Diagnosis of early feline chronic kidney disease

Chronic kidney disease (CKD) (Box 1) is a highly prevalent disease in older cats, estimated to affect 30 percent of cats over the age of 12 (Lulich et al., 1992). There is still much unknown about feline CKD. The risk factors and causes associated with the development of CKD are not well elucidated, with most cases classified as idiopathic in origin. We do know, however, that early diagnosis and management of CKD can slow down the progression of disease.

Dietary management, ideally with a therapeutic renal diet, is arguably the most important aspect of treatment for cats diagnosed with CKD in IRIS Stage 2 onwards (Polzin and Churchill, 2016), where staging is primarily based on blood creatinine levels (Table 1). Generally, this tends to be accepted by most veterinarians. However, they may face more of a clinical conundrum when trying to identify the best diet for a cat with IRIS Stage 1 disease – a stage which, until fairly recently, the veterinarian had not been able to identify in most patients.

So, how should clinicians approach diagnosis, what should these cats be fed and when should we be introducing any dietary changes? This is the first article of a two-part series on early feline chronic kidney disease and will focus on diagnosis. The second article, in next month’s issue, will explore the approach to nutritional support.

Diagnosis

CKD is primarily diagnosed by a history, physical exam and clinical signs compatible with CKD, alongside identification of azotaemia and a USG below 1.035. However, urea and creatinine – the conventional diagnostic test used – are insensitive markers of glomerular filtration rate (GFR) and do not start to rise above the reference range until 75 percent of nephron function has been lost (Polzin and Churchill, 2016). They can also be affected by other factors: creatinine concentrations are affected by hydration and lean muscle mass, and urea is affected by a large number of extra-renal factors.

Although often measured together, creatinine is preferred to urea as a marker of GFR as its concentration is inversely related to GFR, and it is affected by fewer extra-renal factors. Urea is passively absorbed, has a variable excretion rate and may be influenced by a great number of factors, including catabolic or anabolic states, liver disease and protein content of the diet. Creatinine does, however, have an exponential relationship with GFR, so substantial early declines in GFR may be accompanied by only small changes in creatinine, whereas later in disease a large change in creatinine may represent only a small change in GFR (Geddes, 2019) (Figure 1).

Cats with IRIS Stage 1 kidney disease, however, do not have measurable azotaemia and may not show clinical signs of disease. Whilst previously it was challenging to diagnose cats with CKD before azotaemia was present, more clinicians are now starting to identify non-azotaemic cats with IRIS Stage 1 or early IRIS Stage 2 disease (“early” CKD).

Increased screening of cats in senior clinics and suspicious clinical signs (Box 2) or urine samples can prompt further investigation and result in diagnosis of early disease (Table 2).

For example, reduction in USG (below 1.035) – which may be picked up incidentally on a screening urinalysis – usually precedes azotaemia and can be an important early indicator of CKD.

Veterinarians also now have access to a greater number of diagnostic tests, most significantly the advent of a commercially available symmetric dimethylarginine (SDMA) assay. On average, SDMA has been shown to detect CKD 17 months before serum creatinine concentrations increase above the reference range (Hall et al., 2016), and, importantly, is not affected by muscle mass. SDMA is primarily eliminated by renal clearance, and plasma concentrations correlate with GFR (Hall et al., 2016). SDMA increases as a result of reduced renal function, and is a useful biomarker to identify early CKD in non-azotaemic cats (Hall et al., 2016).

Early diagnosis of CKD is important because it has been suggested that early intervention, before clinical signs become evident, can significantly reduce the rate of progression of disease and increase longevity in affected cats (Hall et al., 2016; Geddes, 2019). However, when early CKD is detected, it can present a challenge to the form that these interventions should take, and at what point they should be implemented.

Recommended initial approach for IRIS Stage 1

The recommended approach to a feline patient confirmed to have IRIS Stage 1 kidney disease is prompt measurements of UPC and blood pressure, if not already performed during diagnostic work-up. If both are within normal limits, current advice recommends monitoring the patient, at least every 6 to 12 months dependent on case, to check for azotaemia or development of proteinuria or hypertension. If UPC is higher than 0.4, treatment with telmisartan or benazepril as anti-proteinuric therapies should be started. If systolic blood pressure is found to be persistently over 160mmHg then anti-hypertensive treatment should be commenced with amlodipine or telmisartan (Geddes, 2019). The clinician is referred to the IRIS guidelines for further discussion of such treatments.

Nutritional management for IRIS Stage 1 feline patients

While dietary intervention is regarded as a cornerstone of management of CKD, there is controversy over the timing of renal diet introduction and the degree of protein restriction required (Witzel, 2018; Geddes, 2019). There are a number of different commercially available renal diets in the UK, but the evidence base for recommendation of most therapeutic diets for CKD is centred on starting at IRIS Stage 2 of disease. Studies for clinical efficacy have been historically focused on cats from IRIS Stage 2 onwards, since it is only relatively recently that commercially available tools to identify IRIS Stage 1 have been available. Thus, optimal dietary management for IRIS Stage 1 is currently still unknown.

Part two of this series will focus on the approach to nutritional management of the early CKD patient.