ArticleLiterature Review

Creatinine in the Dog: A Review

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Abstract

Creatinine is the analyte most frequently measured in human and veterinary clinical chemistry laboratories as an indirect measure of glomerular filtration rate (GFR). Although creatinine metabolism and the difficulties of creatinine measurement have been reviewed in human medicine, similar reviews are lacking in veterinary medicine. The aim of this review is to summarize information and data about creatinine metabolism, measurement, and diagnostic significance in the dog. Plasma creatinine originates from the degradation of creatine and creatine phosphate, which are present mainly in muscle and in food. Creatinine is cleared by glomerular filtration with negligible renal secretion and extrarenal metabolism, and its clearance is a good estimate of GFR. Plasma and urine creatinine measurements are based on the nonspecific Jaffé reaction or specific enzymatic reactions; lack of assay accuracy precludes proper interlaboratory comparison of results. Preanalytical factors such as age and breed can have an impact on plasma creatinine (P-creatinine) concentration, while many intraindividual factors of variation have little effect. Dehydration and drugs mainly affect P-creatinine concentration in dogs by decreasing GFR. P-creatinine is increased in renal failure, whatever its cause, and correlates with a decrease in GFR according to a curvilinear relationship, such that P-creatinine is insensitive for detecting moderate decreases of GFR or for monitoring progression of GFR in dogs with severely reduced kidney function. Low sensitivity can be obviated by determining endogenous or exogenous clearance rates of creatinine. A technique for determining plasma clearance following IV bolus injection of exogenous creatinine and subsequent serial measurement of P-creatinine does not require urine collection and with additional studies may become an established technique for creatinine clearance in dogs.

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... However, considering that serum Cys-C concentration is more sensitive to decreased GFR than serum Cre concentration (Miyagawa et al. 2021), increased serum Cys-C concentration in elderly dogs might reflect the latent and subclinical decrease in GFR associated with aging. The previous study reported that serum Cre concentration decreases after 8-10 years of age (Braun et al. 2003), presumably because of decreased muscle mass. It is inferred that serum Cre concentration failed to detect the reduction in GFR because of the decrease in muscle mass in older dogs. ...
... By contrast, serum Cre concentration was higher in Shiba Inus, and lower in Miniature Dachshunds and Chihuahuas. *: P < 0.05, **: P < 0.01, ***: P < 0.001 results of the previous study (Braun et al. 2003;Connolly et al. 2020). It is presumed that higher serum Cre concentration is due to greater muscle mass in male dogs (Braun et al. 2003;Connolly et al. 2020). ...
... *: P < 0.05, **: P < 0.01, ***: P < 0.001 results of the previous study (Braun et al. 2003;Connolly et al. 2020). It is presumed that higher serum Cre concentration is due to greater muscle mass in male dogs (Braun et al. 2003;Connolly et al. 2020). ...
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This study investigated the effects of age, sex and breed on serum cystatin C (Cys-C) and creatinine in small breed dogs. This retrospective study included 250 dogs weighing less than 15 kg without azotemia. Serum Cys-C and creatinine concentrations were analyzed, along with their correlation with age, and the difference between sexes or dog breeds. Serum Cys-C concentration correlated with age (P < 0.001), and did not differ between sexes or dog breeds. By contrast, serum creatinine concentration did not correlate with age. Serum creatinine concentration was higher in males than females (P < 0.05), and was lower in Miniature Dachshunds and Chihuahuas, and was higher in Shiba Inus compared to the general study population (P < 0.001). Serum Cys-C concentration correlates with age, and might be more sensitive to aging-associated subclinical renal dysfunction than serum creatinine concentration in dogs. Unlike serum creatinine concentration, serum Cys-C concentration is not affected by sex or dog breed.
... 5,[10][11][12][13] For animals such as dogs that are generally on meat diets, creatinine is vulnerable to diet-related variability (eg, higher creatinine with meat vs casein-based diets) and other factors including muscle mass and body weight (ie, higher serum creatinine levels with larger muscle mass), housing, circadian and seasonal variation, hydration status, physical activity, drug treatment, and age. 14 In humans, AKI is defined as damage or loss of kidney function for a duration of 7 to 90 days after an AKI initiating event which would parallel renal injury occurring during the acute/subacute nonclinical toxicity study time frame. 15 In contrast, chronic renal failure or chronic kidney disease (CKD) is defined by the persistence of kidney disease for greater than 90 days, which would translate to renal injury that persists in nonclinical toxicity studies of greater than 4 months' duration. ...
... 95,96,97 Unfortunately, GFR is not readily measured directly and is generally assessed using the clearance of bolus-injected surrogates including creatinine, inulin, iohexol, or radiolabeled molecules at specific timepoints. 14,98 However, this is rarely done in the clinic due to cost, availability, difficulty of measurement, and inconvenience. 99,100 Likewise, it is logistically difficult and expensive to include in animal studies. ...
Article
A host of novel renal biomarkers have been developed over the past few decades which have enhanced monitoring of renal disease and drug-induced kidney injury in both preclinical studies and in humans. Since chronic kidney disease (CKD) and acute kidney injury (AKI) share similar underlying mechanisms and the tubulointerstitial compartment has a functional role in the progression of CKD, urinary biomarkers of AKI may provide predictive information in chronic renal disease. Numerous studies have explored whether the recent AKI biomarkers could improve upon the standard clinical biomarkers, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio, for predicting outcomes in CKD patients. This review is an introduction to alternative assays that can be utilized in chronic (>3 months duration) nonclinical safety studies to provide information on renal dysfunction and to demonstrate specific situations where these assays could be utilized in nonclinical drug development. Novel biomarkers such as symmetrical dimethyl arginine, dickkopf homolog 3, and cystatin C predict chronic renal injury in animals, act as surrogates for GFR, and may predict changes in GFR in patients over time, ultimately providing a bridge from preclinical to clinical renal monitoring.
... Circulating creatinine is a breakdown product of creatine phosphate in muscle and therefore Scr concentration will depend on muscle mass and may be significantly decreased in animals with low muscle mass such as geriatric or immature individuals or increased in heavily muscled animals such as greyhounds (Braun et al. 2003). Scr is also influenced by age and breed in dogs and, to a lesser degree cats (e.g. ...
... Birman) (Gunn-Moore et al. 2002), however breed specific reference intervals are not routinely used (Reynolds et al. 2010, Misbach et al. 2014, Rørtveit et al. 2015. Data suggests that plasma creatinine concentrations increase gradually over the first year of life in dogs but then remain stable (Braun et al. 2003) whilst in kittens creatinine concentrations are relatively high at birth but are similar to or lower than adults by 8 weeks of age (Levy et al. 2006). Furthermore, studies have shown that Scr can be affected by diet with increases in Scr following meat ingestion (Watson et al. 1981). ...
Article
Within clinical small animal practice, diagnosis of both chronic kidney disease and acute kidney injury is common. To assess renal function, measurement of glomerular filtration rate is considered the gold standard. Currently, routine tests of kidney function include surrogate markers of glomerular filtration rate such as serum creatinine, and urea, each with their own limitations, whilst urine protein to creatinine ratio gives an indication of glomerular and tubular handling of protein, and urine specific gravity information about urine concentrating ability by the kidney. These parameters are used together with historical and physical examination data to give a diagnosis of kidney disease following which creatinine, proteinuria and blood pressure are used to stage chronic kidney disease and, together with urine output, grade acute kidney injury according to the International Renal Interest Society. However, there has been much concern that creatinine is insensitive when used to indicate early decline in renal function and this has highlighted the need for additional methods of diagnosing and monitoring these patients, with the potential to allow earlier therapeutic intervention. Symmetric dimethylarginine is a novel biomarker, which has been shown to perform as a surrogate marker of glomerular filtration rate in small animals. This article will review current research on symmetric dimethylarginine and the ways in which it may be utilised in small animal practice; current research supports the use of symmetric dimethylarginine as a screening test for detection of early chronic kidney disease according to International Renal Interest Society guidelines, but further research is required in to the usefulness of symmetric dimethylarginine as a tool for monitoring disease and the effect of non‐renal influences.
... Serum creatinine levels also tended to increase as age advanced. Our results are consistent with some studies (4,5,10,20). Moreover, the lower creatinine in young animals, in relation with adults, correlates with smaller body size and decreased muscle mass (1). ...
... All authors have read and approved the nal version of this manuscript. (16) 15 (15)(16)(17)(18)(19)(20) 44 (44-46) CI = con dence interval; ºC = degrees Celsius G = Gaussian; IQR = inter quartile range; LL = low limit; NG = not Gaussian; SD = standard deviation; UL = upper limit. Groups that do not share a letter are signi cantly different Table 2). ...
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Background: Blood biochemistry and reference intervals help to differentiate between healthy and ill patients as well as to provide information for the prognosis, evaluation, and monitoring of a patient; however, these intervals are often obtained from adult animals. It is essential, hence, to understand that puppies and adults are physiologically different, which justifies the need to obtain age-specific biochemical reference intervals. The aim of this research was to assess the potential effect of age, sex, breed, and interaction on routine biochemical analytes and physiological constants (body temperature, heart rate, and respiratory rate) in addition to establish age-specific reference intervals. In order to carry out the research, we selected 197 healthy dogs of different sex and breed classified by age: group I (4-8 wk), group II (9-24 wk), group III (25-52 wk), and group IV (>52 wk). The biochemical analysis measured the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and concentration of cholesterol, triglycerides, total proteins, albumin, globulins, glucose, urea, and creatinine. Statistical analyses used the Analysis of Variance (ANOVA) and General Linear Model (GLM), which allows the comparison of multiple factors at two or more levels (p < 0.05). Results: The results of this study showed that ALT, total protein, albumin, globulin, urea, creatinine, and body temperature levels were lower in puppies compared to adult dogs (p < 0.05) while the enzymatic activity of ALP, LDH, glucose concentration, and heart rate were higher. Moreover, in small breeds, the serum creatinine levels were lower (p < 0.05) whereas sex and interaction did not show a significant effect (p > 0.05). Conclusions: Some biochemical components evince influence by age. For this reason, this research offers specific reference intervals to help the veterinary clinician to interpret the biochemical results of puppies with accuracy.
... The increased creatinine clearance in GAT, ITR and OVH, resulted in corresponding decrease in creatinine half-life, decreased creatinine clearance and increased creatinine half-life. Urinary elimination of creatinine is constant over time and is not affected by extra renal factor (Braun et al., 2003). Food can be responsible for the differences in the amount of urine creatinine (Uechi et al., 1997). ...
... The non significant difference in urine volume in this present study agrees with the report of Brown, (1993) indicating that dogs under anaesthesia and surgery maintain normal urine volume, because renal blood flow and glomerular filtration rate remain constant, due to the intrinsic auto regulatory capacity of the kidney. However, the urine volume for dogs in the present study agrees with the reported value (2.4 ml/min) in various species (Saganuwan, 2018).The non significant difference in plasma clearance agrees with the report of Braun et al., (2003) indicating that urinary elimination of creatinine remained unchanged since concentration of creatinine in plasma is largely influenced by muscle mass. The decrease in AUC and increase in GFR at 24 h shows that propofol was eliminated faster in GAT and ITR. ...
Article
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Differential leucocytes counts and some biochemical parameters could be affected over time by surgical procedures leading to kidney failure. Hence this study evaluates the effects of ovariohysterectomy (OVH), gastrotomy (GAT) and intestinal resection and anastomosis (ITR) on differential leucocyte counts and some biochemical parameters in Nigerian dogs. Twelve dogs of both sexes weighing 10.8±0.7 kg were randomly divided into three experimental groups of four each. The dogs were pre-treated with atropine sulphate (0.04 mg/kg), Xylazine (2 mg/kg) and propofol (6 mg/kg) parenterally, for induction and maintenance of anaesthesia. Pentazocine (3 mg/kg) was injected after surgery. Pre and post-surgery blood samples were obtained at 0, 2, 24, 48, 72, 96, 120 and 144 h respectively to determine differentials in leucocyte counts, electrolytes, lactate, blood urea nitrogen (BUN) and serum creatinine. Mathematical formulas were used to calculate plasma creatinine, creatinine clearance, plasma creatinine clearance, creatinine half- life, urine creatinine and urine volume. There were significant increases (p≤0.05) in mean sodium, chloride and bicarbonate concentrations at 2, 24, 48, 72, 96 and 120 h post-surgery in group 1 and 2, while group 3 had significant decreases (p≤0.05) in sodium, chloride and bicarbonate ions. Lactate value decreased significantly (p<0.05) in group 1, and increased in group 2 and 3 respectively.BUN increased significantly (p<0.05) in group 1,2 and 3.However, there were significant increases (p<0.05) in lymphocyte concentrations in group 1 and 3, respectively. Monocytes decreased significantly (p<0.05) after surgery. Conclusion: Xylazine and propofol anaesthetics cause hyperlactatemia which can be detrimental in surgical patients with co-morbidities.
... However, sCr is an insensitive marker for diagnosing early stage AKI since increased concentrations are not observed until 75% of functional nephron mass is lost and extra-renal factors affect individual baseline levels. 13,14 Furthermore, renal injury can be present without renal dysfunction. 15 AKI might therefore be underdiagnosed in dogs envenomated by V. berus when sCr is used as the sole biomarker for renal injury. ...
... The 16-point SSS was collapsed into 4 groups (0, 1-3, 4-7, [8][9][10][11][12][13][14][15][16]. A weak correlation was found between uClusterin concentration at the first timepoint for each subject and SSS (Spearman's r = 0.365, P < .034, ...
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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 < 0.010), except for T5 (P = 0.222). 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 < 0.036) and T2-T4 (P< 0.036), 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 < 0.001). 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.
... SDMA is highly reliable as the number of confounding factors is limited [6,[10][11][12]. Unlike serum creatinine (sCr), SDMA is not influenced by age in adult dogs, lean body mass or gender [10][11][12][13]. Furthermore, SDMA might have advantages for the early detection of impaired renal function as 35 to 50% less nephron mass must be lost to cause a significant increase compared to sCr [6,8,9,11,13,14]. ...
... Unlike serum creatinine (sCr), SDMA is not influenced by age in adult dogs, lean body mass or gender [10][11][12][13]. Furthermore, SDMA might have advantages for the early detection of impaired renal function as 35 to 50% less nephron mass must be lost to cause a significant increase compared to sCr [6,8,9,11,13,14]. ...
Article
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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.
... Urea didn"t have major contribution to the effective osmolality in ECF, unless it was increased. Braun et al. (2003), DiBartola (2005) and Francey (2007) stated that serum creatinine was considered to be a more reliable parameter than urea for evaluating renal function. ...
... The monstrous gain in the concentration of creatinine, prior to the initiation of dialytic therapy was ascribed to the highly compromised natural clearance (urine output 0.39 ± 0.18 ml/kg/hr, for dead cases) as well as constant rate of generation (Braun et al, 2003). During the first dialysis, the concentration was reduced to mean creatinine of 8.4 mg/dL, which further rose to 10.17mg/dL during first interdialytic period. ...
... Consequently, the sensitivity of serum CREA level for the early stage of IRIS is limited. Although CREA metabolism and measurement and its limitations have been reviewed in human medicine, similar reviews are lacking in veterinary medicine [4] Therefore, in this research CREA and the other indirect kidney factors are studied its correlations. ...
... Whereas muscle mass, diet, inflammation, diabetes, and estrogen therapy have no significant impacts on SDMA concentrations, obesity, sex, and age have effects on SDMA levels [9,12]. 4 CysC is a cysteine protease inhibitor that is filtered by the glomerulus and unaffected by non-renal factors such as inflammation, age, and sex [11]. With greater sensitivity, serum CysC level has been replaced CREA as a marker of GFR in humans [11]. ...
Article
The aim of this study was to determine whether serum symmetric dimethylarginine (SDMA) and cystatin C (CysC) levels can be utilized as more accurate markers of early kidney dysfunction in dogs. Forty-one client-owned dogs with chronic kidney disease (CKD), which were clinically stable, and ten beagles as healthy controls were included. All dogs underwent physical examination, systemic blood pressure measurement, complete blood cell count (CBC), and plasma biochemistry analyses. Frozen serum was used for SDMA and CysC analyses. Data analysis was performed using Kruskal Wallis, Pearson’s correlation, Bland-Altman plots, and receiver operating characteristic (ROC) curve. SDMA and CysC levels were significantly higher in patients with CKD at various International Renal Interest Society (IRIS) stages than in the healthy controls. In particular, CysC level was the only biomarker that could indicate the earliest stage of CKD (IRIS stage I). Similar to these results, CysC level showed better sensitivity and specificity compared to the other biomarkers in early CKD dogs.
... This study is the first to the authors' knowledge to apply a BCS to elephants living and foraging independently in their natural environment without significant human provisioning. Consequently, the results presented differ from those obtained for zoo elephants in America, where most of the animals were very fat (BCS of 4) or obese (5). 39 MTE elephants forage naturally in the forest with changes to food availability throughout the year, and their BCS was considerably lower than in American zoo elephants. ...
... Adding to this, given that the excretion rate of creatinine is constant, it is expected that males with a higher body mass should have higher creatinine levels. 5 Overall, the sex differences observed in health parameters mirror the differences in body size, behavior, and life history between male and female Asian elephants. Male elephants do not reach peak reproduction until their 30s or 40s 34 and experience a significantly higher mortality risk across all ages. ...
Article
The reference intervals of health parameters are valuable tools for veterinarians and conservationists to monitor the health status and viability of endangered species. Natural variation in the health of the long-lived Asian elephant (Elephas maximus) is poorly understood, particularly in relation to differences between males and females. Longitudinal health data were collected from clinical examination, hematology, and serum chemistry analyses over 3 yr from 227 healthy individually marked Asian elephants varying in age and sex. The study population was semicaptive and used in Myanmar's timber industry, but maintained natural feeding and breeding behavior. Body condition score (BCS) and blood pressure were investigated in clinical examinations. Hematological parameters included hematocrit, hemoglobin, total white blood cell count, and differential blood cell counts. Serum chemistry parameters included blood urea nitrogen, creatinine, total protein, albumin, globulins, aspartate aminotransferase, alkaline phosphatase, triglycerides, creatine kinase, glucose, calcium, potassium, sodium, and chloride. To the knowledge of the authors, this is the first description of BCS in an elephant population outside of zoos, and of blood pressure in this species using a novel adaptation of the Intelli Wrap Cuff pressure monitor. Several differences between the sexes were observed, with females generally having higher BCS and triglycerides, and males displaying higher alkaline phosphatase and glucose levels. This study provides important clinical tools that can be used to assess the health status and improve management in this endangered species.
... In contrast to UUN, the UCrn concentration changed with dietary protein level. Ever since Folin proposed that Crn metabolism is unaffected by dietary protein (17), UCrn had been considered to be unaffected by exogenous factors (18,34). In addition, because Crn synthesis depends on muscle mass, UCrn was considered to be constant. ...
... Therefore, we examined dietary amino-acid compositions. Biosynthesis of Cr, the precursor of Crn, begins with the production of guanidinoacetate from arginine and glycine in the kidneys, with arginine:glycine amidinotransferase as a catalyst (34,42). In the next stage, which occurs primarily in the liver and is catalyzed by guanidinoacetate methyltransferase, guanidinoacetate is methylated to yield Cr. ...
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Low protein diets (LPs) constitute a reportedly effective form of nutritional therapy for canine chronic kidney disease and cirrhosis. These diets have long been feared to result in reduced muscle mass due to protein catabolism. This adverse effect, however, remains largely unrecognized in veterinary medicine as there are no easily applicable catabolism indicators. Therefore, we focused on urinary creatinine, a metabolite of protein in the urine, and examined whether its ratio to urinary urea nitrogen (UCrn/UN) can be used to assess protein catabolism. In Experiment 1, we first consecutively fed seven healthy beagles an LP, standard protein (SP), and high protein (HP) diet for 1 week each and then measured the UCrn/UN ratio at 2-h intervals from fasting to 16 h post-prandially. We consequently found that the UCrn/UN ratio was significantly elevated in the LP pre-prandially and at all post-prandial measurement points (P < 0.01). No significant differences were observed between the SP and HP. Analysis of fasting plasma amino-acid concentrations revealed that the concentration of methionine was significantly lower in the LP than in the other diets (P < 0.05). Although the effects of this change in amino-acid concentration were unclear, the UCrn/UN ratio was considered having increased due to a deficiency in protein and/or amino acids during LP feeding. In Experiment 2, we continuously fed five healthy beagles an LP for 18 weeks and then measured the UCrn/UN ratio as described above. We also measured changes in body composition with computed tomography. At weeks 10 and 18, the fasting UCrn/UN ratio was significantly higher than it was prior to the start of the LP; however, post-prandially, the UCrn/UN ratio decreased to the point that the significant difference disappeared. Muscle mass decreased at weeks 10 and 18. These results suggest that the fasting UCrn/UN ratio could be used as an indicator of protein catabolism in LP feeding. Our experiments thus indicate that examination of potential increases in the UCrn/UN ratio 1 week after introduction of LP feeding to healthy dogs could enable detection of body protein catabolism in long-term feeding of LP before muscle breakdown occurs.
... 7,8 In addition, chronic infection with E canis may have an association with the development of kidney disease in dogs. 2 Many dogs recover from acute disease with appropriate therapy, although untreated or inappropriately treated dogs may develop subclinical disease that can persist for months to years. 9 [11][12][13] Traditional biomarkers for kidney function such as Cr and blood urea nitrogen (BUN) in some cases delay identification of an early decline in glomerular filtration rate (GFR) and early diagnosis of kidney disease. 11 Symmetric dimethylarginine (SDMA) has been shown to be well correlated to GFR and helps diagnose CKD earlier in dogs. ...
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Ehrlichiosis is a common vector-borne disease caused by Ehrlichia spp. This retrospective matched cohort study was performed to determine if dogs with Ehrlichia spp. antibodies had an increased incidence of chronic kidney disease (CKD). Exposure to Ehrlichia spp. was defined as having an Ehrlichia spp. antibody–positive result recorded at any point in their available patient history. The outcome of CKD was defined as concurrent increased symmetric dimethylarginine (>14 µg/dL) and creatinine (>1.5 mg/dL) for a minimum of 25 days with inappropriate urine specific gravity (<1.030). Patients were matched using propensity score matching to control for age, geography, and breed. A total of 22,440 patients and controls in E canis–endemic regions of the United States were used in this analysis. Contingency tables were used to compare dogs with and without exposure to Ehrlichia spp.–infected ticks and CKD outcome. The relative risk of CKD for patients exposed to ticks carrying Ehrlichia spp. was found to be 2.12 (95% confidence interval [1.35–3.15], p < 0.0006). This study identified that testing positive for Ehrlichia spp. antibodies in E canis–endemic regions is associated with higher incidence of CKD in dogs.
... A significant, although weak, correlation between sSDMA and sCr has been previously shown in CanL (Torrent et al., 2018). Since body weight loss and muscle wasting is a common clinical manifestation in CanL (Koutinas et al., 1999;Noli and Saridomichelakis, 2014), sSDMA may have an advantage as a kidney disease biomarker compared to sCr as the former, unlike sCr, does not depend on lean body mass (Braun et al., 2003;Hall et al., 2015;Pelander et al., 2019). Regardless, the replacement of sCr from sSDMA for the evaluation of canine CKD (including the CanL-associated CKD) is rather unlikely in the foreseeable future, because the diagnostic performance of sSDMA is not invariably superior to that of sCr and because the complementary use of both biomarkers may be of value in the detection of impaired GFR (Pelander et al., 2019). ...
Article
Canine leishmaniosis (CanL)-associated chronic kidney disease is a leading cause of morbidity and mortality in Mediterranean countries. Novel renal biomarkers, such as serum symmetric dimethylarginine (sSDMA), may be useful surrogates for the detection of renal functional impairment. The objectives of this study were to investigate sSDMA concentrations in dogs with CanL, with and without azotemia, and to establish any potential association with the prevalence and severity of proteinuria, with the prevalence of decreased urine specific gravity and with the LeishVet clinical stages of CanL. Serum samples from 68 dogs with CanL (50 nonazotemic and 18 azotemic) and 17 healthy dogs were retrospectively examined. Increased sSDMA was documented in 26 % of dogs with CanL without azotemia and in 83.3 % of dogs with azotemia. Serum SDMA was significantly higher in azotemic compared to nonazotemic dogs and was associated with the presence and severity of proteinuria, the decreased urine specific gravity and the advanced clinical stages of CanL. The results of the present study indicate that sSDMA may be a useful adjunct to serum creatinine and urine protein/creatinine ratio for the detection of CanL-associated nephropathy, but it is of limited value for distinguishing among the LeishVet clinical stages of CanL.
... The finding of a low prevalence rate of acute kidney injury in this study could be attributed to the fact that serum creatinine and urea are generally insensitive and nonspecific markers for early detection of kidney injury and renal dysfunction (Braun et al., 2003;Defauw et al., 2018). These non-specific bio-markers are only altered when more than 75% of renal mass has been lost (De loor et al., 2013). ...
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The causes of kidney dysfunction could be related to damages to the glomeruli, nephron, tubules, interstitial tissues and renal blood vessels. The aim of this study was to determine the prevalence of increased levels of serum urea and serum creatinine in dogs presented at the University of Nigeria Veterinary Teaching Hospital (UNVTH). A kidney function test was conducted in dogs for a six-month period (January - June) using kidney function biomarkers (creatinine and urea). A total of 45 dogs were examined. For each dog presented, two milliliters of blood were collected from the cephalic vein for serum biochemistry determinations. Data obtained from this study were analyzed using descriptive statistics. CHI square was used to calculate the strength of association between increased levels of serum urea and creatinine, and sex, age and breed. The prevalence of increased level of serum urea was 71.1% while that of increased level of serum creatinine was 8.9%. There were no significant association between increases in serum creatinine or serum urea, and sex, age and breed. The prevalence of acute kidney injury was 8.9%. There was no significant association between acute kidney injury (AKI) and sex, age and breed but the risk of having AKI in older dogs were higher if dehydrated and if there was an obstruction to urinary outflow. The results of this study have shown that a greater number of dogs presented at UNVTH suffered from mild loss of kidney function which was not the reason for their presentation at UNVTH. Therefore, routine kidney function tests should be conducted especially on severely sick dogs, as this will help in choice of the drugs.
... Also, Cr can be falsely lowered in patients with poor muscle mass. 29 Reductions in lean body mass are common with ageing and chronic disease, when accurate detection of alterations in kidney function may become increasingly important. 30 It is interesting that, in this analysis, many of the breeds with increased SDMA concentrations but not increased Cr concentrations were small breeds. ...
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Background Kidney disease, especially chronic kidney disease (CKD), is common in older dogs. The biomarkers symmetric dimethylarginine (SDMA) and creatinine (Cr) are indicators of glomerular filtration rate (GFR). This retrospective study used these biomarkers to identify groups at risk of decreased GFR at the breed level. Methods Data from dogs with a single serum chemistry result that included Cr and SDMA submitted between July 2015 through December 2017 were included. Dogs were identified by breed and age group. Decreased GFR was defined as Cr above 1.9 mg/dl or SDMA above 18 µg/dl. Results Fourteen breeds had a significantly higher percentage of dogs with increased SDMA or Cr for one or more age groups. Geriatric and senior Shetland sheepdogs, Yorkshire terriers and Pomeranians were significantly more likely to have increased renal biomarkers. Boxers were identified with significantly increased renal biomarkers in the age groups spanning two months to 10 years of age. Conclusion Evidence of decreased GFR occurred commonly in older dogs of most breeds, especially geriatric dogs greater than 10 years of age, but there were some exceptions, with more significant changes affecting younger animals of several breeds. The combination of SDMA and Cr identified more cases of decreased GFR than either SDMA or Cr alone.
... The effect of meal on plasma CysC concentration was studied in dog. The concentration of plasma CysC showed a dramatic decrease during the first hour after a meal and this decrease lasted for 9 h and then returned to baseline after 12 h (Braun et al., 2002) in contast to plasma Cr concentration, which increases in dogs during the first 12 h after a meal (Braun et al., 2003). The increased clearance of CysC could explain it's decreased concentration after a meal because its concentration is mainly determined by GFR (Gislefoss et al., 2009). ...
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The livestock sector contributes largely to the economy of India. Different systemic diseases like renal diseases, neurological and cardiovascular diseases cause huge loss in production and productive potential of livestock in India, which is considered as a major concern for both small and large ruminants. Early detection of diseseses is essential to combat the economic loss. An efficient biochemical marker can be developed which would provide more specific, sensitive and reliable measurement of functions of different organs. Determination of endogenous marker Cystatin C may fulfill the above need which can provide a detection platform not only for Kidney function but also for assaying other organs’ function. Cystatin C is a low molecular weight protein which is removed from the bloodstream by glomerular filtration in the kidneys. Thus, it may act as a potential biological tool in diagnosis of renal and other systemic diseases in livestock. This mini-review focuses on the Cystatin C and its clinical importance which can be extensively employed in the livestock sector.
... [8][9][10] In our study, IH achieved a 9% decrease in sCr concentrations, whereas in the IF group, sCr concentrations increased 31%. As an endogenous marker of renal function, SDMA is closely related to GFR, [36][37][38][39][40] less affected by IH clerance, [12][13][14]24,28,30,31 and less affected by hydration status, providing a better clinical representation of kidney function and disease progression than sCr in IHtreated dogs. ...
Article
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Background: Symmetric dimethylarginine (SDMA) is a methylated arginine derived from intranuclear methylation of l-arginine by protein-arginine methyltransferase and released into circulation after proteolysis. It is primarily eliminated by renal excretion, and its concentration is highly correlated with glomerular filtration rate (GFR) in animals and humans and is an earlier indicator of kidney dysfunction than serum creatinine concentration (sCr). Objectives: To evaluate and quantify the effects of IV fluid therapy (IF) or intermittent hemodialysis (IH) on renal function in a randomized group of dogs previously diagnosed with International Renal Interest Society (IRIS) stage 4 chronic kidney disease (CKD). Animals: Twenty-four client-owned dogs with naturally occurring CKD. Methods: Serum from 14 dogs treated by IH and 10 dogs treated with IF was submitted for measurement of sCr and SDMA. Dogs in each treatment group received up to 5 treatment sessions, administered 48 hours apart. Results: Significant differences (P ≤ .05) were seen between treatment groups, but dogs from the IH group were the most affected based on SDMA (P < .001), sCr (P < .001), and blood urea (P < .001) concentrations. Furthermore, for each 10% increase in urea reduction ratio, there was a 6.2 μg/dL decrease in SDMA (P = .002). Conclusions and clinical importance: Although SDMA is dialyzable biomarker and despite its removal by IH, SDMA correlates better with renal function than does sCr in dogs with CKD undergoing IF and IH.
... However, SCr sensitivity is low and shows alterations only after two-thirds of functional renal mass have been lost, so it cannot detect early kidney dysfunction. 2,3 Glomerular filtration rate (GFR) is currently considered the best indicator of renal function and the most sensitive and specific test for early diagnosis of CKD. 4,5 In veterinary practice, a routine method for measuring GFR is based on monitoring plasma clearance of iohexol by high-performance liquid chromatography-ultraviolet (HPLC-UV). ...
Article
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Background: Glomerular filtration rate (GFR) is the most sensitive indicator of initial renal function decline during chronic kidney disease (CKD), but conventional protocols for measuring GFR are labor-intensive and stressful for the dog. Objectives: To assess the diagnostic potential for detecting CKD with simplified GFR protocols based on iohexol plasma clearance. Animals: Seventeen CKD-positive and 23 CKD-negative dogs of different breeds and sex. Methods: Prospective nonrandomized study. Plasma iohexol was measured 5, 15, 60, 90, and 180 minutes after injection. Glomerular filtration rate was calculated using 5 samples (GFR5 ) or simplified protocols based on 1, 2, or 3 samples. The GFR5 and simplified GFR were compared by Bland-Altmann and concordance correlation coefficient (CCC) analysis, and diagnostic accuracy for CKD by receiver operating characteristic curves. A gray zone for each protocol was bounded by the fourth quartile of the CKD-positive population (lower cutoff) and the first quartile of the CKD-negative population (upper cutoff). Results: All simplified protocols gave reliable GFR measurements, comparable to reference GFR5 (CCC >0.92). Simplified protocols which included the 180-minutes sampling granted the best GFR measure (CCC: 0.98), with strong diagnostic potential for CKD (area under the receiver operating characteristic curve ± SE: 0.98 ± 0.01). A double cutoff including a zone of CKD uncertainty guaranteed reliable diagnosis outside the gray area and identified borderline dogs inside it. Conclusions: The simplified GFR protocols offer an accurate, hands-on tool for CKD diagnosis in dogs. The gray zone might help decision-making in the management of early kidney dysfunction.
... Azotemic CKD was diagnosed where there was a persistent increased serum creatinine above the internal laboratory reference interval (RI: <140 µmol/dL) and concurrent inadequate urinary concentration ability (persistent urine specific gravity (USG) < 1.035). Nonazotemic CKD was diagnosed where serum creatinine was normal (<140 µmol/L) but one or more of the following abnormalities was present: (1) inadequate urinary concentration ability (persistent USG < 1.035), (2) abnormal renal imaging findings or (3) serially increasing serum creatinine concentration (over a time period of >3 months) [25]. These cats were staged in accordance with the International Renal Interest Society (IRIS) staging guidelines [26]. ...
Article
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The endothelin-1 (ET-1) system has been implicated in the development and progression of chronic kidney disease (CKD). No information on big ET-1 in feline urine is available. The purpose of this study was to evaluate if urinary big endothelin-1 (bigET-1) is associated with feline CKD. Sixty urine samples were prospectively collected from 13 healthy cats at risk of developing CKD and 22 cats with CKD of different International Renal Interest Society (IRIS) stages (1–4). Urinary bigET-1 was measured using a commercially available ELISA. BigET-1 normalized to urine creatinine (bigET-1:UC) was compared amongst stages and substages, as proposed by IRIS, and correlated with serum creatinine concentration, proteinuria and blood pressure. BigET-1:UC at the time of inclusion was compared between cats that remained stable and cats that progressed after 12 months. BigET-1:UC was significantly higher (p = 0.002) in cats at IRIS stages 3–4 (median: 21.9; range: 1.88–55.6), compared to all other stages, and in proteinuric (n = 8, median: 11.0; range: 0.00–46.4) compared with nonproteinuric cats (n = 38 median: 0.33; range: 0.00–55.6) (p = 0.029). BigET-1:UC was not associated with CKD progression. Urinary bigET-1 increased in advanced stages of CKD and in proteinuric patients, suggesting that ET-1 may be indicative of the severity of feline CKD.
... 6 Presence of renal azotemia reflects irreversible loss of 50% to 75% of functional nephrons, correlating to 50% to 60% decrease in kidney function. 9,10 This discrepancy is attributable to compensatory hyperfiltration of remaining nephrons. With the goal of maintaining the homeostasis, reduction of nephron mass leads to increase in perfusion and filtration of surviving nephrons. ...
Article
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Background Glomerular filtration rate (GFR) is the gold standard in assessing renal function but is impractical. Serum creatinine (sCr) has limited sensitivity in identifying early chronic kidney disease (CKD), whereas symmetric dimethylarginine (SDMA) has been commercialized as more accurate biomarker. Studies comparing SDMA and sCr with GFR in cats are limited. Objectives To further investigate the diagnostic performance of SDMA in nonazotemic and azotemic cats. Animals Forty‐nine client‐owned cats: 17 cats with CKD, 15 cats with diabetes mellitus (DM), and 17 healthy cats. Methods Retrospective study using spare blood samples from cats with documented sCr and GFR results for SDMA analysis. Diagnostic performances of SDMA and sCr were evaluated using correlation coefficients, sensitivities, specificities, and receiver operator characteristic curves. Results Compared to healthy cats and cats with DM, CKD cats had significantly higher SDMAplasma (26.7 ± 9.9 μg/dL) and sCr (249.7 ± 71.6 μmol/L [2.8 ± 0.8 mg/dL]; both P < .001) values. SDMAplasma (τB = −0.57; P < .001) and sCr (τB = −0.56; P < .001) were significantly correlated with GFR. SDMAplasma (τB = 0.52; P < .001) had a significant relationship with sCr. SDMAplasma and sCr had similar sensitivity (76%‐94% and 71%‐88%, respectively) in detecting reduced renal function. Creatinine had higher specificity (94%‐96%) than SDMAplasma (75%‐76%) (P < .05). Conclusion and Clinical Importance In this study of azotemic and nonazotemic cats, SDMA was a reliable marker to identify decreased GFR. However, superiority of SDMA over sCr could not be confirmed.
... Serum creatinine, the surrogate marker of glomerular ltration rate (GFR) routinely used to assess renal function in dogs, is insensitive for diagnosing early or mild dysfunction (10,11). Furthermore, renal damage can be present without subsequent loss of function (12), thus limiting the use of such functional biomarkers in AKI diagnosis. ...
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Background Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 hours after bite, as well as 14 days later, using sCr and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs. Results Thirty-five envenomated dogs and 37 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Compared to controls, urinary albumin /uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1 /uCr were significantly elevated 12 hours (p < 0.001, p< 0.001, p = 0.01), 24 hours (p < 0.001, p < 0.001, p = 0.003) and 36 hours ( p < 0.001, p< 0.001, p = 0.001) after bite. Osteopontin /uCr was higher 24 and 36 hours after bite (p < 0.001), kidney injury molecule-1 /uCr, interleukin-8 /uCr and γ- glutamyl transferase /uCr were significantly higher 36 hours after bite (p = 0.0007, p = 0.0005, p= 0.001). Urinary cystatin C /uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls. Conclusion Urinary biomarker/Cr ratios are indicative of transient non-azotaemia AKI in dogs envenomated by V. berus.
... Evaluation of kidney function is done by direct measurement of Glomerular Filtration rate (GFR), but it is very labour intensive and time consuming [3] . Indirect markers of GFR i.e. serum Creatinine (sCr) and blood Urea Nitrogen (BUN) can be easily measured but the only disadvantage is that they are influenced by non-renal factors, such as age, diet, hydration status and muscle mass [4] . To overcome this problem, an ideal endogenous marker should be evaluated to assay the kidney function. ...
... However, it is not 100% reliable in renal function because it is affected by both protein intake and muscle mass (Braun et al. 2008). Creatinine level decreases with age. ...
Article
Eurasian JHS 2019;2(4(suppl)):179-181 d e r g i p a r k. gov. t r / av ra sya s b d ABSTRACT Chronic Kidney Disease is an important disease mainly in elderly and some breed cats. The duration of clinical findings in renal failure is not sufficient for early diagnosis. The kidney is an organ that can stabilize itself and continue to function until it loses 75% of its function. Unfortunately emergence of clinical findings is only possible at this time and this is the most important factor that makes treatment difficult. Creatinine has an more important place in the diagnosis of renal failure than urea but rise in blood occurs when 75% of kidney function is lost. Therefore, creatinine is not an adjunct parameter in early diagnosis. There is a new biomarker that has just begun to be discovered and is included in the studies for early diagnosis: Symmetric Dimethylarginine (SDMA). SDMA and kidney function are highly correlated. SDMA is a methylated arginine amino acid. SDMA is excreted by the kidneys. In this study, blood results of cats diagnosed with chronic renal failure were compared. Also, SDMA and creatinine were compared in some patients and their effects on diagnosis were considered. SDMA, creatinine and BUN values were measured in a blood sample taken from a 10 year old hybrid female cat. SDMA value (15 µg / dL) was high, creatinine (2.2 mg / dL) and BUN (23 mg / dL) values were within normal ranges. This shows us that kidney function is still working, and renal insufficiency is at an early stage. According to the results, the increase in creatinine is correlated with SDMA. As SDMA increases, the loss of renal function increases as a percentage and leads to an increase in creatinine over time. More detailed information can be gathered on the role of SDMA and creatinine in early diagnosis and its relationship with kidney. ÖZET KBY başlıca yaşlı ve bazı ırk kediler olmak üzere tüm hayvanlarda önemli bir hastalıktır. Böbrek yetersizliğinde klinik bulguların ortaya çıkış süresi erken tanı için yeterli değildir. Böbrek kendini dengeleyebilen ve işlevinin %75'ini kaybedene kadar görevini yerine getirmeye devam edebilen bir organ olduğu için klinik bulguların ortaya çıkması da ancak bu zamanda mümkündür. Maalesef bu durum tedaviyi zorlaştıran en önemli etkendir. Kreatinin Böbrek yetmezliği tanısında üreden bile daha önemli bir yere sahiptir; fakat kanda yükselmesi ancak böbrek fonksiyonunun %75'inin kaybolmasında ortaya çıkmaktadır. Dolayısıyla Kreatinin erken tanıda yardımcı bir parametre değildir. Yeni yeni keşfedilmeye başlanan ve çalışmalarda erken tanı için yer verilen yeni bir biyobelirteç mevcuttur: Simetrik Dimetilarjinin (SDMA). SDMA ve böbrek fonksiyonu yüksek korelasyon içindedir. SDMA bir metillenmiş arginin amino asididir. SDMA böbrekler tarafından atılır. Bu çalışmada kronik böbrek yetmezliği tanısı konmuş kedilere ait kan sonuçları karşılaştırılmıştır ve bazı hastalarda SDMA ile kreatinin karşılaştırılarak tanıdaki etkileri göz önünde bulundurulmuştur. 10 yaşında melez dişi bir kediden alınan kan örneğinde SDMA, kreatinin ve BUN değerlerine bakılmıştır. SDMA değeri 15 µg/dL yani yüksek kreatinin (2.2 mg/dL) ve BUN (23 mg/dL) değerleri ise normal aralıklarda çıkmıştır. Bu bize Böbrek fonksiyonlarının çalıştığını ancak böbrek yetersizliğinin başlangıç aşamasında olduğunu göstermektedir. Burdan çıkarılabilecek sonuca göre SDMA ile Kreatinin artışı korelasyon içindedir ve SDMA yükseldikçe böbrek fonksiyonundaki kayıplar yüzde olarak artmaktadır ve zamanla Kreatininde yükselmesine neden olmaktadır. Daha ayrıntılı çalışmalar yaparak SDMA ile Kreatininin erken tanıdaki rolü ve böbrekle ilişkisi hakkında bilgi toplanabilir. Anahtar kelimeler: Kreatinin, Kronik Böbrek Yetmezliği, SDMA. d e r g i p a r k. gov. t r / av ra sya s b d
... It needs to be taken into account, that dietary protein levels in experimental diets of that study varied between 18% and 22% DM, which is lower than the high-protein diets used in present study. In general, urinary creatinine excretion is considered to be constant in dogs (Braun et al., 2003), although our data indicate a numerical effect by dietary protein level. The urinary concentration of indican was not affected by the experimental treatments. ...
Article
Brewer’s spent grain (BSG) and carrot pomace (CAP) were used as fiber sources in low or high protein diets in dogs. Ten adult Beagles were involved in five feeding periods of 19 days in a cross-over design. Experimental diets contained 7.5 % of total dietary fiber from BSG or CAP and 20 % or 40 % of crude protein in dry matter. A diet with 3.5 % total dietary fiber from both fiber sources and 20 % crude protein was used as reference. Fecal dry matter was 27 % higher for diets with BSG compared to CAP (P < 0.001). Apparent fecal digestibility of crude protein was 7-11 % higher in diets with 40 % protein concentration (P < 0.001), while apparent digestibility of crude fat was 2–3 % higher for diets with CAP (P < 0.001). CAP increased the apparent fecal digestibility of total dietary fiber, phosphorus and magnesium (p<0.001), while 40 % protein diets had a positive impact on total dietary fiber and sodium and a negative effect on magnesium apparent fecal digestibility (p<0.001). Inclusion of CAP increased fecal short chain fatty acids (P = 0.010), mainly acetate (P = 0.001). I-butyrate (P = 0.001), i-valerate (P = 0.002), biogenic amines (P < 0.001) and ammonium (P < 0.001) increased with higher dietary protein levels. Diet induced changes in the fecal microbiome were moderate. Relative abundance of Bifidobacteriales was higher for the low protein diets (P = 0.001). To conclude, BSG and CAP can be used as fiber sources in canine diets and are well tolerated even at higher inclusion rates, the effect on microbial protein fermentation seems to be limited compared to the dietary protein level.
... By contrast, Lobo et al. [2] reported an increase of serum creatinine in lambs as the dietary level of phenolic compounds was increased. On the other hand, it is known that serum creatinine increases in cases of chronic and acute renal failure [54], which suggests that the HM used in the present study did not affect renal health. ...
Article
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The objective of this study was to determine the effects of the supplementation of a polyherbal mixture (HM) on the productive performance, carcass characteristics, meat quality, and the profile of blood metabolites of lambs fed a high-concentrate diet. Thirty-six male Pelibuey lambs (25.21 ± 0.96 kg BW) were housed in individual pens during a 56-day feeding period and were randomly assigned to four treatments: (1) Control (CON): Basal diet without HM; (2) HM1: CON + 1 g of HM kg−1 dry matter (DM); (3) HM2: CON + 2 g of HM kg−1 DM; and (4) HM3: CON + 3 g of HM kg−1 DM. Data were analyzed using the GLM (General Linear Model) procedure of statistical analysis system (SAS), and linear and quadratic effects were tested to evaluate the effects of the HM level. A quadratic increase was observed in the dry matter intake and in daily weight gain (p < 0.05) of lambs fed with HM2 and HM1, respectively. However, final body weight, body condition, carcass characteristics, and meat quality were similar among treatments (p > 0.05). It was observed a linear increase (p < 0.05) in the mean corpuscular hemoglobin concentration. Lymphocytes in blood from lambs supplemented with the HM1 diet increased and segmented neutrophils decreased compared to lambs receiving the CON treatment (p < 0.05). The concentration of uric acid in the blood had a linear increase (p < 0.05) and the serum creatinine level decreased (p < 0.05) as the HM dietary dose increased. In conclusion, dietary inclusion of 2 and 1 g of HM kg−1 of DM improves feed consumption and daily weight gain, respectively, without affecting carcass characteristics, meat quality, and health status on finishing lambs.
... Serum creatinine, the surrogate marker of glomerular filtration rate (GFR) routinely used to assess kidney function in dogs, is insensitive for diagnosing early or mild dysfunction [10,11]. Serum symmetric dimethylarginine (SDMA) is reportedly a more sensitive and specific marker for GFR than sCr in dogs [11]. ...
Article
Full-text available
Background: Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) and symmetric dimethylarginine (SDMA) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 h after bite, as well as 14 days later, using sCr, SDMA and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs. Results: Thirty-five envenomated dogs and 35 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Serum SDMA did not exceed 0.89 μmol/L in any dog. Compared to controls, urinary albumin/uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1/uCr were significantly elevated 12 h (P < 0.0001, P < 0.0001, P = 0.01), 24 h (P < 0.001, P < 0.001, P = 0.002) and 36 h (P < 0.001, P < 0.001, P = 0.0008) after bite. Osteopontin/uCr was higher 24 and 36 h after bite (P < 0.0001), kidney injury molecule-1/uCr, interleukin-8/uCr and γ- glutamyl transferase/uCr were significantly higher 36 h after bite (P = 0.003, P = 0.0005, P = 0.001). Urinary cystatin C/uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls. Conclusion: Urinary biomarker/Cr ratios are indicative of mild transient, non-azotaemic AKI in dogs envenomated by V. berus.
... In determining GFR, serum homocysteine level plays a key role in early diagnosis of kidney diseases compared to serum creatinine level [16,29] . Serum creatinine and blood urea nitrogen measurements are easy for indirect symptoms of GFR [30] . Increased protein catabolism due to fasting, other than prerenal insufficiency, exacerbates the increase in serum urea concentration in calves with diarrhea [2] . ...
Article
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The aim of this study was to investigate the relationship between serum homocysteine (HCY), and creatinine, urea, venous blood gas and electrolytes values in neonatal calves with diarrhea. The study was conducted on a total of 30 calves, 20 with diarrhea and 10 healthy (control), with diarrhea complaints, of different races, sexes and ages ranging from 2-24 days. According to the venous blood gas results, the pCO2 and base deficit values of calves with diarrhea were significantly higher (P
... In determining GFR, serum homocysteine level plays a key role in early diagnosis of kidney diseases compared to serum creatinine level [16,29] . Serum creatinine and blood urea nitrogen measurements are easy for indirect symptoms of GFR [30] . Increased protein catabolism due to fasting, other than prerenal insufficiency, exacerbates the increase in serum urea concentration in calves with diarrhea [2] . ...
Article
Full-text available
The aim of this study was to investigate the relationship between serum homocysteine (HCY), and creatinine, urea, venous blood gas and electrolytes values in neonatal calves with diarrhea. The study was conducted on a total of 30 calves, 20 with diarrhea and 10 healthy (control), with diarrhea complaints, of diff erent races, sexes and ages ranging from 2-24 days. According to the venous blood gas results, the pCO2 and base deficit values of calves with diarrhea were significantly higher (P<0.001) compared to the control group values, while pH, pO2 and HCO3 values were significantly lower (P<0.001). While serum Na + and Cl-concentrations in diarrheic calves did not show any statistical change when compared to the control group (P>0.05), serum K + concentrations were statistically higher (P<0.001). Serum HCY, folate and vitamin B12 concentration values of diarrheic calves were significantly higher (P<0.001) when compared to the control group. As a result; in neonatal calves with diarrhea, it has been concluded that homocystein excretion is disrupted by low renal excretion due to decrease in glomerular filtration rate that caused hyperhomocysteine. In addition, it is thought that this study will shed light on studies that will reveal the eff ect of hyperhomocysteinemia in the cardiovascular system in diarrheic calves. Bu çalışmanın amacı ishalli yenidoğan buzağılarda serum homosistein (HCY) ile kreatinin, üre, venöz kan gazı ve elektrolit değerleri arasındaki ilişkiyi araştırmaktır. Araştırma, ishal şikayeti olan, farklı ırk ve cinsiyette ve yaşları 2-24 gün arasında değişen 20 ishalli ve 10 sağlıklı (kontrol) olmak üzere toplam 30 buzağı üzerinde yürütüldü. Venöz kan gazı sonuçlarına göre, ishalli buzağıların pCO2 ve baz açığı değerleri kontrol grubu değerlerine göre önemli (P<0.001) düzeyde yüksek belirlenirken, pH, pO2 ve HCO3 değerleri anlamlı (P<0.001) düzeyde düşük saptandı. İshalli buzağılarda Na + ve Cl-elektrolit konsantrasyonlarının seviyeleri kontrol grubuna göre anlamlı bulunmazken, serum K + elektrolit konsantrasyon seviyeleri kontrol grubuna göre önemli düzeyde (P<0.001) yüksek tespit edildi. İshalli buzağıların serum HCY, folat ve vitamin B12 konsantrasyon değerleri kontrol grubuna göre anlamlı olarak yüksek (P<0.001) bulundu. Sonuç olarak; yenidoğan ishalli buzağılarda sıvı kaybına bağlı olarak dolaşımdaki sıvı hacmi azalmakta ve böbreklerin glomüler filtrasyon hızı düşmektedir. Böbreklerde düşen glomüler filtrasyon hızına bağlı olarak homosisteinin böbrek yoluyla atılımı aksamakta ve sonucunda da hiperhomosisteine neden olmaktadır. Ayrıca ishal vakalarında artan homosistein konsantrasyonlarının kardiyovasküler sistemde bozukluklara neden olup olmadığına yönelik yapılacak araştırmalara ışık tutacaktır.
... The historical Cr results were obtained through different laboratories, and although Jaffe's reac-tion method has been commonly used for many years, different laboratory reagents of measurement could result in confounding effects of intralaboratory variance. 3 Moreover, one study in cheetahs also found no significant difference between the results from the original sampling compared with the results obtained on the same banked samples, which were frozen for 26 years. 32 Table 2. Summary of histologic lesions found in the kidney of seven tigers (Panthera tigris). ...
Article
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Chronic kidney disease (CKD) is a common cause of morbidity and mortality in captive tigers (Panthera tigris). Blood creatinine (Cr) and blood urea nitrogen measurements are inexpensive and common biomarkers used to evaluate renal function. However, several limitations have been reported regarding their sensitivity and interindividual variability. Symmetric dimethylarginine (SDMA) has been suggested to be a more sensitive biomarker that is less affected by extrarenal factors and has a strong correlation with glomerular filtration rate and blood Cr in several species. This project aimed to identify the usefulness of SDMA as an endogenous marker of kidney function in captive tigers. The hypothesis of this study is that increased circulating SDMA is positively associated with increased blood Cr. SDMA and Cr were measured in 65 banked samples (serum and plasma) from 30 individual captive tigers. The samples were collected over a 38-y period and stored at -21°C. SDMA and Cr concentrations were determined using the commercially available SDMA test and enzymatic colorimetric methods, respectively. SDMA had a significant positive association with Cr (for every 1 unit increase of log SDMA, Cr increased by 82%, P = 0.0002). Age and subspecies influenced Cr but not SDMA concentrations. In one animal, blood SDMA increased above the ZIMS reported range. approximately 3.6 mo before Cr increased. SDMA is currently indicated for the diagnosis of CKD in domestic felids and seems also promising in nondomestic felids. Further prospective studies might improve the understanding of the performance of this biomarker.
... approximately 20-40 mg/kg/day; humans: approximately 1000-2000 mg/day in adults [20-40 mg/kg/day for a body weight of 50 kg]) (Bingham et al., 1988;Braun et al., 2003). In the taxonomy of mammals, raccoons and dogs are classified in Carnivora; thus, dogs are much closer to raccoons than humans. ...
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Toxicological effects of NNIs have been reported for mammals, such as humans, rats, and mice. However, there are limited reports on their toxic effects on wild mammals. To predict NNI‐induced toxic effects on wild mammals, it is necessary to determine the exposure levels and metabolic ability of these species. We considered that raccoons could be an animal model for evaluating NNIs‐induced toxicities on wildlife as they inhabit near agricultural fields and eat crops treated with NNIs. The objective of this study was to estimate the effects of NNIs exposure on wild raccoons. Urinary concentrations of NNI compounds (n=59) and cytochrome P450‐dependent metabolism of NNIs (n=3) were evaluated in wild raccoons captured in Hokkaido, Japan, in 2020. We detected either of the six NNIs or one metabolite, including acetamiprid, imidacloprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, and desmethyl‐acetamiprid in 90% of raccoons (53/59); the average cumulative concentration of the 7 NNI compounds was 3.1 ng/mL. The urinary concentrations were not much different from those reported previously for humans. Furthermore, we performed an in vitro assessment of the ability of raccoons to metabolize NNIs using hepatic microsomes. The amounts of NNI metabolites were measured using LC/ESI/MS/MS and compared with those in rats. Raccoons showed much lower metabolic ability; the Vmax/Km values for raccoons were 1/10 to 1/3 of those for rats. For the first time, we show wild raccoons could be frequently exposed to NNIs in the environment, and the cytochrome P450‐dependent metabolism of NNIs in the livers of raccoons might be low. This study would contribute to better understandings of the effects of NNIs on raccoons, leading to better conservation efforts for wild mammals. This article is protected by copyright. All rights reserved.
... Serum creatinine levels also tended to increase with advancing age. Our results are consistent with some studies [4,5,10,20]. Moreover, the lower creatinine in young animals, in relation to adults, correlates with the smaller body size and lower muscle mass [1]. ...
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Background Blood biochemistry and reference intervals help to differentiate between healthy and ill dogs as well as to provide information for the prognosis, evaluation, and monitoring; however, these intervals are often obtained from adult animals. It is essential to understand that puppies and adults are physiologically different, which justifies the need to obtain age-specific biochemical reference intervals. The aim of this research was to assess the potential effect of age, sex, body size, and their interaction on routine biochemical analytes and physiological constants (body temperature, heart rate, and respiratory rate). To carry out the research, we selected 197 healthy dogs of both sexes and different body sizes (small, medium and large) classified by age: group I (4–8 wk), group II (9–24 wk), group III (25–52 wk), and group IV (> 52 wk). The biochemical analysis included the measurement of the enzymatic activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and the concentrations of cholesterol, triglycerides, total proteins, albumin, globulins, glucose, urea, and creatinine. Statistical analyses used analysis of variance (ANOVA) and a general linear model (GLM), which allows the comparison of multiple factors at two or more levels (p < 0.05). Results The results of this study showed that ALT, total protein, albumin, globulin, urea, creatinine, and body temperature levels were lower in puppies than in adult dogs of group IV (p < 0.05), while the enzymatic activity of ALP, LDH, glucose concentration, and heart rate were higher. Whereas sex, body size and the interaction did not show a significant effect (p > 0.05). Conclusions Some biochemical components are influenced by age. For this reason, this manuscript contributes with additional data for the clinical interpretation of blood biochemical results in puppies.
... Serum creatinine concentration solely reflects changes in glomerular filtration rate (GFR) rather than tubular injury per se, rendering it unsuitable for detecting AKI when the injury is not associated with a measurable decrease in GFR. 8,9 Early recognition of a tubulopathy and International Renal Interest Society (IRIS) Grade-I AKI might allow timely intervention and improve outcome. This can be achieved by utilizing urinary (u) biomarkers, whose activity or concentration in urine soon increase after renal tubular injury. ...
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Background: Early recognition of acute kidney injury (AKI) is hindered by current definitions and use of traditional, insensitive markers. Hypothesis/objectives: Urinary (u) activity of γ-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), and concentrations of heat-shock protein 70 (HSP70) and interleukins (ILs) -6 and -18, are predictive biomarkers for AKI and survival. Animals: Nonazotemic, hospitalized dogs (n = 118) and healthy controls (n = 20). Methods: A prospective observational study. Nonazotemic dogs at risk of AKI were recruited and their urinary biomarker concentrations were measured at presentation. Serum creatinine (sCr) and symmetric dimethylarginine (sSDMA) were measured daily until discharge/death. Results: The overall case fatality rate was 18.6%. Fifteen dogs (12.7%) developed AKI, which was associated with death (relative risk, 3.2; 95% confidence interval [CI], 1.57-6.55). All 5 urinary biomarkers were significantly higher in hospitalized dogs compared to controls, with minimal overlap. uHSP70/uCr, uGGT/uCr, and uIL-6/uCr at presentation were higher in dogs which later developed AKI. Areas under the receiver operator characteristic curve (AUROC) (95% CI) for the 3 biomarkers as predictors of AKI were 0.67 (0.51-0.83), 0.68 (0.55-0.81), and 0.78 (0.65-0.91), respectively. When they were categorically classified as elevated/normal, each additional elevated biomarker increased the odds for AKI (OR, 2.83; 95% CI, 1.23-6.52, P = .01). Agreement between sCr and sSDMA was poor (Cohen's kappa = .071). The AUROC of SDMA at presentation for AKI prediction was 0.73 (0.51-0.95). Conclusions and clinical importance: Kidney injury was common, irrespective of subsequent worsening of azotemia or death. The predictive value of individual urinary biomarkers was reduced by moderate sensitivities and specificities. SDMA showed moderate discriminatory utility for AKI prediction, and often displayed discordant results with sCr.
... Our results are relatively consistent with previous research showing lower albumin [23,70,71] and creatinine [14,22,24,70,71] levels in puppies and young dogs than in adult dogs, and decreasing albumin [24][25][26] and creatinine [14,24] levels in old dogs. Creatinine concentration is affected by lean body mass [72,73] whereas low albumin level is predictive of poor muscle mass and may increase the risk of sarcopenia in the elderly [74]. Thus, the observed association between these measurands and age may reflect differences in the muscle mass of dogs of different ages. ...
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As an individual's metabolism reflects health and disease states well, metabolomics holds a vast potential in biomedical applications. However, normal physiological factors, such as age, can also influence metabolism, challenging the establishment of disease-specific metabolic aberrations. Here, we examined how physiological and diet-related factors drive variance in the metabolism of healthy pet dogs. We analysed 2068 serum samples using a canine nuclear magnetic resonance (NMR) spectroscopy-based metabolomics platform. With generalized linear models, we discovered that age, breed, sex, sterilization, diet type and fasting time significantly affected the canine metabolite profiles. Especially, breed and age caused considerable variation in the metabolite concentrations, and breeds with very different body conformations systematically differed in several lipid measurands. Our results enhance the understanding how normal physiological factors influence canine metabolism, aid accurate interpretation of the NMR results, and suggest the NMR platform might be applied in identifying aberrations in nutrient absorption and metabolism.
... Descriptions of used methods and interassay coefficient of variation are reported elsewhere. 23 Urinary dipstick analysis (Combur 10 Test, COBAS; Roche Diagnostics Ltd), USG using a refractometer (Indiko Plus; ThermoFisher Scientific), and sediment examination were performed immediately after collection. Urinary proteins and Cr were measured by pyrogallol red and kinetic Jaffé methods, respectively, using an automated analyzer, and urinary protein-to-creatinine ratio (UPC) was subsequently determined. ...
Article
Objective: 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. Animals: 14 healthy Beagles. Procedures: 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. Results: 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). Clinical relevance: 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.
... Hence, physiological factors such as age, muscle mass, breed, exercise and the effect of meals should be taken into account when an increase in plasma creatinine is observed. Furthermore, sCr has shown lower sensitivity as a marker of renal function in dogs with portosystemic shunts and in cats with hyperthyroidism [15,29]. To overcome the aforementioned limits of sensitivity and sensibility, the IRIS staging guidelines recommend that sCr should be evaluated in fasted, stable, well-hydrated patients on at least two occasions. ...
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Chronic kidney disease is a common kidney disorder in adult and aged dogs and cats; the management of associated complications and comorbidities generally requires a life-long medical treatment to ensure a good quality of life of affected patients. However, indications and the literature on drug dosing in dogs and cats with chronic kidney disease are often lacking. The aim of this review is to revise the current literature on drug dosing in canine and feline patients with renal impairment, with a special focus on the most commonly used medications to manage chronic kidney disease and possible comorbidities.
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Dogs with babesiosis can present with multiple complications, including acute kidney injury (AKI). The objective of this study was to characterize AKI in dogs with babesiosis caused by Babesia rossi at presentation and after treatment. Thirty-five client-owned dogs with B. rossi infection and 10 control dogs were included in this prospective observational study. Blood and urine were collected in Babesia-infected dogs at presentation (T0, n = 35), after 24 h (T24h, n = 11), and after 1 month (T1m, n = 9). The following urinary kidney injury biomarkers were assessed: urinary protein to creatinine ratio (UPC), urinary glomerular injury biomarkers (immunoglobulin G (uIgG) and C-reactive protein (uCRP)), and urinary tubular injury biomarkers (retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL)). Serum functional renal biomarkers were creatinine (sCr) and symmetric dimethylarginine (sSDMA). Post-mortem kidney biopsies were analyzed by light and transmission electron microscopy. At T0, all kidney injury biomarkers were significantly higher in Babesia-infected dogs compared to healthy controls (P < 0.001), while functional renal biomarkers were not significantly different (P > 0.05). At T24h, all urinary tubular injury biomarkers and UPC decreased significantly (P < 0.01), while glomerular injury biomarkers did not (P = 0.084). At T1m, all urinary kidney injury biomarkers decreased to values not significantly different from healthy controls (P > 0.5). Significant changes in functional renal biomarkers were not seen after treatment (P > 0.05). Dogs with complicated babesiosis had significantly higher glomerular injury biomarkers, UPC, and sSDMA compared to uncomplicated cases (P < 0.05), while all tubular injury biomarkers and sCr were not significantly different (P > 0.1). Dogs with babesiosis caused by B. rossi showed transient kidney injury, which was detected by all kidney injury biomarkers, but remained undetected by functional biomarkers. All infected dogs, irrespective of disease severity, suffered comparable kidney injury based on tubular injury biomarker concentrations, while loss of function was seen more often in dogs with complicated babesiosis based on sSDMA results.
Article
Hyperthyroidism and chronic kidney disease (CKD) are common diseases of geriatric cats, and often occur concurrently. Thus, a thorough understanding of the influence of thyroid function on renal function is of significant value for all feline practitioners. Among other effects, hyperthyroidism causes protein catabolism and increases renal blood flow and glomerular filtration rate (GFR). These effects render traditional renal markers insensitive for the detection of CKD in cats with uncontrolled hyperthyroidism. Furthermore, the development of iatrogenic hypothyroidism with over treatment of hyperthyroidism can be detrimental to renal function and may negatively affect long‐term survival. This review discusses important diagnostic considerations of feline hyperthyroidism, as well as key treatment modalities, with an emphasis on the use of radioiodine and the importance of post treatment monitoring of thyroid and renal parameters. In Australia, a common curative treatment for cats with benign hyperthyroidism (i.e. thyroid hyperplasia or adenoma) is a fixed dose of orally administered radioiodine, regardless of the serum total thyroxine concentration at the time of diagnosis. This review discusses the long term outcomes of this standard of care in comparison with current, relevant research literature from around the world. Finally, this review explores the use of symmetric dimethylarginine (SDMA) in assessing renal function before and after treatment in hyperthyroid cats. SDMA correlates well with GFR and creatinine in non‐hyperthyroid cats, but our understanding of its performance in hyperthyroid cats remains in its infancy.
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Symmetric dimethylarginine (SDMA) is a valuable surrogate marker for decreased glomerular filtration rate (GFR) and is incorporated into the International Renal Interest Society (IRIS) guidelines for diagnosing, staging, and treating chronic kidney disease (CKD). SDMA increases above the reference interval with smaller reductions in GFR rate than does creatinine and persistent mild increases in SDMA can be used to diagnose early-stage CKD. Evaluation of both SDMA and creatinine is recommended for diagnosis and monitoring of animals with CKD.
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It is known that oxidative stress is related to disease in humans and dogs. Many traditional Chinese medicines have been reported to have anti-oxidative effects, but there are no reports that they have anti-oxidative effects in dogs. In this study, we examined the anti-oxidative effects of Juzen-taiho-to, a traditional Chinese medicine, in dogs. Five healthy female beagle dogs (38–41 months of age weighing 8.6–10.7 kg) were orally administered Juzen-taiho-to at 450 mg/kg with food for 28 days. Blood samples were taken from all five dogs on days 0, 7, 14, 21, and 28. Using the blood samples, improvement of the antioxidant level as assessed by the biological antioxidant potential (BAP), reduced oxidative stress level as assessed by derivatives of reactive oxygen metabolites (d-ROMs), and improvement of blood fluidity were examined. Regarding the antioxidant level and blood fluidity, no significant difference was observed, but the oxidative stress level on days 14, 21, and 28 was significantly lower than that on day 0. Thus, Juzen-taiho-to may have anti-oxidative effects in dogs by reducing oxidative stress and be useful for oxidative stress-related diseases in dogs.
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Clinicopathologic evaluation of renal function and renal disease in sick adult horses remains grounded in detection of azotemia, assessment of serum and urine electrolyte concentrations, and evaluation of urinalysis findings, including specific gravity, reagent strip analysis, and sediment examination. Because increases in serum or plasma urea nitrogen and creatinine concentrations are insensitive indicators of a decreased glomerular filtration rate, there is considerable interest in identifying novel biomarkers of renal function or injury in blood and urine, with serum symmetric dimethylarginine concentration being the most recent addition to the commercial market.
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Background The International Renal Interest Society (IRIS) reports guidelines for classification and therapy for dogs suffering from chronic kidney disease (CKD). Dogs in stage 1 show no elevated serum creatinine, but some other sign of kidney disease like elevated Symmetric Dimethylarginin (SDMA), proteinuria, low urine specific gravity or abnormalities in the sonography of the kidneys. Objective of this study was to access the correlation between inclusion criteria and to give an estimation whether a more detailed staging or a substaging for patients with elevated SDMA levels might be useful regarding possible treatment recommendations. Results Sixty patients in IRIS stage 1 were included into the study. Most of these dogs were included due to raised SDMA level (n=22) or sonographic abnormalities of the kidneys (n=16). In order to rank and compare results of ultrasonography, a sonography score was developed. Additionally, results from blood work, urinalysis, ultrasonography and in some cases glomerular filtration rate (GFR) were examined. Correlation analysis showed positive correlation between creatinine and urea and negative correlation between creatinine and urinary protein-to-creatinine ratio (Up/c). Between SDMA, phosphate, urine specific gravity and sonographic findings there is no dependency with any other examined parameter. Conclusion Results showed that patients in IRIS stage 1 are a heterogeneous group and giving precise treatment recommendation might be challenging. If future studies will suggest treatment in this stage of CKD, such as renal diet, a more detailed classification is needed.
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The present study was conducted to determine the haemato-biochemical alterations in dogs suffering from chronic renal failure. A total of 24 dogs brought to the clinics with the history and clinical signs suggestive of renal failure were included in the study. Blood and serum samples were collected and subjected to haematological and biochemical analysis. All the dogs were found to be suffering from renal failure on the basis of elevated level serum creatinine. Staging following IRIS guidelines suggested 58.3% dogs to be in Stage IV of chronic renal failure 29.16% in Stage III, 8.32% in Stage II and 4.16% in Stage I. Haematological analysis depicted significant reduction in haemoglobin, leucocytosis with neutrophilia, decreased PCV and decreased number of platelets. Biochemical analysis showed significant increase in BUN, creatinine, phosphorous and decreased protein levels in diseased dogs in comparison with apparently healthy control dogs considered in the present study
Conference Paper
The purpose of this study is to investigate the effects of continuous exposure to high temperatures on multiple biochemical variables in a group of bakery workers who are professionally exposed to heat continuously for extended periods while working in the bakery. The study included (50) bakery workers and (20) volunteers as a control group. The heat-exposed groups were divided into three groups based on age (15-25, 26-35 and 36-50 years). Their exposure to heat was calculated at an annual rate, with the overlapping effect of smoking on occupational workers exposed to heat. The efficacy of ALP, AST, ALT, total protein, bilirubin, creatine and urea was assessed according to the method included in the measurement kit manufactured by the French company BioMerieux. Cholesterol, triglycerides and HDL were measured by the enzymatic method used by SYRBIO in France. The results of the three age categories showed clear differences. The concentration of total protein, triglycerides and urea increased significantly (P<0.05) in workers exposed to heat in the second age categories. While the concentrations of liver enzymes (ALP, AST and ALT), cholesterol, bilirubin and low-density lipoproteins showed a significant (P<0.05) decrease in the second age category. compared to the control group. While the effect of smoking for workers exposed to heat showed a significant difference. A decrease in the level of an enzyme (ALT), cholesterol and high-density lipoprotein in the group of smokers. While a higher level of triglyceride was observed in the smoker group, compared with nonsmokers than those exposed to heat only, while the rest of the variables are taking the same direction in both groups. The results of the effect of the period of exposure to the temperature at a clear annual rate were significant as there was a significant (P<0.05) decrease in the level of (ALP and ALT), accompanied by an increase in the amount of total protein, cholesterol, low-density lipoproteins and triglycerides in the group who have been exposed to heat for more (15-30) years compared with the group who were exposed for fewer years (2-15). The biochemical alterations in the workers, which were strongly indicative of cellular damages, might have been a consequence of the exposure to high temperature.
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Rocuronium is a non‐depolarising neuromuscular block drug extensively used in canine patients due to its favourable characteristics, including the fastest onset of action among all non‐depolarising neuromuscular blocking agents, lack of active metabolites and intermediate duration of effect. Although rocuronium elimination is relatively independent of kidney function, in the past few years, a growing number of reports describing a prolonged duration of the effect of rocuronium in human patients with renal failure have been published. However, to date, the mechanism behind this phenomenon is unclear. The present case describes the development of extremely prolonged neuromuscular blockade (>5 hours) following a single dose of 0.5 mg/kg rocuronium in a female English bulldog with renal disease where neostigmine failed to provide adequate reversal, which was only subsequently achieved following administration of sugammadex. Aside from renal disease, other possible causes of this prolonged duration (relative drug overdose, hypoalbuminaemia, co‐administered drugs, neostigmine‐induced neuromuscular blockade and idiosyncratic reaction to rocuronium) are also discussed.
Article
Objectives 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. Methods 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. Results 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). Conclusions and relevance 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.
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Kidney disease causes morbidity and mortality in dogs and cats. Serum creatinine concentration is an important surrogate marker for glomerular filtration rate (GFR). However, it is not always sensitive to small decreases in kidney function. Efforts to identify additional, more sensitive surrogate markers of GFR to improve detection of early kidney disease has led to the use of symmetrical dimethylarginine (SDMA) in veterinary medicine. There is insufficient information about the behavior of creatinine after an increase and the expected behavior of creatinine and SDMA in these cats and dogs. This study assesses the probability of persistence of increases in creatinine and the subsequent behavior of creatinine and SDMA in animals with persistently increased creatinine. For enrollment, three paired SDMA and creatinine concentrations were required: baseline (T0) with creatinine and SDMA at or below the upper reference limit (URL), T1, and T2 0.5-18 months after T1. The study included 16,670 cats and 16,712 dogs with increased T1 creatinine concentrations and 49,990 cats and 122,516 dogs with T1 creatinine at or below the URL. The probability of a persistently increased creatinine at T2 was approximately 58% for cats and 49% for dogs after a T1 increase. For animals without a T1 increase the probability of increased creatinine at T2 was only 7% for cats and 3% for dogs. For cats and dogs with persistently increased Cr, the probability of an increased SDMA concentration at T1 was 70-75%. By 24 months, that probability rose to 94% for cats and 88% for dogs.
Article
Symmetric dimethylarginine (SDMA) is a sensitive surrogate marker for glomerular filtration rate; however, there are uncertainties as to how to interpret mild increases (SDMA 15-19 µg/dL). This descriptive study used retrospective data to evaluate whether cats or dogs that had initial SDMA values (at T0) within the reference interval followed by an increased SDMA (at T1) had persistently increased SDMA (at T2; measured from 14 days to 18 months following T1; Persistence Cohort), and if and when cats or dogs with persistently increased SDMA had increased creatinine up to 24 months (Concordance Cohort). The Persistence Cohort included 16,670 cats and 16,712 dogs. If SDMA at T1 was 15-19 µg/dL, the probability of persistence was 53% for cats and 42% for dogs, while creatinine was concurrently increased in 20% of cats and 18% of dogs. For comparison, if SDMA was not increased at T1 the probability of increased SDMA at recheck was only 20% for cats and 9% for dogs. For cats and dogs with a T1 SDMA of 15-19 µg/dL and with persistent increases at T2, the probability of increased creatinine at T1 was 20% for cats and 18% for dogs, rising to 61% and 55%, respectively, by 24 months. When SDMA at T1 was >25 µg/dL, creatinine was increased in 93% of cats and 95% of dogs by 24 months. Mildly increased SDMA results may provide an opportunity to identify some cats and dogs earlier in their kidney disease.
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Metabolomics has proven itself an invaluable research tool, providing comprehensive insight to systemic metabolism. However, the lack of scalable and quantitative methods with known reference intervals and documented reproducibility has prevented the use of metabolomics in the clinical setting. This study describes the development and validation of a quantitative nuclear magnetic resonance (NMR) -based metabolomics platform for canine serum and plasma samples. Altogether 8247 canine samples were analyzed using a Bruker’s 500 MHz NMR spectrometer. Using statistical approaches derived from international guidelines, we defined reference intervals for 123 biomarkers, studied method precision, analyte storage stability, the effect of prolonged contact to red blood cells, differences of blood collection tubes, interference of lipemia, hemolysis and bilirubinemia, method comparison, and demonstrated the method’s practical relevance in a hyperglycemic cohort. Owing to the advantages of quantitative results, high reproducibility, and scalability, this canine metabolomics platform holds great potential for numerous clinical and research applications to improve canine health and well-being.
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The red fox is a highly adaptable mammal that has established itself world-wide in many different environments. Contributing to its success is a social structure based on chemical signalling between individuals. Urine scent marking behaviour has long been known in foxes, but there has not been a recent study of the chemical composition of fox urine. We have used solid-phase microextraction and gas chromatography-mass spectrometry to analyze the urinary volatiles in 15 free-ranging wild foxes (2 female) living in farmlands and bush in Victoria, Australia. Foxes here are routinely culled as feral pests, and the urine was collected by bladder puncture soon after death. Compounds were identified from their mass spectra and Kovats retention indices. There were 53 possible endogenous scent compounds, 10 plant-derived compounds and 5 anthropogenic xenobiotics. Among the plant chemicals were several aromatic apocarotenoids previously found in greater abundance in the fox tail gland. They reflect the dietary consumption of carotenoids, essential for optimal health. One third of all the endogenous volatiles were sulfur compounds, a highly odiferous group which included thiols, methylsulfides and polysulfides. Five of the sulfur compounds (3-isopentenyl thiol, 1- and 2-phenylethyl methyl sulfide, octanethiol and benzyl methyl sulfide) have only been found in foxes, and four others (isopentyl methyl sulfide, 3-isopentenyl methyl sulfide, and 1- and 2-phenylethane thiol) only in some canid, mink and skunk species. This indicates that they are not normal mammalian metabolites and have evolved to serve a specific role. This role is for defence in musteloids and most likely for chemical communication in canids. The total production of sulfur compounds varied greatly between foxes (median 1.2, range 0.4–32.3 μg ‘acetophenone equivalents’/mg creatinine) as did the relative abundance of different chemical types. The urinary scent chemistry may represent a highly evolved system of semiochemicals for communication between foxes.
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Background: Symmetric dimethylarginine (SDMA) is considered a more sensitive indirect estimate of glomerular filtration rate (GFR) than creatinine (Cr). Symmetric dimethylarginine is not affected by sex or muscle mass in small animals. Objectives: To validate a commercial SDMA immunoassay (IA) for equine serum; to compare SDMA and Cr in cohorts of draft horse breeds; and to assess effects of age, sex, and breed. Animals: One hundred and sixty-five healthy draft horses (0.5-16 years), including 63 Percherons, 52 Clydesdales, and 50 Belgians. Methods: Cross-sectional study. The SDMA IA was validated for equine serum by comparison to liquid chromatography-mass spectroscopy (LC-MS) results and other methods. Symmetric dimethylarginine and Cr were compared by analysis of variance and correlation analysis. Results: Median and 95% confidence intervals (CIs) for LC-MS (10.0 [9.4, 10.2] μg/dL) and IA (9.7 [9.5, 10.0] μg/dL) SDMA concentrations were strongly correlated (R = .74, P < .001). Symmetric dimethylarginine was lower (P < .01) in Percherons and Belgians, than in Clydesdales. Median values and 95% CI for Cr were 1.3 (1.2, 1.4), 1.4 (1.3, 1.5), and 1.4 (1.3, 1.5) mg/dL (P = .06) for Percherons, Clydesdales, and Belgians, respectively. Symmetric dimethylarginine was correlated to Cr (LC-MS, R = .60, P < .001; IA, R = .66, P < .001). There were no differences in SDMA or Cr between sexes and there were no correlations between age and SDMA or Cr. Conclusions and clinical importance: Although a significant breed effect on SDMA concentration was found, differences were small and all medians were <14 μg/dL, the cutoff value to support renal dysfunction in dogs and cats.
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Fifty-five blood samples were collected from 28 dogs competing in the 1991 Yukon Quest International Sled-Dog Race to examine race-induced changes in serum biochemical values. Blood was collected after a 36-hour mandatory rest at the midpoint of the race, and again at 2 subsequent checkpoints. The mean speed of dogs between checkpoints was approximately 4.5 mph. There were no significant increases in PCV, or in serum total protein, sodium, or creatinine concentrations during the race. Mean serum potassium concentration decreased significantly (P < 0.05) from 4.8 +/- 0.4 to 4.4 +/- 0.3 to 3.9 +/- 0.3 mEq/L, as did the serum triglyceride concentration (138 +/- 52, 88 +/- 25, 81 +/- 16 mg/dl). Plasma cortisol concentration did not change significantly. Increases in the mean serum activity of creatine kinase (167, 420, 344 U/L), and aspartate aminotransferase (55, 79, 62 U/L) during the race were significant (P < 0.05). Participation in a long-distance sled race was associated with mild changes in routinely measured serum biochemical values in dogs.
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The angiotensin-converting enzyme inhibitor, benazepril was orally administered to dogs for a period 15days before and after renal ablation. Renal ablation by right-side nephrectomy and ligation of one branch of the left renal artery were performed in the animals to impair renal function. One group of dogs received a standard dose (0.5mg/kg) of benazepril; a second group received 20 times the standard dose (10mg/kg). During the period before surgery, neither the standard nor the increased doses produced remarkable changed in clinical signs and laboratory test results. In 1 1/2 nephrectomized dogs, renal plasma flow and glomerular filtration rate decreased to approximately 1/3 of what they had been before surgery, and BUN and plasma creatinine concentrations increased. These variables remained unchanged in both dose groups during the administration period also in 11/2 nephrectomized dogs.
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Serum or plasma creatinine is one of the most often analyzed biological variables in the dog. However, factors causing variations in results are not well known : - analytical factors : analyses can be performed using heparinized plasma or serum, in which creatinine is stable for 24 hours at room temperature and several months at - 20°C. Enzymatic techniques are more specific and give lower results than Jaffé's technique, in which bilirubin, glucose, ketones, and cephalosporins can cause interference. - biological factors : reference intervals for plasma creatinine are poorly defined, extreme values being 35 and 250 μmol/L. Moreover, the main biological factors causing variation have not been documented, except for age (creatinine is higher in young dogs) and the effect of a cooked meat meal which increases creatininemia.
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The authors inoculate 3 strains of Borrelia respectively to 3 dogs in the purpose to contribute to a comparative study of pathogenic effect of these spirochetes in dog. Clinical examinations as well as hematological, biochemical, radiological and serological investigations and research of rheumatoid factor were realized before and after inoculation. It rise up that experimental inoculation of Borrelia to the dog provokes no clinical manifestations contrarily to that is observed in natural infection. Meanwhile fever pics and a seroconversion limited in time were observed. Some hematological variations, mainly leukocytosis, and biological variations notably an increasing of uremia, of creatininaemia and of the blood concentration of creatine kinase were observed.
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Cystatin C is a low-molecular-mass acid protein produced at a constant rate by all nucleated cells and cleared by glomerular filtration. In human medicine it is considered to be a better indicator of renal failure than creatinine. Plasma (Pl-) cystatin C measurements in 179 clinically healthy dogs, using an immunoturbidimetric procedure for human cystatin C, showed a Gaussian distribution with an upper limit of 1.3 mg/l. There were no differences between the sexes. Pl-cystatin C was slightly lower in 1–8-year-old adults than in younger or older dogs. It was also lower in dogs weighing less than 15 kg than in heavier ones. Meals produced a dramatic decrease in Pl-cystatin C that lasted for up to 9h. Pl-cystatin C was elevated in 98% of dogs with renal insufficiency, even in some cases where the Pl-creatinine was normal. Cystatin C may therefore be a useful indicator of renal insufficiency in clinically relevant dogs with borderline P1-creatinine values.
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Interferences caused by bilirubin, hemolysis, and lipemia on 25 clinical chemistry analytes in bovine, canine, equine, and feline sera were studied using the Coulter Dacos and commercial reagents. We present the data as "interferograms", which show the anticipated percent change in serum analyte activity or concentration with varying concentrations of bilirubin, hemoglobin, or lipid. Obvious species differences in response to at least one added interfering substance were found for alanine aminotransferase, aspartate aminotransferase, cholesterol, creatine kinase, globulin, total protein, and urea. The remaining analytes were affected in a linear or complex dose-response relationship or were only affected at the highest concentrations of interfering substances. These data will be useful in aiding interpretation of laboratory test results when common interferences are present in the serum.
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