Symmetric dimethylarginine (SDMA) is a blood biomarker used for the assessment of renal function that is validated in dogs, cats, rats, and horses and has been utilized in a wider range of species to evaluate renal health.1–12 Classic mammalian biochemical parameters such as blood urea nitrogen (BUN) and creatinine (CREAT) do not increase until at least 75% of the kidney mass is diseased or damaged.1,3 Symmetric dimethylarginine increases earlier in states of kidney compromise with increased sensitivity compared with plasma CREAT in mammalian species evaluated.4,9–13 Exploring more sensitive biochemical markers of kidney dysfunction may allow for early intervention and treatment of the disease.
SDMA is a molecule originating from the intracellular methylation of proteins and plays a role in basic cellular metabolism.12 Due to its small size and positive charge, it is freely filtered by glomerular filtration and eliminated primarily by renal clearance.14–16 Protein enzymes needed for the methylation of arginine compounds like SDMA, such as arginine N-methyltransferases, have been identified in chickens, based on sequence homology.17 Given that avian species have glomeruli, evaluating SDMA concentrations could be relevant in birds. Studies have shown that SDMA correlates with glomerular filtration rate (GFR) in cats and dogs.1,14,18 The extensive renal clearance of SDMA explains its potential suitability as an endogenous kidney biomarker.9,12,18 There are several advantages of SDMA in detecting decreased GFR compared with CREAT as SDMA is less affected by extrarenal factors, such as age, sex, and lean body mass.2,5,9,12,19–21
At this time, SDMA has been evaluated in mammalian, fish,10 1 avian,22 and 1 reptile species.23 Many avian species suffer from renal disease including progressive chronic kidney disease, infectious, neoplastic, or metabolic causes.24,25 Common renal pathology reported includes amyloidosis in waterfowl and shorebirds and progressive chronic kidney disease in cockatiels (Nymphicus hollandicus).25,26 Currently available biochemical parameters utilized for avian patients with suspect kidney disease exhibit poor sensitivity for renal pathology and include uric acid, blood urea nitrogen, calcium, and phosphorus concentrations.25,27–29 Unfortunately, other conditions including dehydration, concurrent muscle breakdown, and diet can influence these blood values, confounding the diagnosis.25,30–35 Measurement of glomerular filtration rate has been reported in several avian species but is rarely performed clinically.36 Additional diagnostic options are invasive, such as kidney biopsies or renal scintigraphy, which require anesthesia and may be risky for sick patients.25,32–35 Given the diagnostic advantages proven in mammals and the current diagnostic limitations for the detection of renal pathology in avian patients, SDMA has the potential to improve the evaluation of kidney health and welfare in avian patients.
The specific aims of this study were to assess if chickens had circulating SDMA in their plasma and compare the commercial immunoassay (IA) to the gold standard, LC-MS/MS/MS, for measuring SDMA in chickens and to calculate a reference interval for SDMA in this species.
Methods
The study was approved by the University of Illinois Institutional Animal Care and Use Committee (ID#18059).
Animals
Two-hundred and fifty (Rhode Island red n = 88, leghorn n = 162) adult female chickens were included in the study. The number of birds collected was based upon proprietary assay needs for IA validation, requiring at least 110 mL of plasma as well as targeting having at least 150 individuals for reference interval calculation. All birds had been at the University of Illinois Poultry Research Facility and visually observed daily by research staff for at least 2 years before beginning the study. They were fed a variety of commercial egg layer diets ad libitum.
Blood sample collection
A bird was opportunistically selected from a battery-style cage, had a complete physical examination performed, and was manually restrained for venipuncture. A venous blood sample was aseptically collected from the right jugular vein using a 22-gauge, 1-inch needle (Greiner Bio-One Frickenhausen) attached to a 3.0 or 6.0-mL syringe (Covidien). Most of the obtained blood was placed into a lithium heparin separation tube (Vacuette tube, Greiner Bio-One Frickenhausen), and the remainder was placed into an EDTA microtube (MiniCollect, Greiner Bio-One Frickenhausen), then refrigerated at 4 °C. Plasma tubes were centrifuged within 6 hours of sample collection, and plasma was harvested and sent to a commercial laboratory (IDEXX Laboratories, Inc) in refrigeration where it was immediately stored at −20 °C for batch analysis of SDMA and chemistry analytes. All samples were refrigerated for less than 4 days before freezing.
Plasma biochemical analysis was performed on a commercial analyzer (AU680 Chemistry Analyzer, Beckman Coulter, Inc) that included sodium, potassium, Na/K ratio, calcium, chloride, phosphorus, glucose, BUN, CREAT, BUN:CREAT ratio, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine kinase (CK), total bilirubin as well as conjugated and unconjugated bilirubin, total protein (TP), albumin (ALB), globulin (GLB), albumin: globulin ratio, cholesterol, magnesium (Mg), gamma-glutamyl transferase (GGT), amylase, lipase, bicarbonate, anion gap, thyroid (T4), bile acids, uric acid, and triglycerides. Because of the nature of the study, only renal-focused values were assessed and reported.
Plasma SDMA concentrations were measured using 2 assays: the gold standard liquid chromatography–tandem mass spectrometry (LC-MS/MS)9 and the commercially available IA (AU680 Clinical Chemistry Analyzer, Beckman Coulter, Inc).
Statistical analysis
Normality of data sets was evaluated with a Shapiro-Wilk test. summary statistics (minimum, maximum, mean, median, and standard deviation) of plasma biochemical and SDMA analytes were calculated. Reference intervals, based on the American Society for Veterinary Clinical Pathology guidelines were calculated for LC-MS/MS SDMA concentrations using the “nonparametric” method with a 2-sided 95% reference interval estimated;37 90% CIs about the upper and lower reference limits were obtained by bootstrap estimation, n = 1,000. Chickens were removed from reference interval calculation if they exhibited abnormalities of their renal-focused parameters that may infer that renal disease was present: either hyperuricemia (uric acid greater than 10.5 mg/dL)29,38 or calcium to phosphorus ratio less than 2.25,28
The agreement between SDMA results measured by IA and LC-MS/MS, with the latter serving as the reference standard, was assessed; SDMA-IA values were regressed onto SDMA results measured by LC-MS/MS using a Passing-Bablok linear regression. A scatter plot of these results was created with a line of identity and a Passing-Bablok line of best fit. The correlation of these results was estimated using Kendall’s τ. All statistical analyses were performed using commercially available statistical software (R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing).
Results
Ages ranged from 1–5 years of age, median age of 1 year. Birds weighed between 1.01–2.5 kg, with a median weight of 1.8 kg. The body condition score, based upon published standards,39 was recorded for 247/250 birds, ranging between 0–3 with a median body condition score of 3. Several birds had physical examination findings that were deemed to be minimally significant including mildly increased air sac sounds (36/250, 14.4%), missing a nail (30/250, 12%), or superficial oral plaques (16/250, 6.4%). Five birds out of 250 (2.5%) were deemed not healthy on physical examination based upon the presence of coelomic effusion (4/5) or the presence of a large coelomic mass (1/5); hematologic and biochemical parameters were excluded from these birds.
Hemolysis was not grossly apparent in any of the samples whereas gross lipemia was present in 20 samples, requiring ultracentrifugation before further analysis. Values for renal-associated chemistry indices and SDMA results are listed (Table 1). Birds with volume samples (<2.5 mL) were not included in the assay comparison component of the study which necessitated the prioritization of renal-focused chemistry analytes.
Renal-focused plasma biochemical analytes and symmetric dimethylarginine (SDMA) concentrations in adult female chickens (Gallus gallus).
| Biochemical parameter | N | Mean | SD | Median | Min | Max |
|---|---|---|---|---|---|---|
| Albumin (ALB) (g/dL) | 245 | 1.70 | 1.2 | 2.2 | ||
| Blood urea nitrogen (BUN) (mg/dL) | 245 | 1.00 | 0.0 | 2.0 | ||
| Calcium (mg/dL) | 245 | 27.45 | 5.54 | |||
| Ca:Ph | 245 | 5.29 | 0.01 | |||
| Creatinine (CREAT) (mg/dL) | 158 | 0.10 | 0.0 | 0.2 | ||
| Phosphorus (mg/dL) | 245 | 5.32 | 1.17 | 2.4 | 7.9 | |
| Uric acid (mg/dL) | 110 | 4.15 | 0 | 6.9 | ||
| Total protein (TP) (g/dL) | 245 | 5.24 | 0.64 | 3.2 | 7.5 | |
| SDMA - IA (ug/dL) | 182 | 7.00 | 1 | 12 | ||
| SDMA - LC-MS (ug/dL) | 220 | 7.4 | 5 | 15 |
Normally distributed data is expressed as mean, SD (standard deviation), min (minimum), and max (maximum) while nonnormally distributed data is expressed as median, min, and max. IA = Immunoassay; LC-MS = Liquid chromatography mass spectrometry.
The accuracy of SDMA-IA measurements was assessed against the LC-MS/MS reference method. The ranges of SDMA concentrations measured by LC-MS/MS were 5.0–15.0 μg/dL, whereas the range of SDMA concentration measured by IA was 1.0–12.0 μg/dL. The Passing-Bablok linear regression of SDMA concentrations by IA onto SDMA concentrations by LC-MS/MS had a slope of the estimate of 1.67 (95% CI [1.35 to 2.14]) and an intercept estimate of −5.76 (95% CI [−9.90 to −3.35). Kendall’s τ correlation was estimated as τ = 0.39 (Figure 1). There was a negative proportional bias and positive systemic bias when comparing IA to LC-MS/MS. No chickens exhibited hyperuricemia or decreased Ca:Ph requiring exclusion from SDMA reference interval calculations; thus, the SDMA results of the 220 samples that were measured by LC-MS/MS were used to determine the 95% SDMA reference interval. The distribution of SDMA measured by LC-MS is shown (Figure 2). The upper reference limit was estimated as 10.62 with 90% CI [9.87 to 12.46] and the lower reference limit was estimated as 5.58 with 90% CI [5.20 to 5.76].
A Passing-Bablok regression line was fit between 2 different testing methodologies (immunoassay [IA] and liquid chromatography mass spectrometry [LC-MS]) evaluating symmetric dimethylarginine (SDMA) in adult female healthy chickens (Gallus gallus; n = 182) to estimate bias between methods. The dashed line represents when y = x.
Citation: American Journal of Veterinary Research 84, 9; 10.2460/ajvr.22.12.0222
Histogram depicting symmetric dimethylarginine (SDMA) concentrations in healthy adult female chickens (Gallus gallus; n = 220) measured by liquid chromatography–tandem mass spectrometry.
Citation: American Journal of Veterinary Research 84, 9; 10.2460/ajvr.22.12.0222
Discussion
The SDMA reference interval established in this study (5.58–10.62 μg/dL) is comparable with the current canine and feline SDMA reference intervals (dog, 0–14 μg/dL; cat, 0–14 μg/dL). It is important to note that the chicken reference interval is reported from the LC-MS/MS methodology, as SDMA measured through the IA methodology demonstrated low agreement with this reference method (LC-MS/MS) and cannot be recommended as a clinical diagnostic at this time. Although SDMA-IA represents a faster less labor-intensive assay than the gold standard, SDMA-LC-MS/MS, the presence of lipids, hemoglobin, and asymmetric dimethylarginine are known to interfere with the commercial SDMA-IA in canine patients.13,40 Although hemoglobin was not directly tested for, the lack of visible hemolysis makes the presence of hemoglobin unlikely in our samples. Many of the birds did exhibit gross lipemia, likely from folliculogenesis, necessitating ultracentrifugation. Although the precise reason for the lack of agreement between the 2 assays is unknown, researchers or clinicians looking to investigate SDMA in this species should utilize the LC-MS/MS methodology, the gold standard assay, over SDMA-IA measurements.
Several other nontraditional species have had SDMA plasma concentrations reported in the literature. In some species, a reference interval has been created for potential clinical use.7,8,10,11,22,23 The SDMA-IA assay has been validated for use in several species including cheetahs (Acinonyx jubatus),7 tigers (Panthera tigris),11 and Hermann’s tortoise (Testudo hermanii).23 In a recent study evaluating SDMA concentrations in greater flamingos (Phoenicopterus roseus), only values from the SDMA-IA assay were assessed.22 The results of the data presented here do not support that the SDMA-IA assay is a replacement for the gold standard mass spectrometry assay in chickens and we counsel future researchers to consider that not all species may be able to use results from the SDMA-IA assay interchangeably with the gold standard SDMA-LC/MS/MS assay. Clinicians and researchers interested in SDMA concentrations in chickens, and potentially other avian species, should pursue the SDMA-LC/MS/MS method.
It is unknown if SDMA is a renal-specific marker for avian species as it is in mammalian species. Avian kidneys are structurally and physically different in several ways from most mammals; including a few nephrons having a loop of Henle, uricotelic nature, and the presence of a renal portal system.25 Additionally, it is unknown if SDMA, compared with asymmetric dimethylarginine, is further metabolized after production in avian species. Future studies should continue to evaluate SDMA and asymmetric dimethylarginine as potential renal markers in various avian species, particularly those that commonly suffer from renal pathology.
Only a narrow range of SDMA concentrations was evaluated in the study (1–15 μg/dL including both testing methodologies). Given that this is the first study to evaluate SDMA in this species, the scope was small and focused on proof of concept. To further assess the analytical validity of the SDMA-IA assay, a method comparison study evaluating samples with SDMA concentrations spanning the measurement interval would be needed. Further, to assess the clinical validity of SDMA measurements, studies using birds with proven natural or induced renal disease will need to be performed. However, the results from this study support that SDMA does circulate in chicken plasma in similar concentrations to other mammals and may be used to advance the understanding of avian renal pathology.
Clinically, most chickens in this study were deemed healthy at the time of blood draw based on physical examinations. Given that renal parameters often used to assess renal health, such as uric acid and Ca:Ph, were within what would be considered normal in laying hens, we have low concern for underlying nephropathies, but cannot rule out that some birds had subclinical renal disease. Future studies should compare healthy chickens confirmed via histology or histopathology to those with confirmed experimental or naturally occurring renal disease and assess the utility of SDMA in these cases.
A limitation of this study is that all birds included were of female sex. While previous studies have shown no association of sex to SDMA values,41 future studies should include both hens and roosters. Similarly, all chickens in this study were adults and of only 2 different breeds. Given that SDMA has been shown to differ amongst breeds of mammalian species,21,41,42 future studies should evaluate SDMA values in various ages and breeds.21,42
Acknowledgments
Drs. Coyne, Drake, Murphy, and Obare are current or previous employees of IDEXX Laboratories, Inc. Drs. Coyne, Drake, and Obare report ownership interest in IDEXX Laboratories Inc.
The authors would like to thank the students of the Wildlife Epidemiology lab for their assistance in data collection and sample processing.
References
- 1.↑
Hall JA, Yerramilli M, Obare E, Yerramilli M, Jewell DE. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. J Vet Intern Med. 2014;28(6):1676–1683. doi:10.1111/jvim.12445
- 2.↑
Hall JA, Yerramilli M, Obare E, Yerramilli M, Almes K, Jewell DE. Serum concentrations of symmetric dimethylarginine and creatinine in dogs with naturally occurring chronic kidney disease. J Vet Intern Med. 2016;30(3):794–802. doi:10.1111/jvim.13942
- 3.↑
Yerramilli M, Farace G, Quinn J, Yerramilli M. Kidney disease and the nexus of chronic kidney disease and acute kidney injury. Vet Clin Small Anim. 2016;46(6):961–993. doi:10.1016/j.cvsm.2016.06.011
- 4.↑
Yerramilli M, Yerramilli M, Obare E, Jewell DE, Hall JA. Symmetric dimethylarginine (SDMA) increases earlier than serum creatinine in dogs with chronic kidney disease (CKD). J Vet Intern Med. 2014;28(3):1084–1085.
- 5.↑
Dahlem DP, Neiger R, Schweighauser A, et al. Plasma symmetric dimethylarginine concentration in dogs with acute kidney injury and chronic kidney disease. J Vet Intern Med. 2017;31(3):799–804. doi:10.1111/jvim.14694
- 6.
Rentko V, Nabity M, Yerramilli M, Obare E, Aguiar J, Relford R. Determination of serum symmetric dimethylarginine reference limit in clinically healthy dogs. J Vet Intern Med. 2013;27(3):750.
- 7.↑
Waugh L, Lyon S, Cole GA, et al. Retrospective analysis and validation of serum symmetric dimethylarginine (SDMA) concentrations in cheetahs (Acinonyx jubatus). J Zoo Wildl Med. 2018;49(3):623–631. doi:10.1638/2017-0056.1
- 8.↑
Lamglait B, Vandenbunder-Beltrame M. Evaluation of symmetric dimethylarginine as an early biomarker of chronic kidney disease in captive cheetahs (Acinonyx jubatus). J Zoo Wildl Med. 2017;48(3):874–877. doi:10.1638/2016-0224.1
- 9.↑
Nabity MB, Lees GE, Boggess MM, et al. 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. doi:10.1111/jvim.12835
- 10.↑
Raulic J, Lamglait B, Vergneau-Grosset C. Use of symmetric dimethylarginine to detect renal lesions in fish: a preliminary study in brook trout (Salvelinus fontalis). J Zoo Wildl Med. 2021;52(3):1024–1029.
- 11.↑
Mota SM, Brandao J, Guthrie A. Comparison of blood symmetric dimethylarginine and creatinine as endogenous markers of kidney function in captive tigers (Panthera tigris). J Zoo Wildl Med. 2021;52(3):628–637.
- 12.↑
Kopke MA, Burchel RK, Ruaux CG, Burton SE, Lopez-Villalobos N, Gal A. Variability of symmetric dimethylarginine in apparently healthy dogs. J Vet Intern Med. 2018;32(2):736–742. doi:10.1111/jvim.15050
- 13.↑
Hamlin DM, Schultze AE, Coyne MJ, et al. Evaluation of renal biomarkers, including symmetric dimethylarginine, following gentamicin-induced proximal tubular injury in the rat. Kidney360. 2021;3(2):341–356. doi:10.34067/KID.0006542020
- 14.↑
Hall JA, MacLeay J, Yerramilli M, et al. Positive impact of nutritional interventions on serum symmetric dimethylarginine and creatinine concentrations in client owned geriatric cats. PLoS ONE. 2016; 11(4):e0153654. doi:10.1371/journal.pone.0153654
- 15.
Schwedhelm E, Boger RH. The role of asymmetric and symmetric dimethylarginines in renal disease. Nat Rev Nephrol. 2011;7(5):275–285. doi:10.1038/nrneph.2011.31
- 16.↑
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. doi:10.1093/ndt/gfl292
- 17.↑
Wang Y, Li C. Evolutionarily conserved protein arginine methyltransferases in non-mammalian animal systems. FEBS J. 2012;279(6):932. doi:10.1111/j.1742-4658.2012.08490.x
- 18.↑
Braff J, Obare E, Yerramilli M, Elliott J, Yerramilli Ml. Relationship between serum symmetric dimethylarginine concentration and glomerular filtration rate in cats. J Vet Intern Med. 2014;28(6):1699–1701. doi:10.1111/jvim.12446
- 19.↑
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. doi:10.1111/jvim.12607
- 20.
Pedersen LG, Tarnow I, Olsen LH, Terrlink T, Pedersen HD. Body size, but neither age nor asymptomatic mitral regurgitation, influences plasma concentrations of dimethylarginines in dogs. Res Vet Sci. 2006;80(3):336–342. doi:10.1016/j.rvsc.2005.07.005
- 21.↑
Moesgaard SG, Holte AV, Mogensen T, et al. Effects of breed, gender, exercise and white-coat effect on markers of endothelial function in dogs. Res Vet Sci. 2007; 82(3):409–415. doi:10.1016/j.rvsc.2006.09.003
- 22.↑
Van Zanten TC, Xie S. Evaluation of symmetric dimethylarginine as an endogenous marker of renal disease in greater flamingos (Phoenicopterus roseus). J Zoo Wildl Med. 2023; 53(4):644–653.
- 23.↑
Lehmann V, Altherr B, Pantchev N, et al. Symmetrical dimethylarginine as a diagnostic parameter in Hermann’s tortoises (Testudo hermanii). Front Vet Sci. 2022; 22:9:824748. doi:10.3389/fvets.2022.824748
- 24.↑
Nemeth NM, Gonzalez-Astudillo V, Oesterle PT, Howerth EW. A 5-year retrospective review of avian diseases diagnosed at the department of pathology, University of Georgia. J Comp Pathol. 2016;155(2–3):105–120. doi:10.1016/j.jcpa.2016.05.006
- 25.↑
Echols MS. Evaluating and treating the kidneys. In: Harrison GJ, Lightfoot TL eds. Clinical Avian Medicine Vol 2. Spix Publishing. 2006:451–492.
- 26.↑
Landman WJ, Gruys E, Gielkens AL. Avian Amyloidosis. Avian Pathol. 1998; 27(5):437–449. doi:10.1080/03079459808419367
- 27.↑
Phelps CA. Laboratory tests. In: Mayer J, Donnelly TM, eds. Clinical Veterinary Advisor: Birds and Exotic Pets. 1st ed. Elsevier; 2013:610–612.
- 28.↑
Manley C. Laboratory tests, phosphorus. In: Mayer J, Donnelly TM, eds. Clinical Veterinary Advisor: Birds and Exotic Pets. 1st ed. Elsevier; 2013:636–637.
- 29.↑
Hersey-Benner C. Laboratory tests, uric acid. In: Mayer J, Donnelly TM, eds. Clinical Veterinary Advisor: Birds and Exotic Pets. 1st ed. Elsevier; 2013:649–650.
- 30.↑
Kuge R, Morikawa Y, Hasegawa Y. Uric acid and dehydration in children with gastroenteritis. Pediatr Int. 2017;59(11):1151–1156. doi:10.1111/ped.13366
- 31.
Lin ZJ, Zhang B, Liu XQ, Yang HL. Abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model induced by high fat diet. Chin Med Sci J. 2009;24(3):191–194. doi:10.1016/S1001-9294(09)60088-2
- 32.↑
Marshall KL, Craig LE, Jones MP, Daniel GB. Quantitative renal scintigraphy in domestic pigeons (Columba livia domestica) exposed to toxic doses of gentamicin. Am J Vet Res. 2003;64(4):453–462. doi:10.2460/ajvr.2003.64.453
- 33.
Wimsatt J, Canon N, Pearce RD, Vap LM, Getzy DM. Assessment of novel avian disease markers for the detection of experimental nephrotoxicosis in pigeons (Columba livia). J Zoo Wildl Med. 2009;40(3):487–494. doi:10.1638/2008-0169.1
- 34.
Scope A, Schwendenwein I, Schauberger G. Plasma exogenous creatinine excretion for the assessment of renal function in avian medicine – pharmacokinetic modeling in racing pigeons (Columba livia). J Avian Med Surg. 2013;27(3):173–179. doi:10.1647/2012-015
- 35.↑
Wimsatt J, Pearce R, Steyn PF, Vap L, Glover DK. Comparative renal disposition of creatine, and technetium diagnostic contract agents in the pigeon (Columba livia). J Zoo Wildl Med. 2020;50(4):891–896. doi:10.1638/2018-0214
- 36.↑
Gasthuys E, Montesinos A, Caekebeke N, et al. Comparative physiology of glomerular filtration rate by plasma clearance of exogenous creatinine and exo-iohexol in six different avian species. Sci Rep. 2019;9(1):19699. doi:10.1038/s41598-019-56096-5
- 37.↑
Friedrichs KR, Harr KE, Freeman KP, et al. ASVCP reference interval guidelines: determination of de novo reference intervals in veterinary species and other related topics. Vet Clin Pathol. 2012;41(4):441–453. doi:10.1111/vcp.12006
- 38.↑
Kaiser JC, Reider H, Pabilonia KL, Moore AR. Establishment of biochemical reference values for backyard chickens in Colorado (Gallus gallus domesticus). Vet Clin Pathol. 2022; 51: 577–584. doi:10.1111/vcp.13136
- 39.↑
Gregory N, Robins JK. A body condition scoring system for layer hens. New Zealand J Agric Res. 1998;41(4):555–559. doi:10.1080/00288233.1998.9513338
- 40.↑
Ernst R, Ogeer J, McCrann D, et al. Comparative performance of IDEXX SDMA test and the DLD SDMA ELISA for the measurement of SDMA in canine and feline serum. PLoS ONE. 2018; 13(10): e0205030. doi:10.1371/journal.pone.0205030
- 41.↑
Siwinska N, Zak A, Slowikowska M, Niedzwiedz A, Paslawska U. Serum symmetric dimethylarginine concentration in healthy horses and horses with acute kidney injury. BMC Vet Res. 2020;16(1):396. doi:10.1186/s12917-020-02621-y
- 42.↑
Coyne M, Szlosek D, Clements C, McCarnn D 3rd, Olavessen L. Association between breed and renal biomarkers of glomerular filtration rate in dogs. Vet Rec. 2020;187(10):e82. doi:10.1136/vr.105733
