Abstract
This study investigated the effects of age, sex and breed on serum cystatin C (Cys-C) and creatinine in small breed dogs. This retrospective study included 250 dogs weighing less than 15 kg without azotemia. Serum Cys-C and creatinine concentrations were analyzed, along with their correlation with age, and the difference between sexes or dog breeds. Serum Cys-C concentration correlated with age (P < 0.001), and did not differ between sexes or dog breeds. By contrast, serum creatinine concentration did not correlate with age. Serum creatinine concentration was higher in males than females (P < 0.05), and was lower in Miniature Dachshunds and Chihuahuas, and was higher in Shiba Inus compared to the general study population (P < 0.001). Serum Cys-C concentration correlates with age, and might be more sensitive to aging-associated subclinical renal dysfunction than serum creatinine concentration in dogs. Unlike serum creatinine concentration, serum Cys-C concentration is not affected by sex or dog breed.
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Data availability
The datasets analyzed in the present study are available from the corresponding author on reasonable request.
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References
Abrahamson M, Olafsson I, Palsdottir A, Ulvsback M, Lundwall A, Jensson O, Grubb A (1990) Structure and expression of the human cystatin C gene. Biochem J 268:287–294. https://doi.org/10.1042/bj2680287
Almy FS, Christopher MM, King DP, Brown SA (2002) Evaluation of cystatin C as an endogenous marker of glomerular filtration rate in dogs. J Vet Intern Med 16:45–51. https://doi.org/10.1111/j.1939-1676.2002.tb01605.x
Braun JP, Perxachs A, Perchereaus D, Delafarge F (2002) Plasma Cystatin C in the Dog: Reference values and variations with renal failure. Clin Pathol 11:44–49. https://doi.org/10.1007/s580-002-8081-2
Braun JP, Lefebvre HP, Watson AD (2003) Creatinine in the dog: a review. Vet Clin Pathol 32:162–179. https://doi.org/10.1111/j.1939-165X.2003.tb00332.x
Connolly SL, Nelson S, Jones T, Kahn J, Constable PD (2020) The effect of age and sex on selected hematologic and serum biochemical analytes in 4,804 elite endurance-trained sled dogs participating in the Iditarod Trail Sled Dog Race pre-race examination program. PLoS ONE 15:e0237706
Denic A, Glassock RK, Rule AD (2016) Structural and functional changes with aging kidney. Adv Chronic Kidney Dis 23:19–28. https://doi.org/10.1053/j.ackd.2015.08.004
Feeman WE, Guillermo Couto C, Gray TL (2003) Serum creatinine concentrations in retired racing Greyhounds. Vet Clin Pathol 32:40–42
Filler G, Bokenkamp A, Hofmann W, Bricon TL, Martinez-Bru C, Grubb A (2005) Cystatin C as a marker of GFR-history, indications, and future research. Clin Biochem 38:1–8. https://doi.org/10.1016/j.clinbiochem.2004.09.025
Finney H, Newman DJ, Thakkar H, Fell JM, Price CP (2000) Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children. Arch Dis Child 82:71–75. https://doi.org/10.1136/adc.82.1.71
Finney H, Newman DJ, Price CP (2000) Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance. Ann Clin Biochem 37:49–59. https://doi.org/10.1258/0004563001901524
Ghys L, Paepe D, Smets P, Lefebvre H, Delanghe J, Daminet S (2014) Cystatin C: a new renal marker and its potential use in small animal medicine. J Vet Intern Med 28:1152–1164. https://doi.org/10.1111/jvim.12366
Hari P, Ramakrishinan L, Gupta R, Kumar R, Bagga A (2014) Cystatin C-based glomerular filtration rate estimating equations in early chronic kidney disease. Indian Pediatr 51:273–277. https://doi.org/10.1007/s13312-014-0400-5
Iwasa N, Takashima S, Iwasa T, Iwasa K, Suzuki T, Kobatake Y, Kitagawa H, Nishii N (2018) Serum cystatin C concentration measured routinely is a prognostic maker for renal disease in dogs. Res Vet Sci 119:122–126. https://doi.org/10.1016/j.rvsc.2018.06.014
Jensen AL, Bomholt M, Moe L (2001) Preliminary Evaluation of a Particle-enhanced turbidimetric immunoassay (PETIA) for the determination of serum cystatin C-Like immunoreactivity in dogs. Vet Clin Pathol 30:86–90
Kanda Y (2013) Investigation of the freely available easy-to-use soft ware ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244
Kaseda R, Iino N, Hosojima M, Takeda T, Hosaka K, Kobayashi A, Yamamoto K, Suzuki A, Kasai A, Suzuki Y, Gejyo F, Saito A (2007) Megalin-mediated endocytosis of cystatin C in proximal tubule cells. Biochem Biophys Res Commun 357:1130–1134. https://doi.org/10.1016/j.bbrc.2007.04.072
Knight EL, Verhave JC, Spiegelman D, Hillege HL, de Zeeuw D, Curhan GC, de Jong PE (2004) Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int 65:1416–1421. https://doi.org/10.1111/j.1523-1755.2004.00517.x
Laterza OF, Price CP, Scott MG (2002) Cystatin C: an improved estimator of glomerular filtration rate? Clin Chem 48:699–707. https://doi.org/10.1093/clinchem/48.5.699
Miyagawa Y, Takemura N, Hirose H (2009) Evaluation of the measurement of serum cystatin C by an enzyme-linked immunosorbent assay for humans as a marker of the glomerular filtration rate in dogs. J Vet Med Sci 71:1169–1176. https://doi.org/10.1292/jvms.71.1169
Miyagawa Y, Akanabe R, Ogawa M, Nagkawa M, Miyakawa H, Takemura N (2021) Serum cystatin C concentration can be used to evaluate glomerular filtration rate in small dogs. J Vet Med Sci 82:1828–1834. https://doi.org/10.1292/jvms.20-0201
Pagitz M, Frommlet F, Schwendenwein I (2007) Evaluation of biological variance of cystatin c in comparison with other endogenous markers of glomerular filtration rate in healthy dogs. J Vet Intern Med 21:936–942. https://doi.org/10.1111/j.1939-1676.2007.tb03046.x
Pelander L, Haggstrom J, Larsson A, Syme H, Elliott J, Heiene R, Ljungvall I (2019) Comparison of the diagnostic value of symmetric dimethylarginine, cystatin C, and creatinine for detection of decreased glomerular filtration rate in dogs. J Vet Intern Med 33:630–639. https://doi.org/10.1111/jvim.15445
Peralta CA, Shlipak MG, Judd S, Cushman S, McClellan W, Zakai NA, Safford MM, Zhang X, Muntner P, Warnock D (2011) Detection of chronic kidney disease with creatinine, cystatin C, and urine Albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality. JAMA 305:1545–1552. https://doi.org/10.1001/jama.2011.468
Tenstad O, Roald AB, Grubb A, Aukland K (1996) Renal handling of radio- labelled human cystatin C in the rat. Scand J Clin Lab Invest 56:409–414. https://doi.org/10.3109/00365519609088795
Tvarijonaviciute A, Ceron JJ, Holden SL, Biourge V, Morris PJ, German AJ (2013) Effect of weight loss in obese dogs on indicators of renal function or disease. J Vet Intern Med 27:31–38. https://doi.org/10.1111/jvim.12029
Wehner A, Hartmann K, Hirschberger J (2008) Utility of serum cystatin c as a clinical measure of renal function in dogs. J Am Anim Hosp Assoc 44:131–138. https://doi.org/10.5326/0440131
Wu C, Lin J, Caffrey JL, Chang M, Hwang J, Lin Y (2010) Cystatin C and long-term mortality among subjects with normal creatinine-based estimated glomerular filtration rates. J Am Coll Cardiol 56:1930–1936. https://doi.org/10.1016/j.jacc.2010.04.069
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Study conception was carried out by Naoki Iwasa, Satoshi Takashima, Yui Kobatake and Naohito Nishii. Data acquisition was done by Naoki Iwasa, Tatsuo Iwasa, Kazuko Iwasa, Rie Kumazawa, Saki Nomura, Sara Asami and Mamu Shimizu. Data were analyzed by Satoshi Takashima, Yui Kobatake and Naohito Nishii. First draft was written by Naoki Iwasa. Satoshi Takashima, Tatsuo Iwasa, Kazuko Iwasa, Rie Kumazawa, Saki Nomura, Sara Asami, Mamu Shimizu, Yui Kobatake and Naohito Nishii contributed to improve the manuscript. All authors read and approved the final version of the manuscript.
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This work is a retrospective observational study. All dog owners were given the opportunity to opt out from the present study, and this was communicated via the bulletin board in our animal hospital.
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Iwasa, N., Takashima, S., Iwasa, T. et al. Effect of age, sex, and breed on serum cystatin C and creatinine concentrations in dogs. Vet Res Commun 46, 183–188 (2022). https://doi.org/10.1007/s11259-021-09844-w
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DOI: https://doi.org/10.1007/s11259-021-09844-w