiency). Erythropoietin administration is not without risk and can result in iron deficiency, hypertension, polycythaemia and the production of antierythropoietin antibodies. It is usually reserved for the treatment of cats in which all other causes of anaemia have been excluded or treated, that are symptomatic and that have a PCV <20%. Hyperparathyroidism as present in 84% of cats with CKD in one study (Barber and Elliot, 1998) and a relative or absolute deficiency of calcitriol is believed to play a key role in the development of renal secondary hyperparathyroidism.
Parathyroid hormone
Parathyroid hormone is thought to act as a uraemic toxin and may also cause lethargy, weakness, anorexia and immunodeficiency among other wideranging systemic effects. In addition, calcitriol may also have important renal effects unrelated to parathyroid hormone. There have been anecdotal suggestions that calcitriol therapy may improve the quality of life of cats with CKD; however, a randomised controlled clinical trial of cats with stage 2-4 CKD did not show any evidence of altered mortality, improved appetite or quality of life with treatment (Polzin et al, 2008). At this time, good evidence for the treatment of cats with CKD with calcitriol is lacking. Many of the above complications can be addressed simultaneously by feeding a prescription renal diet (see Table 2). Although these diets are often more expensive than maintenance feline diets, currently available evidence from published clinical trials suggests that this is the single most effective treatment for feline CKD (Plantinga et al, 2005; Elliott et al, 2000; Ross et al, 2006). A diet change to a prescription kidney diet is the initial treatment of choice in cats with IRIS stage 2-4 CKD. Without a doubt, changing the diet can be difficult in cats, particularly in those with CKD, and this process should not be rushed. Feeding a prescription renal diet should not be started when cats are acutely ill and hospitalised. Diets should be introduced gradually over a period of at least seven days and often 3-4 weeks and it can be helpful to offer both the old and new diets side-by-side. The temperature, texture and formulation of food may all be important and some cats will accept one brand or flavour but not others. Introduction of a renal diet is likely to be easier earlier in the course of the disease. It is important for owners to understand the significant benefits of renal diets not only to decrease mortality but also to decrease the frequency of uraemic episodes and therefore improve quality of life. Without the understanding of owners, a successful transition to a prescription diet is less likely to be successful. Having started appropriate treatment, it is essential to institute a plan for regular monitoring. This is important to: assess whether the management of previously diagnosed complications is adequate, gauge disease progression, monitor for the development of new complications, and provide client support. The frequency of monitoring will depend on the stage of disease and severity of concurrent problems. It is likely to be frequent initially (every 1-2 weeks) and then may be reduced to every 3 to 12 months thereafter, providing the patient is stable. In addition to collecting a history and performing a full physical examination, re-check examinations will include blood pressure and ocular examinations, blood sampling for haematology and biochemistry (including phosphorus, calcium and electrolytes) and urine sample collection for urinalysis (including urine proteinto- creatinine ratio) and culture. Twenty per cent of cats with CKD suffer from a urinary tract infection at some point in their disease and this can result in pyelonephritis and disease progression. These infections are often clinically silent and will therefore not be detected without urine culture. Feline CKD is typically a slowly progressive disease and sudden patient deterioration may suggest the development of another disease or an episode of acute-on-chronic disease. Such patients should therefore undergo investigations to try and identify conditions which may be treatable and reversible, enabling the cat to return to its previously stable state. Although feline chronic renal disease is an incurable and usually progressive condition, medical management combined with regular monitoring and appropriate treatment modification enables cats to survive many years after the initial diagnosis with a good quality of life.
References
Boyd, L. M., Langston, C., Thompson, K., Zivin, K. and Imanishi, M. (2008) Survival in cats with naturally occurring chronic kidney disease (2000-2002). J Vet Intern Med 22: 1,111-1,117.
Syme, H. M., Markwell, P. J., Pfeiffer, D. and Elliott, J. (2006) Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med 20: 528-535.
Mizutani, H., Koyama, H., Watanabe, T., Kitagawa, H., Nakano, M., Kajiwara, K. and King, J. N. (2006) Evaluation of the clinical efficacy of benazepril in the treatment of chronic renal insufficiency in cats. J Vet Intern Med 20: 1,074-1,079.
Barber, P. and Elliott, J. (1998) Feline chronic renal failure: calcium homeostasis in 80 cases diagnosed between 1992 and 1995. J Small Anim Pract 39: 108-116. Polzin, D. J., Ross S. and Osborne, C. A.
(2008) Calcitriol. In: Bonagura, J. D., ed. Current Veterinary Therapy XIV. Philadelphia: Saunders Elsevier. Plantinga, E. A., Everts, H., Kastelein, A. M. and Beynen, A. C. (2005) Retrospective
study of the survival of cats with acquired chronic renal insufficiency offered different commercial diets. Vet Rec 157:
185-187. Elliott, J., Rawlings, J. M., Markwell, P. J. and Barber, P. J. (2000) Survival of cats with naturally occurring chronic renal failure: effect of dietary management. J Small Anim Pract 41: 235-242. Ross, S. J., Osborne, C. A., Kirk, C. A., Lowry, S. R., Koehler, L.A, and Polzin, D. J. (2006) Clinical evaluation of dietary
modifications for treatment of spontaneous chronic renal disease in cats. J Am Vet Med Assoc 229: 949-957.
Further reading
Kidder, A. C. and Chew, D. J. (2009) Treatment options for hyperphosphatemia in feline CKD: what’s out there? J Feline Med Surg 11: 913-924. Polzin, D. J. (2011) Chronic kidney disease in small animals. Vet Clin North Am Small Anim Pract 41: 15-30.
