Association between glomerular filtration rate and plasma N-terminal pro-atrial natriuretic peptide concentration in dogs.

OBJECTIVES: To investigate the association between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate in dogs. MATERIALS AND METHODS: Dogs were classified into four categories by bodyweight. Dogs were divided into four groups (Groups 1 to 4) based on glomerular filtration rate estimates using plasma iohexol clearance per bodyweight category. Generalised linear models were built to explore the relationship between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate and the effect of confounders on plasma N-terminal pro-atrial natriuretic peptide concentration. RESULTS: Fifty-three dogs were included (Group 1, 25; Group 2, seven; Group 3, five; and Group 4, 16). The medians (interquartile range) N-terminal pro-atrial natriuretic peptide concentrations for Groups 1 to 4 were 7224 pg/mL (4766 to 10,254 mg/dL), 8958 pg/mL (4935 to 11,271 mg/dL), 9280 pg/mL (9195 to 10,384 mg/dL) and 12,683 pg/mL (9133 to 19,217 mg/dL), respectively. Group 4, estimated to have the highest reduction in glomerular filtration rate, had a higher plasma N-terminal pro-atrial natriuretic peptide concentration than Groups 1 to 3. Based on the final generalised linear model, influencing factors for plasma N-terminal pro-atrial natriuretic peptide concentration were plasma iohexol clearance (-0.136; 95% confidence interval, -0.227 to -0.046) and bodyweight (-0.058; 95% confidence interval, -0.098 to -0.018). CLINICAL SIGNIFICANCE: N-terminal pro-atrial natriuretic peptide concentration is associated with the glomerular filtration rate.

Comparison of serum creatinine, point-of-care symmetric dimethylarginine and renal imaging with glomerular filtration rate measured by renal scintigraphy in healthy and early chronic kidney diseased cats.

The aim of this study was to evaluate routinely used tests to diagnose cats in early stages of chronic kidney disease (CKD) and to describe a model for evaluating these variables simultaneously. Apparently healthy cats were screened using serum creatinine (sCr), point-of-care symmetric dimethylarginine (POC SDMA), urinalysis, urine protein/creatinine ratio (UPC) and imaging evaluation. Those parameters were compared to glomerular filtration rate (GFR) assessed by renal scintigraphy. Forty-four cats were included and consisted of 14 (31.8%) healthy cats (absence of abnormalities in renal morphology and sCr less than 1.6 mg/dL), 20 (45.5%) cats classified as CKD I (presence of abnormalities in renal morphology and sCr less than 1.6 mg/dL) and ten (22.7%) as CKD II (sCr equal to or greater than 1.6 mg/dL, with or without abnormalities in renal morphology). A large number (40.9%) of apparently healthy cats presented reduction in GFR, which included half of CKD I patients. Point-of-care SDMA was not a good predictor for decreased GFR, nor was it correlated with the variables GFR and sCr. Glomerular filtration rate was significantly lower in CKD I and II groups in comparison with healthy cats, but there was no significant difference between the CKD I and II groups. Multivariate logistic regression model identified three variables that affected the odds of a cat having decreased GFR (< 2.5 mL/min/kg): sCr (OR = 18.3; p = 0.019; CI = 1.6-207.2), and the ultrasonographic findings 'reduced corticomedullary definition' (OR = 19.9; p = 0.022; CI = 1.6-254.0) and 'irregular contour' (OR = 65.6; p = 0.003; CI = 4.2-1038.2). Renal ultrasonography evaluation should always be considered for screening early CKD in apparently healthy cats.

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

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

Effects of an intravenous infusion of diltiazem on glomerular filtration rate, electrolyte excretion, and urine output in healthy dogs.

BACKGROUND: Acute kidney injury (AKI) in dogs has a high case fatality rate. Diltiazem might improve renal function, but effect of intravenous infusion has not been adequately studied in dogs. HYPOTHESIS/OBJECTIVES: To determine if an intravenous infusion of diltiazem improves renal function through changes in glomerular filtration rate (GFR), fractional excretion of sodium (FENa), and urine output (UOP) in healthy dogs. ANIMALS: Ten healthy adult dogs. METHODS: Prospective, unmasked, crossover study. Dogs were randomized to receive diltiazem (loading dose of 240 µg/kg followed by 6 µg/kg/min for 300 min) or the same volume of 5% dextrose in water (D5W). The opposite treatment was given after a 7-day washout period. GFR and FENa were obtained at baseline and after infusion. UOP was measured starting 1 hour before diltiazem administration. RESULTS: GFR did not significantly increase from baseline with diltiazem (before diltiazem median = 2.371 mL/min/kg, range = 1.605-4.359; after diltiazem median = 2.305 mL/min/kg, range = 1.629-4.387; median difference = 0.080 mL/min/kg, 95% confidence interval [CI] = -0.417 to 0.757; P = .85), and there was no difference in D5W GFR before and after diltiazem (median = 2.389 mL/min/kg, range = 1.600-3.557; median difference = 0.036 mL/min/kg, 95% CI = -0.241 to 1.112; P = .69). FENa did not increase from baseline after administration of diltiazem (median difference = 0%, 95% CI = -0.1 to 0.1; P = .81), and there was no difference in D5W FENa (median difference = 0.1%, 95% CI = -0.1 to 0.2; P = .26). UOP did not increase with diltiazem (P = .06). CONCLUSION AND CLINICAL IMPORTANCE: Intravenous administration of diltiazem does not improve markers of renal function in healthy dogs. Further studies are needed in dogs with AKI.

Hyperthyroid cats and their kidneys: a literature review.

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.

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

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.

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

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

Renal Magnesium Handling: A Comparison Between Dogs With Chronic Kidney Disease and Healthy Elderly Dogs.

Chronic kidney disease (CKD) and aging are known to possibly cause a progressive reduction in glomerular filtration rate, which may be associated with an increase in fractional excretion of electrolytes due to an adaptive response of the remaining functioning nephrons. However, the behavior of magnesium excretion has not been studied in CKD and healthy elderly dogs. The objective was to evaluate the fractional excretion of magnesium (FEMg) in dogs with (CKD) compared to healthy elderly dogs. Sixteen healthy elderly dogs and 43 dogs with CKD were divided into 3 groups (CKD 2 [n = 14], CKD 3 [n = 17], CKD 4 [n = 12]), in accordance with the current International Renal Interest Society (IRIS) criteria that were used in this study. Blood samples were obtained by jugular venipuncture and urine samples were obtained by cystocentesis. The FEMg was evaluated at a single time point in both urine and blood samples. FEMg was significantly higher in dogs with CKD compared to healthy elderly dogs, especially in advanced stages. This preliminary study demonstrates that FEMg may be altered in dogs with CKD. Further research is warranted to elucidate magnesium's potential role in cardiovascular and arterial calcification in dogs with CKD as observed in humans with CKD.

Assessment of glomerular filtration rate measurement in dogs using dynamic contrast CT compared to serum iohexol clearance.

Dynamic contrast CT with Patlak plot analysis can be used to determine the glomerular filtration rate (GFR). However, several studies have shown different GFR values and they are most likely less than the values by the standard techniques. The purpose of this prospective, experimental, and method comparison study was to evaluate the GFR using a CT technique (CT-GFR) in 12 healthy dogs compared to serum iohexol clearance (SIC-GFR). All dogs were anesthetized and placed in the right lateral recumbency position and the caudal part was lifted inside the CT gantry. A single-slice dynamic CT of the aorta and both kidneys was scanned sequentially every 2 s for 2 min after a bolus injection (3 mL/s) of iohexol (300 mg/kg). Time attenuation curves (TAC) were constructed and the GFR per volume of kidney was calculated using the Patlak plot analysis method based on 30-120 s time intervals, and results were compared to global GFR from SIC that was determined with eight blood samples for up to 240 min. The CT-GFR value (1.85 ± 0.48 mL/min/kg) was significantly less than the SIC-GFR value (3.40 ± 0.80 mL/min/kg; P < .05). The CT-GFR was correlated with SIC-GFR by the coefficient of correlation (r) at 0.61 (P = .046). In conclusion, the CT-GFR underestimated SIC-GFR and should be used carefully. We suggest that the GFR should be calculated using the equation derived from linear regression between CT-GFR and the standard GFR method. With its own particular parameters, each institute should have its own prediction equation.

Impact of allogeneic feline uterine-derived mesenchymal stromal cell intravenous treatment on renal function of nephrectomized cats with chronic kidney disease.

Chronic kidney disease (CKD) is a common condition and leading cause of mortality in cats. Mesenchymal stromal cells (MSCs) may have a therapeutic effect on CKD. The aim of this pilot study was to determine efficacy of systemically-administered allogeneic uterine tissue-derived MSCs (UMSCs) in cats with CKD. Eighteen renal-compromised, unilaterally nephrectomized cats received two doses of 3 × 107 allogeneic UMSCs given intravenously (IV) with a 2-week dose interval. The primary endpoint was renal function, with treatment success defined by a 20% increase in glomerular filtration rate (GFR; iohexol clearance) and/or a 20% decrease in plasma creatinine in 50% of the cats. Secondary endpoints included diet and water consumption, body weight, urine characteristics, and adverse events. Treatment was well tolerated and associated with a statistically meaningful increase in GFR on Days 13, 28, 57, 99, 121 and 182, compared with baseline (P < 0.0001 for Days 13 to 99 inclusive; P = 0.0029 and P = 0.0225 for Days 121 and 182, respectively). Greater than 50% of the cats demonstrated a 20% increase in GFR on all days except Day 150, at which point GFR measurements were consistently above baseline. Statistically meaningful increases in diet and water consumption were observed. Substantial improvements in GFR were observed throughout the six-month evaluation period (excluding Day 150) in more than 50% of cats, thereby meeting the primary endpoint. Therefore, this IV-administered, allogeneic cellular therapy may support both renal function and clinical status of cats with CKD.

Exogenous creatinine clearence indexed to body surface area allows estimation of GFR and across species comparison.

The assessment of renal function in birds is difficult because sensitive biomarkers are lacking. Previous studies have demonstrated the feasibility of measuring the exogenous creatinine clearance in pigeons, indicating the potential use of this technique for the assessment of renal function in birds. The aim of the study was to index the exogenous creatinine elimination rate by body surface area, enabling comparison between different species. Exploratory data on common buzzards (Buteo buteo), Eurasian eagle-owls (Bubo bubo), domestic goose (Anser anser domesticus) and racing pigeons (Columba livia) were collected and indexed by body surface area. A sterile creatinine solution was administered at a dose DM = 50 mg kg-1 i.m. into the deep pectoral muscle of 52 clinically healthy birds of the four species with different body masses. The time course of the plasma creatinine concentration was measured and analyzed by a parametric pharmacokinetic Bateman model, followed by indexing the exogenous creatinine clearance (ECC) by body surface area. The exploratory ECC values for birds with a mean body mass ranging from 0.42 kg (pigeon) to 8.2 kg (goose) were between 0.4261 mL min-1 dm-2 (CI 0.3882-0.4672) and 0.8717 mL min-1 dm-2 (CI 0.8091-0.9362). ECC indexed by body surface area turned out to be independent from body mass. Resulting exploratory data covering species with different body masses are comparable with published data from very complex studies of avian renal function.

Serum cystatin C concentration can be used to evaluate glomerular filtration rate in small dogs.

Serum cystatin C levels (CysC) are used in human medicine to document progressive kidney failure. Although CysC are not thought to be useful for the diagnosis of kidney dysfunction in dogs, there has been no specific consideration of body weight as a confounding issue. The aim of this study was to assess that the utility of CysC for the diagnosis of decreased glomerular filtration rate (GFR) in smaller vs. larger dogs. In clinically healthy dogs, serum creatinine (Cre) and CysC correlate directly with body weight; we found that dogs weighing <20 kg had significantly lower CysC than those weighing ≥20 kg (0.27 ± 0.07 vs. 0.34 ± 0.05 mg/l, respectively, P<0.001). In dogs weighing <20 kg, CysC had superior diagnostic accuracy for the detection of mildly decreased plasma iohexol clearance (PCio) (<1.8 ml/min/kg) compared with Cre (sensitivity 100% vs. 80.9% and specificity 100% vs. 85.7%); this was not true for dogs weighing ≥20 kg. Additionally, using a cut-off PCio of <1.8 ml/min/kg, the area under receiver-operating characteristics curve (AUC) of CysC was significantly higher than that of Cre in dogs weighing <20 kg (P<0.05); this was not true for dogs weighing ≥20 kg (P=0.695). In conclusion, CysC is a useful marker for the detection of a mild decreasing GFR compared with Cre in dogs weighing <20 kg.

Plasma symmetric dimethylarginine and creatinine concentrations and glomerular filtration rate in cats with normal and decreased renal function.

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.

Effects of low-dose meloxicam in cats with chronic kidney disease.

OBJECTIVES: Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival. This study aimed to prospectively evaluate the renal effects of low-dose meloxicam treatment (0.02 mg/kg/day) over 6 months in cats with chronic kidney disease (CKD). METHODS: Twenty-one cats with stable International Renal Interest Society stage 2 or 3 CKD were recruited and randomized to placebo or meloxicam groups. Cats were evaluated at baseline and at 1, 3 and 6 months, including blood pressure, chemistry, symmetric dimethylarginine (SDMA), glomerular filtration rate (GFR), urinalysis, urine protein:creatinine ratio (UPC), urine transforming growth factor-beta (ß):creatinine ratio, urine clusterin, urine cystatin B and serum inosine. RESULTS: No statistical difference was observed in systolic blood pressure, blood urea nitrogen, creatinine, SDMA, GFR, urine transforming growth factor-ß:creatinine ratio, urine clusterin, urine cystatin B or serum inosine in cats receiving meloxicam vs placebo. Mean UPC was greater in the meloxicam group (0.33) than the placebo group (0.1) at 6 months (P = 0.006). Four cats had meloxicam discontinued owing to potential (mainly gastrointestinal) adverse effects. CONCLUSIONS AND RELEVANCE: No decline in renal excretory function was observed when meloxicam was administered to cats with CKD. However, gastrointestinal adverse effects were observed, and cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. As proteinuria is associated with negative outcomes (progression of azotemia and hypertension) in cats with CKD, this finding suggests that meloxicam should be used with caution in cats with CKD and UPC monitored. Until further research is available, clinicians should weigh the risk of potential increased proteinuria against quality of life benefits when considering meloxicam for analgesia in cats with renal disease.

The new age of renal biomarkers: does SDMA solve all of our problems?

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.

Effect of non-steroidal anti-inflammatory drugs on glomerular filtration rate and urinary N-acetyl-ß-D-glucosaminidase activity in cats after dental surgery.

OBJECTIVE: To compare the effects of meloxicam or carprofen on glomerular filtration rate (GFR), and to evaluate the effect of meloxicam on urinary N-acetyl-ß-D-glucosaminidase (NAG) activity, of cats after dental surgery. STUDY DESIGN: Randomized, blinded, controlled trial. ANIMALS: A total of 24 mixed breed cats. METHODS: Cats were randomly assigned to one of three groups (n = 8 per group): meloxicam (0.2 mg kg-1); carprofen (4 mg kg-1); or saline (2 mL). Acepromazine (0.04 mg kg-1) and buprenorphine (0.02 mg kg-1) were administered intramuscularly as preanaesthetic medication. Test drugs were injected subcutaneously at the time of preanaesthetic medication. Anaesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. Mean arterial blood pressure (MAP), respiratory rate (fR), heart rate (HR) and haemoglobin oxygen saturation values (SpO2) were recorded. All cats underwent ultrasonic dental scaling with polishing. Teeth extraction involved mucosal flap creation, removal of alveolar bone and flap closure. Plasma iohexol clearance (ICL), a measure of GFR, was estimated before and 24 hours after anaesthesia induction in all cats. Urinary NAG index was estimated in saline and meloxicam groups at the same time points as GFR. Between-group and -time point differences in GFR and NAG index were compared using mixed model analyses. Data are presented as mean ± standard deviation (p < 0.05). RESULTS: There was no significant difference in plasma ICL rate (range: from 1.22 ± 0.05 to 1.27 ± 0.04 mL kg minute-1) between groups or between time points. Urinary NAG index (range: from 1.0 ± 0.19 to 1.36 ± 0.29 Units gram-1) was not significantly different between meloxicam and saline groups. MAP, HR, fR and SpO2 did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam and carprofen appeared to produce nonsignificant effects on GFR, and meloxicam did not affect the urinary NAG activity, of cats after dental surgery.

Association between breed and renal biomarkers of glomerular filtration rate in dogs.

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.

Evaluation of serum biomarkers and proteinuria for the early detection of renal damage in dogs with heartworm (Dirofilaria immitis).

Glomerulonephropathy associated with Dirofilaria immitis (heartworm) is relatively frequent in infected dogs. Given the importance and the scarcity of studies focused on its prevalence and diagnosis, the objective was to determine the prevalence of proteinuria and functional indicators of glomerular filtration rate in dogs with heartworm disease and discuss its utility in the detection of renal impairment. Sera and urine from 47 infected dogs were analyzed in a reference laboratory. Urea, creatinine, plasma proteins and serum symmetric dimethylarginine (SDMA) were analyzed in sera, while the UPC ratio was performed in urine. Dogs were further evaluated for the presence/absence of microfilariae, pulmonary and systemic hypertension, and the parasite burden was assessed. The results showed that 19.1 % of dogs showed proteinuria (UPC > 0.5) and 17 % showed borderline proteinuria (UPC 0.2-0.5). Creatinine and SDMA were high (>1.8 mg/dl and ≥18 µg/dl, respectively) in 4.2 % of dogs. UPC ratio was significantly increased in dogs with high parasite burden and in dogs with microfilariemia (p < 0.05). Dogs with pulmonary hypertension showed higher increases in proteinuria as well, which was probably due to the chronicity of the infection. No significant differences were found in serum and urine values regarding systemic blood pressure. Despite the limitations of this study, proteinuria/borderline proteinuria was present in 36.2 % of dogs with heartworm disease, and this may be due to glomerular disease. Therefore, the detection of proteinuria, along with other renal biomarkers in the diagnostic protocols, could help identify kidney alterations or risk of renal damage in heartworm disease.

Measurements of echocardiographic indices and biomarkers of kidney injury in dogs with chronic kidney disease.

Pathophysiological cardiac and renal interactions are termed cardiovascular-renal disorder (CvRD). Cardiovascular disease/dysfunction secondary to kidney disease (CvRDK), is a leading cause of death in human chronic kidney disease (CKD) patients. The presence and clinical impact of CvRDK in dogs with CKD is unknown. We hypothesized that echocardiographic measurements, and cardiac and renal biomarkers, will be altered in dogs with CKD and associated with survival. Eleven dogs with CKD (n = 6 IRIS stage 2, n = 5 IRIS stage 3) and without primary cardiac disease, plus 12 healthy age-matched control dogs, were recruited to this prospective observational study. Dogs underwent standard echocardiography, glomerular filtration rate (GFR) estimation by iohexol clearance, and measurement of plasma cardiac troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP), plasma and urinary cystatin B, and urinary clusterin and neutrophil gelatinase-associated lipocalin (NGAL). Values were compared between groups, and their association with all-cause mortality explored. Dogs with CKD had significantly lower GFR and higher NT-proBNP, urinary cystatin B, clusterin, and NGAL, compared to controls (P < 0.05). Echocardiographic measurements were similar between dogs with CKD and controls. Median follow-up time was 666 days, during which six dogs with CKD died. Risk of death was associated with increasing age, serum total protein, and normalized left ventricular posterior wall thickness (LVPWDN) and decreasing bodyweight and packed cell volume. Although baseline differences in echocardiographic measurements were not evident between dogs with moderate CKD and controls, the presence of CvRDK was suggested by the association between LVPWDN and survival.

Clinical utility of estimation of glomerular filtration rate in dogs.

BACKGROUND: Glomerular filtration rate (GFR) estimation is the gold standard for assessment of renal function, although the clinical utility of this test is unclear. OBJECTIVES: To describe the clinical utility of GFR estimation in dogs. ANIMALS: Medical records of 132 dogs that had serum iohexol clearance measured between 2012 and 2017. METHODS: Iohexol clearance and clinical records were reviewed and submitting practices contacted to obtain outcome data. Dogs were classified into 4 groups based on the reason for performing GFR estimation: A1 (screening for pre-azotemic chronic kidney disease [CKD], n = 105), A2 (confirmation of azotemic CKD, n = 3), B (screening for pre-azotemic acute kidney injury, n = 19), and C (miscellaneous causes, n = 5). Descriptive review of the clinical utility of GFR estimation is provided. RESULTS: For dogs in Group A1, renal disease was diagnosed in 9/9 dogs with a GFR ≥40% decreased below the mean GFR of their body weight category, in 5/6 dogs with a ≥30% but <40% reduction in GFR and in 7/9 dogs with a ≥20% but <30% reduction in GFR. CONCLUSIONS AND CLINICAL IMPORTANCE: Glomerular filtration rate estimation is useful for the diagnosis of CKD before the onset of azotemia.