NSAIDs: Acute kidney injury (acute renal failure)

Prostaglandins have a vasodilatory action, and so local production in the kidney is important for maintaining normal renal perfusion. NSAID interference will therefore lower renal blood flow, giving rise to nephrotoxicity, and so use in renal patients must be carefully considered. Care must also be taken when administering these drugs peri-operatively.

Prostaglandin synthesis by rat glomerular mesangial cells in culture.

Effects of aspirin and NSAIDs on prostaglandin synthesis

The long¬term renal toxicity of NSAIDs may be caused by ..

Figure 3. Pathogenesis of gastric damage by NSAIDs. Current evidence indicates that the majority of harmful effects mediated by NSAIDs result from inhibition of the synthesis of mucosal-protective prostaglandins produced by constitutive COX-1 activity. Direct drug-mediated irritant effects on epithelial cells appear to play only a minor role in GI toxicity. The presence of infections by the bacterium H pylori represents a separate risk factor that increases the likelihood of developing duodenal ulcers (Feldman, 2014).

Mechanisms of NSAID Induced Functional Renal Toxicity

NSAIDs work by suppressing the production of prostaglandins. Prostaglandins are chemical messengers that mediate inflammation, fever and the sensation of pain. NSAIDs block the production of prostaglandins by inhibiting the action of an enzyme, cyclooxygenase (COX). This enzyme is responsible for converting precursor acids into prostaglandins.

By inhibiting prostaglandin synthesis NSAIDs prevent …

NSAIDs block the synthesis of prostaglandin G 2.

NSAIDs-induced hypertension is due to the effects on renal function. Specifically, NSAIDs cause dose-related increases in sodium and water retention. In addition, NSAID use may reduce the effect of antihypertensive drugs except calcium channel blockers.

NSAIDs & the Kidney: Acute Renal Failure

on prostaglandin and leukotriene synthesis in ..

Various nephrotoxicity syndromes are seen with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). The most common is reversible, hemodynamically mediated renal insufficiency. The role of prostaglandin inhibition by NSAIDs is discussed in the context of renal prostaglandin physiology. Potential differences among NSAIDs are reviewed. The 'renal sparing' effect of sulindac may be attributable to the relative preservation of renal prostaglandin synthesis. Salsalate, although anti-inflammatory, demonstrates weak prostaglandin inhibition at therapeutic doses. A framework is developed for the clinical application of these considerations. Along a continuum of increasing risk factors for NSAID nephrotoxicity, or increasing NSAID dose, there likely exists a therapeutic window where differences among NSAIDs are most relevant.

impaired prostaglandin synthesis would badly affect the kidney functions.

and decreased renal prostaglandin synthesis

Since normal articular chondrocytes produce very little PGE2 and osteoarthritic chondrocytes produce a lot of it through the COX-2 enzyme, it would make sense from a traditional medical point of view to attack arthritis pain from this angle. This is especially true since the over expression of the COX-2 protein (and thus increased PGE2 levels) plays an important role in many pathophysiolgic states, including systemic inflammation, fever, cancer, angiogenesis, Alzheimer’s disease, and inflammatory arthritis.96 Yes, in certain conditions inflammation is harmful, but it is a big leap to assume everywhere there is PGE2 it is harming tissue. The articular chondrocytes make PGE2 in response to injury to stimulate healing. Osteoarthritic cartilage spontaneously releases PGE2 in levels at least 50-fold higher than normal cartilage and 18-fold higher than normal cartilage stimulated with cytokines and endotoxin.97-100 The inflammation that occurs through PGE2 when a normal or osteoarthritic joint is injured is the body’s immune system response to try and get the joint injury repaired.101 When a person uses medications that block this response, while pain may be improved, the repair mechanisms for the joint are inhibited. The long-term consequences, of course can be an acceleration of the degenerative osteoarthritic process. (See Figure 16.) Long-term NSAID treatment not only blocks PGE2 production by direct inhibition of COX-2 activity but by down-regulating COX-2 synthesis.102

This response has been attributed to inhibition of renal prostaglandin synthesis.

prostaglandin synthesis is increased, ..

NSAIDs reduce the blood flow to the kidneys, which makes them work more slowly. This is due to the inhibition of production of the vasodilatory renal prostaglandins. When the kidneys are not working well, fluid builds up in the body leading to edema. The more fluid in the bloodstream -- the higher blood pressure. The reduced blood flow can permanently damage the kidneys. It can eventually lead to kidney failure and require dialysis.