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.
Chronic kidney disease
Glomerular filtration rate
Urine protein-to-creatinine concentration ratio
Liberty Research Inc, Waverly, NY.
Purina Pro Plan Chicken and Liver Adult Cat Entrée, Nestle Purina PetCare Co, St Louis, Mo.
Aspirin, 81 mg/tablet, lot No. 209135F, Bayer Healthcare, Morristown, NJ.
Metacam, 5 mg meloxicam/mL solution, lot No. 065ZNO1, Boehringer Ingelheim Vetmedica Inc, St Joseph, Mo.
Empty gelatin capsules, size 1, Wonder Laboratories, White House, Tenn.
Spectrum CCX, Abbott Diagnostics, Irving, Tex.
Statview 4.5, Abacus Concepts Inc, Berkeley, Calif.
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