Study flags hidden renal biomarker changes in geriatric dogs

A new study in Veterinary Sciences suggests that some clinically healthy geriatric dogs may already show renal biomarker abnormalities even when serum creatinine remains normal. In a cohort of 61 neutered geriatric dogs screened to exclude overt disease and extrarenal laboratory abnormalities, researchers identified a subgroup with normal creatinine but at least one elevated renal biomarker, describing this as an altered renal biochemical phenotype rather than confirmed early chronic kidney disease. More than one in four dogs, 27.9%, met that subclinical definition, with serum cystatin C driving most of those classifications. (mdpi.com)

The study lands in a familiar clinical gap. In dogs, creatinine, BUN, and SDMA are widely used to assess renal function, but these are primarily filtration markers and can miss earlier or subtler injury, especially in older patients where muscle mass and other non-renal factors complicate interpretation. IRIS says current markers can delay diagnosis of both stable CKD and acute kidney injury, and it has highlighted the future potential of “active kidney injury” biomarkers to improve detection and monitoring. At the same time, IRIS staging still centers on creatinine and SDMA, with urinalysis, urine culture, blood pressure measurement, proteinuria assessment, and imaging used to build the broader diagnostic picture. (iris-kidney.com)

In this new report, the dogs were divided into 36 controls, 17 subclinical dogs with normal serum creatinine but at least one elevated biomarker, and 8 dogs with azotemic CKD. The central finding was that serum cystatin C identified nearly all dogs in the subclinical group, while the urinary NAG index was also increased compared with controls. By contrast, urine protein-to-creatinine ratio did not differ across groups and remained within reference limits in every dog, including those with elevated cystatin C. That matters because proteinuria is often part of standard renal screening, but it would not have flagged these animals. Still, the authors explicitly note important limitations: cystatin C was part of the grouping strategy, and no independent glomerular filtration rate measurement was obtained, so the study cannot establish whether these dogs truly had early renal dysfunction. (mdpi.com)

That caution fits with the broader literature. A 2023 review of urinary kidney biomarkers in dogs and cats concluded that many urinary markers show promise for identifying glomerular and tubular damage, but most are not yet widely available and all need more study before broad clinical adoption. Separately, a 2025 longitudinal study of apparently healthy aging dogs found that over two years, 20% developed CKD, and the best predictors of azotemic CKD were muscle wasting, functional markers, and urinary retinol-binding protein-to-creatinine ratio, rather than proteinuria alone. That study did include serum cystatin C in its biomarker panel, but its conclusions did not position cystatin C as the standout predictor in the way this new cross-sectional paper does. (pubmed.ncbi.nlm.nih.gov)

There is also some tension in the evidence base around cystatin C itself. A recent systematic review and meta-analysis reported that serum cystatin C has limited utility in current clinical practice and no proven superiority over creatinine or SDMA, although the analysis focused on broader renal disease applications and not specifically on clinically healthy geriatric dogs with normal creatinine. Earlier and disease-specific studies have been more favorable, suggesting cystatin C may help detect early CKD better than creatinine alone. Taken together, the literature points less to consensus than to an unsettled biomarker landscape. (pubmed.ncbi.nlm.nih.gov)

Why it matters: For veterinarians, the practical takeaway is not that cystatin C or urinary NAG should immediately be added to every senior wellness panel. It's that normal creatinine, normal UPC, and an outwardly healthy geriatric patient do not necessarily close the book on renal risk. This study strengthens the case for thoughtful, layered renal screening in older dogs, especially when body condition, muscle loss, urine concentration, blood pressure, or serial trends raise concern. It also highlights a familiar translational challenge: promising biomarkers can reveal biologic signals before the profession knows exactly how to act on them. Until outcome-linked validation is available, these assays may be most useful in referral settings, research, or selected cases where conventional markers and clinical suspicion don't align. (iris-kidney.com)

What to watch: The next inflection point will be prospective studies that pair cystatin C and urinary NAG with measured glomerular filtration rate, serial follow-up, and eventual CKD outcomes. If those studies show that biomarker-positive, creatinine-normal geriatric dogs are more likely to progress, the findings could influence future screening recommendations for senior and geriatric patients. If not, this paper may remain an important but preliminary description of biochemical variation in aging dogs rather than a practice-changing diagnostic advance. (mdpi.com)