Objective—To determine whether administration of meloxicam or acetylsalicylic acid alters glomerular filtration rate (GFR) in cats with renal azotemia.
Animals—6 young adult cats.
Procedures—3 sexually intact male cats and 3 sexually intact female cats had surgically reduced renal mass and azotemia comparable to International Renal Interest Society chronic kidney disease stages 2 and 3. Renal function was evaluated by measurement of serum creatinine concentration, urinary clearance of exogenously administered creatinine, and the urine protein-to-creatinine concentration ratio (UP:C). Measurements taken in cats receiving placebo at the beginning and end of the study were compared with results obtained at the end of 7 days of treatment with either meloxicam (0.2 mg/kg, SC, on day 1; 0.1 mg/kg, SC, on days 2 to 7) or acetylsalicylic acid (20 mg/kg, PO, on days 1, 4, and 7).
Results—No significant treatment effects on urinary clearance of exogenously administered creatinine, serum creatinine concentration, or UP:C were detected. Mean ± SEM serum creatinine concentration and urinary clearance of exogenously administered creatinine measurements following 7 days of treatment with meloxicam (serum creatinine concentration, 2.67 ± 0.17 mg/dL; urinary clearance of exogenously administered creatinine, 1.34 ± 0.08 mL/min/kg) and acetylsalicylic acid (serum creatinine concentration, 2.62 ± 0.12 mg/dL; urinary clearance of exogenously administered creatinine, 1.35 ± 0.07 mL/min/kg) were not significantly different from the mean baseline values for these variables (serum creatinine concentration, 2.77 ± 0.14 mg/dL; urinary clearance of exogenously administered creatinine, 1.36 ± 0.07 mL/min/kg).
Conclusions and Clinical Relevance—Neither meloxicam nor acetylsalicylic acid had a measurable effect on urinary clearance of exogenously administered creatinine, serum creatinine concentration, or UP:C. These results are consistent with the hypothesis that GFR of euvolemic cats with normal or reduced renal function is not dependent on cyclooxygenase function.
Objective—To determine the effects of carprofen and etodolac on renal function in euvolemic dogs and dogs with extracellular fluid volume depletion induced via administration of furosemide.
Animals—12 female Beagles.
Procedures—Dogs received a placebo, furosemide, carprofen, etodolac, furosemide and carprofen, and furosemide and etodolac. The order in which dogs received treatments was determined via a randomization procedure. Values of urine specific gravity, various plasma biochemical variables, glomerular filtration rate (GFR [urinary clearance of creatinine]), and renal plasma flow (urinary clearance of para-aminohippuric acid) were determined before and after 8 days of drug administration. A washout time of approximately 12 days was allowed between treatment periods.
Results—Administration of furosemide, furosemide and carprofen, and furosemide and etodolac caused changes in urine specific gravity and values of plasma biochemical variables. Administration of carprofen or etodolac alone did not have a significant effect on renal plasma flow or GFR. Concurrent administration of furosemide and carprofen or furosemide and etodolac caused a significant decrease in GFR. After 12-day washout periods, mean values of GFR were similar to values before drug administration for all treatments.
Conclusions and Clinical Relevance—Results indicated GFR decreased after 8 days of concurrent administration of furosemide and carprofen or furosemide and etodolac to dogs. Administration of preferential cyclooxygenase-2 inhibitors to dogs with extracellular fluid volume depletion or to dogs treated with diuretics may transiently impair renal function.
Objective—To evaluate the effect of renal autograft ischemia and reperfusion associated with renal transplantation on pulse rate and pressure and arterial blood pressure variables in clinically normal cats.
Procedures—A radiotelemetric implant was placed in each cat to measure hemodynamic variables; baseline data were recorded before surgery. Standard heterotopic renal implantation and contralateral nephrectomy were performed (day 0). Autografts were stored in cold sucrose phosphate solution for 30 minutes (n = 5) or 3 hours (5); cats were anephric during this period. Hemodynamic variables were recorded every 5 minutes for up to 16 days after surgery; mean daily values were calculated.
Results—Data from 6 cats were available for analysis. Two cats developed ureteral obstructions and became azotemic at 111 and 197 hours after kidney reperfusion. Mean serum creatinine and BUN concentrations were greater than baseline values on days 1 and 2. Although changes from baseline hemodynamic values were detected in some cats, arterial blood pressure measurements did not change significantly from baseline at any time point. Compared with baseline data, mean pulse rate was increased on days 1 and 2 and days 6 through 12; mean pulse pressure was increased on days 1 and 2.
Conclusions and Clinical Relevance—In clinically normal cats, hypertension was not induced by clinically relevant periods of ischemia-reperfusion injury of renal autografts and was not an inherent consequence of the transplantation process. Causes of marked posttransplantation hypertension in cats with chronic kidney disease require further investigation.
To establish a reference interval for glomerular filtration rate (GFR) determined by measuring serum clearance of a single IV dose of inulin in clinically normal cheetahs (Acinonyx jubatus) and compare serum symmetric dimethylarginine (SDMA) concentration in cheetahs with GFR.
33 cheetahs housed at 3 institutions.
A single bolus of inulin (3,000 mg/m2) was administered IV, and 5 serial blood samples were collected and analyzed for serum inulin concentration with the anthrone technique. The GFR was estimated with a modified slope-intercept method for the slow component of the serum concentration-versus-time curve. Blood urea nitrogen and serum creatinine concentrations were measured in samples obtained immediately prior to inulin administration, and serum SDMA concentration was measured in stored samples.
Mean ± SD measured GFR was 1.58 ± 0.39 mL/min/kg, and the calculated reference interval was 0.84 to 2.37 mL/min/kg. There were significant negative correlations between GFR and serum creatinine concentration (r = −0.499), BUN concentration (r = −0.592), and age (r = −0.463). Serum SDMA concentration was not significantly correlated with GFR (r = 0.385), BUN concentration (r = −0.281), or serum creatinine concentration (r = 0.165).
CONCLUSIONS AND CLINICAL RELEVANCE
A reference interval for GFR in clinically normal cheetahs was obtained. Further evaluation of animals with renal disease is needed to determine whether measuring serum clearance of a single IV dose of inulin is a reliable diagnostic test for early detection of renal disease in cheetahs.
To use RNA sequencing (RNAseq) to characterize renal transcriptional activities of genes associated with proinflammatory and profibrotic pathways in ischemia-induced chronic kidney disease (CKD) in cats.
Banked renal tissues from 6 cats with experimentally induced CKD (renal ischemia [RI] group) and 9 healthy cats (control group).
Transcriptome analysis with RNAseq, followed by gene ontology and cluster analyses, were performed on banked tissue samples of the right kidneys (control kidneys) from cats in the control group and of both kidneys from cats in the RI group, in which unilateral (right) RI had been induced 6 months before the cats were euthanized and the ischemic kidneys (IKs) and contralateral nonischemic kidneys (CNIKs) were harvested. Results for the IKs, CNIKs, and control kidneys were compared to identify potential differentially expressed genes and overrepresented proinflammatory and profibrotic pathways.
Genes from the gene ontology pathways of collagen binding (eg, transforming growth factor-β1), metalloendopeptidase activity (eg, metalloproteinase [MMP]-7, MMP-9, MMP-11, MMP-13, MMP-16, MMP-23B, and MMP-28), chemokine activity, and T-cell migration were overrepresented as upregulated in tissue samples of the IKs versus control kidneys. Genes associated with the extracellular matrix (eg, TIMP-1, fibulin-1, secreted phosphoprotein-1, matrix Gla protein, and connective tissue growth factor) were upregulated in tissue samples from both the IKs and CNIKs, compared with tissues from the control kidneys.
CONCLUSIONS AND CLINICAL RELEVANCE
Unilateral ischemic injury differentially altered gene expression in both kidneys, compared with control kidneys. Fibulin-1, secreted phosphoprotein-1, and matrix Gla protein may be candidate biomarkers of active kidney injury in cats.
To characterize transcription of profibrotic mediators in renal tissues of cats with ischemia-induced chronic kidney disease (CKD).
Banked renal tissues from 6 cats with experimentally induced CKD (RI group) and 8 healthy control cats.
For cats of the RI group, both kidneys were harvested 6 months after ischemia was induced for 90 minutes in 1 kidney. For control cats, the right kidney was evaluated. All kidney specimens were histologically examined for fibrosis, inflammation, and tubular atrophy. Renal tissue homogenates underwent reverse transcription quantitative PCR assay evaluation to characterize gene transcription of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β1, and vascular endothelial growth factor A. Gene transcription and histologic lesions were compared among ischemic and contralateral kidneys of the RI group and control kidneys.
Ischemic kidneys had greater transcript levels of MMP-7, MMP-9, and transforming growth factor-β1 relative to control kidneys and of MMP-2 relative to contralateral kidneys. Transcription of TIMP-1 was upregulated and that of vascular endothelial growth factor A was downregulated in ischemic and contralateral kidneys relative to control kidneys. Transcription of HIF-1α did not differ among kidney groups. For ischemic kidneys, there were strong positive correlations between transcription of HIF-1α, MMP-2, MMP-7, and TIMP-1 and severity of fibrosis.
CONCLUSIONS AND CLINICAL RELEVANCE
Transcription of genes involved in profibrotic pathways remained altered in both kidneys 6 months after transient renal ischemia. This suggested that a single unilateral renal insult can have lasting effects on both kidneys.