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For those of you that utilize Idexx as your reference laboratory, you have probably already seen the urinary cystatin B results showing up on your blood work results. The lab then provides a diagnostic algorithm when urinary cystatin B is above the reference interval. But what does an elevated urinary cystatin B really mean? And when should I recommend further diagnostic workup? Well, there is still little known about urinary cystatin B in the clinical setting, but I’ve summarized my perspective as a curious, but hopeful, internist.

We all learn that our current urinary markers of disease (BUN, Creatinine, and even SDMA) are poor indicators of early renal disease or damage. Most of us can even recite the statistic that patients have lost 66% of renal function by the time they have lost urinary concentrating ability and 75% of renal function before any clinical azotemia is detectable. Many advancements in the field of human and veterinary nephrology have focused on markers of early renal damage with various clinical successes. It is thought that elevated urinary cystatin B levels could indicate active release of cystatin B from the renal tubule epithelial cells, therefore indicating active damage to the renal tissue. An elevated urinary cystatin B level may indicate active renal damage before renal function values rise much like an elevated ALT may indicate active liver damage before increased bilirubin indicates liver failure.

Cystatin B is a small (11 kDalton), ubiquitous, intra-cellular protein. It functions as a cysteine protease inhibitor in cells, but its function in the body is likely not relevant to its function as a diagnostic test. Because it is primarily an intra-cellular protein, we know that it is found in trace amounts in the serum and urine of healthy individuals. There has been a recent publication in the Journal of Veterinary Internal Medicine (April 2023) reporting that healthy dogs had low levels of urinary cystatin B levels. The study’s main conclusion was that over a 2-year study period, dogs with stable chronic renal disease had low baseline urinary cystatin B levels, while dogs with advancing chronic renal disease had significantly higher baseline urinary cystatin B levels.

What the study was unable to define was what is the impact of other systemic diseases or inflammation on urinary cystatin B levels. In other words, is an elevated urinary cystatin specific to active renal damage or could it rise with any systemic inflammation? Cystatin B is present in many cells of the body and is small enough to be freely filtered by the glomerulus of the kidneys. It stands to reason that diseases that cause increased systemic inflammation, likely cause increased serum cystatin B, and therefore likely cause increased urinary cystatin B levels. So, the question remains, what do I do with an elevated urinary cystatin B?

Time will tell how useful urinary cystatin B will be in the early detection of renal disease. Based on the limited literature available, the most likely clinical use of urinary cystatin B will be in helping to determine the presence of active renal injury in canine patients with known chronic renal disease. Dogs with increased urinary cystatin B levels, should likely be monitored more closely for advancing disease. I suspect that we will learn that many sick or injured patients have both elevated serum and urinary cystatin B levels, and that the clinical utility of the urinary cystatin B test will be as a screening tool for early renal disease. At this time, I am not aware of any publications validating its use in feline patients.

Jeremy Diroff, DVM, DACVIM
Small Animal Internal Medicine
Maine Veterinary Medical Center