The occurrence of chronic kidney disease is underestimated in both human and veterinary medicine. Glomerular filtration rate (GFR) is considered the gold standard for evaluating kidney function. However, GFR assessment is time‐consuming and labor‐intensive and therefore not routinely used in practice. The commonly used indirect GFR markers, serum creatinine (sCr) and urea, are not sufficiently sensitive or specific to detect early renal dysfunction. Serum cystatin C (sCysC), a proteinase inhibitor, has most of the properties required for an endogenous GFR marker. In human medicine, numerous studies have evaluated its potential use as a GFR marker in several populations. In veterinary medicine, this marker is gaining interest. The measurement is easy, which makes it an interesting parameter for clinical use. This review summarizes current knowledge about cystatin C (CysC) in humans, dogs, and cats, including its history, assays, relationship with GFR, and biological and clinical variations in both human and veterinary medicine.

Old cats (>10 years) had significantly higher SBP, heart rate, murmur frequency, thrombocyte count, urine protein:creatinine ratio and serum urea and bilirubin concentrations, and significantly lower body condition score, haematocrit, albumin and total calcium concentrations than middle-aged cats (6-10 years). The common occurrence of physical examination and laboratory abnormalities in apparently healthy old cats underlines the need for regular health checks and the development of age-dependent laboratory reference intervals.

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The human nephelometric assay showed satisfactory validation results for feline CysC. Cats with CKD had a significantly higher sCysC concentration and uCysC/uCr ratio compared with healthy cats. Additional studies are necessary to evaluate CysC as an early marker of renal damage in cats.

BackgroundSerum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in‐depth clinical validation is required.ObjectivesTo evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA).AnimalsNinety cats were included: 49 CKD and 41 healthy cats.MethodsSerum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo‐iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT < 1.7 mL/min/kg were calculated. Serum CysC results of PENIA and PETIA were correlated with GFR. Statistical analysis was performed using general linear modeling.ResultsCats with CKD had significantly higher mean ± SD sCysC (1.4 ± 0.5 mg/L) (P < .001) and uCysC/urinary creatinine (uCr) (291 ± 411 mg/mol) (P < .001) compared to healthy cats (sCysC 1.0 ± 0.3 and uCysC/uCr 0.32 ± 0.97). UCysC was detected in 35/49 CKD cats. R 2 values between GFR and sCysC or sCr were 0.39 and 0.71, respectively (sCysC or sCr = μ + GFR + ε). Sensitivity and specificity were 22 and 100% for sCysC and 83 and 93% for sCr. Serum CysC could not distinguish healthy from CKD cats, nor normal from borderline or low GFR, in contrast with sCr.ConclusionSerum CysC is not a reliable marker of reduced GFR in cats and uCysC could not be detected in all CKD cats.

Based on evaluation of routine kidney variables, GFR and uCysC as a tubular marker at a single time point, a major impact of feline DM on kidney function could not be demonstrated.

This study demonstrated that sCysC is increased in cats with hyperthyroidism, in contrast with sCr, but not in cats with FIV. Many hyperthyroid cats, but only four cats with FIV, had an elevated uCysC/uCr ratio. Further studies may reveal if uCysC might be a valuable marker for tubular dysfunction in cats.

A PENIA measured sCysC linearly and precisely. There were no clinically relevant renal alterations over time in dogs with DM, although persistent proteinuria was observed. In dogs with HAC, sCysC measurement was not useful, although significant GFR changes occurred over time.