Correlation of renal function biomarkers in the first diagnostic approach for chronic kidney disease in dogs

Correlación de biomarcadores de función renal en el primer acercamiento diagnóstico de la enfermedad renal crónica en perros

Objective. To determine the correlation of kidney function biomarkers at the first evaluation in dogs with different risk factors identified for developing chronic kidney disease (CKD). Materials and methods. A descriptive, prospective study of cases and controls of 388 animals, divided into five groups: control group (CG), and four groups of potentially kidney-diseased dogs (pCKD) was carried out. Clinical history, physical examination, body condition score (BCS), complete blood count, biochemical profile with symmetrical dimethylarginine (SDMA), urinalysis, urine protein/creatinine ratio (UPC), and systemic blood pressure were analyzed. Non-parametric statistics were used, and data were expressed as medians and percentiles; for BCS, Xi² was used. For biomarkers, Spearman’s correlation was performed. Results. For SDMA and serum creatinine (sCr), a moderate correlation was observed for pCKD (r = 0.69, p ˂ 0.001). Significant differences were observed in the variables age (p = 0.002) and BCS (p ˂ 0.001) between the CG and the pCKD. Animals with mild azotemia (sCr 125–250 mmol/L) and/or with an SDMA value of 18–35 mg/dL, with or without proteinuria, had a greater probability of presenting an increase in SDMA when the BCS was below 5/9 (OR = 3.55, p = 0.005). Conclusions. SDMA is a useful complementary biomarker in pre-azotemic stages and advanced stages where there is cachexia and sarcopenia. Biomarkers must be evaluated together to have a complete perspective of renal function in animals with risk factors for developing CKD.

1. Acierno MJ, Brown S, Coleman AE, Jepson RE, Papich M, Stepien RL, Syme HM. ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med. 2018; 32(6):1803–1822. https://doi.org/10.1111/jvim.15331
2. Bartges J. Chronic kidney disease in dogs and cats. Vet Clin Small Anim. 2012; 42:669–692. http://dx.doi.org/10.1016/j.cvsm.2012.04.008
3. Roura X. Risk factors in dogs and cats for development of chronic kidney disease. International Renal Interest Society (IRIS): España; 2019. http://www.iris-kidney.com/education/risk_factors.html
4. Perini-Perera S, Del-Ángel-Caraza J,Pérez-Sánchez AP, Quijano-Hernández IA and Recillas-Morales S. Evaluation of Chronic Kidney Disease Progression in Dogs With Therapeutic Management of Risk Factors. Front Vet Sci. 2021; 8:621084. https://doi.org/10.3389/fvets.2021.621084
5. Braun JP, Lefebvre HP, Watson ADJ. Creatinine in the Dog: A Review. Vet Clin Pathol. 2003; 32(4):163-179. https://doi.org/10.1111/j.1939-165X.2003.tb00332.x
6. Hokamp JA, Cianciolo RE, Boggess M, Lees GE, Benali SL, Kovarsky M, Nabity MB. Correlation of urine and serum biomarkers with renal damage and survival in dogs with naturally occurring proteinuric chronic kidney disease. J Vet Intern Med. 2016; 30(2):591-601. https://doi.org/10.1111/jvim.13832
7. IRIS. IRIS Staging of CKD (modified 2019). International Renal Interest Society: España; 2019. http://www.iris-kidney.com/pdf/IRIS_Staging_of_CKD_modified_2019.pdf
8. Kielstein JT, Salpeter SR, Bode-Boeger SM, Cooke JP, Fliser D. Symmetric dimethylarginine (SDMA) as endogenous marker of renal function—a meta-analysis. Nephrol Dial Transplant. 2006; 21(9):2446–2451.https://doi.org/10.1093/ndt/gfl292
9. McKenna M, Pelligand L, Elliott J, Cotter D, Jepson R. Relationship between serum iohexol clearance, serum SDMA concentration, and serum creatinina concentration in non-azotemic dogs. J Vet Intern Med. 2020; 34(1):186-194. https://doi.org/10.1111/jvim.15659
10. Vaden D, Elliott J. Management of Proteinuria in dogs and cats with chronic kidney disease. Vet Clin Small Anim. 2016; 46:1115–1130. https://doi.org/10.1016/j.cvsm.2016.06.009
11. Santarossa A, Parr JM, Verbrugghe A. The importance of assessing body composition of dogs and cats methods available for use in clinical practice. J Am vet Med Assoc. 2017; 251(5):521-529. https://doi.org/10.2460/javma.251.5.521
12. Mukaka MM. A guide to appropriate use of correlation coefficient in medical research. Malawi Med J. 2012; 24(3):69-71. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576830/pdf/MMJ2403-0069.pdf
13. O’Neill DG, Elliott J, Church DB, McGreevy PD, Thomson PC, Brodbelt DC. Chronic kidney disease in dogs in UK veterinary practices: prevalence, risk Factors, and survival. J Vet Intern Med. 2013; 27(4):814-821. http://doi.org/10.1111/jvim.12090
14. Pelander L, Ljungvall I, Egenvall A, Syme H, Elliott J, Häggström J. Incidence of and mortality from kidney disease in over 600,000 insured Swedish dogs. Vet Rec. 2015; 176(25):656. http://doi.org/10.1136/vr.103059
15. Rudinsky AJ, Harjes LM, Byron J, Chew DJ, Toribio RE, Langston C, Parker VL. Factors aule AD. Structural and functional changes with the aging kidney. Adv Chronic Kidney Dis. 2016; 23(1):19-28. http://doi.org/10.1053/j.ackd.2015.08.004
16. Denic A, Glassock RJ, Rule AD. Structural and functional changes with the aging kidney. Adv Chronic Kidney Dis. 2016; 23(1):19-28. http://doi.org/10.1053/j.ackd.2015.08.004
17. Nabity MB, Lees GE, Boggess MM, Yerramilli M, Obare E, Yerramilli M, Rakitin A, Aguiar J, Relford R. Symmetric dimethylarginine assay validation, stability, and evaluation as a marker for the early detection of chronic kidney disease in dogs. J Vet Intern Med. 2015; 29(4):1036-1044. http://doi.org/10.1111/jvim.12835
18. Hall JA, MacLeay J, Yerramilli M, Obare E, Yerramilli M, Schiefelbein H, Paetau-Robinson I, Jewell DE. Positive impact of nutritional interventions on serum symmetric dimethylarginine and creatinine concentrations in client-owned geriatric cats. PLOS ONE 2016; 11(4):e0153654. https://doi.org/10.1371/journal.pone.0153654
19. Hall JA, Yerramilli M, Obare E, Yerramilli M, Yu S, Jewell DE. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L carnitine, and medium-chain triglycerides. Vet J. 2014; 202(3):588-596. http://doi.corg/10.1016/j.tvjl.2014
20. Freeman LM. Cachexia and sarcopenia: emerging syndromes of importance in dogs and cats. J Vet Intern Med. 2012; 26:3–17 http://doi.org/10.1111/j.1939-1676.2011.00838.x
21. Freeman LM, Lachaud MP, Matthews S, Rhodes L, Zollers B. Evaluation of weight loss over time in cats with chronic kidney disease. J Vet Intern. 2016; 30(5):1661-1666. http://doi.org/10.1111/jvim.14561
22. Hall JA, Yerramilli M, Obare e, Yerramilli M, Melendez LD, Jewell DE. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med. 2015; 29(3):808-814. http://doi.org/10.1111/jvim.12607
23. Dahlem DP, Neiger R, Schweighauser A, Francey T, Yerramilli M, Obare E, Steinbach SML. Plasma symmetric dimethylarginine concentration in dogs with acute kidney injury and chronic kidney disease. J Vet Intern Med. 2017; 31(3):799-804. http://doi.org/10.1111/jvim.14694
24. Sargent HJ, Elliott J, Jepson RE. The new age of renal biomarkers: does SDMA solve all of our problems? J Small Anim Pract. 2020; 62(2):71-81. http://doi.org/10.1111/jsap.13236
25. Elliot J. Physiology of blood pressure regulation and pathophysiology of hypertension. In: Elliot J, Syme HM & Jepson RE, editors. Hypertension in the dog and cat. London: Springer UK; 2020. https://doi.org/10.1007/978-3-030-33020-0
26. Polzin DJ. Chronic kidney disease. In: Bartges J & Polzin DJ, editors. Nephrology and urology of small animals. London: Wiley-Blackwell UK; 2011.