Making a diagnosis of chronic kidney disease (CKD) in cats marks the start of a new and complex journey to provide optimal treatment for the patient. A successful outcome depends on attention to detail and a good working relationship with the carer and patient. If it is possible to institute good treatment measures, many patients with CKD survive for several years following diagnosis, with an excellent quality of life.
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AFTER a diagnosis of chronic kidney disease (CKD) attention moves to treating and managing the disease. Treatment should include addressing any underlying disease which is contributing to ongoing renal damage, strategies aimed at reducing progression of disease and symptomatic support of complications of CKD, such as poor appetite and dehydration. CKD is a progressive condition and, ultimately, despite its chronicity, is likely to be responsible for the patient's death. Phosphate-restriction, ideally through feeding a specially formulated renal diet, has been shown to be the most effective management option. Cats with CKD that will eat a renal diet live on average two to three times longer than those fed a standard commercial cat food, so all efforts should be put into supporting transition to a renal diet. Further treatments, tailored to the individual's needs, can make a big difference to quality of life.
What aspects of management should be considered in all patients?
Management of CKD should aim to:
▪ Identify and treat any underlying disease.
▪ Where possible, use strategies that are known or thought to slow the progression of renal disease.
▪ Provide supportive and symptomatic treatments to improve quality of life.
Identifying underlying disease
Diagnosing underlying disease is important to halt ongoing renal damage and slow progression of CKD. Investigations such as ultrasonography, radiography, urine culture, renal biopsy and other tests, according to the individual's needs, may be required to identify underlying disease. Examples of conditions where diagnosis makes a difference to the treatment recommendations for CKD would include renal lymphoma and bacterial pyelonephritis where specific treatment can improve the patient outcome. In many CKD patients, the underlying cause of the disease cannot be identified.
Strategies aimed at slowing the progression of renal disease
The most proven general treatment for CKD is feeding a specially designed renal diet. A number of studies have shown that feeding one of these diets improves quality and length of life of affected cats. Renal diets are modified in a number of ways to support cats with CKD, including being protein and phosphate-restricted, supplemented in potassium and B vitamins, higher in fat and calories, highly palatable and non-acidifying. The greatest benefit of feeding a renal diet is thought to be the phosphate-restriction.
In normal cats, excess phosphorus consumed in the diet is excreted by the kidneys and renal excretion of phosphate is dependent on glomerular filtration. Therefore, cats with CKD are vulnerable to phosphate retention and hyperphosphataemia. Regulation of phosphate excretion is under the control of parathyroid hormone (PTH) which has a phosphaturic effect. PTH increases renal reabsorption of filtered calcium while increasing renal excretion of phosphate. PTH has other effects including mobilisation of calcium (and phosphate) from bone, and increasing calcitriol production, which facilitates calcium absorption from the intestine. Hyperphosphataemia and reduced renal production of calcitriol contribute to the development of renal secondary hyperparathyroidism (R2HPTH); a condition which more recently has been referred to as feline mineral and bone disorder. In a healthy cat, increased amounts of PTH would help to correct hyperphosphataemia by increasing renal elimination of this substance. However, this strategy is only effective when there are sufficient functioning nephrons available to respond. Once the renal mass is below a critical level, increases in PTH are counter-productive and merely result in mobilisation of calcium and phosphate from the bone. Calcium and phosphate mobilisation may lead to renal osteodystrophy and clinical consequences including ‘rubber jaw’. Release of calcium and phosphate also leads to soft tissue mineralisation. Where present, nephrocalcinosis is especially damaging to renal function.
Unless treated, R2HPTH progressively worsens. High levels of PTH are thought to contribute to the uraemic state through acting as one of the uraemic toxins. High levels of PTH also contribute to ongoing renal damage by causing calcium influx into renal tubular cells and precipitation of calcium phosphate in the lumen of the tubules. R2HPTH is seen in most – if not all - cats with CKD and may precede azotaemia.
Hyperphosphataemia is used as a marker of R2HPTH; if phosphate levels are raised in a cat with CKD they can be assumed to be suffering from R2HPTH. If phosphate levels are normal unfortunately this does not rule out R2HPTH. The International Renal Interest Society (www.iris-kidney.com) recommend phosphate restriction for all cats with azotaemic CKD (IRIS stages 2, 3, 4) irrespective of their blood phosphate levels and have guidelines regarding ideal (target) blood phosphate levels (Table 1). The aim of phosphate restriction is to prevent and reverse development of R2HPTH and hence slow progression of renal disease.
Use of a renal diet and/or phosphate binder is effective in achieving phosphate restriction. Acceptance of a renal diet can take several weeks or months to achieve and success depends on supporting carers through this period. Cats with CKD can be challenging to transition to a new diet and often require treatment for complications that have a negative impact on appetite. If feeding a renal diet is not possible then senior cat food is preferable to standard commercial cat food. If blood phosphate levels remain above IRIS target levels (Table 1) in spite of phosphate restriction, a combination of renal diet and one or more phosphate binders may be required.
A number of phosphate binders are available. Used alone with a standard commercial cat food, phosphate binders may provide sufficient phosphate-restriction for a cat in IRIS stage 2 CKD, but those in more advanced stages are likely to need a phosphate-restricted diet to maintain normophosphataemia. ‘Veterinary’ formulated options include calcium carbonate (eg, Pronefra, Virbac; Ipakitine, Vétoquinol, Easypill Cat Kidney Support, Vetinnov); other options include human formulations such as aluminium hydroxide (eg, Alu-cap, Meda Pharmaceuticals) and lanthanum carbonate (Fosrenol, Shire Pharmaceuticals Contracts). Phosphate binders should be mixed with food and included with every meal that the cat eats. They work by binding to phosphate present in the food, retaining this in the bowel and hence limiting the amount of phosphate that can be absorbed by the body. Calcium-containing binders should be avoided in hypercalcaemic patients and in those receiving calcitriol.
Loss of nephrons leads to activation of the renin angiotensin aldosterone system (RAAS), which results in hypertrophy of residual nephrons with reduced arteriolar resistance and increased glomerular blood flow. As renal disease progresses, the afferent arteriolar tone decreases more than the efferent arteriole tone, resulting in glomerular hypertension and hyperfiltration. Although this increase helps support glomerular filtration rate and excretory function, ultimately RAAS activation has negative consequences including proteinuria, renal damage, fibrosis and further progression of renal disease. Angiotensin II is responsible for many of the damaging effects of RAAS activation.
Two veterinary-licensed options exist for suppression of the RAAS in cats with CKD:
▪ The angiotensin receptor blocker (ARB) telmisartan works by preventing angiotensin II from binding to one of its receptors, the angiotensin receptor-1 (AT-1). The AT-1 receptor mediates the most harmful consequences of angiotensin II, whereas the AT-2 receptor is thought to result in some beneficial effects in cats with CKD.
▪ Angiotensin converting enzyme inhibitors (ACEI) such as benazepril work by blocking the production of angiotensin II.
IRIS currently recommend that CKD patients are treated with medications that suppress the RAAS if suffering from a persistent renal proteinuria. Patients are classed as proteinuric if their urine protein to creatinine ratio (UPC) is over 0.4 and borderline proteinuric if their UPC is between 0.2 and 04. RAAS suppression using telmisartan or benazepril has been shown to be effective in reducing proteinuria although as yet a survival benefit has not been shown.
Some clinicians advocate treating borderline proteinuric cats (UPC 0.2 to 0.4) on the basis that survival times in these cats are reduced compared to non-proteinuric CKD cats (UPC <0.2) and this is considered logical by the panel responsible for the recently published International Society of Feline Medicine (ISFM) consensus guidelines on diagnosis and management of CKD (Sparkes and others 2016). ACEI and ARBs should only be used in clinically stable, normally hydrated cats. There may be some benefits in treating non-proteinuric CKD patients with an ARB or ACEI since some studies have shown improved quality of life and a tendency for the renal disease to progress more slowly in these cats.
Telmisartan has a potential advantage over an ACEI by not being susceptible to ‘ACE escape’ – the phenomenon whereby alternative pathways allow angiotensin II to continue to be produced despite administration of an ACEI. Telmisartan also offers a more targeted mode of action, sparing the AT-2 receptor which may mediate some beneficial effects. A recent field study of cats with CKD showed that telmisartan was effective in significantly reducing proteinuria at all assessment points in the 180 day study, whereas benazepril was not (Sent and others 2015).
Supportive and symptomatic treatments
A variety of supportive and symptomatic treatments may be helpful in the individual patient. These should be chosen according to the individual patient's needs and include:
Patients with CKD are vulnerable to dehydration. Dehydration worsens renal perfusion and therefore renal function leading to exacerbation of complications associated with CKD such as metabolic acidosis and poor appetite. Dehydrated patients should be rehydrated and all patients should be encouraged to maintain normal hydration through tactics including feeding a moist diet and ensuring that access to water is easy and plentiful. Detailed guidelines on tactics that can encourage increased water intake are available in the ‘free downloads’ section of my website (Caney 2011). Subcutaneous fluids (eg, 50 to 100 ml Hartmann's solution once daily) can be helpful in cats struggling to maintain normal hydration (Fig 1).
Prevention/treatment of hyperphosphataemia
Around two-thirds of CKD patients are hyperphosphataemic as a result of their renal disease. This should be addressed as discussed earlier.
Prevention/treatment of metabolic acidosis
Metabolic acidosis (blood bicarbonate or total CO2 <14 mmol/l) is a common complication of CKD, especially in those patients that are suffering from dehydration, and is estimated to affect more than 60 per cent of patients at some point in the course of their illness. In many patients, where present, the metabolic acidosis resolves on correction of dehydration with only a small number of patients requiring more aggressive management such as intravenous sodium bicarbonate* and/or oral potassium citrate* (40 to 75 mg/kg twice daily as a starting dose) Maintaining optimal hydration (as discussed above) and feeding a renal diet minimise the incidence of metabolic acidosis.
Support of poor appetite
Variable to poor appetite is common in cats with CKD, estimated to affect more than 30 per cent of patients. Where documented, it is important to look for and address treatable causes of poor appetite such as dehydration, hypokalaemia, nausea and anaemia. General nursing support, such as sitting with the cat, gently warming the food and offering the food by hand can help. Appetite stimulants such as mirtazapine* (1 to 2 mg per cat every 48 hours, as needed), which also has some antiemetic effects, can be useful. In cats that are bright and relatively well but where appetite remains poor, one long-term possibility includes placing a feeding tube such as an oesophagostomy or gastrostomy tube (Fig 2).
Support of anaemia
Anaemia is a potential complication of CKD, estimated to affect around a third of patients, and may lead to poor appetite, lethargy and weakness. Anaemia develops due to a lack of production of erythropoietin by the diseased kidneys, reduced survival of red blood cells and potentially blood loss from gastric ulcers and excessive blood sampling. Patients may suffer from a relative or absolute iron deficiency, which can contribute to anaemia development. Iron deficiency should be differentiated from chronic disease by assessing iron status (iron saturation, total iron binding capacity [TIBC] and iron levels) and looking for features consistent with iron deficiency, such as microcytic and hypochromic red cells. Low/normal serum iron and saturation with a low TIBC is generally considered compatible with an anaemia of chronic disease; in a patient with iron deficiency, iron levels and saturation are low while TIBC is normal. Treatment of anaemia is generally recommended once the packed-cell volume (PCV) falls to around 20 per cent and most successful is a combination of an erythrocyte stimulating agent, such as darbepoetin* (induction dose 1 µg/kg subcutaneously once a week) combined with intramuscular iron dextran (50 mg per cat, can be repeated monthly if needed). Once the PCV reaches the reference range, the dose and/or frequency of darbepoetin can be reduced (eg, 1 µg/kg subcutaneously every two to three weeks) to maintain red blood cell parameters within the reference range. Management of anaemia associated with CKD is reviewed in detail by Chalhoub and others (2011).
Treatment of systemic hypertension
Systemic hypertension is estimated to be present in around 20 to 30 per cent of patients with CKD and has potentially life-threatening consequences. IRIS recommends that systolic blood pressure (SBP) is assessed in all patients and treated if persistently elevated (SBP >160 mmHg on two to three occasions) or if high on a single occasion in a patient also found to have evidence of target organ damage such as retinal haemorrhage, oedema or detachment. Systemic hypertension can be treated with amlodipine (Amodip, Ceva Animal Health) at a dose of 0.625 or 1.25 mg per cat once daily. Mild hypertension (SBP 160 to 180 mmHg) may respond adequately to an ACEI (eg, benazepril 0.5 to 1.0 mg/kg once daily) or ARB (eg, telmisartan 1 to 3 mg/kg once daily). Refractory cases of systemic hypertension can respond to a combination of amlodipine with either an ACEI or ARB at the above doses.
Treatment and prevention of hypokalaemia
Up to a quarter of CKD patients suffer from hypokalaemia as a result of inappropriate kaliuresis and inadequate intake through diet related to poor appetite. Typically, the resulting hypokalaemia is mild (potassium 3.0 to 3.5 mmol/l) and can be difficult to identify clinically. Cats with more severe hypokalaemia may show evidence of muscle weakness with ventroflexion of the neck (Fig 3), evident in the most severe of cases. Hypokalaemia can be corrected using potassium chloride in intravenous or subcutaneous fluids and/or oral potassium gluconate (1 to 2 mmol per cat once or twice daily). Hypokalaemia can be prevented by feeding a renal diet since this is supplemented in potassium. Acidifying diets, high protein diets and potassium deficient diets should be avoided. In cats receiving subcutaneous fluids, potassium chloride can be added to the bag before administering to the patient, for example, 10 mmol potassium chloride per 500 ml fluids.
Management of nausea and vomiting
Uraemia associated with CKD commonly causes nausea and vomiting which can have a significant negative impact on quality of life and contribute to weight loss. Symptomatic treatment options include mirtazapine* (also an appetite stimulant) (1 to 2 mg per cat every 48 hours), maropitant (1 to 2 mg/kg once daily), H2 blockers such as famotidine* (0.5 to 1 mg/kg once daily) and proton pump blockers such as omeprazole* (0.5 to 1 mg/kg once or twice daily).
Bacterial urinary tract infections
Patients with CKD are vulnerable to bacterial lower urinary tract infections with up to a quarter of patients suffering from this at some point in the course of their illness. Current recommendations are that these should be treated if the patient shows clinical signs (systemic and/or lower urinary), if pyuria is present, where ultrasound evidence of pyelonephritis is present and/or if renal function has recently deteriorated. An appropriate antibiotic should be chosen on the basis of culture and sensitivity testing. Typically a prolonged course of treatment (eg, four to six weeks) is needed to eliminate the infection. Repeat urine culture is recommended during the treatment period and seven to 10 days after treatment has concluded to confirm treatment success. If recurrent or refractory infections are encountered, ultrasound of the kidneys and bladder is indicated to look for evidence of a nidus or other explanation.
Proteinuria is an acknowledged complication of feline CKD through activation of the RAAS. Treatment of proteinuria should be considered as discussed earlier.
Compliance and owner support
A successful outcome depends on an individualised approach that is developed with involvement of the cat's owner. CKD is a complex disease and many owners appreciate support and education in how best to care for their cat. A recent survey of owners of cats receiving long-term medical management for their hyperthyroidism reported that 47 per cent of owners requested more leaflets and printed information to help them learn more about their cat's condition, and it is likely that owners of cats with CKD will have similar priorities (Caney 2013). Support and tuition in how to administer medications is also important. Owners should be encouraged to be open about any difficulties they are having so that these can be supported as best as possible. Tips for supporting medication are presented in Table 2.
Managing patients with additional medical needs
Since CKD is common in older cats it is not unusual for these patients to have additional illnesses. Common examples would include hyperthyroidism, diabetes mellitus and osteoarthritis.
Managing cats with concurrent hyperthyroidism
All treatments for hyperthyroidism have the potential to worsen renal function since they cause a reduction in renal blood flow. This has the potential to ‘unmask’ kidney disease that was previously unknown and to worsen pre-existing renal disease. Unfortunately, there is no way to predict which cats will suffer renal problems following treatment of their thyroid disease. Fortunately, most cats with hyperthyroidism can be optimally treated, even when CKD is present, and it is only those with very severe renal disease (IRIS stage 4) where optimal management of hyperthyroidism may precipitate a clinical deterioration. Optimal management of hyperthyroidism is desirable since hyperthyroidism itself can contribute to the progression of CKD.
Managing cats with concurrent diabetes mellitus
While a low phosphate and low protein diet is recommended for cats with CKD, a high protein and low carbohydrate diet is generally recommended for cats with diabetes. If both CKD and diabetes mellitus are present, the best dietary approach is usually to concentrate on whichever condition is the biggest concern for the cat; for example, if the renal disease is mild, a phosphate binder added to a diabetic diet might be most appropriate in addition to other strategies for management of both conditions (Sparkes and others 2015, 2016).
Managing cats with concurrent osteoarthritis
Osteoarthritis is a common cause of mobility problems in older cats. Environmental modification can help affected cats to cope more easily; for example, by providing comfortable beds that are easy for the cat to step on and off and/or steps to allow cats access to their favourite sleeping places. In severely affected cats, non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, can be very effective in reducing pain and are usually very well tolerated. Potential adverse effects include gastrointestinal signs (eg, vomiting, loss of appetite) and renal damage. Renal damage is most likely in cats that are dehydrated or hypotensive when dosed. Several published studies have shown that most cats with concurrent osteoarthritis and CKD can safely receive a low daily dose of meloxicam (eg, 0.01 to 0.03 mg/kg once daily), should they need it, without adversely affecting their renal function. For cats with CKD receiving an NSAID for osteoarthritis, the following general guidelines exist for owners:
▪ Do what you can to encourage maintenance of normal hydration: feed a moist diet, encourage drinking by using water fountains, and so on (Caney 2011).
▪ Do not administer the NSAID if your cat appears unwell (eg, not eating, vomiting).
▪ Mix the NSAID with food: if your cat is unwell and does not eat, it will not receive the medication.
▪ Use at the lowest effective dose.
For those cats that cannot tolerate an NSAID, other painkiller options that might be helpful would include opiates like buprenorphine.
Where anaesthesia is needed in CKD patients, for example for dental treatment, the patients should be stabilised preoperatively so that their hydration is optimal, electrolytes are normal and they are in as good a state as possible to cope with anaesthesia. Anaesthetic regimes which may result in hypotension should be avoided and blood pressure should be monitored and supported, as necessary, throughout the procedure.
Check-ups for cats with CKD
Monitoring visits are very important to ensure that owners are supported and that clinical problems are identified and treated promptly. Compliance to medication and diet is enhanced by veterinary support; a recent study showed improved compliance to a renal diet in those cats whose owners had received a veterinary recommendation to feed this diet (Caney 2016). The required frequency of check-ups varies according to the patient's needs but should initially be at least once a month. All check-ups should include weighing the patient and assessing for clinical problems (such as dehydration). Blood pressure and laboratory monitoring should be checked according to the patient's needs and owner's concerns; I measure blood pressure every three to six months and reassess blood and urine parameters every six to 12 months, depending on the individual patient's needs. Check-ups can be performed by a veterinary nurse/technician working under direction of a veterinary surgeon.
CKD is often a challenging condition to manage but treatment is extremely successful in most patients where optimal treatment is possible. Attention to detail and providing an individualised plan leads to the best treatment outcome.
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