Which class of diuretic is most likely to transiently raise renin (Renin) levels?

From the Guidelines

Loop diuretics are most likely to transiently raise renin levels. This class includes medications such as furosemide (Lasix), bumetanide, and torsemide. According to a recent study published in the European Journal of Heart Failure 1, loop diuretics activate the renin-angiotensin-aldosterone system (RAAS) in at least two independent ways. Firstly, the excretion of a significant amount of water and Na+ mediated by diuretics automatically activates counterbalance mechanisms to maintain sodium/volume equilibrium, including the RAAS. Secondly, loop diuretics act by blocking the Na cotransporters in the nephron’s lumen and macula densa cells, which precipitates in direct renin secretion.

The mechanism of this effect can be broken down into the following steps:

• Reduced blood volume is sensed by the juxtaglomerular cells in the kidney.
• These cells release renin into the bloodstream.
• Renin converts angiotensinogen to angiotensin I.
• Angiotensin I is then converted to angiotensin II, which causes vasoconstriction and stimulates aldosterone release.
• Aldosterone promotes sodium and water retention, attempting to restore blood volume.

This increase in renin is typically transient because as fluid balance is restored, the stimulus for renin release diminishes. However, in cases of chronic diuretic use or underlying conditions affecting kidney function, renin levels may remain elevated, as noted in the study 1. Clinicians should be aware of this effect when interpreting renin levels in patients on loop diuretics, as it may not necessarily indicate an underlying pathology of the renin-angiotensin system.

Key points to consider:

• Loop diuretics are first-line drugs used to alleviate congestion in acute heart failure.
• They effectively stimulate sodium/water excretion, providing transient symptomatic relief.
• However, they do not target the culprit pathophysiological processes of sodium avidity and may not modify the natural trajectory of the disease.
• Chronic exposure to loop diuretics, such as furosemide, can lead to RAAS overactivation and diminished tubular response to the drug, necessitating further escalation of doses 1.

From the FDA Drug Label

Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation

• The class of diuretic that is most likely to transiently raise renin levels is Loop Diuretics, as suggested by the interaction with indomethacin, which affects plasma renin levels.
• Furosemide is a loop diuretic, and its use with indomethacin may lead to changes in renin levels 2.

From the Research

Diuretic Class and Renin Levels

• The class of diuretic most likely to transiently raise renin levels is loop diuretics, as they inhibit the Na(+)-K(+)-2 Cl- transport system in the macula densa, leading to an increase in renin release 3.
• Loop diuretics, such as furosemide, have been shown to increase plasma renin activity in both hydropenic and volume-expanded rats 3.
• The mechanism of loop diuretic-mediated renin release is thought to involve an effect on the macula densa, which is essential for the renin secretory action of these diuretics 3.
• In contrast, thiazide-type diuretics do not appear to increase renin release to the same extent as loop diuretics, and may even decrease plasma renin activity in some cases 4.
• The use of loop diuretics in clinical practice is common, particularly in the treatment of edematous patients with congestive heart failure, cirrhosis with ascites, and nephritic edema 5, 6.