The Renal Effects of NSAIDs in Dogs

Abstract

The quality of life for dogs with osteoarthritis can often be improved with nonsteroidal anti-inflammatory drugs (NSAIDs); however, the number of adverse drug events associated with NSAID use reported to the Federal Drug Administration Center for Veterinary Medicine is higher than that for any other companion animal drug. Of those events, adverse renal reactions are the second most reported. NSAIDs produce pharmacologic effects via inhibition of cyclooxygenase (COX), which decreases production of prostanoids. Prostaglandins are synthesized by both the COX-1 and COX-2 enzymes in the healthy kidney and influence renal blood flow, glomerular filtration rate, renin release, and Na excretion. There are important species differences in the renal expression of COX-1 and COX-2. For example, dogs have higher basal levels of COX-2 expression in the kidney compared with humans. In addition, in dogs with chronic kidney disease, an increase in COX-2 expression occurs and synthesis of prostaglandins shifts to the COX-2 pathway. For those reasons, NSAIDs that target COX-2 may be expected to adversely affect renal function in dogs, especially dogs with chronic kidney disease. The purpose of this review was to evaluate the literature to report the renal effects of NSAIDs in dogs.

The attitudes of owners and veterinary professionals in the United Kingdom to the risk of adverse events associated with using non-steroidal anti-inflammatory drugs (NSAIDs) to treat dogs with osteoarthritis

“…Many dogs dropped out of the study as their owners perceived analgesia was inadequate but the authors concluded that dose reduction may be effective for some individuals. Use of the lowest effective dose is in dogs advocated by some authors for safety reasons (Lomas and Grauer, 2015) and is advised for doctors using NSAIDs in humans with osteoarthritis (Zhang et al, 2008). More research is urgently needed into the efficacy of low-dose NSAIDs in dogs with naturally occurring osteoarthritis.…”

Monitoring side effects of long‐term NSAID use in dogs with chronic osteoarthritis

“…However, it is also important for the normal function of many tissues, including the kidney and brain. Both enzymes convert arachidonic acid to prostanoids, leading to prostaglandin release in target tissues and the stimulation of pain signals, among other effects (Lomas and Grauer 2015). …”

“…Mild adverse effects remain common however (Table 1), and serious and fatal adverse events do still occur (Moreau and others 2005, Lomas and Grauer 2015). …”

“…This is particularly important when activation of the renin–angiotensin–aldosterone system causes vasoconstriction via norepinephrine, angiotensin II and vasopressin release. Prostaglandin inhibition as a result of NSAID administration will inhibit vasodilation, potentially reducing renal blood flow and glomerular filtration rate (GFR) (Lomas and Grauer 2015). …”

“…There is no NSAID that has been proven to be completely safe for use in dogs (Lomas and others 2013), possibly as a result of higher expression of COX-2 in the canine kidney compared to other species (Lomas and Grauer 2015). …”