NSAIDs, the kidney and the triple whammy
NSAIDs (non-steroidal anti-inflammatory drugs) can lower kidney filtration: by blocking prostaglandins (local chemical messengers) they let the afferent arteriole, the vessel carrying blood into each glomerulus, narrow.
Remember
NSAIDs take away the prostaglandins that keep the afferent arteriole open. Add a diuretic and either an ACE inhibitor (a blood-pressure and heart drug) or an angiotensin receptor blocker, and acute kidney injury (filtration falls and creatinine rises) can follow: the triple whammy.
Memory aid
the NSAID closes the way in, the ACE inhibitor opens the way out, and the diuretic empties the tank
It lets you recall what each of the three drugs in the triple whammy does: the NSAID narrows the vessel carrying blood into the glomerulus, the ACE inhibitor relaxes the vessel carrying blood out, and the diuretic can lower the circulating volume.
Filtration in the kidney depends on the pressure inside each glomerulus, the tuft of filtering capillaries. Blood comes in through the afferent arteriole (afferent means arriving) and goes out through the efferent arteriole (efferent means exiting). Pressure is held up when the afferent arteriole stays open and the efferent arteriole stays relatively tight.
In the kidney, prostaglandins widen the afferent arteriole, and this keeps blood flow and filtration up when the circulation is under strain. NSAIDs block cyclo-oxygenase (COX), the enzyme that makes prostaglandins. Pressure in the glomerulus then falls as the afferent arteriole narrows, and the glomerular filtration rate (GFR, the volume of plasma filtered per minute) drops. Creatinine, a waste product that is normally filtered out, builds up in the blood. The change is haemodynamic (a blood-flow effect), and it is usually reversible when the NSAID is stopped.
People who depend on this widening are most affected, such as those with chronic kidney disease, heart failure or low blood volume.
The triple whammy adds an ACE inhibitor (or an angiotensin receptor blocker) and a diuretic to the NSAID. An ACE inhibitor lowers angiotensin II, the hormone that normally tightens the efferent arteriole, so that vessel relaxes and pressure leaks away. A diuretic can lower the circulating volume, and so can poor intake. An NSAID plus an ACE inhibitor (or an angiotensin receptor blocker) plus a diuretic, especially when the person is dehydrated, markedly raises the risk of acute kidney injury. In UK practice this combination is a preventable cause of acute kidney injury.
Key facts
- Mechanism
- NSAIDs lower renal prostaglandins, so the afferent arteriole constricts and the glomerular filtration rate falls.
- Who is at risk
- People who depend on prostaglandin-mediated afferent dilation, such as those with chronic kidney disease, heart failure or low blood volume.
- ACE inhibitor effect
- An ACE inhibitor lowers angiotensin II, so the efferent arteriole dilates (relaxes) and glomerular pressure falls.
- Triple whammy
- An NSAID plus an ACE inhibitor (or an angiotensin receptor blocker) plus a diuretic, especially when dehydrated, markedly raises the risk of acute kidney injury.
- Other renal effects
- The same loss of prostaglandins causes salt and water retention, and hyperkalaemia (a high blood potassium level) can occur.
- Outlook
- The acute fall in filtration is usually reversible if the NSAID is stopped promptly.
Exam traps
- Raised angiotensin II would narrow the efferent arteriole rather than widen it. Dilation of the efferent arteriole with a lower filtration rate fits ACE inhibitors, which block angiotensin II formation, not NSAIDs.
- The potassium problem linked to NSAIDs is hyperkalaemia (a high blood potassium level), not hypokalaemia (a low level).
- NSAIDs do not usually lower blood pressure: they cause salt and water retention and blunt the effect of blood-pressure-lowering drugs. The fall in filtration with NSAIDs comes from local narrowing of the afferent arteriole, not a fall in blood pressure.
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