Serum Symmetric Dimethylarginine Research Articles

Simultaneous Quantification of Serum Symmetric Dimethylarginine, Asymmetric Dimethylarginine and Creatinine for Use in a Routine Clinical Laboratory.

Background Symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) are naturally occurring amino acids classed as uremic toxins by the EUTOX working group. SDMA is principally excreted through the kidneys and is a well-known renal function marker, ADMA is a potent inhibitor of nitric oxide production. Here, we describe the development of a rapid and sensitive liquid chromatography tandem mass spectrometry method for simultaneous measurement of SDMA, ADMA and creatinine. Method Serum samples were prepared by protein precipitation and dilution with acetonitrile prior to injection onto a Waters TQS-Micro. Multiple reaction monitoring was used to detect SDMA, ADMA, creatinine, and their corresponding internal standard transitions after separation with a HILIC analytical column. Sample stability and intra-individual variation studies were also assessed following ethical approval. Results The retention time for creatinine was 0.43, SDMA 1.10 and ADMA 1.14 minutes. Mean recovery for creatinine was 103%, SDMA was 100% and ADMA was 103%, matrix effects were minimal (<6%). Lower limit of quantitation for creatinine and SDMA/ADMA was 17.5 µmol/L and 0.1 µmol/L respectively. Analytical imprecision showed a coefficient of variation <10% for all analytes across the working range of the assays. Intra-individual variation for creatinine was 4.7%, SDMA 7.5% and ADMA 7.6%. Discussion We have developed a rapid assay for LC-MS/MS measurement of SDMA, ADMA and creatinine in a routine clinical laboratory. It is simple, reproducible, and easy to perform. The stability of SDMA and ADMA pre- and post-centrifugation allows for their routine use without any special sample handling requirements.

Glomerular filtration rate determined by measuring serum clearance of iohexol in unanesthetized cheetahs (Acinonyx jubatus) with comparison to serum symmetric dimethylarginine.

One of the more common diseases affecting zoo-managed cheetahs (Acinonyx jubatus) is chronic renal disease, which can impact their welfare and ultimately shortens their lifespan. Early diagnosis, for which estimating Glomerular Filtration Rate (GFR) is one such tool, is imperative to help mitigate the negative impacts of this insidious disease. GFR was determined by measuring the serum clearance of iohexol in nine clinically normal, cheetahs managed under human care that presented for voluntary blood collection. A 2-sample iohexol clearance method was performed, along with serum symmetric dimethylarginine (SDMA) determination. SDMA has shown promise in humans, dogs, and cats, as an early biomarker of renal disease. Additionally, the relationship between GFR and SDMA, along with serum creatinine and BUN were analyzed. The mean values for the uncorrected GFR and corrected GFR were 2.08 ± 0.215 mL/min/kg body weight and 1.87 ± 0.173 mL/min/kg body weight, respectively. No significant correlations were observed between GFR, SDMA, serum creatinine, or BUN. Both the uncorrected and corrected iohexol-based GFR values were similar to an inulin-based GFR reference interval determined in zoo managed cheetahs and a reported domestic cat iohexol-based GFR reference interval. Serum SDMA values support previous research suggesting cheetahs have a separate reference interval from domestic cats (0-14 μg/dL). Measuring GFR by the serum clearance of iohexol shows promise as a readily available, cheap, and easily administered clearance marker that can be used in cheetahs trained for voluntary blood collection, thereby avoiding the need for anesthesia.

High dietary Mucuna pruriens utilis seed meal compromises growth performance, carcass traits, haemato-biochemistry, and meat quality of broilers.

Usage of soyabean meal (SBM) in broiler diets is economically and environmentally unsustainable thus necessitating investigation of alternative protein sources. Therefore, this study investigated effects of incremental inclusion levels of Mucuna pruriens utilis seed meal (MSM) for partial substitution of SBM in broiler diets. In a completely randomized design (CRD), 400day-old Ross 308 chicks were allotted to 5 iso-caloric-nitrogenous MSM-containing (0, 5, 10, 15, and 20%) dietary treatments. Each treatment was replicated 8 times, with each pen having 10 birds, during starter (d1 - 14), grower (d15 - 28), and finisher (d29 - 42) phases. Results showed that dietary MSM decreased feed intake (FI: quadratic: P < 0.001), body weight gain (BWG: linear: P < 0.001), and feed conversion efficiency (FCE: linear: P < 0.001) as it linearly decreased slaughter weight (SW: P < 0.001), hot carcass weight (HCW: P < 0.001), cold carcass weight (CCW: P < 0.001), dressing percentage (P < 0.001), and breast weight (P < 0.05). In contrast, dietary MSM linearly increased the weights of the liver (P < 0.01), proventriculus (P < 0.001), gizzard (P < 0.001), duodenum (P = 0.01), jejunum (P < 0.001), ileum (P < 0.001), caecum (P < 0.01), and colon (P < 0.01). Also, dietary MSM quadratically increased blood heterophils (P < 0.05) and alkaline phosphatase activity (P < 0.05) of the chickens whilst linearly increasing their serum amylase (P = 0.001) and lipase (P = 0.001) activities and linearly decreasing their serum symmetric dimethylarginine (SDMA: P = 0.001) and cholesterol (P < 0.05). Further, dietary MSM linearly decreased chicken breast meat ultimate pH (P < 0.05) whilst linearly increasing its cooking loss (P < 0.01), drip loss (P < 0.05) and shear force (P < 0.01). In conclusion, dietary MSM compromised growth performance, carcass characteristics, and meat quality of broilers as it increased the weights of their digestive-metabolic organs.

225 Kidney function and nitrogen excretion in Brown Swiss and Holstein dairy cows

Abstract The agricultural sector contributes to nitrogen (N) emissions since farm animals excrete considerable N amounts via feces and urine. To reduce N emissions by dairy cattle, methods predicting accurately individual N emissions are of great interest. Recent data showed that Brown Swiss (BS) cows have greater urea concentrations in milk and blood than Holstein (HO) cows. However, it is still unknown if greater BUN concentrations in a particular breed are congruently reflected by concomitantly increased contents of nitrogenous compounds in other media (e.g., urine and saliva). Thus, the present study simultaneously assessed biomarkers for kidney function like urea, and creatinine and symmetric dimethylarginine (SDMA) concentrations in several body fluids (i.e., blood, urine, milk, and saliva) as well as nitrogen excretion in feces in BS and HO cows under identical feeding conditions. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. Concentrations of urea and creatinine were measured in serum, urine, and saliva. Symmetric dimethylarginine was determined in serum, which is an established indicator for glomerular filtration rate (GFR). Feces were analyzed for dry matter content and nitrogen concentrations. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P &amp;lt; 0.05. Dry matter intake and body weight were similar in BS and HO cows (P &amp;gt; 0.05). No differences between BS and HO were observed for milk yield, fecal DM and nitrogen content. BS cows showed greater urea concentration (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL), and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than HO cows (P &amp;lt; 0.01). Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P &amp;lt; 0.01) with 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L for urea, 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l creatinine, and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL SDMA, respectively. Urea and creatinine concentrations in urine and saliva did not differ among breeds. Despite greater urea and creatinine concentrations in blood, and milk urea content in BS compared with HO, excretion of these parameters did not differ between breeds in urine. Our results suggest a reduced renal glomerular filtration rate in BS compared with HO. The underlying mechanisms require further investigations.

Validation of a reference interval for symmetric dimethylarginine in healthy goats and its comparison to values in goats with obstructive urolithiasis.

Symmetric dimethylarginine (SDMA), a sensitive biomarker for detecting renal injury, has not been characterized in goats. Obstructive urolithiasis (OU) is the most common urinary tract disease in male small ruminants. Establish an SDMA reference interval (RI) in healthy adult goats and describe SDMA concentrations in goats with OU. We hypothesize that the SDMA RI in healthy adult goats will be similar to that of other adult veterinary species and that SDMA can be utilized to assess the renal function of goats experiencing OU. Fifty-five healthy adult male and female goats from a university herd were enrolled for SDMA RI development. Twenty male and female goats from a university herd were enrolled for validation of the SDMA RI established. Thirteen male goats diagnosed with OU were enrolled. Clinical trial. Serum samples for all animals enrolled were collected and analyzed for SDMA using an immunoassay (IDEXX Laboratories, Inc); goats with OU had additional blood work analyzed (PCV, total solids, and serum biochemistry). Symmetric dimethylarginine and other values in goats with OU were analyzed and compared at specific time points. The SDMA RI for healthy, adult goats is 8.03 μg/dL (90% CI 4.81-11.04) to 25.93 μg/dL (90% CI 22.88-28.97). There was no correlation identified between serum creatinine and SDMA in goats with OU. The SDMA RI for adult goats is higher than in other adult large animal species. Use of SDMA in goats with OU is not useful in assessing their renal function.

Kidney function, but not nitrogen excretion, differs between Brown Swiss and Holstein dairy cows

Brown Swiss (BS) cows have greater urea concentrations in milk and blood compared with Holstein (HO) cows. We tested the hypothesis that BS and HO cows differ in kidney function and nitrogen excretion. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. To test the glomerular filtration rate (GFR) and urea excretion, concentrations of creatinine and urea were measured in serum, urine, and saliva. As an additional marker to estimate GFR, we determined symmetric dimethylarginine (SDMA) in serum. Feces were analyzed for dry matter content and nitrogen concentration. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P < 0.05. Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P < 0.01): 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L (urea), 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l (creatinine), and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL (SDMA). We observed a greater urea concentration in BS cows (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL) and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than in HO cows (P < 0.01). Urea and creatinine concentrations in urine and saliva did not differ among breeds. No differences between BS and HO were observed for milk yield, fecal DM, and fecal nitrogen content. Dry matter intake and body weight were similar in BS and HO cows (P > 0.05). Despite greater urea, creatinine, and SDMA concentrations in blood as well as a higher milk urea content in BS compared with HO, respective concentrations in urine did not differ between breeds. In conclusion, our results demonstrate a lower renal GFR in BS compared with HO cows, thereby contributing to the greater plasma urea concentration in BS cows. However, estimation of nitrogen excretion via milk, urine, and feces does not entirely reflect nitrogen turnover within the animal.

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.

Reference intervals for selected blood and urinary parameters related to renal function in clinically healthy ferrets (Mustela putorius furo)

BackgroundDiagnosis of chronic kidney disease can be challenging in ferrets. Physiological creatinine values are lower than in dogs and cats and marked elevations may only be detected in advanced disease. In canine and feline patients, specific staging, and treatment guidelines are available, based on serum creatinine, symmetric dimethylarginine (SDMA) levels, presence of proteinuria, and blood pressure measurement. No such guidelines exist for ferrets, and there is a lack of data concerning certain laboratory parameters. MethodsBlood and urine samples were taken from 60 clinically healthy pet ferrets to establish species-specific reference intervals for serum SDMA and urine protein/creatinine ratio (UPC ratio). Liquid-chromatography tandem mass spectrometry (HPLC-MS) was used for determination of serum SDMA, a colorimetric spectrophotometric method for urinary protein and an enzymatic method for urine creatinine. ResultsThe calculated reference interval for serum SDMA (2.78–7.66 µg/dL) was found to be lower than in dogs and cats, while the UPC ratio is similar to dogs (<0.5). Conclusions and clinical relevanceSerum SDMA reference intervals for ferrets may be lower than internals published for dogs and cats, while the UPC ratio appears to be similar to the ratio for dogs.

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.

Renal biomarkers, clinical parameters, and renal Doppler velocimetry in bitches with cystic endometrial hyperplasia-pyometra complex.

Cystic endometrial hyperplasia (CEH)-pyometra complex is the most common uterine infection in adult and elderly bitches and can cause renal dysfunction. The aim of this study was to measure and compare urinary creatinine, urea, symmetric dimethylarginine (SDMA), urinary protein-creatinine ratio (UPC), measurement of systolic blood pressure (SBP), and Doppler velocimetry of renal arteries in patients with CEH-pyometra complex before and after an average of 6 months of treatment, evaluating the possibility of the changes persisting. The evaluation was conducted at two moments: M1 (at the diagnosis of CEH-pyometra, n = 36) and M2 (after an average of six months of treatment, n = 16). For the control group, eight bitches with no changes in blood tests or history of conditions underwent Doppler ultrasound evaluation of the renal arteries. At both M1 and M2, we measured creatinine, urea, and serum SDMA, UPC, SBP, and Doppler ultrasound of the renal arteries. Patients were evaluated according to the following groups: azotemic (AZO) and non-azotemic (NAZO), and open and closed cervix pyometra. The parameters were compared between animals present in both moments presented as M1R (bitches that were in M1 and M2) and M2. Statistical significance was considered when p < .05. The medians found for creatinine in M1 were as follows: 1.15 mg/dL, being 1.8 mg/dL for AZO (12/36) and 0.95 mg/dL for NAZO (24/36); and in M2: 0.85 mg/dL (16/16), being 1.15 mg/dL for AZO (4/16) and 0.8 mg/dL for NAZO (12/36). For urea, in M1 it was 36 mg/dL (32/36), with AZO being 103 mg/dL (11/32) and 33 mg/dL in NAZO (21/32); and in M2 32 mg/dL (16/ 16), being 29 mg/dL for AZO (4/36), and 31 mg/dL for NAZO (3/15). The median SDMA measured in M1R was 17 μg/dL (15/16), with AZO being 31 μg/dL (3/15), and NAZO being 16.5 μg/dL (12/15); and in M2, SDMA was 12 μg/dL (16/16), with AZO being 12.5 μg/dL (4/16), and NAZO being 12 μg/dL (12/16). The median UPC measured in M1 was 1.15 (10/36), with AZO being 0.25 (1/10), and NAZO being 1.38 (9/10); and in M2, it was 0.2 (13/16), being 0.1 in AZO (4/13), and 0.2 (9/16) in NAZO. For SBP, in M1, it was 118 mmHg (30/36), with AZO being 102 mmHg (10/30) and 133 mmHg in NAZO (20/30); and in M2 142.5 mmHg (12/16), being 155 mmHg for AZO (4/12), and 140 mg/dL for NAZO (8/12). When comparing animals with open and closed cervixes, a difference was found between SDMA measurements (p = .001). There was a distinction between PI and RI of the left and right kidneys consecutively (p = .007; p = .033; p = .019; p = .041). Correlations found in M1: SDMA × PI RIM DIR (r = 0.873; p = .002), SDMA × PSV RIM ESQ (r = 0.840; p = .004), SDMA × EDV RIM ESQ (r = 0.675; p = .046). With this study, we conclude a return to normality of renal biomarkers and clinical parameters after six months. Yet, there is a persistence of Doppler velocimetric measurements between the two moments. Thus, this parameter is not suitable for identifying and classifying chronic kidney injury in bitches with pyometra.

Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.

Matrix metalloproteinase-9 is increased in renal tissue in human kidney disease, but its role as a biomarker for kidney disease has not been fully evaluated yet. The aim of this study was to evaluate serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) concentrations in dehydrated horses. Dehydrated horses were prospectively included. Blood and urinary samples were taken at admission, and after 12, 24, and 48 h (t0, t12, t24, t48), an anti-equine MMP-9 sandwich ELISA was used. Four healthy horses served as the controls. Serum creatinine, urea, symmetric dimethylarginine (SDMA), urine-specific gravity, urinary protein concentration, fractional sodium excretion, and urinary gamma-glutamyl transferase/creatinine ratio (uGGT/Cr) were measured. Statistical analysis included a repeated measures ANOVA and mixed linear regression model. Overall, 40 dehydrated horses were included (mild dehydration 13/40, moderate 16/40, severe 11/40). Acute kidney injury was found in 1/40 horses; 7/40 horses showed elevated serum creatinine, 11/40 horses elevated serum SDMA, and 5/28 elevated uGGT/Cr at presentation. In dehydrated horses, sMMP-9 concentrations were significantly higher on t0 (median: 589 ng/mL, range: 172-3597 ng/mL) compared to t12 (340 ng/mL, 132-1213 ng/mL), t24 (308 ng/mL, 162-1048 ng/mL), and t48 (258 ng/mL, 130-744 ng/mL). In healthy horses, sMMP-9 (239 ng/mL, 142-508 ng/mL) showed no differences over time or compared to patients. uMMP-9 and uMMP-9/creatinine did not differ over time or to the controls. No differences were found between dehydration groups. Urinary casts (p = 0.001; estimate = 135) and uGGT/Cr (p = 0.03; estimate = 6.5) correlated with sMMP-9. Serum urea was associated with uMMP-9/Cr (p = 0.01, estimate 0.9). In conclusion, sMMP-9 was elevated at arrival in dehydrated patients compared to later measurements. Correlations to uGGT/Cr and urinary casts need further evaluation.

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

Cross-sectional characterization of renal function in cats with caudal stomatitis.

The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats. A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis. Affected gingiva was biopsied to confirm the diagnosis of stomatitis. Renal biochemical analyses from the experimental group were compared with those of 44 age-matched controls without CS enrolled prospectively or retrospectively after presenting to the primary institution for routine healthcare. Control cats were included if they were clinically stable, their chronic illnesses were well managed and minimal dental disease was present on examination. Renal biomarkers were compared between groups using a t-test or the Mann-Whitney U-test. Frequency of azotemia, proteinuria and the clinical diagnosis of renal disease were compared using Fisher's exact test. Relative to the control group, cats in the CS group had significantly lower serum creatinine (P <0.001) and albumin concentrations (P <0.001), urine specific gravity (P = 0.024) and hematocrit (P = 0.003), and higher serum phosphorus (P <0.001), potassium (P <0.001) and globulin concentrations (P <0.001), white blood cell count (P <0.001) and urine protein:creatinine ratio (P = 0.009). There were no significant differences in serum symmetric dimethylarginine or urea nitrogen concentrations. No clinically significant findings were noted on urine protein electrophoresis. There were no significant differences in the frequency of azotemia, proteinuria or renal disease categories between the two groups. The present study does not demonstrate a significant difference in the frequency of kidney disease between cats with and without CS. Longitudinal evaluation is warranted to investigate the relationship between renal disease and CS.

Changes in symmetric dimethylarginine and glomerular filtration rates in hyperthyroid cats undergoing radioiodine therapy.

The aims of this study were to evaluate concentrations of symmetric dimethylarginine (SDMA) in hyperthyroid cats before and after radioiodine treatment, and to compare results with other variables used to assess kidney function in cats (creatinine, urine specific gravity [USG] and glomerular filtration rate [GFR] measured by renal scintigraphy). Thirteen cats diagnosed with hyperthyroidism based on clinical signs and increased serum total thyroxine (TT4) were included in this prospective study. Study design included physical examination, complete blood count, serum chemistry, TT4, urinalysis and SDMA before treatment (T0) and at 1 month (T1) and 3 months post-treatment (T3). GFR was quantified by renal scintigraphy at T0 and T3. Median GFR decreased significantly from baseline (3.18 ml/kg/min; range 1.35-4.87) at T3 (2.22 ml/kg/min; range 1.81-3.42 [P = 0.005]). While median creatinine and serum urea nitrogen increased post-treatment (creatinine: T0 = 0.8 mg/dl [range 0.4-1.1], T1 = 1.3 mg/dl [range 0.9-2]; T3 = 1.65 mg/dl [range 0.8-2.8]; P <0.001; serum urea nitrogen: T0 = 23 mg/dl [range 15-26]; T1 = 27 mg/dl [range 20-40]; T3 = 27.5 mg/dl [range 20-36]; P <0.001), SDMA and USG did not change significantly (SDMA: T0 = 11 µg/dl [range 7-15]; T1 = 12 µg/dl [range 6-16]; T3 = 10.5 µg/dl [range 8-21]; P = 0.789; USG: T0 = 1.030 [range 1.011-1.059]; T1 = 1.035 [range 1.012-1.044]; T3 = 1.030 [range 1.007-1.055]; P = 0.792). Our data suggest that factors other than GFR may affect serum SDMA in hyperthyroid cats and that SDMA does not offer an advantage over other biomarkers traditionally used to predict changes in renal function following radioiodine therapy.

Cystatin-c May Indicate Subclinical Renal Involvement, While Orosomucoid Is Associated with Fatigue in Patients with Long-COVID Syndrome.

Long-COVID syndrome is associated with high healthcare costs, but its pathophysiology is not yet fully understood. Inflammation, renal impairment or disturbance of the NO system emerge as potential pathogenetic factors. We aimed to investigate the relationship between symptoms of long-COVID syndrome and serum levels of cystatin-c (CYSC), orosomucoid (ORM), l-arginine, symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). A total of 114 patients suffering from long-COVID syndrome were included in this observational cohort study. We found that serum CYSC was independently associated with the anti-spike immunoglobulin (S-Ig) serum level (OR: 5.377, 95% CI: 1.822-12.361; p = 0.02), while serum ORM (OR: 9.670 (95% CI: 1.34-9.93; p = 0.025) independently predicted fatigue in patients with long-COVID syndrome, both measured at baseline visit. Additionally, the serum CYSC concentrations measured at the baseline visit showed a positive correlation with the serum SDMA levels. The severity of abdominal and muscle pain indicated by patients at the baseline visit showed a negative correlation with the serum level of L-arginine. In summary, serum CYSC may indicate subclinical renal impairment, while serum ORM is associated with fatigue in long-COVID syndrome. The potential role of l-arginine in alleviating pain requires further studies.

Renal resistive index in obese and non‑obese cats.

This study aimed to compare renal function between obese and normal‑weight healthy cats, using intrarenal resistive index (RI), serum symmetric dimethylarginine (SDMA), and serum creatinine, and to identify the variables that might influence intrarenal RI. Thirty crossbred client‑owned cats met the inclusion criteria and were allocated into two groups: Control and Obese. Body weight, body mass index (BMI), body condition score (BCS), SAP, serum SDMA, urea, and creatinine were evaluated. B‑mode and Doppler ultrasound of the kidneys were done. RI evaluation was in the interlobar artery. SDMA and intrarenal RI were compared between groups, also considering the gender of the cats. A correlation analysis between intrarenal RI with the other parameters was performed. SDMA was higher in the Obese group. Intrarenal RI was higher in females than males in the Obese group. Obese females presented higher RI and SDMA than Control females. A positive correlation was observed between RI, age, body weight, and BMI. Six obese cats (40%) showed increased RI. The increase in body weight, BCS, and BMI resulted in a simultaneous increase in RI and SDMA. The RI may assist in monitoring renal function, and may be associated with preclinical kidney changes in obese cats.

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.