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A new kidney biomarker detected for cats

Hall JA, Yerramilli M, et al.  Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease.  J Vet Intern Med 2014;28:1676-83.

Chronic kidney disease (CKD) is a major cause of serious illness and death in senior and geriatric cats. Early detection of CKD is key in successful management of the disease and in slowing its inevitable progression, as well as improving the quality of life of the affected patient.  To date, laboratory and clinical findings used to diagnose CKD, such as increased serum creatinine (sCr) and decreased urine specific gravity, weight loss, uremic halitosis, and decreased kidney size, are not detectable early in the course of disease, only manifesting after there is a significant loss of nephrons and major decrease in glomerular filtration rate (GFR). 

Glomerular filtration rate is the “gold standard” for measurement of renal function in humans and animals; however, its measurement is technically impractical in the veterinary clinical setting, and sCr is used as a surrogate biomarker for GFR in animals.  Variables such as muscle mass, breed, and sex can affect sCr. Baseline concentrations of sCr in a healthy individual cat are usually not measured in clinical practice, and sCr is a relatively insensitive marker of GFR, as it remains within the reference range until about 75% of nephrons are non-functional. In humans, symmetric dimethylarginine (SDMA), a product of protein methylation that is eliminated predominantly by renal clearance, is used as an accurate and precise biomarker for estimated GFR, and is considered to be a more sensitive biomarker for renal dysfunction than sCr.

Cats enrolled in the study had an annual physical examination, complete blood count, biochemical panel, urinanalysis, and where indicated by urinanalysis results, urine culture.  They were housed in an enriched environment in a nutrition research facility that allowed for seasonal natural light, indoor exercise, and access to toys.  The study animals included 21 cats with CKD having a mean age of 14.3 years (15 spayed females and 6 neutered males); 15 of these were persistently azotemic, while 4 were nonazotemic but had reduced GFR based on iohexol clearance, and 2 were nonazotemic but had oxalate nephroliths.  These CKD cats had no evidence of any other confounding disease; their mean body weight was 4.0 kg. The control animals were 21 healthy geriatric cats from the same colony, with a mean age of 11.7 years, 12 spayed females and 9 neutered males; their mean body weight was 4.5 kg. Serum samples from the subjects had been frozen and banked as part of annual examinations or as part of protocols for other studies.

The cats with CKD were either IRIS stage 1 (sCr < 1.6 mg/dL) or 2 (sCr 1.6-2.8 mg/dL) and nonproteinuric (UPC ratio < 0.2) or borderline proteinuric (UPC ratio 0.2-0.4) at time of diagnosis. Based on evaluation of the serum samples, these researchers found that serum SDMA increased by a mean of 14.6 months before sCr increased above the normal reference range in each sample. Serum SDMA concentrations varied inversely with GFR.  All of the healthy geriatric cats had serum SDMA and sCr within the normal reference interval. The significant positive correlation found between serum SDMA and sCr supports the fact that SDMA is principally excreted by the kidneys. Nonazotemic cats with SDMA > 14 µg/dL eventually progressed to azotemic CKD.

Provided pre-renal (volume responsive) causes of decreased GFR and causes of acute kidney injury have been ruled out, these researchers found that a single increased SDMA concentration is moderately effective for confirming CKD, with a positive predictive value of 86%.  A negative test result provides the owner and clinician significant reassurance that the cat does not have CKD (negative predictive value, 100%).  A commercialized test based on the SDMA biomarker would be very useful in helping owners and veterinarians become more proactive in detecting and managing early CKD in cats. [PJS]

See also:
Jepson RE, Syme HM, et al.  Plasma asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine, and nitrite/nitrate concentrations in cats  with chronic kidney disease and hypertension. J Vet Intern Med 2008; 22:317-24.  

Braff J, Obare E, Yerramilla M, et al. Relationship between serum symmetric dimethylarginine concentration and glomerular filtration rate in cats. J Vet Intern Med. 2014 Nov; 28(6): 1699-1701.