Chronic kidney disease in asymptomatic cats

Introduction

Chronic kidney disease (CKD) is an important cause of morbidity and mortality in cats 1,2. Various clinical tests are employed for its diagnosis, including blood tests (urea, creatinine and SDMA (symmetric dimethylarginine)), urinalysis (including urinary protein-to-creatinine ratio (UPC)), abdominal ultrasonography, and measurement of blood pressure (BP) 2,3,4,5. Timely diagnosis of CKD is important, as it allows treatment to be introduced early in the course of the condition, helping delay progression of the condition, preserving residual renal function, and promoting good quality of life, so that a cat is more likely to have “chronic kidney disease” rather than the detrimental “end-stage renal failure” 2,4,5. This article describes a study aimed at assessing the potential for CKD to be present in cats that show no physical signs of the disease, with the aim of determining whether the condition frequently manifests itself silently.

Material and methods

Animals

Thirty-two mixed-breed asymptomatic cats that had no diagnosis of CKD were selected. All cats had adequate body condition score and normal hydration status. Other potential candidates for the study were excluded for various reasons; these included cats with clinical signs suggestive of CKD (weight loss, polyuria, polydipsia, dysorexia, emesis, diarrhea, reduced muscle mass index, or reduced body condition score), along with individuals that were receiving drugs which could alter serum urea or creatinine levels, increase the glomerular filtration rate, or modify urinary specific gravity (USG). Any cat with an abnormal complete blood count or abnormal ultrasound (with a dilated renal pelvis > 0.5 cm, suggestive of hydronephrosis) was also excluded.

The 32 cats were aged between 1-14 years, with a mean age (± standard deviation) of 5.91 (± 3.79) years. Most (13/32) were classified as adults (3-6 years old), with 8 considered as junior (1-2 years old), 7 as mature (7-10 years) and 4 as senior (11-14 years). There were no “super senior” cats (i.e., over 14 years of age). 53.1% were males and 46.9% females. The mean weight was 4.90 (± 1.18) kg, and the mean body condition score was 6.19 (± 1.12) (Table 1).

Methods

The 32 cats were subject to the following procedures:

• Complete blood count (CBC) plus serum urea and creatinine analysis on fasting samples.
• Urinalysis on samples obtained by cystocentesis. Where isosthenuria or proteinuria were observed, it was recommended to repeat the tests after 7 days to check for persistence, and to ensure that no extra-renal conditions were present.
• Abdominal ultrasound, performed by a dedicated sonographer (Figure 1).
• Systolic blood pressure by indirect (Doppler) method. Where systemic arterial hypertension (BP > 150 mmHg) was detected, the test was repeated to verify persistence. It was also necessary to ensure that conditions other than CKD, which can affect BP, were not present (Figure 2). 

Statistical analysis and boxplot graphics were performed. Descriptive statistics consisted of mean, standard deviation, and minimum and maximum values, and Pearson’s correlation was applied, after using the Wilcoxon test, considering a statistically significant difference when the p value was less than 0.05.

Results

With the normal IRIS reference value for creatinine being < 1.6 mg/dL 6, cats with creatinine levels at or above this may be suspected of having chronic kidney disease (In line with the IRIS guidelines, a second blood test to evaluate the elevated creatinine level would be recommended to confirm the diagnosis, and where available, SDMA can be used to support the diagnosis of CKD). The observed creatinine values ranged between 1.43-6.00 mg/dL, with a mean (± SD) of 2.10 mg/dL (± 0.78) (Table 1). Using the IRIS scoring system (Box 1), only 2 of the 32 cats did not have azotemia, with serum creatinine values of 1.43 (C25) and 1.50 mg/dL (C29). However, both cats had abnormal renal morphology on ultrasound, so were classified as being IRIS stage 1. The other 30 cats had creatinine values between 1.60-6.00 mg/dL, with a mean of 2.20 mg/dL (± 0.79); 28 (87.5%) were considered to be IRIS stage 2, with one cat (C15 – creatinine 2.94 mg/dL) classified as stage 3, and one (C24 – creatinine 6.00 mg/dL) classified as stage 4 (Figure 3). 

Box 1. IRIS staging of CKD based on blood creatinine concentration in cats.

Urea levels ranged between 45.0-98.0 mg/dL, with a mean of 65.40 mg/dL (± 14.27). The same minimum and maximum urea values were observed in cats considered as being IRIS stage 2, with a mean of 33.4 mg/dL (± 13.70 mg/dL). For the two cats in IRIS stage 1, the urea values were 45.0 (C25) and 53.0 (C29) mg/dL; the cat in IRIS stage 3 (C15) had a urea of 54 mg/dL, whilst in the cat considered as IRIS stage 4 (C24), the urea was 68.0 mg/dL (Figure 4). 

No correlation (Pearson) was observed between serum creatinine and body weight (r=-0.1961; p=0.2906), between creatinine and BCS (r=-0.2014; p=0.2690), between urea and creatinine (r=0.1355; p=0.4595), and between age and creatinine (r=-0.2355; p=0.1945).

Six cats were aggressive when measuring BP; it is recognized that this can favor situational systemic hypertension 6,8, and since it was not possible to reevaluate them after 7 days, this data was ignored, but based on their blood tests, these cats were categorized as IRIS stage 2, and three of them (C13, C16 and C25) also had renal ultrasound changes (Table 2). The other 26 cats were considered to have no sustained increase in BP, with values between 110-150 mmHg, a mean of 127.90 mmHg (± 14.13) (Table 1).

Table 2. Renal ultrasonographic findings.

Alongside the azotemia, 75.0% of cats (24/32) presented with some morphological abnormality on ultrasound examination consistent with CKD. These included loss of corticomedullary definition (15.63%; 5/32); irregular contours (28.13%; 9/32); and reduced kidney size and/or elevated cortical echogenicity (56.2%; 18/32). 22 of the cats with altered renal morphology had creatinine levels greater than 1.6 mg/dL (68.75%) (Tables 1 and 2, Figure 3).

Cystocentesis was performed in 19 cats; the remaining 13 cats were not sampled, either because there was insufficient urine to allow sampling, and/or they did not return for a second attempt at collection. On urinalysis, all USG results were greater than 1.040, whilst proteinuria, measured via reagent strip (Figure 5), was observed in 6 cats (18.75%), although sediment examination showed nothing noteworthy. Urine collection was not repeated during the study, so persistent proteinuria could not be confirmed.

Discussion

Traditionally, although CKD is described as being prevalent in cats 1,2,3 the observations in this study were surprising, as all 32 cats, despite being asymptomatic, had at least one marker that was suggestive of a diagnosis of CKD.

Abdominal ultrasound is an important tool in identifying CKD 1,4,9, and although this was a cross-sectional study, it is thought that the sonographic alterations identified are permanent, and on this finding alone at least 24/32 cats (75%) in the study would be suspected of having CKD; of these, only two were not azotemic at the time of the examination (Tables 1 and 2).

Given that the diagnosis of CKD in cats can be made via identification of azotemia on at least two occasions (once other causes of azotemia can be excluded) 1,4,9, 93.75% of cats in this study would be highly suspected to be in IRIS stages 1 and 2, with one cat in stage 3 and one in stage 4 (Table 1). Furthermore, 68.75% of the cats had both azotemia and altered renal morphology, which would strongly corroborate a diagnosis of CKD 1,2,4,5. So although there was no follow-up to confirm that azotemia was persistent, no pre-renal or post-renal causes of azotemia in these cats were identified.

Of the 30 azotemic cats in the study, only eight (25%) did not present any ultrasonographic abnormalities. Since creatinine is increased in cats with greater muscle mass, it is hypothesized that this may explain this finding. One option to verify this would be to do SDMA assessment 3, although this assay was not performed in the study. However, there was no correlation between creatinine and body weight, or between creatinine and BCS, so it is possible that the number of cats assessed may have influenced this result.

It is known that the prevalence of CKD increases with age 7,10,11, being more frequent in geriatric cats. However, in the present study the mean age was 5.91 years old, and 53.13% of the cats (17/32) were younger than 5 years old. Additionally, only mixed-breed cats were selected, but previous studies have shown a higher frequency of CKD due to genetic predisposition in some pedigree breeds (Persian, Maine Coon, Siamese, Burmese, and Abyssinian). No sexual predisposition was demonstrated, which correlates with findings in previous studies 1,2. A larger scale study would be interesting to help confirm these findings.

Feline CKD can develop from acquired causes, such secondary to acute kidney injury, as well as the presence of other diseases such as hyperthyroidism 1,2,12,13. In this study it was not possible to assign any etiology for the azotemia, but it is possible that aging could have been the cause in 4 of the cats, and given that 8 of the cats were juvenile, further studies into possible etiologies of feline CKD are required.

Urinalysis is an important step in the diagnosis of CKD, and for the screening of proteinuria and isosthenuria, in addition to being useful in the diagnosis of extrarenal conditions 1,2,4,5,9. In the present study, even though the urinalysis has been only possible in 19 out of the 32 cats, no abnormal levels of USG were observed; this correlates with previous studies, which demonstrate that the loss of ability to concentrate urine in cats occurs later in the disease process compared to dogs with CKD 1,4,13.

In the present study, persistent systemic hypertension or proteinuria were not verified; given that both are important factors for the diagnosis of CKD, this may be regarded as a limitation, but it does not appear to have impacted the observed results. It is important to emphasize that reevaluation of the cats would be recommended to confirm if pathological renal proteinuria or systemic hypertension was persistent 6,7,8,14. Since systemic hypertension can cause damage to target organs (heart, eyes, brain, and kidneys), and increase the risk of progression of CKD 6,7,8, BP should be monitored regularly in all cats with CKD. Given that many of the cats in this study were quite young, the small sample size is to be emphasized, and it is not suggested that essentially every cat, even those under 5 years of age, has some degree of renal disease. Larger scale studies which involve repeated blood tests (including SDMA) would be helpful in further investigating the incidence of occult CKD in the feline species.

Conclusion

The observations presented here corroborate with other studies that have shown chronic kidney disease (CKD) in cats can occur silently. It is therefore concluded that the prevalence of the condition in asymptomatic cats could be high, and that routine use of CKD markers (determination of creatinine and SDMA levels, urinalysis, potentially associated with blood pressure measurement and renal ultrasound) is to be recommended, even in apparently healthy cats, as early diagnosis favors access to greater therapeutic opportunities and better prognosis.