Why the study?
Recent studies suggest megalin reabsorbs renin and angiotensinogen and might contribute to renal angiotensin production, but its role in renin-angiotensin system activity required critical evaluation.
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Design
Review
Megalin mediates the reabsorption of renin and angiotensinogen, suggesting that urinary RAS components indicate reduced reabsorption rather than local renal production.
PURPOSE OF REVIEW: Megalin is well known for its role in the reabsorption of proteins from the ultrafiltrate. Recent studies suggest that megalin also reabsorbs renin and angiotensinogen. Indeed, without megalin urinary renin and angiotensinogen levels massively increase, and even prorenin becomes detectable in urine. RECENT FINDINGS: Intriguingly, megalin might also contribute to renal angiotensin production, as evidenced from studies in megalin knockout mice. This review discusses these topics critically, concluding that urinary renin-angiotensin system components reflect diminished reabsorption rather than release from renal tissue sites and that alterations in renal renin levels or megalin-dependent signaling need to be ruled out before concluding that angiotensin production at renal tissue sites is truly megalin dependent. Future studies should evaluate megalin-mediated renin/angiotensinogen transcytosis (allowing interstitial angiotensin generation), and determine whether megalin prefers prorenin over renin, thus explaining why urine normally contains no prorenin.
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Sun et al. (2020) studied this question.
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