• 1. Khan KN, Venturini CM & Bunch RT, et al. Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal anti-inflammatory drug-related nephrotoxicity. Toxicol Pathol 1998; 26:612620.

    • Search Google Scholar
    • Export Citation
  • 2. Yabuki A, Mitani S & Sawa M, et al. A comparative study of chronic kidney disease in dogs and cats: induction of cyclooxygenases. Res Vet Sci 2012; 93:892897.

    • Search Google Scholar
    • Export Citation
  • 3. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231:232235.

  • 4. Bergh MS, Budsberg SC. The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine. J Vet Intern Med 2005; 19:633643.

    • Search Google Scholar
    • Export Citation
  • 5. Goodman LA, Brown SA & Torres BT, et al. Effects of meloxicam on plasma iohexol clearance as a marker of glomerular filtration rate in conscious healthy cats. Am J Vet Res 2009; 70:826830.

    • Search Google Scholar
    • Export Citation
  • 6. Surdyk KK, Sloan DL, Brown SA. Evaluation of the renal effects of carprofen and etodolac in euvolemic and volume-depleted dogs. Am J Vet Res 2012; 73:14851490.

    • Search Google Scholar
    • Export Citation
  • 7. Surdyk KK, Sloan DL, Brown SA. Evaluation of the renal effects of ibuprofen and carprofen in euvolemic and volume-depleted dogs. Int J Appl Res Vet Med 2011; 9:129136.

    • Search Google Scholar
    • Export Citation
  • 8. Brown SA, Brown CA & Crowell WA, et al. Beneficial effects of chronic administration of dietary omega-3 polyunsaturated fatty acids in dogs with renal insufficiency. J Lab Clin Med 1998; 131:447455.

    • Search Google Scholar
    • Export Citation
  • 9. Brown SA, Brown CA & Crowell WA, et al. Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs. J Lab Clin Med 2000; 135:275286.

    • Search Google Scholar
    • Export Citation
  • 10. Gooch K, Culleton B & Manns B, et al. NSAID use and progression of chronic kidney disease. Am J Med 2007; 120:281287.

  • 11. Gowan R, Lingaard A & Johnston L, et al. Retrospective case-control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease. J Feline Med Surg 2011; 13:752761.

    • Search Google Scholar
    • Export Citation
  • 12. Brown SA, Brown CA & Jacobs G, et al. Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. Am J Vet Res 2001; 62:375383.

    • Search Google Scholar
    • Export Citation
  • 13. Brown S, Rickertsen M, Sheldon S. Effects of an intestinal phosphorus binder on serum phosphorus and parathyroid hormone concentration in cats with reduced renal function. Int J Appl Res Vet Med 2008; 6:155160.

    • Search Google Scholar
    • Export Citation
  • 14. Brown SA, Finco DR & Boudinot D, et al. Evaluation of a single injection method, using iohexol, for estimating glomerular filtration rate in cats and dogs. Am J Vet Res 1996; 57:105110.

    • Search Google Scholar
    • Export Citation
  • 15. Elliott J, Watson A. Chronic kidney disease: staging and management. In: Bonagura J, Twedt D, eds. Current veterinary therapy XIV. St Louis: Saunders-Elsevier, 2009; 883892.

    • Search Google Scholar
    • Export Citation
  • 16. Brown SA, Brown CA. Single-nephron adaptations to partial renal ablation in cats. Am J Physiol 1995; 269:R1002R1008.

  • 17. King JN, Gunn-Moore DA & Tasker S, et al. Tolerability and efficacy of benazepril in cats with chronic kidney disease. J Vet Intern Med 2006; 20:10541064.

    • Search Google Scholar
    • Export Citation
  • 18. Syme HM, Markwell PJ & Pfeiffer D, et al. Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med 2006; 20:528535.

    • Search Google Scholar
    • Export Citation
  • 19. Zhang Q, Qiu J & Liu Y, et al. Cyclooxygenase 2 promotes parathyroid hyperplasia in ESRD. J Am Soc Nephrol 2011; 22:664672.

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Evaluation of glomerular filtration rate in cats with reduced renal mass and administered meloxicam and acetylsalicylic acid

Kathryn K. Surdyk DVM, PhD1, Cathy A. Brown VMD, PhD2, and Scott A. Brown VMD, PhD3
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  • 1 Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 2 Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 3 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

Abstract

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.

Abstract

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.

Cyclooxygenase has multiple isoforms, including COX-1 and COX-2, which are constitutively expressed in the kidneys of animals of many species, including dogs1 and cats.2 Products of renal COX activity, prostaglandins, and thromboxanes modulate GFR in some species,1–4 suggesting that feline GFR may in some way depend on COX activity.

However, meloxicam administration to clinically normal euvolemic cats has no measurable short-term effect on GFR, as evaluated by plasma clearance of iohexol.5 This finding is consistent with studies6,7 in dogs, which reveal that NSAIDs, whether selective for COX-2 or not, have no adverse effect on GFR in euvolemic dogs. However, NSAIDs, including COX-2-selective agents, can have an adverse effect on GFR in certain settings. In particular, NSAIDs reduce GFR in volume-depleted dogs,6,7 a situation wherein renal function is at least partially dependent on intact COX activity.

In cats and dogs with CKD, COX expression is reportedly altered, with increased COX-2 expression in particular.2 Furthermore, in chronically azotemic dogs, manipulations that alter renal eicosanoid production by COXs can have important effects on disease progression8 and glomerular hemodynamics.9 In humans with CKD, there is increased risk of nephrotoxicosis from NSAIDs.10 On the basis of these findings, it seems reasonable to speculate that the administration of NSAIDs to cats with CKD would adversely affect GFR.

In contrast, the long-term administration of meloxicam to azotemic, geriatric cats with spontaneous CKD has no adverse effects and actually appears to slow progression of CKD.11 However, the short-term effects of COX inhibition on GFR were not investigated in that study,11 and the dosages used (0.01 to 0.03 mg/kg/d) were lower than those (0.1 to 0.2 mg/kg/d) often used for short-term analgesia in cats.

The purpose of the study reported here was to determine whether there is a short-term effect of administration of meloxicam or acetylsalicylic acid at commonly recommended dosages on GFR and proteinuria in euvolemic cats with reduced renal function and stable azotemia equivalent to the International Renal Interest Society CKD stages 2 and 3.

Materials and Methods

Animals—Six 24- to 36-month-old cats (3 sexually intact females and 3 sexually intact males) initially weighing 3.64 ± 0.20 kg were procured from a commercial supplier.a Each cat had normal findings on physical examination, concentrations of SUN and serum creatinine within reference range, and UP:C within reference range. This study complied with the Animal Welfare Act, the US Public Health Service Policy on the Humane Care and Use of Laboratory Animals, the National Research Council Guide for the Care and Use of Laboratory Animals, and the University of Georgia Animal Care and Use Committee.

Animal preparation—All cats underwent right nephrectomy and infarction of approximately five-sixths of the left kidney by ligation of a variable number of branches of the renal artery as described12 approximately 18 months prior to this study. These cats were part of a previous study13 of the effects of an intestinal phosphorus-binding agent on blood phosphorus and parathyroid hormone concentrations, which was completed 2 months prior to the start of the present study. Renal biopsy specimens obtained at the time of renal mass reduction as wedge biopsies of tissue immediately after infarction were determined to be normal in all 6 cats via light microscopy.

Diets—The cats were provided ad libitum access to water and were fed a canned feline maintenance dietb throughout the study, which contained approximately 0.47% phosphorus, 0.50% calcium, 0.12% sodium, and 76% moisture on an as-fed basis. The cats were offered a preweighed amount of food daily (approx 35 kcal/kg of body weight, twice daily) with food being provided between 8:00 AM and 10:00 AM and between 3:00 PM and 5:00 PM. Daily food intake was determined, and amount of food was adjusted prior to this study to maintain stable body weights.

Pharmacological agents—Acetylsalicylic acidc was administered orally at a dosage of 20 mg/kg and was given every 72 hours on days 1, 4, and 7. Meloxicamd was administered SC at a dosage of 0.2 mg/kg on day 1 and 0.1 mg/kg on days 2 to 7. During the initial (baseline) and final (time control) periods, the cats received placeboe PO once daily. For all medications, the daily doses were administered between 7:00 AM and 9:00 AM.

Study protocol—This trial was 35 days in duration, divided into 5 periods of 7 days' duration each. During the baseline period, cats received oral placebo once daily. During the subsequent period (NSAID administration period 1), 3 cats were randomly assigned to receive acetylsalicylic acid and the other 3 cats received meloxicam. Following NSAID administration period 1, there was a washout period of 7 days' duration, during which no medications were administered. The subsequent period was NSAID administration period 2, during which cat medication assignments were reversed from those of NSAID administration period 1. There was a 7-day time control period after NSAID administration period 2, during which the cats received placebo.

Renal clearance studies were conducted between 10:00 am and 2:00 pm on day 7 of the baseline period, NSAID administration periods 1 and 2, and the time control period. These studies occurred between 1 and 5 hours after drug administration in the morning of day 7 for the NSAID administration periods. During each period, food intake was quantified daily, and cats were observed twice daily for the presence of vomiting, diarrhea, or any other evidence of clinical illness.

Renal clearance studies—The GFR was estimated as urinary clearance of exogenously administered creatinine, in accordance with a described procedure.12 During this procedure, urine was obtained by urethral catheterization for aerobic bacterial culture of urine and for determination of the UP:C, urine flow rate, and urine creatinine concentration. Blood was obtained with a saphenous venous catheter for measurement of serum creatinine concentration. Serum and urine creatinine concentrations were determined by means of a semiautomated device.f For each renal clearance study, the urinary clearance of exogenously administered creatinine was determined as the mean of at least 2 replicate measurements, with the value being calculated via the standard urinary clearance formula.12

Statistical analysis—Results are reported as mean ± SEM values. Statistical analyses were performed with the aid of a commercial software package.g Statistical comparisons were made by use of ANOVA with inclusion of an effect for drug treatment and time (multiple measurements were obtained) in the model. Values of P < 0.05 were considered significant.

Results

The mean quantity of food offered was 117 ± 9 g/cat, and there were no significant treatment or time effects in food intake, which was 106 ± 7 g/cat/d during the baseline period, 105 ± 8 g/cat/d during the meloxicam period, 107 ± 6 g/cat/d during the acetylsalicylic acid period, and 104 ± 8 g/cat/d during the time control period. There were no significant effects of treatment or time on body weight (Table 1). The mean meloxicam dosage (administered SC, once daily) administered on day 1 was 0.20 ± 0.01 mg/kg and for days 2 to 7 was 0.10 ± 0.01 mg/kg. The mean acetylsalicylic acid dosage (PO, once daily on days 1, 4, and 7) was 20.5 ± 1.0 mg/kg. The baseline serum creatinine concentration in all 6 cats significantly exceeded the mean ± 2 SD value for serum creatinine concentration of 1.02 to 1.68 mg/dL in clinically normal cats.14 The serum creatinine concentration for 3 of the cats (2.3, 2.4, and 2.8 mg/dL) corresponded to the range of serum creatinine concentrations for International Renal Interest Society CKD stage 2.15 The baseline value for serum creatinine concentration for the remaining 3 cats (3.0, 3.0, and 3.1 mg/dL) corresponded to International Renal Interest Society CKD stage 3. The urinary clearance of exogenously administered creatinine in these cats represented a 42% to 59% reduction from the mean urinary clearance of exogenously administered creatinine in clinically normal cats of 2.83 ± 0.33 mL/min/kg.14 The baseline UP:C in these cats corresponded to the International Renal Interest Society substages15 for nonproteinuric (1 cat; UP:C, 0.14), borderline proteinuric (2 cats; UP:C, 0.37 and 0.40), or proteinuric (3 cats; UP:C, 0.42, 0.45, and 0.55). There were no significant differences in GFR or UP:C between male and female cats.

Table 1—

Results (mean ± SEM) of measurements of variables in 6 cats with reduced renal mass and treated with meloxicam or acetylsalicylic acid.

VariableBaseline (placebo)MeloxicamAcetylsalicylic acidTime control (placebo)
Body weight (kg)3.85 ± 0.293.86 ± 0.303.88 ± 0.283.90 ± 0.31
Serum creatinine (mg/dL)2.77 ± 0.142.67 ± 0.172.62 ± 0.122.59 ± 0.16
GFR (mL/min/kg)1.36 ± 0.071.34 ± 0.081.35 ± 0.071.35 ± 0.07
UP:C0.39 ± 0.060.42 ± 0.070.38 ± 0.080.41 ± 0.06

During the 5 periods of this 35-day study, there were no significant time or treatment effects for variables of renal function (serum creatinine concentration, urinary clearance of exogenously administered creatinine, or UP:C; Table 1). Results of urinary clearance of exogenously administered creatinine measurements in individual cats revealed no consistent pattern of change. Twice-daily clinical observations of cats throughout the study revealed no vomiting or diarrhea and no evidence of clinical illness or adverse effect of the administration of either drug. Results of all bacteriologic cultures of urine obtained at the time of renal clearance studies were negative.

Discussion

Results of the present study indicated that short-term administration of meloxicam or acetylsalicylic acid did not measurably affect GFR in euvolemic cats with surgically induced azotemia equivalent to International Renal Interest Society CKD stages 2 to 3. These results, taken together with previous findings in which the short-term administration of meloxicam did not measurably alter the GFR in cats with normal kidney function,5 suggest that renal COX does not have a measureable effect on GFR in euvolemic cats whether GFR is normal or chronically reduced.

Although CKD is a risk factor for the development of NSAID nephrotoxicosis in humans,10 the previous study11 determined that meloxicam has no measurable adverse effect on kidney function as assessed by serum creatinine concentration and UP:C when used long term at low dosages (0.01 to 0.03 mg/kg/d) in azotemic geriatric cats. Although confirmatory studies are needed, the use of meloxicam in that setting was actually beneficially renoprotective. It is interesting to note that COX-2 is upregulated in the kidneys of cats with spontaneous CKD.2 Additional studies are needed to determine whether this protection can be confirmed and, if so, whether it is specific to meloxicam or to COX-2-selective NSAIDs and dosage dependent. Nevertheless, in the present study, no measurable effects on GFR were associated with short-term administration of a nonselective (acetylsalicylic acid) and COX-2-selective (meloxicam) NSAID.

Previous micropuncture studies16 revealed that cats with similarly induced renal dysfunction have glomerular hypertension, hyperfiltration, and hyperperfusion. Glomerular hypertension and hyperfiltration are differentially affected by angiotensin-converting enzyme inhibition in azotemic cats12 and dietary n-3 polyunsaturated fatty acids supplementation in azotemic dogs.9 Both manipulations reduce the severity of glomerular hypertension while sustaining GFR and are renoprotective in certain settings.8,17 The effect of NSAIDs on feline glomerular pressure has not been studied, but it is interesting that the degree of upregulation of COX-2 in the macula densa is correlated with the severity of glomerular disease in cats with spontaneous CKD.2

Proteinuria is an important finding in cats with CKD that is linked to disease progression.18 We were not able to identify a link between proteinuria and disease progression in the present study or in a previous study11 of spontaneous feline CKD and meloxicam. Urine samples obtained by urethral catheterization were used to determine UP:C and for bacteriologic cultures of urine. Although urethral catheterization may induce a urinary tract infection or transiently cause hematuria and associated increases in the UP:C, results of bacteriologic cultures of urine and urinalyses suggested that artifactual increase of UP:C was not an important factor. Evaluation of potential mechanisms for effects of NSAIDs in feline CKD remains an important consideration that is worthy of further investigation. For example, if COX-2-selective NSAIDs resolve glomerular hypertension or other pathogenic mechanisms without altering GFR, this could be of substantial benefit to cats with CKD. There are other known effects of NSAIDs in CKD in other species that may be relevant to cats. For example, in humans with CKD, inhibition of COX-2 blunts the development of parathyroid hyperfunction and lowers parathyroid hormone concentrations.19

There were limitations to this study and ample reason for concern about the use of NSAIDs in feline CKD, particularly with chronic administration. The cats of the present study were sexually intact males and females, and although comparisons did not ascertain a sex-specific effect, the small numbers of animals studied precluded any firm conclusions in this regard. In the present study, GFR was not measured at the end of the washout period between administration of meloxicam and acetylsalicylic acid. However, considering that the GFR after either administration of NSAID was not different from the adjacent control measurement, it seems unlikely that an unmeasured change in GFR occurred during the intervening washout period. This study addressed neither the cumulative effects of the long-term use of the dosages nor interactions of NSAIDs with other medications used in treatment of feline CKD. Furthermore, the authors are unaware of reports of COX expression in cats with CKD induced as in the present study. Animals with CKD may develop dehydration and electrolyte abnormalities, conditions that place dogs at risk for reductions of GFR from NSAID administration.6,7 Alterations in the pattern of renal blood flow and associated medullary cytotoxicosis represent a mechanism of nephrotoxicosis from NSAIDs that were not fully investigated in the present study. Nonetheless, results of the present study were consistent with the assertion that euvolemic cats with chronic azotemia are unlikely to have an acute reduction in GFR associated with NSAID administration.

Short-term administration of meloxicam or acetylsalicylic acid had no measurable effect on GFR in cats with chronic azotemia equivalent to International Renal Interest Society CKD stages 2 and 3. Results of the present study, taken together with those of a study11 of the chronic use of meloxicam in geriatric cats with spontaneous CKD, are consistent with the controversial hypothesis that manipulations that interfere with COX-2 function can slow the rate of progression of feline CKD without causing short-term reductions in GFR.

ABBREVIATIONS

CKD

Chronic kidney disease

COX

Cyclooxygenase

GFR

Glomerular filtration rate

UP:C

Urine protein-to-creatinine concentration ratio

a.

Liberty Research Inc, Waverly, NY.

b.

Purina Pro Plan Chicken and Liver Adult Cat Entrée, Nestle Purina PetCare Co, St Louis, Mo.

c.

Aspirin, 81 mg/tablet, lot No. 209135F, Bayer Healthcare, Morristown, NJ.

d.

Metacam, 5 mg meloxicam/mL solution, lot No. 065ZNO1, Boehringer Ingelheim Vetmedica Inc, St Joseph, Mo.

e.

Empty gelatin capsules, size 1, Wonder Laboratories, White House, Tenn.

f.

Spectrum CCX, Abbott Diagnostics, Irving, Tex.

g.

Statview 4.5, Abacus Concepts Inc, Berkeley, Calif.

References

  • 1. Khan KN, Venturini CM & Bunch RT, et al. Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal anti-inflammatory drug-related nephrotoxicity. Toxicol Pathol 1998; 26:612620.

    • Search Google Scholar
    • Export Citation
  • 2. Yabuki A, Mitani S & Sawa M, et al. A comparative study of chronic kidney disease in dogs and cats: induction of cyclooxygenases. Res Vet Sci 2012; 93:892897.

    • Search Google Scholar
    • Export Citation
  • 3. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231:232235.

  • 4. Bergh MS, Budsberg SC. The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine. J Vet Intern Med 2005; 19:633643.

    • Search Google Scholar
    • Export Citation
  • 5. Goodman LA, Brown SA & Torres BT, et al. Effects of meloxicam on plasma iohexol clearance as a marker of glomerular filtration rate in conscious healthy cats. Am J Vet Res 2009; 70:826830.

    • Search Google Scholar
    • Export Citation
  • 6. Surdyk KK, Sloan DL, Brown SA. Evaluation of the renal effects of carprofen and etodolac in euvolemic and volume-depleted dogs. Am J Vet Res 2012; 73:14851490.

    • Search Google Scholar
    • Export Citation
  • 7. Surdyk KK, Sloan DL, Brown SA. Evaluation of the renal effects of ibuprofen and carprofen in euvolemic and volume-depleted dogs. Int J Appl Res Vet Med 2011; 9:129136.

    • Search Google Scholar
    • Export Citation
  • 8. Brown SA, Brown CA & Crowell WA, et al. Beneficial effects of chronic administration of dietary omega-3 polyunsaturated fatty acids in dogs with renal insufficiency. J Lab Clin Med 1998; 131:447455.

    • Search Google Scholar
    • Export Citation
  • 9. Brown SA, Brown CA & Crowell WA, et al. Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs. J Lab Clin Med 2000; 135:275286.

    • Search Google Scholar
    • Export Citation
  • 10. Gooch K, Culleton B & Manns B, et al. NSAID use and progression of chronic kidney disease. Am J Med 2007; 120:281287.

  • 11. Gowan R, Lingaard A & Johnston L, et al. Retrospective case-control study of the effects of long-term dosing with meloxicam on renal function in aged cats with degenerative joint disease. J Feline Med Surg 2011; 13:752761.

    • Search Google Scholar
    • Export Citation
  • 12. Brown SA, Brown CA & Jacobs G, et al. Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. Am J Vet Res 2001; 62:375383.

    • Search Google Scholar
    • Export Citation
  • 13. Brown S, Rickertsen M, Sheldon S. Effects of an intestinal phosphorus binder on serum phosphorus and parathyroid hormone concentration in cats with reduced renal function. Int J Appl Res Vet Med 2008; 6:155160.

    • Search Google Scholar
    • Export Citation
  • 14. Brown SA, Finco DR & Boudinot D, et al. Evaluation of a single injection method, using iohexol, for estimating glomerular filtration rate in cats and dogs. Am J Vet Res 1996; 57:105110.

    • Search Google Scholar
    • Export Citation
  • 15. Elliott J, Watson A. Chronic kidney disease: staging and management. In: Bonagura J, Twedt D, eds. Current veterinary therapy XIV. St Louis: Saunders-Elsevier, 2009; 883892.

    • Search Google Scholar
    • Export Citation
  • 16. Brown SA, Brown CA. Single-nephron adaptations to partial renal ablation in cats. Am J Physiol 1995; 269:R1002R1008.

  • 17. King JN, Gunn-Moore DA & Tasker S, et al. Tolerability and efficacy of benazepril in cats with chronic kidney disease. J Vet Intern Med 2006; 20:10541064.

    • Search Google Scholar
    • Export Citation
  • 18. Syme HM, Markwell PJ & Pfeiffer D, et al. Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria. J Vet Intern Med 2006; 20:528535.

    • Search Google Scholar
    • Export Citation
  • 19. Zhang Q, Qiu J & Liu Y, et al. Cyclooxygenase 2 promotes parathyroid hyperplasia in ESRD. J Am Soc Nephrol 2011; 22:664672.

Contributor Notes

Supported in part by the Veterinary Medical Experiment Station of the University of Georgia and Boehringer Ingelheim Vetmedica Inc.

Address correspondence to Dr. Scott Brown (SBrown01@uga.edu).