Chronic kidney disease (CKD) is one of the most common causes of morbidity and mortality in older cats – estimated to affect more than 30% of cats older than 10 years of age.

Unfortunately, a diagnosis of this illness is often only made following the appearance of clinical signs associated with azotaemia (raised urea and/or creatinine). By this stage, often greater than 75% of the renal function has been lost.

Screening of apparently healthy cats is recommended to facilitate earlier interventions and monitoring, which help to prolong life and aid quality of life.

Screening recommendations

Since older cats are more vulnerable to developing CKD, these patients should be targeted for assessment.

The author recommends following International Cat Care’s guidelines regarding the frequency and nature of diagnostic tests (Table 1). In essence, these involve seeing older cats more frequently and doing more detailed health assessments.

Table 1. International Cat Care’s Cat Care for Life guidelines on the frequency and nature of preventive health care assessments for apparently healthy cats
Age of cat	Life stage/s	Frequency of check	What is evaluated?
0 to 6 years	Kitten, junior and prime	Once a year	• History • General physical examination • Bodyweight and body condition score
7 to 10 years	Mature	Once a year	• History • General physical examination • Bodyweight and body condition score • Blood pressure • Blood tests: haematology, serum biochemistry (including renal and hepatic parameters, electrolytes and proteins) • Urinalysis: dipstick and specific gravity
11 to 14 years	Senior	Six-monthly to 12-monthly	• History • General physical examination • Bodyweight and body condition score • Blood pressure • Blood tests: haematology, serum biochemistry and total thyroxine • Urinalysis: dipstick and specific gravity
15 years and older	Super senior	Six-monthly to 12-monthly	• History • General physical examination • Bodyweight and body condition score • Blood pressure • Blood tests: haematology, serum biochemistry and total thyroxine • Urinalysis: dipstick and specific gravity

Detailed history and thorough physical examination

Many clues of CKD are non-specific. Attention should be paid to looking for indicators of ill health – such as reduced appetite, increased thirst, weight loss, dehydration and abnormal renal palpation. It is important to note that physical examination of patients with renal disease is often normal.

Bodyweight assessment

Weight loss is a valuable, although non‑specific, indicator of ill health. For cats older than 11 years of age, weight checks every three to six months are justified (Figure 1).

A recent publication reported a median weight loss of 8.9% bodyweight in the year preceding a diagnosis of CKD, with weight loss evident as early as three years prior to the diagnosis being made (Freeman et al, 2016).

Urine screening

Renal disease is typically associated with a reduction in the ability to produce concentrated urine. For cats, this means a urine specific gravity (USG) lower than 1.035. Unless another reason exists for this “low” USG – such as a cat that receives a very liquid diet or is receiving diuretic treatment – further investigations are recommended.

Renal disease is not the sole cause of reduced USG – other common conditions that can cause this include hyperthyroidism and diabetes mellitus. Dipstick testing for glucose is helpful to rule out diabetes mellitus.

In those cats where renal disease is confirmed, further urinalysis (ideally using a cystocentesis‑collected sample) is indicated. This should include a sediment examination, bacterial culture and protein estimation (ideally urine protein to creatinine ratio; UPC) to further characterise the severity of disease and identify complications.

Free catch samples can be used for these further tests, but interpretation of results may be complicated by contamination from the urethra, genital tract and litter tray.

Blood screening

Many cats in early renal disease show few or no clinical signs. Blood screening allows the identification of azotaemia (raised urea and/or creatinine) in addition to looking for complications associated with renal disease, such as hyperphosphataemia, hypokalaemia and anaemia.

Creatinine is derived from muscle turnover; therefore, levels greater than 140μmol/L should be considered abnormal in cats with reduced muscle mass, such as many older cats.

Where available, a symmetric dimethylarginine (SDMA) assay is an advantage. SDMA is a serum biomarker that is renally excreted. Unlike creatinine, SDMA levels are not affected by muscle mass, so this test may be more reliable in assessing renal function in a poorly muscled elderly cat (Braff et al, 2014; Hall et al, 2014).

International Renal Interest Society (IRIS) guidelines on interpretation of creatinine and SDMA are included in Table 2.

Table 2. Classification of azotaemia using International Renal Interest Society (IRIS) guidelines
IRIS stage	Description	Creatinine results	Symmetric dimethylarginine results	Target phosphate levels (mmol/L)
1	Non-azotaemic	Lower than 140μmol/L	Greater than 14µg/dL	Lower than 1.5
2	Mild azotaemia	140μmol/L to 250μmol/L		Lower than 1.5
3	Moderate azotaemia	251μmol/L to 440μmol/L	Greater than or equal to 25µg/dL	Lower than 1.6
4	Severe azotaemia	Greater than 440μmol/L	Greater than or equal to 45µg/dL	Lower than 1.9

Additional recommendations for older cats

Blood pressure measurement is to be encouraged in all older cats, since systemic hypertension is a common diagnosis in these patients (Figure 2).

Cats with renal disease are especially vulnerable to developing systemic hypertension – up to 60% of patients typically suffer from this potentially life‑threatening complication.

How is a CKD diagnosis confirmed?

A diagnosis of CKD is typically confirmed when:

creatinine is elevated, greater than 140μmol/L, and/or SDMA is elevated greater than 14μg/dL

USG is lower than 1.035

the above changes have been present for several weeks or longer

clinical signs (or lack of) are compatible with a diagnosis of CKD

Measurement of the glomerular filtration rate (GFR; the amount of blood passing through the glomeruli of the kidneys each minute) is considered to be the most reliable test of kidney function and is commercially possible at a number of laboratories using an iohexol clearance assay, although this is an expensive test to perform.

GFR assessment is not essential in all cases of CKD. It is most helpful when assessing cats with early renal disease that are not yet azotaemic – for example, IRIS Stage 1 and early stage 2 CKD – and in screening cats known to be at risk of renal disease – for example, cats with congenital renal problems.

Monitoring GFR test results over a period of time can be valuable in tracking progression of renal disease.

Other important tests

Further assessment in confirmed cases of CKD is helpful in finding complications and learning more about the cause of the renal disease (Table 3).

Table 3. Further testing recommendations for cats with renal disease
Test	Comment
Detailed history	• Look for evidence of clinical signs that would benefit from symptomatic treatment – for example, appetite stimulants, antiemetics. • Look for potential cause/s of the kidney disease, such as intoxication (for example, lilies).
Physical exam	Look for clinical complications – for example, dehydration, anaemia, presence of additional concurrent disease.
Haematology	Look for anaemia, leukocytosis (infection).
Serum biochemistry including proteins, electrolytes (sodium, potassium, calcium, phosphorus), glucose, liver enzymes, total thyroxine	Look for hypokalaemia, hyperphosphataemia, hypoproteinaemia, hypercalcaemia and evidence of additional concurrent diseases that may affect management (for example, hyperthyroidism).
Urine dipstick	Identify severe proteinuria, concurrent diabetes mellitus. Note, dipsticks are unreliable for assessment of specific gravity, leukocytes, nitrites and urobilinogen. Dipsticks are also unreliable for identification of mild‑moderate proteinuria.
Urine culture	Identify bacterial urinary tract infections.
Urine protein (UPC)	Look for evidence of renal proteinuria and quantify severity. International Renal Interest Society guidelines for interpretation of proteinuria in azotaemic cats: • UPC lower than 0.2 – non-proteinuric • UPC 0.2 to 0.4 – borderline proteinuria • UPC greater than 0.4 – proteinuria • UPC greater than 2 – severe proteinuria, likely due to glomerular disease
Urine sediment	May help identify cause of the renal disease – for example, pyelonephritis.
Blood pressure	Identify patients suffering from systemic hypertension.
Acid-base status?	Selected renal patients, look for metabolic acidosis.
Parathyroid hormone?	Selected renal patients, confirm renal secondary hyperparathyroidism.
Ionised calcium?	Relevant in hypercalcaemic renal patients.
Imaging (if possible)	May help identify cause of the renal disease (for example, polycystic kidney disease, renal stones, neoplasia, FIP) and some complications of CKD (for example, pyelonephritis).
Biopsy?	May be indicated in renomegaly patients (for example, lymphoma possible) and those with marked renal proteinuria (UPC greater than 2).

Management

Management of CKD should aim to:

identify and treat any underlying disease that is contributing to ongoing renal damage – for example, pyelonephritis or renal lymphoma

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

Strategies aimed at slowing progression of renal disease

CKD is considered to be a progressive condition – it will get worse with time, although the rate of progression varies considerably between patients. Findings with a negative prognostic association include renal proteinuria, hyperphosphataemia, anaemia, worse stage of CKD, low albumin and low USG.

Two maladaptive processes triggered in patients with CKD have been studied in some detail:

mineral and bone disorders

activation of the renin‑angiotensin‑aldosterone system (RAAS)

Addressing these maladaptive processes is one strategy used, with the aim of slowing the progression of renal disease and, therefore, resulting in prolongation of life and improved quality of life.

Mineral and bone disorders

Phosphate retention occurs in cats with CKD as a result of their reduced ability to renally excrete phosphate. Phosphate retention triggers a cascade of maladaptive responses that have a number of deleterious consequences – including enhanced progression of renal disease, reduced quality of life and reduced lifespan.

Feeding a specially designed therapeutic renal diet (TRD) that contains limited amounts of phosphate is proven to improve quality of life and lifespan for cats with CKD (Sparkes et al, 2016). Acceptance of a TRD 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 (Table 4).

Table 4. Supportive and symptomatic options can be beneficial in improving the quality of life of cats with chronic kidney disease (CKD). These options are reviewed in more detail in the International Society of Feline Medicine consensus guidelines on the diagnosis and management of feline CKD (Sparkes et al, 2016)
Clinical complication	Approximate proportion of CKD patients affected	Treatment options	Comments
Hyperphosphataemia	Greater than 67 per cent	• Phosphate-restricted diet – ideally a therapeutic renal diet. Senior cat food is preferable to standard commercial cat food. • Oral phosphate binders – with standard cat food or “renal” diet. For example, aluminium hydroxide, calcium carbonate, magnesium carbonate.	• The International Renal Interest Society (IRIS) recommends phosphate restriction for all cats with azotaemic CKD (IRIS stages 2 to 4), irrespective of their blood phosphate levels. If blood phosphate levels remain above IRIS target levels in spite of phosphate restriction, a combination of renal diet and one or more phosphate binders may be required. • Phosphate binders should be mixed with food; they work by binding to phosphate present in the diet, retaining this in the bowel and, therefore, limiting the amount of phosphate that can be absorbed by the body. • Avoid calcium-containing binders in hypercalcaemic patients and those receiving calcitriol.
Dehydration	Greater than 60 per cent	• Correct dehydration with fluid therapy, as appropriate. • Tactics to encourage increased fluid intake – for example, moist rather than dry food, water fountains. • Home administration of SC fluids.	Dehydration reduces renal perfusion and worsens renal function, leading to exacerbation of complications associated with CKD.
Metabolic acidosis (blood bicarbonate or total CO2 levels lower than 16mmol/L)	Greater than 60 per cent	• Correct dehydration with fluid therapy, as appropriate. • Feed a non-acidifying renal diet. • Potassium citrate 40mg/kg to 75mg/kg every 12 hours starting dose.	• Metabolic acidosis is common in association with dehydration and often resolves on correction of this. • Feeding a renal diet helps minimise acidosis development. • Aim for blood bicarbonate or total CO2 levels in the range of 16mmol/L to 24mmol/L.
Poor appetite	Greater than 30 per cent	• Nursing tactics – for example, hand feed, warm the food gently. • Mirtazapine* 1mg to 2mg per cat PO every 48 hours, as needed. • Cyproheptadine* 1mg to 2mg per cat PO every 12 hours to 24 hours, as needed. • Consider placement of an oesophagostomy feeding tube.	Ensure other treatable causes of poor appetite – such as hypokalaemia, dehydration, nausea and anaemia – are addressed before considering an appetite stimulant. Mirtazapine or cyproheptadine should be chosen and not used in combination.
Anaemia	Greater than 30 per cent	• Recombinant human erythropoietin – for example, epoeitin*, darbepoietin* • Iron supplementation as needed – for example, 50mg iron dextran IM monthly as needed, or 30mg to 60mg ferrous fumarate per day PO.	• Care should be taken not to oversupplement if using injectable iron. Cats suffering from iron deficiency have low serum iron and iron saturation with a normal total iron binding capacity. • Management of anaemia associated with CKD is reviewed in detail elsewhere (Chalhoub et al, 2011).
Systemic hypertension (systolic blood pressure persistently greater than 160mmHg)	20 per cent to 30 per cent	• Amlodipine 0.0625mg/kg to 0.25mg/kg PO every 24 hours. • Telmisartan 2mg/kg PO every 24 hours.	Amlodipine is the first choice medication for cats with severe hypertension; amlodipine and telmisartan can be used concurrently in cats with refractory hypertension.
Hypokalaemia (potassium lower than 4mmol/L)	20 per cent to 25 per cent	• Oral potassium gluconate: 1mmol to 2mmol per cat PO every 12 hours to 24 hours. • Therapeutic renal diets are supplemented in potassium. Avoid acidifying and high-protein diets. • Patients receiving SC fluids at home: 10mmol potassium chloride can be added to 500ml bag of fluids (mix thoroughly).	Often, hypokalaemia associated with CKD is mild and can be difficult to identify clinically. Severely affected cats may suffer from ventroflexion of the neck.
Nausea and vomiting	20 per cent to 25 per cent	• Maropitant 1mg/kg to 2mg/kg PO every 24 hours (licensed for up to five days use). • Mirtazapine* 1mg to 2mg per cat PO every 48 hours, as needed. • Omeprazole* 0.5mg/kg to 1mg/kg PO every 12 hours to 24 hours. • Famotidine* 0.5mg/kg to 1mg/kg PO every 24 hours.
Bacterial urinary tract infection (UTI)	20 per cent to 25 per cent	Appropriate antibiotic chosen following culture and susceptibility testing; long courses (four to six weeks) may be needed in some patients.	UTIs may be present in the absence of specific lower urinary tract signs. Treatment is recommended when clinical signs (urinary or systemic) are present, where pyuria is documented, where ultrasound evidence of pyelonephritis is present and if renal function has deteriorated.
Renal proteinuria (urine protein to creatinine ratio [UPC] persistently greater than 0.4)	Greater than 20 per cent	• Telmisartan 1mg/kg PO every 24 hours. • Benazepril 0.5mg/kg PO every 24 hours.	• Rule out pre-renal and post-renal proteinuria, and confirm persistence of proteinuria before making a diagnosis of renal proteinuria. • Consider treatment of borderline proteinuria (UPC 0.2 to 0.4), since the prognosis for these cats is significantly worse than non-proteinuric cats (UPC lower than 0.2).
* = Not veterinary licensed for this indication; PO = By mouth.

IRIS recommends phosphate restriction for all cats with azotaemic CKD (IRIS stages 2 to 4), irrespective of their blood phosphate levels.

If feeding a TRD is not possible then senior cat food is preferable to standard commercial cat food.

Phosphate binders are useful if a TRD cannot be used, or if the TRD alone is insufficient to control serum phosphate. IRIS has provided guidelines for “target” phosphate levels (Table 2) – if a patient’s blood phosphate level is greater than the target levels then a combination of TRD and phosphate binder/s is justified.

RAAS activation

Loss of nephrons leads to activation of the 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 GFR and excretory function, RAAS activation ultimately 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.

Assessment of renal proteinuria is helpful in judging whether RAAS activation is present in a patient. IRIS recommends that CKD patients are classed as proteinuric if their UPC is greater than 0.4, and borderline proteinuric if their UPC is between 0.2 and 0.4.

RAAS suppression using telmisartan (an angiotensin receptor blocker; ARB) or benazepril (an angiotensin-converting enzyme inhibitor; ACEI) has been shown to be effective in reducing proteinuria, although a survival benefit has not been shown yet.

Some clinicians advocate treating borderline proteinuric cats on the basis that survival times in these cats are reduced compared to non‑proteinuric CKD cats (UPC lower than 0.2); this is considered logical by the panel responsible for the International Society of Feline Medicine consensus guidelines on diagnosis and management of CKD (Sparkes et al, 2016).

ACEIs and ARBs should only be used in clinically stable, normally hydrated cats. Some benefits may exist in treating non-proteinuric CKD patients with an ACEI or ARB, since some studies have shown improved quality of life and a tendency for the renal disease to progress more slowly in these cats.

Supportive and symptomatic treatments

A variety of supportive and symptomatic treatments may be helpful in the individual patient, according to their needs, and are summarised in Table 4. A successful outcome depends on an individualised approach 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. Monitoring visits are very important to ensure 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 TRD in those cats whose owners had received a veterinary recommendation to feed this (Caney, 2017).

The required frequency of check-ups varies according to the patient’s needs, but should initially be at least once a month. Check-ups can be performed by a veterinary nurse/technician working under direction of a veterinary surgeon.

Summary and conclusions

CKD is a common illness affecting at least a third of the elderly cat population. Diagnosis in the early stages is often “hampered” by an absence of clinical signs; therefore, proactive steps are needed to identify patients suffering from this condition.

Early diagnosis has the potential to be associated with a better patient outcome, since it allows appropriate, targeted therapy at the earliest possible time point.

Since CKD is a progressive condition, it is hoped early interventions will slow the progression of disease and help maintain quality of life for as long as possible. Once diagnosed, CKD can often be managed very successfully for several years following diagnosis. Attention to detail and providing an individualised plan leads to the best treatment outcome.