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

Mortier F, van Leeuwenberg R, Daminet S, Paepe D. Determination of age-specific reference intervals for selected serum and urinary biomarkers in elderly cats. Journal of Feline Medicine and Surgery. 2023;25(11). doi:10.1177/1098612X231207492

Laboratory testing in cats is commonly performed to screen for early detection of medical conditions in apparently healthy animals, and to identify disease in patients presenting for medical concerns. Many laboratory tests, including blood work and urinalyses, give results that are compared to general “Reference Intervals” (RIs) considered as “normal” ranges for the patient population. Currently, the RIs that most commercial labs use for cats include animals from all age groups, from young adult to seniors.

It is, however, well known that there are changes to what is “normal” as patient’s age. For example, growing animals often have higher levels of alkaline phosphatase (ALP), thyroxine (T4), and calcium than healthy adults. In human medicine, it is also understood that some values (for example creatinine) increase with age.

There is some concern that using the same reference interval for all cats, regardless of age, may result in either over- or under- diagnosis of common diseases in feline patients due to these natural differences.

The authors’ aim was to define age-specific RIs for certain key biomarkers related to chronic kidney disease (CKD) and hyperthyroidism, as these are common diseases of older cats. The RIs were determined for elderly cats in general, and separately for mature adult cats (aged 7-10 yrs) and senior cats (aged > 10 yrs).

The prospective study included 206 healthy elderly pet cats (134 mature adults and 72 seniors) from Belgium and the Netherlands seen at the Small Animal Department of Ghent University. More females than males were recruited. These cats did not show any signs of disease upon screening via thorough history, physical exam, blood work and urinalysis.

The authors collected blood samples and measured the kidney values creatinine, SDMA, phosphorus, and calcium, as well as total thyroxine. They also collected urine and measured the urine protein:creatinine ratio (UPCR) and the specific gravity. These are both used as markers of kidney disease. Statistical analysis was used to determine the reference interval following the guidelines from the American Society of Veterinary Clinical Pathology. These were compared to the laboratory reference population.

The authors found that there were significant differences in the reference interval for several analytes. In particular, the RI for creatinine was lower in older cats (71-167umol/L) than in the reference population (80-203umol/L); lower in older cats (14.2-38.6nmol/L) than the reference population (10-6nmol/L) for TT4 and lower in older cats (0.9-1.7) than the reference population (0.8-2.2mmol/L) for phosphorus, and higher in older cats (6.0-17.8ug/dL) than the reference population (0-14ug/dL) for SDMA. No difference was seen in the other analyzed results.

There were only small, non-clinically relevant differences present between the “mature adult” and “senior” categories.

Only a few publications have reported age-related differences in biomarkers for cats. The value of this study is that it may allow interpretation of results in an older feline population separately from that of the general population.

Based on these results, the authors of this study concluded that age-appropriate reference intervals should be considered for accurate interpretation of laboratory results in elderly cats.

While an interesting paper that has the potential to enact significant change in laboratory medicine, there are some limitations to this study. The authors do not specify what the age range of cats used for laboratory RI generation were, and so it is unclear how this population differs from that of the study group. In some cases, it is unclear if the populations used were fully “healthy”, for example the RI for creatinine extends to 203umol/L, a level almost certainly associated with renal dysfunction. Results from one reference lab and population do not always translate to other groups, and so the results of this study may not be translated to laboratory tests in other geographic areas, with different populations of cats. Indeed, this is demonstrated by the fact that the RIs used for some analytes (ie creatinine) are significantly different from those used by commercial reference labs in other regions.

Further work on this topic would be very valuable, and may include extension of these investigations to other analytes (including Complete Blood Count results), accounting for young as well as elderly cats, and considering the effect of sex and breed, both of which may affect lab results (especially creatinine) in other species.   ~MK


See also:
Paepe D, Verjans G, Duchateau L,et al. Routine health screening: findings in apparently healthy middle-aged and old cats. J Feline Med Surg. 2013 Jan;15(1):8-19.

Lin TL, Chung SH, Sung CH, et al. Establishment of feline in-house reference intervals for hematologic and biochemical parameters and potential age-related differences. Pol J Vet Sci. 2019 Sep;22(3):599-608.

Ghys LFE, D Paepe D, Duchateau L et al. Biological validation of feline serum cystatin C: The effect of breed, age and sex and establishment of a reference interval. Vet J. 2015 May;204(2):168-73.