Table 3.
List of studies on cystatin C and their analytical and clinical characteristics.
| Study | Assay Used | Sample Type | Nr. of Horses Included | Nr. of Horses with AKI or CKD | Comparison to Traditional Kidney Assessment | Association with Clinical State | Validation Phase | Reference Range Healthy Horses | Extrarenal Factors Influencing Reference Range | Limitations | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Siwińska, N., Żak, A., Pasławska, U. Evaluation of Serum and Urine Neutrophil Gelatinase-associated Lipocalin and Cystatin C as Biomarkers of Acute Kidney Injury in Horses. J Vet Res. 2021 May 16;65(2):245–252 [25]. |
Commercially available ELISA kits (MyBioSource, San Diego, CA, USA, catalogue number MBS022947) validated by the manufacturer for use with serum and urine samples of equine origin |
Serum (S), urine (U) | 30 healthy horses 30 horses at risk of AKI (colics or nephrotoxic drugs) 11 horses with AKI |
30 at risk of AKI 11 with AKI |
S cystatin C correlated to urea U cystatin C correlated to urea, creatinine, urine protein and urine GGT/protein ratio |
U & S cystatin C higher in colics and AKI horses vs. non AKI | Phase I: mentioned that test is validated but no validation data available Phase II overlap healthy—AKI risk—AKI Phase III—Se & Sp best cut off value S Cystatin C 0.53 mg/L with Se 0.64, Sp 0.85, PPV 0.44, NPV 0.94; best cut off value U Cystatin C 0.20 mg/L with Se 0.82, Sp 0.85, PPV 0.50, NPV 0.96 More effective detecting negative than positive results |
S median 0.25 mg/L (1st and 3rd quartile: 0.19–0.37 mg/L) U median 0.1 mg/L (1st and 3rd quartile 0.07–0.13 mg/L) |
n/a | Small nr. of cases |
| 2 | Ahmadpour, S., Esmaeilnejad, B., Dalir-Naghadeh, B., Asri-Rezaei, S. Alterations of cardiac and renal biomarkers in horses naturally infected with Theileria equi. Comp Immunol Microbiol Infect Dis. 2020 May 30;71:101502 [26]. |
Commercially available ELISA kits (MyBioSource, San Diego, CA, USA, catalogue number MBS022947) | serum | 28 horses (3–4 year old) infected with Theileria equi; 20 healthy control horses | 0 | Correlation to urea and creatinine; minimal increase in creatinine and urea, but significant increase in cystatin C -> can identify kidney damage earlier than creatinine and urea | Cystatin C significantly increased in horses with Theleria equi infection (> cut off value set by Siwinska et al. 2021); association to the level of parasitemia. | Phase II overlap healthy—Theileria equi | 0.11 ± 0.07 ng/mL | n/a | Small nr. of horses |
| 3 | Arosalo, B.M., Raekallio, M., Rajamäki, M., Holopainen, E., Kastevaara, T., Salonen, H., Sankari, S. Detecting early kidney damage in horses with colic by measuring matrix metalloproteinase -9 and -2, other enzymes, urinary glucose and total proteins. Acta Vet Scand. 2007 Jan 23;49(1):4 [24]. |
Dako Cytomation latex immunoassay® (Dako Cytomation, Glostrup, Denmark) based on turbidimetry (particle-enhanced tur- bidimetric immunoassay, PETIA) using human cystatin- C-specific antibodies | serum | 7 healthy control horses admitted for elective castration; 5 sick horses admitted for colic and undergoing emergency celiotomy | 0 (all colic horses had serum creatinine below 162 micromol/L) |
n/a | No correlation noted | n/a | Cystatin-C concentrations were below the threshold level of the test (<0.39 mg/L) | n/a | Human cystatin-C test did not work, indicating no or very little cross-reactivity between human and equine cystatin-C specific antibody |