Serum Symmetric Dimethylarginine Research Articles

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

IntroductionSerum 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.MethodsThis 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.ResultsIn 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).DiscussionIn 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.

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

Diagnosis 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. Blood 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. The 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).

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.

Renoprotective effects of docosahexaenoic acid in cats with early chronic kidney disease due to polycystic kidney disease: a pilot study.

Lipids containing n-3 fatty acids have been reported to have protective effects on renal function, with docosahexaenoic acid (DHA) expected to be particularly effective. However, no reports have demonstrated the renoprotective effects of DHA-enriched lipids in cats with chronic kidney disease (CKD). Therefore, the aim of this pilot study was to examine the renoprotective effects of DHA-enriched fish oil in cats. Five healthy cats and five cats with early non-azotaemic CKD due to autosomal dominant polycystic kidney disease (PKD) were orally administered DHA-enriched fish oil in liquid form (250 or 500 mg/kg body weight [BW] and 250 mg/kg BW of DHA, respectively) for 28 days. Inappropriately dilute urine and markedly increased urinary N-acetyl-d-glucosamine (NAG) index were detected in cats with PKD before DHA-enriched fish oil administration. Changes in the fatty acid composition ratio in the blood of all 10 cats were assessed after orally administering 250 mg/kg of DHA. Post-administration, no adverse clinical effects were observed, and blood and urine tests were within the reference intervals in healthy cats. Cats with PKD showed significantly decreased serum symmetric dimethylarginine (SDMA), urine protein:creatinine ratio (UPC) and urinary NAG index at post-administration. Furthermore, oral administration of DHA-enriched fish oils significantly decreased the blood concentration ratio of arachidonic acid (AA) in cats with PKD post-administration. Furthermore, the concentration ratio of DHA in the blood significantly increased in both healthy cats and cats with PKD, and the DHA:AA ratio also increased. Oral administration of DHA-enriched fish oils for 28 days significantly decreased blood AA levels and significantly increased DHA concentration and DHA:AA ratios in cats with PKD, and improved the SDMA, UPC and urinary NAG index, suggesting its potential for renoprotective effects in cats with early non-azotaemic CKD due to PKD.

Efficacy of domperidone plus renal diet in slowing the progression of chronic kidney disease in dogs with leishmaniosis

BackgroundChronic kidney disease (CKD) represents the main cause of mortality in dogs with leishmaniosis. Domperidone has recently been reported to improve kidney function in leishmaniotic dogs affected by CKD. Serum symmetric dimethylarginine (sSDMA) has also been shown to be a useful biomarker for earlier detection of decreased kidney function when compared to serum creatinine (sCr). This study aimed to assess the efficacy of domperidone plus renal diet in slowing the progression of nephropathy in leishmaniotic dogs with CKD, evaluating sSDMA and sCr as markers of kidney function.MethodsThis study was a therapeutic, prospective, randomized, controlled, 11-month-long field trial. Dogs were recruited if classified as “exposed” to or “infected” with Leishmania infantum and affected by CKD at early stages. After enrolment (T0), dogs were randomized into groups T (treatment) and C (control). All dogs were fed a renal diet and then followed up at 90 (T1), 210 (T2), and 330 (T3) days after inclusion in the study. At T1 and T2, dogs in group T received an oral suspension of domperidone (1 ml/10 kg once a day for up to 28 days).ResultsTwenty-two dogs (i.e., n = 12 in group T and n = 10 in group C) completed the study. At T0, the entire population of enrolled dogs presented a mean sSDMA value of 16.5 ± 3.4 μg/dl. At T1 (i.e., after 3 months of renal diet), sSDMA was significantly decreased in both groups, with an sSDMA of 13.1 ± 4.4 μg/dl for the entire population involved. From T1 to T3, sSDMA gradually increased in group C, while remaining stable in group T, which continued to show a significantly lower value of sSDMA at T3 than at T0. Regarding sCr, at T0 and T1, the mean values of the entire population of dogs were 1.1 ± 0.3 and 1.0 ± 0.4 mg/dl, respectively, with no statistical differences between groups T and C. In group T, sCr decreased significantly from T0 to T1, while returning at T3 to values similar to T0.ConclusionsIn this study, domperidone plus renal diet reduced the progression of kidney disease in leishmaniotic dogs affected by CKD.Graphical

Prospective evaluation of novel biomarkers of acute kidney injury in dogs following cardiac surgery under cardiopulmonary bypass.

To assess the occurrence of acute kidney injury (AKI) in dogs undergoing cardiac surgery under cardiopulmonary bypass (CPB) and explore associations between traditional and novel serum and urinary biomarkers. Prospective cohort study conducted between July 2018 and April 2019. University teaching hospital. Nineteen dogs undergoing cardiac surgery under CPB with preoperative serum creatinine <140μmol/L (<1.6mg/dl). Blood and urine samples were obtained at 4 time points: preoperatively following general anesthesia induction, immediately postoperatively, and 2 and 4 days postoperatively (T1 , T2 , T3 , and T4 ). AKI was defined as an increase in serum creatinine ≥26.4μmol/L (≥0.3mg/dl) above baseline within 48hours. Serum creatinine, C-reactive protein (CRP), symmetric dimethylarginine (SDMA), inosine, beta-aminoisobutyric acid (BAIB), urinary clusterin (uClus), and urinary cystatin B (uCysB) were measured. Data were log-transformed (log10 ) when appropriate and assessed using linear mixed-effects models. AKI occurred in 3 of 19 dogs (15.8%, 95% confidence interval: 0.047-0.384). Inosine increased at T2 (adjusted mean±standard error: 53±5.6) in all dogs, and then gradually decreased. Log10 uCysB increased at T2 (2.3±0.1) in all dogs and remained high. Log10 CRP and log10 uClus increased significantly at T3 (1.9±0.1 and 3.6±0.1, respectively) in all dogs and remained increased. There was a significant positive association between serum creatinine and SDMA (P<0.001, estimate±standard error: 0.06±0.00), between log10 CRP and log10 uClus (P<0.001, 0.35±0.08), between SDMA and creatinine as well as between SDMA and BAIB (P<0.001, 11.1±0.83 and P<0.001, 1.06±0.22, respectively) for all dogs at all time points. Inosine and uCysB concentrations changed in all dogs immediately following a surgery under CPB and may indicate tubular injury. Further studies are required to ascertain the usefulness of those biomarkers in early detection of AKI.

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.

Evaluation of renal injury and function biomarkers, including symmetric dimethylarginine (SDMA), in the rat passive Heymann nephritis (PHN) model

Symmetric dimethylarginine (SDMA) is a serum biomarker of excretory renal function which consistently correlates with glomerular filtration rate (GFR) across multiple species including rats, dogs, and humans. In human and veterinary clinical settings SDMA demonstrates enhanced sensitivity for detection of declining renal function as compared to other serum biomarkers, but application in preclinical study designs thus far has been limited. The purpose of this study was to determine the performance of serum SDMA in a rat passive Heyman nephritis model of glomerulopathy. In addition to SDMA other biomarkers of excretory renal function were measured including serum creatinine (sCr), blood urea nitrogen (BUN), and cystatin C along with creatinine clearance. Urinary renal biomarkers including microalbumin (μALB), clusterin (CLU), cystatin C, kidney injury marker-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin (OPN) were also measured. PHN was induced using commercial sheep anti-Fx1A serum. Tissue, serum, and urine were collected from groups of control and anti-Fx1A-treated animals for biomarker evaluation, hematology, urinalysis, serum biochemistry, and histologic examination of kidney. Over the course of a 28-day study, concentrations of the urinary biomarkers μALB, CLU, cystatin C, NGAL, KIM-1 and the serum biomarker cystatin C increased significantly in anti-Fx1A-treated rats as compared to controls but no significant increase in serum SDMA, sCr, BUN, or creatinine clearance were noted in anti-Fx1A-treated rats. Given lack of direct GFR measurement or significant change in the renal function biomarkers sCr, BUN, and creatinine clearance, it is unclear if GFR differed significantly between control and anti-Fx1A-treated rats in this study, though urinary biomarkers and histopathologic findings supported renal injury in anti-Fx1A-treated rats over the time course investigated. This study is among the first to investigate serum SDMA in a rat model relevant to preclinical safety assessment and serves to inform future experimental designs and biomarker selection when evaluation of glomerular injury is of priority.