The Case for Cautious Consumption: NSAIDs in Chronic Kidney Disease

Sriram Sriperumbuduri; Swapnil Hiremath

Disclosures

Curr Opin Nephrol Hypertens. 2019;28(2):163-170. 

In This Article

Pharmacological Effects of NSAIDs on the Kidney

NSAIDs actions are mainly from inhibition of prostaglandin synthesis.[6] Prostaglandins are ubiquitous substances synthesized in various tissues in the body which act in an autocrine and paracrine fashion. They are derived from arachidonic acid and the conversion involves enzymes including cyclooxygenase (COX), lipoxygenase and mixed-function oxygenase. The COX pathway is inhibited by NSAIDs: with the acetylation from aspirin being irreversible, and the other NSAID inhibition being reversible. COX converts arachidonic acid along prostaglandin G2 and H2 pathway forming prostaglandins E2, F2, D2, I2 (also called prostacyclin), and thromboxane A2 (TxA2). Although prostaglandins E2 and F2 promote diuresis and natriuresis (action on collecting tubule and medullary interstitial cells), prostacyclin causes vasodilatation, renin release (action on vasculature and glomerulus) and inhibition of platelet aggregation. TxA2, on the other hand, causes increased platelet activation, aggregation and vasoconstriction. Thus the isolated effects of the individual prostanoids may sometimes be opposite, and hence the net effect of COX (and consequently COX inhibition from an NSAID) depends on the degree of prostaglandin synthesis in various cell and tissue types. COX itself exists in two isoforms, COX1 and COX2. Although COX1 is a constitutive enzyme with expression predominantly in platelets, gastric mucosa, kidneys and vascular endothelium, COX2 is induced in specific conditions, for example inflammation. Given this preamble, some renal effects are understandable consequences, as outlined in Table 1.

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