Chronic kidney disease (CKD) is a common problem that affects an estimated 0.5 to 7% of dogs. Radiographic signs of osteoarthritis
(OA) occur in 20% of dogs. The majority of OA and CKD are acquired and both conditions are more prevalent in older dogs.
Use of non-steroidal anti-inflammatory drugs (NSAIDs) has dramatically improved the quality of life for many dogs with OA.
The potential nephrotoxicity of NSAIDs however make their use problematic in dogs with CKD. Thorough evaluation of renal
function prior to the use of NSAIDs and follow-up monitoring for any adverse effects on renal function is extremely important
in the older dog. Newer evidence suggests that the cyclooxygenase (COX) II enzyme is important in maintaining renal blood
flow (RBF) in dogs and therefore, COX II selective/specific NSAIDs at least have the potential to adversely affect renal function
in dogs. In contrast, the hepatotoxicity associated with NSAIDs in dogs appears to idiosyncratic and unrelated the COX selectivity
of the drug.
Potential nephrotoxicity of NSAIDs
Renal damage and disease can be caused by acute or chronic insults to the kidney. The terms renal disease and renal damage
are used to denote the presence of renal lesions; these terms however imply nothing about renal function or the cause, distribution,
or severity of the renal lesions. Acute kidney injury (AKI) often results from ischemic or toxic insults and usually affects
the tubular portion of the nephron. Early detection of AKI facilitates appropriate intervention that can arrest or at least
attenuate tubular cell damage and the development of established acute renal failure (ARF). In contrast, nephron damage associated
with CKD is usually irreversible and can be progressive. Pre-existing CKD increases the risk of AKI associated with the use
of potentially nephrotoxic drugs.
Renal prostaglandins help regulate RBF and glomerular filtration rate (GFR), renin release, and sodium excretion. Potential
adverse effects of renal prostaglandin inhibition with NSAIDs can include decreased RBF and GFR, hypertension, salt retention
and edema. Since both COX-1 and COX-2 enzymes are present/expressed in the canine kidney, any NSAID, regardless of its COX
specificity or sparing properties, has the potential to produce adverse renal effects. In particular, dogs express higher
basal levels of COX-2 in the kidney than some other species and may be uniquely sensitive to the nephrotoxic effects of COX-2
selective drugs. Although a number of studies have shown no adverse effects of the commonly used NSAIDs in dogs with normal
kidneys, increased BUN and creatinine are common adverse events listed for NSAIDs at the FDA Adverse Drug Event website.
Dogs in field trials of deracoxib and firocoxib had increased BUN at the end of the trials, while dogs treated with etodolac
did not. In cases where RBF is decreased (e.g., dehydration and decreased cardiac output), the vasodilatory effects of renal
prostaglandins are critical in the maintenance of renal perfusion and the potential for adverse effects associated with NSAID
use is increased. There is also concern that patients treated with drugs that can decrease GFR (such as angiotension-converting
enzyme (ACE) inhibitors) may have increased renal toxicity when treated with NSAIDs. Studies of elderly human patients have
confirmed this effect, but in a study of normal dogs treated with enalapril and tepoxalin no alteration of GFR was noted.