Renal cyclooxygenase-2 (COX-2). Physiological, pathophysiological, and clinical implications.
OBJECTIVE
The role of COX-2 for renal function during renal development, for physiology and pathophysiology of renal diseases and the side effects of available COX-2 inhibitors, has gained increasing interest. We aimed therefore to review the respective role of renal COX-2.


METHODS
Review of relevant recent publications in the field, and in addition of in part unpublished data obtained in our laboratories.


RESULTS
COX-2 is 'constitutively' localized in the kidney i.e. in macula densa, TALH, interstitial cells, and is of utmost importance for normal renal development. Renal COX-2 is regulated by for example sodium and volume intake, angiotensin II, glucocorticoids often involving specific COX-2 promotor response elements. COX-2 derived prostanoids are required for preservation of renal blood flow and glomerular filtration especially in states of fluid deficit, they promote natriuresis, and furthermore may stimulate renin secretion during low-sodium intake/loop diuretic use. Conversely, COX-2 inhibitors decrease glomerular filtration, and renal perfusion, sometimes even causing acute renal failure. In addition, COX-2 inhibitors cause sodium retention, edema formation, cardiac failure and hypertension. The role of COX-2 derived prostanoids in renal inflammation or failure including diabetic nephropathy and renal transplantation remains at present controversial.


CONCLUSIONS
COX-2 is one of the major players in renal physiology and pathophysiology. One focus of future work should be placed on COX-2 in primary renal diseases.
Krämer
Bernhard K
BK
Nephrologie, Klinik und Poliklinik für Innere Medizin II, Regensburg, Germany. bernhard.kraemer@klinik.uni-regensburg.de
Kammerl
Martin C
MC
Kömhoff
Martin
M
D000818:Animals; D051546:Cyclooxygenase 2; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology; D007674:Kidney Diseases / Q000503:physiopathology; D008565:Membrane Proteins; D009318:Natriuresis / Q000502:physiology; D009393:Nephritis / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology*; D012083:Renin / Q000378:metabolism
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin