evidence is emerging about the added value of sodium-glucose cotransporter 2 (SGLT2) inhibitors, beyond their glucose-lowering effect, when they are used to treat patients with or without diabetes who have proteinuria and declining kidney function
various mechanisms have been proposed to explain the renoprotective effect of SGLT2 inhibitors
including a reduction in pressure within the glomerular capillaries, with resulting protection of glomerular podocytes, which are the targets of injury in most, if not all, proteinuric kidney diseases
preventing angiotensin II-mediated constriction of the efferent arteriole by blockade of the renin-angiotensin system is the cornerstone of antiproteinuric therapy to limit progressive podocyte injury and loss in diabetic and nondiabetic kidney disease
as well as due to constriction of the efferent arteriorole, hyperfiltration also occurs through loss of regulation of the afferent arteriole
thought that the beneficial effects in renal disease of SGLT2 inhibitors is thought to be primarily mediated through constriction of the afferent arteriole and prevention of hyperfiltration (1)
SGLT2 inhibition reduces reabsorption of glucose and sodium within the proximal tubule, which reestablishes sodium delivery to the macula densa and leads to a correction of hyperfiltration through tubuloglomerular feedback and afferent vasoconstriction
dysfunctional podocytes cannot sufficiently counteract elevated glomerular capillary pressure, suggesting that SGLT2-mediated afferent arteriole vasoconstriction may be beneficial
effect of SGLT2 inhibitors appears to be consistent across all levels of kidney function, down to an estimated GFR of 30 ml per minute per 1.73 m2 of body-surface area, whereas glucose-lowering effects are directly proportional to glomerular filtration and are substantially decreased when kidney function declines, underscoring the importance of regulating glomerular hemodynamics in progressive renal disease
Reference:
Benzing C, Salant T. Insights into Glomerular Filtration and Albuminuria. N Engl J Med 2021;384:1437-46 DOI: 10.1056/NEJMra1808786
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