Key result
Hemodynamic and metabolic pathways interact to promote diabetic kidney disease progression and offer novel targets.
Highlights the interplay of hemodynamic and metabolic pathways in diabetic kidney disease, supporting the use of RAAS blockade, SGLT2 inhibitors, and GLP1 receptor agonists.
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Potential multi-pathway therapies for diabetic kidney disease merit investigation; leaves open validation in randomized trials.
The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such as methylglyoxal which activate intracellular pathways to promote fibrosis and inflammation in the kidney. Recent studies have identified a novel molecular interaction between hemodynamic and metabolic pathways which could lead to new treatments for DKD. This should lead to a further improvement in the outlook of DKD building on positive results from RAAS blockade and more recently newer classes of glucose-lowering agents such as SGLT2 inhibitors and GLP1 receptor agonists.
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Patel et al. (2020) conducted a review in Diabetic kidney disease. Hemodynamic and metabolic pathways, including vasoactive hormones and reactive oxygen species, interact to promote diabetic kidney disease progression, offering novel targets for future therapies.
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