Serum Symmetric Dimethylarginine Concentrations Research Articles

Comparison of serum SDMA and creatinine as a biomarker for the detection of meloxicam-induced kidney injury in cats.

Serum symmetric dimethylarginine (SDMA) and creatinine are commonly used biomarkers of renal function in cats. We hypothesize that the serum analytes creatinine and SDMA are equally effective at detecting impaired renal function caused by meloxicam-induced renal injury in cats. Our primary objective was to compare serum concentrations of SDMA and creatinine in cats before, during, and after induction of renal injury from repeated dosages of meloxicam in the context of a small pilot study. This follow-up study results from data collected in a well-controlled study that included 12 healthy female adult purpose-bred cats. Cats in the treatment group received meloxicam 0.3 mg/kg subcutaneously (SC) every 24 h for 31 days. Cats in the control group received saline (0.1 mL SC). Renal injury was defined as the presence of tubular damage, basement membrane damage, and/or interstitial inflammation in histological sections of kidney tissue. Serum creatinine and SDMA concentration were measured every 4 days. In the control group, no cats developed renal azotemia. In the treatment group, four out of six cats developed elevated serum creatinine and histopathological evidence of renal injury. Three of these cats developed an elevation in serum SDMA. The time to the development of renal azotemia using serum creatinine or SDMA was not significantly different (p > 0.05). In this pilot study, there was no evidence that serum SDMA was superior to serum creatinine at detecting impaired renal function caused by meloxicam-induced renal injury in cats.

Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4–132.6; 79.2–114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5–12; 7–9]; sCr, 57.2 µmol/L [35.2–212.2; 52.8–92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7–13; 8–10]; sCr, 70.4 µmol/L [61.6–79.2; 61.6–70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

Serum symmetric dimethylarginine in older dogs: Reference interval and comparison of a gold standard method with the ELISA.

Serum symmetric dimethylarginine (SDMA) is used to screen for renal dysfunction in dogs. The gold standard technique for measuring SDMA, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is not widely available. Age-specific reference intervals for SDMA in older dogs are lacking. Prospective study in older dogs to validate a commercially available LC-MS/MS method for SDMA, compare SDMA concentrations with concentrations measured using ELISA and obtain a reference interval (RI) for older dogs using both methods. Client-owned older dogs undergoing health screening. The LC-MS/MS method was analytically validated (limit of detection, precision, and linearity). Serum was sent cooled overnight for ELISA or was frozen at -80°C until batch analysis using LC-MS/MS. Results of LC-MS/MS and ELISA were compared and RIs for older dogs were calculated according to international guidelines. The LC-MS/MS method showed good linearity (r2 = .99) and precision (coefficient of variation <10%), with a laboratory RI between 8.0 and 14.0 μg/dL. Paired measurements were available from 118 different dogs. Median SDMA concentration were 9.4 (range, 5.0-21.2) using LC-MS/MS and 12.0 (range, 5.0-22.0) μg/dL using ELISA. Both methods significantly differed with a mean difference of 2.2 μg/dL. The RI for older dogs for LC-MS/MS was 4.4-15.0 μg/dL, and for ELISA was 6.4-17.4 μg/dL. The ELISA provided significantly higher SDMA concentrations compared to the validated LC-MS/MS method, indicating the need for device- or assay-specific RI. The obtained age-specific RI for SDMA is considerably higher in older dogs compared to the general laboratory RI.

Effect of storage temperature and time on measurement of serum symmetric dimethylarginine concentration using point-of-care and commercial laboratory analyzers in cats and dogs.

Stability of serum symmetric dimethylarginine (sSDMA) during short- and long-term storage has not been assessed for the immunoassay of the Point-of-Care IDEXX Catalyst DX (POC) analyzer and the Enzyme Multiplied Immunoassay Technique of IDEXX commercial laboratory (CL). Also, the agreement between both analyzers is questioned. To determine (a) the effect of storage time and temperature on sSDMA measured by POC and CL; (b) the agreement between sSDMA measured by POC and CL; and (c) the imprecision of the POC. Serum of cats (n = 17) and dogs (n = 18) with a range of SDMA concentrations (6 to >100 μg/dL). Based on an equivalence trial with predefined equivalence range (-3.0 to +3.0 μg/dL) and using T0 as baseline, stability was evaluated after 24 hours at 22°C and 4°C (POC); after 7 days at 4°C (POC and CL) and after 10 and 24 months at -24°C and -80°C (CL). Bland-Altman plots enabled method comparison. Imprecision of the POC was assessed by duplicate sSDMA measurements at T0. The POC analyzer produced equivalent sSDMA measurements if samples were stored for 24 hours at 4°C (95% confidence interval [CI]: -2.5-2.0 μg/dL), but not when stored for 24 hours at room temperature (RT; 95% CI: -4.1 to 0.5 μg/dL) or after 7 days at 4°C (95% CI: -3.6-1.0 μg/dL). The CL analyzer was less affected by preanalytical variation with clinically similar results obtained when samples were stored for 7 days at 4°C (95% CI: -2.2 to 2.4 μg/dL) and for at least 24 months at -24°C (95% CI: -1.7 to 2.9 μg/dL) and -80°C (95% CI: -1.5 to 3 μg/dL). A relevant mean difference of -2.3 μg/dL between both analyzers was found. Duplicate POC measurements were equivalent (95% CI: -2.6 to 2.0 μg/dL). Delayed analysis may significantly change sSDMA depending on storage and measurement conditions. Interchangeable use of assays should be done with caution because analytical variation could be interpreted as clinically relevant change.

Evaluation of renal values during treatment for heartworm disease in 27 client-owned dogs

BackgroundCanine heartworm disease (CHD) caused by Dirofilaria immitis remains a common preventable disease with increasing incidence in some parts of the USA. The treatment guidelines of the American Heartworm Society (AHS) currently recommend monthly macrocyclic lactone administration, 28 days of doxycycline given orally every 12 h and three injections of melarsomine dihydrochloride (1 injection on day 2 of treatment followed 30 days later by 2 injections 24 h apart). Minocycline has also been utilized when doxycycline is unavailable. The systemic effects of CHD, which particularly impact cardiac and renal function, have been described, with infected dogs often experiencing renal damage characterized by an increase in serum concentrations of renal biomarkers. Although the AHS treatment protocol for CHD has been shown to be safe and effective in most cases, the potential for complications remains. No study as of yet has evaluated changes in symmetric dimethylarginine (SDMA), a sensitive marker of renal function, during treatment for CHD. The purpose of the present study was to evaluate renal function in dogs by measuring serum creatinine and SDMA concentrations during the adulticide treatment period.MethodsSerum creatinine and SDMA concentrations were measured in 27 client-owned dogs affected by CHD at the following time points: prior to starting doxycycline or minocycline therapy (baseline), during doxycycline or minocycline therapy (interim), at the time of the first dose of melarsomine (first dose), at the time of the second dose of melarsomine (second dose) and at the dog’s follow-up visit after treatment, occurring between 1 and 6 months after completion of therapy (post-treatment). Concentrations of creatinine and SDMA were compared between time points using a mixed effects linear model.ResultsMean SDMA concentrations following the second dose of melarsomine were significantly lower (−1.80 ug/dL, t-test, df = 99.067, t = −2.694, P-Value = 0.00829) than baseline concentrations. There were no other statistically significant differences in the concentration of either biomarker between the baseline and the other time points in CHD dogs undergoing treatment.ConclusionsThe results suggest that the current AHS protocol may not have a substantial impact on renal function.Graphical

Association of serum ADMA, SDMA and L-NMMA concentrations with disease progression in COVID-19 patients.

This study determines and compares the concentrations of arginine and methylated arginine products ((asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), n-monomethyl-1-arginine (L-NMMA) and homoarginine (HA)) for assessment of their association with disease severity in serum samples of COVID-19 patients. Serum arginine and methylated arginine products of 57 mild-moderate and 29 severe (N = 86) COVID-19 patients and 21 controls were determined by tandem mass spectrometry. Moreover, the concentrations of some of the routine clinical laboratory parameters -neutrophil lymphocyte ratio (NLR), C-reactive protein, ferritin, D-dimer, and fibrinogen measured during COVID-19 follow-up were also taken into consideration and compared with the concentrations of arginine and methylated arginine products. Serum ADMA, SDMA and L-NMMA were found to be significantly higher in severe COVID-19 patients, than in both mild-moderate patients and the control group (P < 0.001 for each). In addition, multiple logistic regression analysis indicated L-NMMA (cut-off =120 nmol/L OR = 34, 95% confidence interval (CI) = 3.5-302.0, P= 0.002), CRP (cut-off = 32 mg/L, OR = 37, 95% CI = 4.8-287.0, P < 0.001), and NLR (cut-off = 7, OR = 22, 95% CI = 1.4-335.0, P = 0.020) as independent risk factors for identification of severe patients. The concentration of methylated arginine metabolites are significantly altered in COVID-19 disease. The results of this study indicate a significant correlation between the severity of COVID-19 disease and concentrations of CRP, NLR and L-NMMA.

Outcome of Acquired Fanconi Syndrome Associated with Ingestion of Jerky Treats in 30 Dogs.

Acquired canine proximal renal tubulopathy (Fanconi syndrome) related to excessive ingestion of jerky treats has been recognized since 2007. This study aimed to improve knowledge about the syndrome's characteristics, especially long-term outcome. By reaching out to veterinarians and dog owners, dogs suspected of jerky induced Fanconi syndrome were identified. The dog's medical records were reviewed, and owners interviewed. Data was analyzed using linear mixed models (p &lt; 0.05 was considered statistically significant) and descriptive statistics are reported. Thirty dogs, median body weight 6.8 (range 1.2-59) kg and age 6.5 (0.5-14) years, were enrolled as suspected cases based on history of jerkey ingestion and confirmed normoglycemic/hypoglycemic glycosuria. Clinical signs included polydipsia (23/30), polyuria (21/30), lethargy (19/30), weight loss (15/30), hyporexia (11/30), vomiting (7/30), diarrhea (7/30) and no clinical signs (2/30). Para-clinical findings included azotemia (6/28), hypophosphatemia (9/25), metabolic acidosis (3/8), hypokalemia (6/20), proteinuria (13/26), aminoaciduria (4/4), hematuria (22/29) and ketonuria (7/27). Clinical signs resolved in 22/28 within 11 (0.3-52) weeks and glycosuria resolved in 28/30 within 6.5 (1-31) weeks. There were no associations between serum creatinine and urea and the amount/duration of jerky ingestion. Serum symmetric dimethylarginine concentrations were only available for a few dogs, therefore no conclusion was achieved on a possible association with duration of jerky ingestion. Apart from a larger percentage of dogs achieving complete recovery, the current findings are in agreement with previous reports.

Symmetric Dimethylarginine is a Promising Biomarker for the Early Detection of Age-Related Kidney Dysfunction in Zoo Felids

Abstract Chronic renal failure is one of the leading causes of death in African lions, cheetahs, and tigers. Conventional methods to measure renal dysfunction include measuring serum creatinine and blood urea nitrogen (BUN). Symmetric dimethylarginine (SDMA) measurement is a reliable predictor of renal dysfunction in the domestic cat because SDMA serum levels increase early when the kidneys are damaged. Serum SDMA levels were assessed and correlated with creatinine as well as BUN from healthy captive Bengal tigers and lions at the Everland Zoo in Korea. Serum SDMA concentrations were increasingly associated with increased age in lions. However, SDMA concentrations were higher in some young Bengal tigers than in older ones, which may allow for earlier renal dysfunction detection in these young cats than would be BUN and creatinine alone. In Bengal tigers, the correlation between the SDMA and BUN was slightly higher than that between SDMA and creatinine. In lions, SDMA correlated better with creatinine than with BUN concentration. These results show that serum SDMA concentration can be used as a biomarker for age-associated renal dysfunction. SDMA measurement may be an essential preventive management method in zoos.

Evaluation of symmetric dimethylarginine in cats with acute kidney injury and chronic kidney disease.

BackgroundSerum symmetric dimethylarginine (SDMA) concentrations are considered a biomarker for renal dysfunction in dogs and humans with acute kidney injury (AKI). No studies have assessed SDMA in cats with AKI.Hypothesis/ObjectivesSDMA correctly identifies cats with azotemic AKI.AnimalsFifteen control cats, 22 with novel AKI, 13 with acute on chronic‐AKI (AoC) and 19 with chronic kidney disease (CKD).MethodsRetrospective study. Cats with azotemia (serum creatinine concentrations >1.7 mg/dL) were defined as having AKI or CKD based on history, clinical signs, clinicopathological findings and diagnostic imaging, and classified using the International Renal Interest Society (IRIS) grading/staging systems. Serum SDMA concentrations were compared between groups with nonparametric methods, and correlations assessed using Spearman's correlation coefficient. Data are presented as median [range].ResultsSDMA concentrations were 11 (8‐21) μg/dL, 36 (9‐170)μg/dL, 33 (22‐75) μg/dL and 25 (12‐69) μg/dL in control, novel AKI, AoC and CKD cats. SDMA concentrations were significantly higher in cats with novel AKI (P < .001), AoC (P < .001) and CKD (P < .01) compared to controls. SDMA concentrations were significantly higher in cats with more advanced AKI (IRIS grade IV‐V) compared to less severe AKI (IRIS grade II). Serum creatinine and SDMA concentrations had a significant correlation in cats with novel AKI (r s = 0.826, n = 22; P < .001) and a significant correlation when all cats across all 4 groups were considered together (r s = 0.837, n = 69; P < .001).Conclusions and Clinical ImportanceSerum SDMA concentrations are elevated in cats with established AKI (novel and AoC) and CKD, providing evidence for use of SDMA as a biomarker for AKI in cats.

Short course of immune-suppressive doses of prednisolone, evaluated through a prospective double-masked placebo-controlled clinical trial in healthy Beagles, is associated with sustained modifications in renal, hydration, and electrolytic status.

To investigate the effects and duration of orally administered prednisolone on renal function evaluated by glomerular filtration rate (GFR) determination and creatinine (Cr) and symmetric dimethylarginine (SDMA) concentrations as well as on urinalysis, electrolytes, and hydric status in healthy dogs. 14 healthy Beagles. In this prospective double-masked placebo-controlled study, dogs were randomized after baseline evaluation to receive a 7-day course of either prednisolone (1.5 to 2.0 mg/kg, PO, q 12 h) or a placebo. A repeated-measure design was performed, each dog participating in 4 successive sampling sessions. Clinical data, systolic blood pressure, CBC, and biochemical analyses including serum SDMA concentration, GFR determination, urine output quantification, and complete urinalysis were performed for all dogs the day before (D0) and at the end of steroid administration (D7) as well as 2 weeks (D21) and 4 weeks (D35) after the end of treatment. At D7, when compared with baseline, GFR increased significantly in treated dogs, whereas creatinine and SDMA concentrations decreased significantly. GFR and Cr but not SDMA modifications persisted significantly at D21. None of the variables differed significantly from baseline at D35. The OR of presenting an albumin band on urine electrophoresis was 2.4 times as high in treated versus control dogs (OR, 36; 95% CI, 1.8 to 719.4; P = 0.02). A short-term course of immune-suppressive prednisolone treatment in healthy dogs leads to a sustained but reversible renal hyperfiltration state. Modification in electrolytic variables can affect the clinical interpretation of blood work in such patients.

Renal biomarkers in cats: A review of the current status in chronic kidney disease.

Serum creatinine concentration, the classical biomarker of chronic kidney disease (CKD) in cats, has important limitations that decrease its value as a biomarker of early CKD. Recently, serum symmetric dimethylarginine concentration was introduced as a novel glomerular filtration rate biomarker for the early detection of CKD in cats. However, data on its specificity are still limited. The limitations of conventional biomarkers and the desire for early therapeutic intervention in cats with CKD to improve outcomes have prompted the discovery and validation of novel renal biomarkers to detect glomerular or tubular dysfunction. Changes in the serum or urinary concentrations of these biomarkers may indicate early kidney damage or predict the progression of kidney before changes in conventional biomarkers are detectable. This review summarizes current knowledge on renal biomarkers in CKD in cats, a field that has progressed substantially over the last 5 years.

Assessment of serum symmetric dimethylarginine and creatinine concentrations in cats with urethral obstruction.

The aims of this study were to evaluate serum symmetric dimethylarginine (SDMA) and creatinine concentrations in cats with urethral obstruction pre- and post-decompression of the obstruction, and to determine if pre-decompression values were predictive of post-decompression renal function, as measured by SDMA and creatinine. This was a prospective observational study. Twenty-five client-owned cats with urethral obstruction were hospitalized for decompression of the obstruction. Serum SDMA and creatinine were prospectively assessed at presentation, 24 h post-decompression and 5-20 days post-decompression. Urinalysis and culture were assessed at presentation and at the final follow-up. Exclusion criteria included positive urine culture, reobstruction or failure to obtain required samples. Mean SDMA concentration dropped by 41.8% from an initial pre-decompression concentration of 17.6 µg/dl to 10.3 µg/dl 24 h post-decompression (P <0.001). The mean creatinine value dropped by 38.4% from an initial pre-decompression concentration of 2.5 mg/dl to 1.5 mg/dl 24 h post-decompression (P <0.001). There was no association between SDMA concentration at initial presentation and SDMA concentration 5-20 days after urethral catheterization (Spearman's ρ = 0.205, P = 0.314). Creatinine concentration upon initial presentation was associated with the 5-20 day values after urethral catheterization (Spearman's ρ = 0.583, P <0.002). Twenty percent of cases were excluded due to bacterial growth on initial urine culture. SDMA and creatinine concentrations were significantly higher in these cases (median 59 µg/dl and 10.9 mg/dl, respectively) compared with those with negative cultures (median 14 µg/dl and 1.6 mg/dl [P <0.002 and P <0.001], respectively). Both SDMA and creatinine decreased significantly after urethral catheterization, suggesting that renal function post-decompression cannot be predicted by the pre-decompression concentrations of these values.

Serum symmetric dimethylarginine concentration in healthy neonatal Thoroughbred foals.

Symmetric dimethylarginine (SDMA) is widely used in other species as a marker of renal dysfunction and is considered a more sensitive indicator of glomerular filtration rate than creatinine. Reference ranges are established in healthy adult horses (≤14μg/dL) and concentrations are increased in horses with acute kidney injury (median 32μg/dL; range 15-92). To establish the normal range of SDMA concentrations in neonatal Thoroughbreds. Cross-sectional. Blood samples were collected from Thoroughbred foals <36h old deemed healthy by physical examination. Exclusion criteria included foals from mares undergoing treatment for placentitis and foals that developed clinical disease or died/euthanised <2weeks from birth. Biochemistry and serum SDMA concentrations were obtained. Subjects included 120 foals. Median age was 13.5h (range 1.0-34.0). Median and 95% confidence interval for SDMA concentration was 69.0µg/dL (63.0, 75.0; range 35.0-376.0). A cut-off value of 168µg/dL would include 95% of individuals and is therefore suggested. Serum SDMA concentration was correlated with age (R=-.3, P=.003), creatinine concentration (R=.6, P≤.001) and urea concentration (R=.3, P=.002). Limitations include a small sample size, no consideration of subclinical disease and a short follow-up period. In equine neonates, SDMA concentration is higher than in adult horses, older foals and adults with acute kidney injury. Therefore, currently SDMA cannot be used as a marker of renal dysfunction in this age group. Further work is required to assess whether SDMA concentration is increased in neonates with renal disease and, if so, what cut-off should be used.

Evaluation of Urinary Clusterin and Cystatin B as Biomarkers for Renal Injury in Dogs Envenomated by the European Adder (Vipera berus)

Dogs are commonly bitten by the European adder (Vipera berus) but studies investigating the effects of envenomation are limited. Snakebite-related kidney injury is reported in dogs but diagnosis of acute kidney injury (AKI) might be limited by the insensitivity of routinely used renal function biomarkers. The aim of this study was to evaluate novel biomarkers of renal injury (urinary cystatin B and urinary clusterin) and biomarkers of renal function (serum creatinine and serum symmetric dimethylarginine), and urine protein to creatinine ratio in dogs envenomated by V. berus. Biomarkers were measured at presentation (T1), 12 hours (T2), 24 hours (T3), 36 hours (T4), and 14 days (T5) after snakebite and compared to a group of healthy control dogs. A secondary aim was to investigate the association between biomarker concentrations and severity of clinical signs of envenomation using a snakebite severity score (SSS). Urinary cystatin B concentrations were significantly higher at all timepoints in envenomated dogs compared to controls (P < .010), except for T5 (P = .222). Absolute urinary clusterin concentrations were not significantly different to controls at any timepoint. Compared to controls, serum creatinine and serum symmetric dimethylarginine concentrations were significantly lower in envenomated dogs at T1-T4 (P < .036) and T2-T4 (P < .036), respectively. Urine protein to creatinine ratio was higher in envenomated dogs compared to controls at T2 and T3. Urinary cystatin B concentrations at T1 were correlated with SSS (Spearman's ρ = 0.690, P < .001). The increased urinary cystatin B concentrations observed in dogs envenomated by V. berus in comparison to controls may indicate renal tubular injury in these patients.

Symmetric dimethylarginine and renal function analysis in horses with dehydration.

Acute dehydration caused by a variety of diseases in horses can lead to acute kidney injury. However, current renal biomarkers usually indicate renal damage late in the course of the disease. A novel biomarker would be helpful to diagnose renal disease earlier. (1) To estimate the correlation of serum symmetric dimethylarginine (SDMA) concentrations with the degree of dehydration, traditional renal biomarkers and renal function analysis, and (2) to determine the value of SDMA as a prognostic and early biomarker of renal injury in horses. Prospective cohort. Serum SDMA, creatinine and urea concentrations and renal function analysis were measured in 41 horses with dehydration at 4 time points until 48h after admission. Horses were grouped according to their dehydration level into mildly, moderately and severely dehydrated groups. Serum SDMA concentrations at admission correlated with creatinine concentrations (r=.412, P<.001). Differences in SDMA concentrations at admission were detected among dehydration levels but not between survivors and nonsurvivors. Significant correlations of SDMA concentrations with other markers of renal function analysis and short-term outcome were not observed. Besides the small sample size and low statistical power, missing urine samples at specific time points were also 1 of the main limitations. Only 1 of the horses developed acute kidney injury, which made the evaluation of the predictive value of SDMA difficult. SDMA concentrations correlated significantly with creatinine concentrations in dehydrated horses. Further research is needed to reveal the application of SDMA in horse.

Serum Symmetric Dimethylarginine Concentration in Greyhound Pups and Adults

Greyhounds have developed numerous physiologic and hematologic adaptations specific to the breed. Adult Greyhounds have significantly higher serum creatinine (sCr) concentrations than non-Greyhound dogs; this is primarily attributed to their large muscle mass. Adult Greyhounds also have significantly higher symmetric dimethylarginine (SDMA) concentrations than non-Greyhound dogs. In this study we evaluated serum SDMA and sCr concentrations in 48 Greyhound pups from 11 litters, with no exposure to racing, in order to determine if the higher SDMA or sCr concentration in adults is a breed-related trait or is associated with extra-physiological causes (e.g., racing environment, drug administration, etc.). The distribution of SDMA concentration for all the pups (mean: 0.70 µmol/L; 95% CI: 0.70-0.74 µmol/L) was not statistically different from that found in a group of 183 adult Greyhounds; whereas, distribution of sCr concentration in the pups (mean: 76.9 µmol/L; 95% CI: 70.7-83.1 µmol/L) was significantly different than that observed in adult Greyhounds, suggesting that the 2 samples were drawn from different populations. This study provides evidence to support that the higher serum SDMA concentration in Greyhounds is a breed-related trait.

Altered methylarginine levels after surgery in subjects with multinodular goiter.

Thyroid disorders are important risk factor for cardiovascular diseases. Levels of methylarginines such as asymmetric dimethyl arginine (ADMA), L-monomethyl arginine (L-NMMA), symmetric dimethyl arginine (SDMA) are increase in cardiovascular diseases. Multinodular goiter (MNG) is the most common type of goiter in adults. To date, no study has been conducted to determine the levels of methylarginine in euthyroid MNG patients. Our aim in this study is to compare levels of methylarginines and related metabolites in the preoperative, postoperative MNG patients and controls. Serum ADMA, SDMA, L-NMMA, homoarginine (hArg), arginine and citrulline concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). ADMA (p<0.001), L-NMMA (p=0.002), l-arginine (p=0.006) and citrulline (p<0.001) levels were statistically significantly higher in preop group than postop group. ADMA (p=0.003), L-NMMA (p=0.003) levels were statistically significantly higher and SDMA/ADMA (p<0.001), hArg/ADMA (p<0.001) levels were statistically significantly lower in preop group than control group. The levels of methylarginines and related metabolites altered in the euthyroid MNG patients compared to the control group, and more importantly, there were significant differences between the preop and postop groups. Therefore, these metabolites can be useful in the diagnosis and prognosis of thyroid disorders, even if thyroid hormone levels are normal.

Serum symmetric dimethylarginine shows a relatively consistent long-term concentration in healthy dogs with a significant effect of increased body fat percentage.

Symmetric dimethylarginine (SDMA) is a promising renal marker that correlates well with the glomerular filtration rate and could allow earlier detection of impaired renal function. The main objectives of this study were to assess the long-term variability of SDMA in healthy dogs and examine the influence of an increased body fat percentage on the level of SDMA. Sixteen lean Beagles were randomly assigned to the control group or weight-change group in age- and gender-matched pairs. The energy intake of the control group (n = 8) was strictly regulated to maintain an ideal body weight for 83 weeks, while the weight-change group (n = 8) was fed to induce weight gain (week 0–47), to maintain stable excessive body weight (week 47–56) and to lose weight (week 56–83), consecutively. At 8 specified time points, the body condition score, body composition, glomerular filtration rate, serum concentration of SDMA and creatinine were analyzed. In the control group, the within-subject coefficient of variation, between-subject coefficient of variation, reference change value (type I error = 5%) and index of individuality were 0.16, 0.22, 0.43 and 0.73, respectively. The control group and weight-change group did not differ significantly in SDMA concentration. SDMA showed a significant negative association (coefficient = -0.07) with body fat percentage (p<0.01) in the weight-change group and a significant positive association (coefficient = 7.79) with serum creatinine (p<0.01) in the entire study population. In conclusion, SDMA concentration has high long-term stability in healthy adult dogs. For the evaluation of SDMA concentrations, subject-specific reference values are preferred over a population-based reference value seen their higher sensitivity. Moreover, an increased body fat percentage does seem to affect the serum SDMA concentration of otherwise healthy dogs, but its clinical relevance has to be clarified in further research.

Detecting acute kidney injury in horses by measuring the concentration of symmetric dimethylarginine in serum

BackgroundAcute kidney injury (AKI) in horses may develop as a complication of a primary disease or following the administration of nephrotoxic drugs, and may pose a diagnostic challenge. Hence, the main objective of this study was to evaluate the concentrations and diagnostic significance of serum symmetric dimethylarginine (SDMA) and conventional renal dysfunction biomarkers in healthy horses, horses at risk of developing AKI, and horses with clinically evident AKI. A second aim was to assess how gastrointestinal disease and exposure to potentially nephrotoxic drugs affected SDMA levels. Thirty healthy horses, 30 horses with gastrointestinal disease and/or receiving phenylbutazone or gentamicin (risk group) and 11 horses with AKI were included in the study. Serum SDMA levels were measured using commercially available enzyme immunoassay tests.ResultsSDMA levels in healthy horses, horses at risk of AKI and horses with AKI were 12 µg/dL (11–14), 12 µg/dL (11–13) and 20 µg/dL (20–37), respectively (all results presented as a median (quartile 1–quartile 3)). There was a significant difference in SDMA concentration between the healthy horses and those with AKI, whereas the SDMA levels in healthy horses and those at risk of AKI were comparable. A SDMA cut-off value of 19 µg/dL was established. Horses from the risk group had higher urine protein concentration and urine protein to creatinine ratio compared with healthy horses. Furthermore, horses with colic from the risk group presented with elevated urine γ-glutamyl transpeptidase to creatinine ratio.ConclusionThe SDMA cut-off value established in healthy horses was higher than previously reported. The SDMA level correlated with the azotaemia levels. Horses from the AKI risk group had normal SDMA levels but single urine parameters was abnormal indicating their higher sensitivity in assessing subclinical kidney dysfunction.

Asymmetric dimethylarginine–A potential cardiac biomarker in horses

Introduction/objectivesAsymmetric dimethylarginine (ADMA) is a cardiac biomarker in humans, symmetric dimethylarginine (SDMA) a renal biomarker in humans, cats, and dogs. The purpose of this prospective study was to investigate if measuring serum ADMA and SDMA concentrations via ELISA allows detection of cardiac disease in horses in a routine laboratory setting. In this context, reference values in horses were established. Animals, materials, and methodsSeventy-eight horses with no known medical history were compared to 23 horses with confirmed structural cardiac disease with/or without arrhythmias. Horses underwent physical examination, electrocardiography, echocardiography and venous blood sampling and were staged based on the severity of cardiac disease from 0 to II. Asymmetric dimethylarginine and SDMA were measured via ELISA and crosschecked using liquid chromatograph triple quadrupole mass spectrometry. Reference intervals with 90th percent confidence intervals were evaluated and standard software was used to test for significant differences in ADMA, SDMA, and the l-arginine/ADMA ratio between groups. ResultsThe reference ranges were 1.7–3.8 μmol/L and 0.3–0.8 μmol/L for ADMA and SDMA, respectively. Serum ADMA was higher in horses with heart disease compared to healthy horses (p < 0.01) and highest in horses with stage II heart disease (p = 0.02). The l-Arginine/ADMA ratio was significantly higher in healthy animals than those with cardiac disease (p = 0.001). ConclusionsReference values for serum ADMA and SDMA using ELISA methods are presented in horses. This study confirms the association between heart disease and increased serum ADMA concentration as well as a decreased l-Arginine/ADMA ratio in horses.