TY - JOUR
T1 - Renal and cardiovascular effects of selective cyclooxygenase-2 inhibitors
AU - Komers, Radko
AU - Anderson, Sharon
AU - Epstein, Murray
N1 - Funding Information:
Supported in part by grants from the American Diabetes Association and grant no. AG 14669 from the National Institutes of Health.
PY - 2001
Y1 - 2001
N2 - Selective inhibition of cyclooxygenase-2 (COX-2) was proposed as a novel anti-inflammatory and analgesic treatment with a reduced profile of gastrointestinal side effects compared with conventional nonsteroidal anti-Inflammatory drugs (NSAIDs). Although perceived as an inducible enzyme by inflammatory and other stimuli, COX-2 is constitutively expressed in the kidney. In this review, we focus on renal and cardiovascular (CV) physiological and pathophysiological characteristics of COX-2 and renal and CV aspects of treatment with selective COX-2 inhibitors. Both clinical and experimental studies have shown that renal and CV effects of COX-2 inhibitors are similar to those of NSAIDs. These effects include sodium, potassium, and water retention and decreases in renal function, as well as mild to modest increases in blood pressure (BP) and edema. These deleterious effects are amplified in patients with volume and/or sodium depletion. The concomitant administration of COX-2 inhibitors may destabilize BP control in hypertensive patients treated with antihypertensive agents. In contrast to the normal kidney, which could constitute a target for adverse actions of COX-2 inhibitors, recent experimental studies showed increased renal COX-2 expression in several models of renal injury, such as the remnant kidney, renovascular hypertension, and diabetes, and implicated COX-2 in the progression of renal failure. This suggests that COX-2 inhibitors may confer a renoprotective effect in diverse renal disorders. These intriguing formulations must be delineated further in appropriately designed prospective clinical trials.
AB - Selective inhibition of cyclooxygenase-2 (COX-2) was proposed as a novel anti-inflammatory and analgesic treatment with a reduced profile of gastrointestinal side effects compared with conventional nonsteroidal anti-Inflammatory drugs (NSAIDs). Although perceived as an inducible enzyme by inflammatory and other stimuli, COX-2 is constitutively expressed in the kidney. In this review, we focus on renal and cardiovascular (CV) physiological and pathophysiological characteristics of COX-2 and renal and CV aspects of treatment with selective COX-2 inhibitors. Both clinical and experimental studies have shown that renal and CV effects of COX-2 inhibitors are similar to those of NSAIDs. These effects include sodium, potassium, and water retention and decreases in renal function, as well as mild to modest increases in blood pressure (BP) and edema. These deleterious effects are amplified in patients with volume and/or sodium depletion. The concomitant administration of COX-2 inhibitors may destabilize BP control in hypertensive patients treated with antihypertensive agents. In contrast to the normal kidney, which could constitute a target for adverse actions of COX-2 inhibitors, recent experimental studies showed increased renal COX-2 expression in several models of renal injury, such as the remnant kidney, renovascular hypertension, and diabetes, and implicated COX-2 in the progression of renal failure. This suggests that COX-2 inhibitors may confer a renoprotective effect in diverse renal disorders. These intriguing formulations must be delineated further in appropriately designed prospective clinical trials.
KW - Blood pressure (BP)
KW - Cyclooxygenase-2 (COX-2)
KW - Hypertension
KW - Nonsteroidal anti-inflammatory drugs (NSAIDs)
KW - Renal
KW - Renal dysfunction
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U2 - 10.1053/ajkd.2001.29203
DO - 10.1053/ajkd.2001.29203
M3 - Article
C2 - 11728945
AN - SCOPUS:0035722949
SN - 0272-6386
VL - 38
SP - 1145
EP - 1157
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -