Determination of age-specific reference intervals for selected serum and urinary biomarkers in elderly cats

Abstract

Objectives

Annual health screening is recommended in elderly cats to allow the early detection of conditions such as chronic kidney disease (CKD) and hyperthyroidism. Nevertheless, age-specific reference intervals (RIs) for renal and thyroid parameters in this population are lacking. The aim of this study was to determine age-specific RIs for selected serum and urine biomarkers related to CKD and hyperthyroidism, namely serum creatinine (sCr), symmetric dimethylarginine (SDMA), phosphate (P), total calcium (tCa), total thyroxine (TT4), urinary protein:creatinine ratio (UPC) and urine specific gravity (USG). These RIs were established for elderly cats (aged ⩾7 years) in general, as well as for mature adult cats (aged 7–10 years) and senior cats (aged >10 years) separately.

Methods

A prospective study was conducted on client-owned cats aged ⩾7 years and considered healthy by their owners. The cats were screened to rule out metabolic and systemic diseases by means of a thorough history, complete physical examination, blood examination and urinalysis. The data from 206 healthy elderly cats (134 mature adult and 72 senior cats) were included. Age-appropriate RIs were determined following the guidelines of the American Society of Veterinary Clinical Pathology and compared with existing laboratory RIs.

Results

Clinically relevant differences between the age-specific RI and the laboratory RI were found for several variables. Compared with the laboratory RI, the upper limit of the RI for cats aged ⩾7 years was lower for sCr, TT4 and P, and higher for SDMA. The lower limit of the age-appropriate RI was lower for USG. The new RI was almost identical to the existing laboratory RI for tCa and UPC.

Conclusions and relevance

Using age-specific RIs for renal and thyroid biomarkers in mature adult and senior cats has important clinical consequences for the interpretation of health screening results in elderly cats. This confirms the need to adapt laboratory RIs to the specific animal population for which the RI will be used.

Keywords

Mature adult senior geriatric health screening kidney thyroid

Introduction

Chronic kidney disease (CKD) can occur at all ages, but is more common in older cats.^1–4 Hyperthyroidism can be diagnosed in mature adult cats (aged 7–10 years), but its prevalence increases to 8.7–21.1% in cats aged ⩾10 years presented to primary care veterinary practices in the UK and Ireland.^5,6 Annual health screening is strongly recommended in order to, among other things, improve the early detection of renal and thyroid disease in mature adult (aged 7–10 years) and senior (aged >10 years) cats, even when still apparently healthy.^1,7

The early diagnosis of CKD remains challenging as many cats remain free of clinical signs until they reach the advanced stages of CKD, with polydipsia (or polyuria) possibly being recognised earlier in the course of disease.^3,8 In veterinary practice, the diagnosis of CKD is most often based on the presence of combined renal azotaemia (ie, serum creatinine [sCr] exceeding the laboratory reference interval [RI]) in combination with urine specific gravity (USG) <1.035.^4,9 The diagnosis of hyperthyroidism in cats is most often based on total thyroxine (TT4) concentrations above the laboratory RI.^7,10 This disease may occur concurrently with CKD in aged cats, and can mask and even worsen coexisting CKD.³ After the treatment of hyperthyroidism, renal disease becomes apparent in 15.3–24% of previously hyperthyroid cats.^11
–13

The diagnostic value of laboratory tests depends on the correct interpretation of the results, which requires the use of appropriate RIs determined for the population examined.¹⁴ The need for age-specific RIs in elderly cats has previously been suggested.^15,16 The aim of this study was to define age-specific RIs in aged cats for selected serum and urinary biomarkers used in the screening process for CKD and hyperthyroidism, and measured by a commercial laboratory. For sCr, symmetric dimethylarginine (SDMA), TT4, total calcium (tCa), phosphate (P), urinary protein:creatinine ratio (UPC) and USG, 95% RIs were determined for elderly cats in general, as well as for two specific age groups (mature adult and senior cats) separately.

Materials and methods

Animals

Data from healthy client-owned cats aged ⩾7 years and recruited for a prospective longitudinal study were used. The protocol for the longitudinal study was approved by the local ethical committee of the Faculty of Veterinary Medicine, Ghent University, Belgium, and the deontology and ethics committee of the Belgian Federal Agency for the Safety of the Food Chain (EC 2018/54). Informed signed consent from the owner was required for participation. Cats were presented at the Small Animal Department of Ghent University, Belgium, between August 2019 and December 2020 and divided into two groups following the Feline Life Stage Guidelines of the American Animal Hospital Association and the American Association of Feline Practitioners: mature adult (aged 7–10 years) and senior cats (aged >10 years).¹

To be included, cats needed to be healthy according to the owner, meaning no changes in general behaviour, normal eating and drinking behaviour, a stable body weight and absence of clinical signs. In addition, cats could not have significant abnormalities on extensive physical examination (including blood pressure measurement using a Doppler ultrasonic technique [Doppler Vet BP; Sonomed]) performed by a single operator, and needed to be negative on feline immunodeficiency virus (FIV) antibody testing (ELISA; IDEXX Laboratories) and feline leukaemia virus (FeLV) antigen testing (ELISA; IDEXX Laboratories). Cats were excluded if they had received medication (except preventive medication) within 2 months before inclusion or preventive medication (vaccination, deworming, tick and flea prevention) within 1 week before presentation. Cats with previously diagnosed metabolic or clinically relevant cardiovascular, inflammatory or systemic disease were excluded, as were cats with abnormalities on blood and urine examination leading to the diagnosis of a metabolic or systemic disease (eg, azotaemic CKD, hyperthyroidism, diabetes mellitus). In addition, cats with a persistent combination of sCr ⩾140 μmol/l and USG <1.035 or SDMA ⩾18 µg/dl and USG <1.035 (compatible with CKD in International Renal Interest Society [IRIS] stage 2 or higher) were excluded to avoid potential inclusion of cats with early CKD, as clinical signs or abnormalities on physical examination are usually mild or absent in this stage.¹⁷

Procedures

Owners were asked to fill out a detailed history questionnaire and to keep their cats fasted for at least 12 h before presentation; water could be given ad libitum. A single operator collected samples from all cats. Blood (5 ml) was collected from the jugular vein with a 23 G needle or, in anxious cats, from the cephalic or saphenous vein with a 21 G needle. Urine (10 ml) was collected by cystocentesis with a 23 G needle or, in obese cats, a 22 G needle. Macroscopic and microscopic evaluation of urine samples (after centrifugation for 3 mins at 450 g) were performed on site as soon as possible, by the same operator and first author of this study.

Blood and urine samples were transported overnight at ambient temperature to the commercial laboratory (IDEXX Laboratories, Kornwestheim and Leipzig, Germany), where analysis was performed as soon as possible after sample arrival. Blood examination consisted of a complete blood count (CBC), extensive serum biochemistry profile (including electrolytes, SDMA, TT4, serum amyloid A and serum protein electrophoresis), FIV antibody testing and FeLV antigen testing. Routine urinalysis consisted of USG measurement (Euromex refractometer), dipstick, manual sediment analysis, bacterial culture and UPC measurement. UPC results of samples with macroscopic haematuria, pyuria or a positive bacterial urine culture were excluded because of their potential effect on UPC.^18–20

The following serum variables were assessed for age-specific RI determination: sCr, determined by a colorimetric reaction using a modified Jaffe assay using picrate at alkaline pH (Beckman Coulter, Inc); SDMA, determined with a commercially available high-throughput immunoassay (SDMA Test; IDEXX Laboratories, Inc); TT4, determined using an automated enzyme immunoassay method (DRI T4 assay; Microgenics); and P and tCa, both determined using a chemiluminescent reaction (Phosphomolybdate-UV and Cresolphthalein complexone, bichromatic, respectively) (Beckman Coulter, Inc). Urinary values measured for age-appropriate RI determination were USG, using a hand held refractometer (Euromex Microscopes Holland), and UPC (urinary protein concentration measured using a colorimetric reaction with pyrogallol red molybdate, and urine creatinine concentration measured using a modified Jaffe assay; Beckman Coulter).

Statistical analysis

The statistical analysis was performed using Excel version 2303 for Windows (Microsoft) and MedCalc version 22.003. A non-parametric method with a 90% confidence interval (CI) of reference limits was used to determine 95% RIs if the sample size was ⩾120, following the guidelines developed by the American Society of Veterinary Clinical Pathology (ASVCP) to reliably define laboratory RIs in healthy populations of individuals.¹⁴ If the sample size was ⩾40 but <120, a robust method with 90% CI of reference limits was used for 95% RI determination.¹⁴ For USG, a non-parametric method for RI determination was used for the senior group despite the sample size of 72, due to non-Gaussian distribution of data and the robust method not being possible.¹⁴ For sCr, SDMA, P, tCa and TT4, a double-sided 95% RI was chosen. For UPC, a right-sided 95% RI was determined, and for USG, a left-sided 95% RI was calculated.

Results

Data from 206 healthy cats were included for the determination of age-appropriate RIs, namely 134 mature adult (aged 7–10 years) and 72 senior cats (aged >10 years). Age, body weight and sex distribution for the complete population and both subgroups are shown in Table 1. Included breeds were domestic shorthair or longhair (n = 147), British Shorthair and Longhair (n = 29), Ragdoll (n = 7), Maine Coon (n = 4), Birman (n = 3), Scottish Fold (n = 3), Balinese (n = 2), Siamese (n = 2) and one each of Norwegian Forest Cat, Russian Blue, Oriental Shorthair, Chartreux, Exotic Shorthair, Persian, Scottish Straight, Munchkin and Sphynx. In accordance with the inclusion criteria, none of the included cats had clinical signs of CKD or hyperthyroidism that were noted by the owners at home or during the physical examination in the clinic.

Table 1

Age, body weight, sex and neuter status for the total population of healthy elderly cats (aged ⩾7 years), as well as for the subgroups of mature adult cats (aged 7–10 years) and senior cats (aged >10 years)

	All cats (n = 206)	Mature adult (n = 134)	Senior (n = 72)
Age (years)	10 (7–18)	8 (7–10)	12 (11–18)
Body weight (kg)	4.4 (2.2–9.5)	4.6 (2.6–9.5)	4.1 (2.2–8.7)
Females (intact/spayed)	126 (5/121)	79 (4/75)	47 (1/46)
Males (intact/castrated)	80 (0/80)	55 (0/55)	25 (0/25)

Data are n or median (range)

Median values and ranges of serum and urinary variables, and their newly determined age-specific RIs, are shown for the total healthy elderly population (aged ⩾7 years) (Table 2), mature adult cats (aged 7–10 years) (Table 3) and senior cats (aged >10 years) (Table 4). An overview of the newly determined age-specific RIs and the pre-existing laboratory RI for comparison is given in Table 5. To illustrate the distribution of laboratory results in elderly cats leading to the newly established 95% RIs, the histograms for sCr, SDMA and TT4 results of all elderly cats are shown in Figures 1 –3. Histograms for all investigated variables and age groups are provided as supplementary materials (Figures S1–S7).

Table 2

sCr, SDMA, P, tCa, TT4, UPC and USG in 206 healthy elderly cats (aged ⩾7 years) with their newly determined 95% RIs including the 90% CIs for the LL and UL

Variable	Median (range)	Age-specific RI LL (90% CI)	Age-specific RI UL (90% CI)
sCr (μmol/l)	113 (62–184)	71 (63–76)	167 (156–177)
SDMA (μg/dl)	11 (4–21)	6.0 (5.0–7.0)	17.8 (16.0–20.0)
P (mmol/l)	1.3 (0.6–1.9)	0.9 (0.8–0.9)	1.7 (1.7–1.9)
tCa (mmol/l)	2.4 (2.0–3.1)	2.1 (2.0–2.2)	3.0 (2.8–3.1)
TT4 (nmol/l)	24.5 (10.3–59.2)	14.2 (11.6–16.7)	38.6 (36.0–45.0)
UPC	0.16 (0.05–0.88)	N/A	0.33 (0.28–0.38)
USG	>1.050 (1.008–>1.050)	1.025 (1.018–1.032)	N/A

CI = confidence interval; LL = lower limit; N/A = not applicable; P = inorganic phosphate; RI = reference interval; sCr = serum creatinine; SDMA = symmetric dimethylarginine; tCa = total calcium; TT4 = total thyroxine; UPC = urinary protein:creatinine ratio; UL = upper limit; USG = urine specific gravity

Table 3

sCr, SDMA, P, tCa, TT4, UPC and USG in 134 healthy mature adult cats (aged 7–10 years) with their newly determined 95% RIs including the 90% CIs for the LL and UL

Variable	Median (range)	Age-specific RI LL (90% CI)	Age-specific RI UL (90% CI)
sCr (μmol/l)	114 (62–172)	70 (62–80)	164 (151–172)
SDMA (μg/dl)	10 (5–21)	5.4 (5.0–7.0)	18.6 (16.0–21.0)
P (mmol/l)	1.3 (0.6–1.9)	0.8 (0.6–0.9)	1.7 (1.6–1.9)
tCa (mmol/l)	2.4 (2.0–3.0)	2.1 (2.0–2.3)	2.9 (2.7–3.0)
TT4 (nmol/l)	24.5 (10.3–59.2)	13.4 (10.3–16.7)	39.4 (36.0–59.2)
UPC	0.15 (0.05–0.51)	N/A	0.30 (0.26–0.38)
USG	>1.050 (1.012–>1.050)	1.024 (1.014–1.032)	N/A

Table 4

sCr, SDMA, P, tCa, TT4, UPC and USG in 72 healthy senior cats (aged >10 years) with their newly determined 95% RIs including the 90% CIs for the LL and UL

Variable	Median (range)	Age-specific RI LL (90% CI)	Age-specific RI UL (90% CI)
sCr (μmol/l)	112 (68–184)	63 (55–72)	165 (155–174)
SDMA (μg/dl)	12 (4–19)	5.4 (4.5–6.6)	17.1 (16.0–17.9)
P (mmol/l)	1.4 (0.9–1.9)	0.9 (0.8–1.0)	1.8 (1.7–1.9)
tCa (mmol/l)	2.4 (2.1–3.1)	2.0 (1.9–2.1)	2.9 (2.8–3.0)
TT4 (nmol/l)	24.5 (11.6–45.0)	13.1 (10.8–15.5)	36.1 (33.8–38.3)
UPC	0.16 (0.07–0.88)	N/A	0.36 (0.27–0.43)
USG	>1.050 (1.008–>1.050)	1.026 (1.008–1.034)	N/A

Table 5

The newly determined 95% RIs for sCr, SDMA, P, tCa, TT4, UPC and USG in all healthy elderly cats (aged ⩾7 years) and the subgroups of mature adult cats (aged 7–10 years) and senior cats (aged >10 years), and the existing laboratory RI

Variable	Age-specific RI, all elderly cats (n = 206)	Age-specific RI, mature adult cats (n = 134)	Age-specific RI, senior cats (n = 72)	Laboratory RI
sCr (μmol/l)	71–167	70–164	63–165	80–203
SDMA (μg/dl)	6.0–17.8	5.4–18.6	5.4–17.1	0–14
P (mmol/l)	0.9–1.7	0.8–1.7	0.9–1.8	0.8–2.2
tCa (mmol/l)	2.1–3.0	2.1–2.9	2.0–2.9	2.2–2.9
TT4 (nmol/l)	14.2–38.6	13.4–39.4	13.1–36.1	10–60
UPC	⩽0.33	⩽0.30	⩽0.36	<0.33
USG	⩾1.025	⩾1.024	⩾1.026	>1.035

LL = lower limit; N/A = not available; P = inorganic phosphate; RI = reference interval; sCr = serum creatinine; SDMA = symmetric dimethylarginine; tCa = total calcium; TT4 = total thyroxine; UPC = urinary protein:creatinine ratio; UL = upper limit; USG = urine specific gravity

Figure 1

Histogram for serum creatinine results of all 206 healthy elderly cats (aged ⩾7 years). The upper and lower limits of the 95% reference interval are established by excluding the 2.5% highest (n = 5) and 2.5% lowest (n = 5) results

Figure 2

Histogram for serum symmetric dimethylarginine (SDMA) results of all 206 healthy elderly cats (aged ⩾7 years). The upper and lower limits of the 95% reference interval are established by excluding the 2.5% highest (n = 5) and 2.5% lowest (n = 5) results

Figure 3

Histogram for serum total thyroxine (TT4) results of all 206 healthy elderly cats (aged ⩾7 years). The upper and lower limits of the 95% reference interval are established by excluding the 2.5% highest (n = 5) and 2.5% lowest (n = 5) results

For several variables (sCr, SDMA, P, TT4 and USG), differences between the age-specific and laboratory RIs were found (Table 5). Compared with the laboratory RIs, the upper limit of the RI for elderly cats was lower for sCr, TT4 and P, and higher for SDMA. The lower limit for USG was lower in the newly established RI. For tCa and UPC, the age-specific RI was almost identical to the laboratory RI.

None of the 206 cats had a sCr concentration >203 μmol/l, TT4 >60 nmol/l or P >2.2 mmol/l (RIs of the commercial laboratory). An increased SDMA concentration above the laboratory RI (>14 μg/dl) was present in 21/206 (10.2%) cats, and the increase persisted in three of these cats (1.5% of all cats), potentially indicating early CKD (IRIS stage 1).¹⁷ tCa exceeded the laboratory RI upper reference limit (>2.9 mmol/l) in 5/206 (2.4%) cats. USG was below the laboratory reference limit in 23/206 (11.2%) cats and was persistently <1.035 in six of these cats (2.9% of all cats), compatible with IRIS stage 1 CKD.¹⁷ UPC was above the laboratory RI (⩾0.33) in 10/206 (4.9%) cats. A UPC value above the IRIS threshold for proteinuria (>0.4) was measured in 3/206 (1.5%) cats (0.51, 0.53 and 0.88) without evidence of a pre-renal (dysproteinaemia, haemoglobinuria) or post-renal (macroscopic haematuria, pyuria or a positive urine culture) component. In these three cats, UPC was rechecked within 2 months and was <0.4 in two cats, excluding persistent proteinuria. In one cat (0.5% of all cats), the UPC remained >0.4, leading to a diagnosis of persistent renal proteinuria, which is compatible with IRIS stage 1 CKD.¹⁷ In total, 9/206 (4.4%) of the included cats had potential early CKD (IRIS stage 1) based on UPC, USG and/or SDMA results.

Discussion

To the authors’ knowledge, this is the first study to determine age-specific RIs for sCr, SDMA, P, tCa, TT4, UPC and USG in cats and compare these with the general RIs provided by the commercial laboratory that performed the analyses. There are only a few published studies reporting age-related differences in selected serum or haematological biomarkers in elderly cats.^15,16,21,22 Yet, acknowledging such differences may influence the interpretation of health screening results in elderly cats. For example, sCr has been shown to be correlated with lean body mass, and both decrease with increasing age in cats and dogs.^23,24 This implies that the upper reference limit of the RI for sCr needs to be adjusted downwards in older cats. An age effect was also shown for thyroid hormones in healthy cats aged 6 months to 14 years, with TT4 gradually decreasing with increasing age.²⁵ When general RIs for cats of all ages are applied to interpret sCr and TT4 results of elderly cats, values within the (upper) RI might thus already represent mildly elevated values for that age group.

In the current study, clinically relevant differences between the newly determined RI and the laboratory RI were found for several variables (sCr, SDMA, P, TT4 and USG), confirming the need for age-appropriate RIs.

The upper reference limit for sCr in elderly cats (167 µmol/l) is markedly lower than the laboratory RI limit (203 µmol/l), likely partly explained by the decrease in lean body mass (including muscle) that occurs with normal ageing in cats.^23,26 This lower upper reference limit implies that elderly cats with sCr persistently >167 µmol/l should be considered azotaemic. As a consequence, CKD can be diagnosed earlier when using the age-specific RI for sCr, if inadequate urine concentration is present and pre-renal azotaemia is therefore ruled out (as well as post-renal azotaemia). On the other hand, the newly determined upper reference limit for serum SDMA (17.8 µg/dl) is higher than the existing laboratory RI limit (14 µg/dl). This means that when applying the laboratory RI in cats aged ⩾7 years, renal dysfunction might be overestimated based on serum SDMA and only values ⩾18 µg/dl may be reason for concern, again if combined with inadequate urine concentration to rule out pre-renal causes.

For USG, the lower reference limit of the age-specific RI is lower than the laboratory RI. For this study, cat owners were urged to allow their cat to drink before presentation in order to avoid (subclinical) dehydration, which might not have been the case for the cats that were included for determination of the laboratory RI. On the other hand, it cannot be excluded that some of the healthy cats in this study already had mildly decreased renal function affecting USG but not yet the other renal biomarkers, since a glomerular filtration rate (GFR) measurement was not performed.

Mineral and bone disorder is a common consequence of feline CKD and is associated with disease progression and death.^27
–29 The disorder is caused by phosphate retention due to decreased GFR and leads to altered calcium homeostasis, ultimately resulting in hyperphosphataemia and total hypercalcaemia.²⁸ High plasma P concentration predicts progression of feline CKD,³⁰ and an increase in serum P is associated with an increased risk of death in cats with CKD.³¹ Hypercalcaemia is a well-established risk factor for vascular and soft tissue calcifications in human patients with CKD.²⁸ Since these mineral and bone disturbances are associated with declining renal function and increased mortality, P and tCa are two serum variables that are regularly monitored in cats with CKD.³² Previously, low serum P was reported in 40% of healthy mature adult and aged cats, likely due to an inappropriate laboratory RI (1.35–2.97 mmol/l) rather than pathological changes.¹⁵ So, age-specific RIs for these variables are important in order to reliably interpret these values in elderly cats, the population most at risk for CKD. The age-appropriate RI for tCa was almost identical to the existing laboratory RI, but the newly determined upper reference limit for P (1.7 mmol/l) was lower than the laboratory RI upper limit (2.2 mmol/l). Therefore, hyperphosphataemia could be overlooked in elderly cats when using the general laboratory RI.

For TT4, the existing laboratory RI (10–60 nmol/l) includes a grey zone (30–60 nmol/l) in which older cats and cats with consistent clinical signs may have concurrent non-thyroidal illness or early hyperthyroidism. According to our data, a value ⩾39 nmol/l is unusual in mature adult and senior cats, facilitating the diagnosis of hyperthyroidism in aged cats with compatible clinical signs. In cats aged ⩾7 years with TT4 above the age-specific RI, but without clinical signs of hyperthyroidism, more frequent monitoring of TT4 is advisable to allow the early detection of a continuous increase in TT4 or the occurrence of compatible signs (such as weight loss, tachycardia, hypertension or elevated liver enzymes). This is in concordance with a recent study including a large number (531,765) of cats aged <1 year to 20 years that had TT4 measured by enzyme immunoassay as well, but in a different laboratory. The conclusion was that cats aged ⩾7 years and with TT4 concentrations within the laboratory RI but >45 nmol/l should be evaluated for hyperthyroidism more closely, to aid in earlier identification of hyperthyroidism.³³

The observed differences between the newly determined RIs and existing laboratory RIs are at least partly a consequence of physiological changes associated with increasing age in cats (eg, decreased muscle mass leading to lower sCr concentration, age-related decline in TT4 concentration). However, factors other than age might also play a role, such as the size of the reference population, criteria used to define the health status of the reference population, feeding status of the included cats and geographical variation. For example, for the determination of the sCr laboratory RI, samples of 175 adult cats of various ages and breeds were included, originating from seven different veterinary clinics and three reference laboratories.³⁴ In this document, the criteria used to define the health status of included cats are not specified, except that they were considered ‘clinically normal’. It is also not clear whether urinalysis results were taken into account as well when determining health status.³⁴ In the current study including only elderly cats (aged ⩾7 years), a larger population (n = 206) of this age group was used and health status was determined based on an extensive health screening performed by an experienced veterinarian. This means that health status was established more thoroughly than can be done by reference laboratories receiving only a serum sample and limited clinical information. It is also not clear whether cats were kept fasted for determination of the laboratory RI. In the current study, owners were asked to keep their cat fasted for at least 12 h before blood sampling, but it was not possible to check whether all of the owners complied. Lastly, geographical variations may occur and could also have played a role in the observed differences. The existing laboratory RI is based on a population of cats from the USA,³⁴ whereas this study included European cats from Belgium and the Netherlands.

Where present, observed differences between age-specific RIs for mature adult vs senior cats were small (Table 5, third and fourth columns). For SDMA, the lower upper reference limit for senior vs mature adult cats (17.1 vs 18.6 µg/dl) is surprising, considering the increasing SDMA concentrations found with increasing age in healthy cats, likely due to decreasing GFR.²³

The present study has some limitations. First, this study was not breed or sex specific. Although this represents the general cat population examined by veterinarians, breed-specific RIs might be needed for some variables.^35–37 A second limitation is the possible influence of the geographical location on the established RIs, meaning that our results may not reflect the cat population worldwide. Therefore, we recommend establishing clinic-specific RIs for both in-house and external laboratory results, in order to improve (early) diagnosis, monitoring and treatment of aged cats. Detailed information on how to determine clinic-specific RIs is provided in the ASVCP guidelines.¹⁴ A third limitation is that GFR measurement was not performed, so renal function could not be assessed more precisely than is done in clinical practice (ie, based on sCr and SDMA in combination with USG and UPC). Lastly, it is important to note that for the interpretation of sCr results in cats, subject-based RIs are more appropriate than population-based RIs.^38,39 Detecting an increase in sCr compared with the previous measurement in the same cat can help diagnose renal disease early, even when sCr is still within the (age-specific) population-based RI.³⁹

Conclusions

This study demonstrated important differences between age-specific RIs of elderly cats, determined in accordance with ASVCP guidelines, and general RIs provided by the commercial laboratory. The upper reference limit of the age-appropriate RI is lower for sCr, P and TT4, meaning that azotaemia, hyperphosphataemia and hyperthyroidism can be overlooked when applying the general laboratory RI to results of cats aged ⩾7 years. For SDMA, on the other hand, values ⩽17 µg/dl might not necessarily be concerning in mature adult and senior cats. This study confirms that age-appropriate RIs should be considered for accurate interpretation of laboratory results in elderly cats.

Supplemental Material

Supplemental Material Figure S1:

Histograms for serum creatinine for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years) and (c) senior cats (>10 years).

Supplemental Material

Supplemental Material Figure S2:

Histograms for serum inorganic phosphate for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years) and (c) senior cats (>10 years).

Supplemental Material

Supplemental Material Figure S3:

The histograms for serum SDMA for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Supplemental Material

Supplemental Material Figure S4:

The histograms for serum total calcium for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Supplemental Material

Supplemental Material Figure S5:

The histograms for serum total thyroxine for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Supplemental Material

Supplemental Material Figure S6:

The histograms for urinary protein:creatinine concentration for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Supplemental Material

Supplemental Material Figure S7:

The histograms for urine specific gravity for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Footnotes

Acknowledgements

The authors would like to thank all cat owners for letting their cat participate in the study and therefore enabling this research.

Accepted: 26 September 2023

Supplementary material

The following files are available as supplementary material:

Figure S1: Histograms for serum creatinine for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years) and (c) senior cats (>10 years).

Figure S2: Histograms for serum inorganic phosphate for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years) and (c) senior cats (>10 years).

Figure S3: The histograms for serum SDMA for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Figure S4: The histograms for serum total calcium for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Figure S5: The histograms for serum total thyroxine for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Figure S6: The histograms for urinary protein:creatinine concentration for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Figure S7: The histograms for urine specific gravity for (a) all cats (⩾7 years), (b) mature adult cats (7–10 years), and (c) senior cats (>10 years).

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

This study is part of a PhD project financed by the Bijzonder Onderzoeksfonds (BOF) of Ghent University. Laboratory analysis for this study was financially supported by IDEXX Laboratories, Inc.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Femke Mortier

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