Table 2.

List of studies on symmetric dimethylarginine (SDMA) concentrations in blood in horses and its analytical and clinical characteristics.

	Study	Assay Used	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	Lo, H.C., Winter, J.C., Merle, R., Gehlen, H. Symmetric dimethylarginine and renal function analysis in horses with dehydration. Equine Vet J. 10 June 2021 [19].	DLD SDMA ELISA kit (DLD Diagnostika GmbH) (validated by [16])	41 horses with dehydration	1 with AKI for 48 h, 1 with AKI for 12 h	Good correlation with creatinine, not with urea	Dehydration severity AKI: SDMA elevated 2 cases with normal creatinine but with elevated SDMA (subclinical AKI?) Lower in survivors than non-survivors, but not statistical	Phase II	n/a	Dehydration	Limited AKI cases
2	Bozorgmanesh, R., Thornton, J., Snyder, J., Fletcher, C., Mack, R., Coyne, M., Murphy, R., Hegarty, E., Slovis, N. Symmetric dimethylarginine concentrations in healthy neonatal foals and mares. J Vet Intern Med. 2021 Nov;35(6):2891–2896 [20].	IDEXX SDMA high throughput immunoassay (validated by [15])	104 healthy periparturient TB mares (last month of gestation) and 125 their full-term foals (first month of life)	0	SDMA higher than adult values during first month; creatinine only for the first 12 h after birth	n/a	n/a	Birth 0–100 microgr/dL; 1–4 days old 0–85 microgr/dL; 5–10 days old 0–36 microgr/dL; 20–30 days old 0–24 microgr/dL; mares <14 microgr/dL	No correlation between mare SDMA and foal SDMA	Upper limit assay 100 microgr/dL
3	Gough, R.L., McGovern, K.F. Serum symmetric dimethylarginine concentration in healthy neonatal Thoroughbred foals. Equine Vet J. 2021 [21].	IDEXX ELISA (presumably the same as validated [15])	120 healthy neonatal TB foals <36 h	0	Correlation with creatinine and urea	n/a	n/a	<168 microgr/dL	Correlation with age, no difference between sexes	No consideration of subclinical disease
4	Ertelt, A., Stumpff, F., Merle, R., Kuban, S., Bollinger, L., Liertz, S., Gehlen, H. Asymmetric dimethylarginine-A potential cardiac biomarker in horses. J Vet Cardiol. 2021 Feb;33:43–51 [14].	Commercial human ELISA & cross checked with liquid chromatograph triple quadrupole mass spectrometry	78 adult horses with unknown medical history, 23 adult horses with confirmed structural cardiac disease	0	n/a	No difference between horse with or without cardiac disease	(Phase I) Phase II	0.3–0.8 micromol/L	n/a	No information on kidney status
5	Schott, H.C., 2nd, Gallant, L.R., Coyne, M., Murphy, R., Cross, J., Strong-Townsend, M., Szlosek, D., Yerramilli, M., Li, J. Symmetric dimethylarginine and creatinine concentrations in serum of healthy draft horses. J Vet Intern Med. 2021 Mar;35(2):1147–1154 [15].	Immunoassay IDEXX, added to an automated multichannel chemistry analyzer allowing high throughput, compared to liquid chromatography-mass spectroscopy	165 healthy adult (>0.5 years old) draft horses	1 AKI (or dehydration), 7 elevated SDMA with normal—mild increased creatinine	Correlated to creatinine, not to urea nitrogen	n/a	Phase I	Draft horses <14 microgr/dL	Age: no correlation Sex: no difference Breed: lower in Percherons and Belgians than in Percherons Weight or BCS: no correlations
6	Siwinska, N., Zak, A., Paslawska, U. Detecting acute kidney injury in horses by measuring the concentration of symmetric dimethylarginine in serum. Acta Vet Scand. 2021 Jan 15;63(1):3 [18].	Enzyme immunoassay (EIA) on the Beckmann Coulter analyzer (IDEXX) (mentioned to be validated by [17])	30 healthy adult horses, 30 horses in risk group (with gastro-intestinal disease and/or receiving PBZ/gentamicin), 11 horses with AKI	11 AKI	Correlated to creatinine and urea, SG and urinary protein.	Health category: SDMA comparable between healthy and at risk, but increased in AKI. At risk group showed no increase in SDMA but increase in traditional renal values (urinary protein and urinary protein/cr ratio and urinary GGT/creatinine ratio) -> limited use of SDMA in subclinical cases	Phase II	<19 microgr/dL	n/a
7	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 Oct 20;16(1):396 [16].	Commercially available and non-species specific enzyme imunoassay ELISA kit (DLD Diagnostika GmbH) from Labor der SYNLAB vet GmHb (Ausburg, Germnay)—validation info in supplementary data)	53 healthy horses (17 2–6 month old foals and 36 adults) and 23 horses with AKI	23 AKI	Correlated with creatinine	AKI: higher than healthy	Phase I (validation in supplementary data) Phase II	Healthy foals 1.5 ± 0.4 micromol/L healthy adults 0.53 ± 0.14 micromol/L	Age: higher in foals, no effect in adults Sex: no effect Body weight: no effect
8	Ertelt, A., Merle, R., Stumpff, F., Bollinger, L., Liertz, S., Weber, C., Gehlen, H. Evaluation of Different Blood Parameters From Endurance Horses Competing at 160 km. J Equine Vet Sci. 2021 [13].	Commercially available fast ELISA run by DLD Gesellschaft fur Diagnostika und medizinische Gerate mbH, Hamburg, Germany—validated	52 healthy endurance horses—finishers versus non-finishers	0	n/a	Pre vs. post-race	Phase I—validation info provided Phase II	Before racing all in ref range of 0.3–0.8 micromol/L	Exercise and finishing endurance: SDMA higher after the race in finishers (7 above ref range) Distance: more increased SDMA with longer distance
9	Frączkowska, K., Trzebuniak, Z., Żak, A., Siwińska, N. Measurement of Selected Renal Biochemical Parameters in Healthy Adult Donkeys Considering the Influence of Gender, Age and Blood Freezing. Animals. 2021 Jun 11;11(6):1748 [17].	Validated enzyme immunoassay performed on a Beckman Coulter analyzer (USA)	65 healthy adult donkeys	0	n/a	n/a	No analytical validation data available in study, but mentioned to be validated	<14 microgr/dL	Freezing and storing for 1 year: no effect Sex: no effect Age: no effect

Legend: AKI—acute kidney injury; CKD—chronic kidney disease; SDMA—symmetric dimethylarginine; ELISA—enzyme linked immunosorbent assay; SG—specific gravity. References: [13,14,15,16,17,18,19,20,21].