2019
DOI: 10.1002/dmrr.3171
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SGLT2 inhibition to address the unmet needs in diabetic nephropathy

Abstract: Summary Current treatment of diabetic nephropathy is effective; however, substantial gaps in care still remain and new therapies are urgently needed to reduce the global burden of the complication. Desirable properties of an “ideal” new drug should include primary prevention of microalbuminuria, additive/synergistic anti‐proteinuric effect in combination therapy with renin angiotensin system blockers, reduction of chronic kidney disease progression to lower the risk of end‐stage renal disease, and cardiovascul… Show more

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Cited by 27 publications
(30 citation statements)
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References 91 publications
(194 reference statements)
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“…The particular efficacy of RAS blockers in the treatment of DKD is due to their ability to reduce not only systemic blood pressure, but also glomerular capillary pressure via vasodilation of the efferent arteriole. Similarly, SGLT2i are believed to slow DKD progression predominantly by reducing glomerular capillary pressure via vasoconstriction of the afferent arteriole [11]. Therefore, RAS blockers and SGLT2i appears to have complementary positive effects on renal hemodynamic.…”
Section: Introductionmentioning
confidence: 99%
“…The particular efficacy of RAS blockers in the treatment of DKD is due to their ability to reduce not only systemic blood pressure, but also glomerular capillary pressure via vasodilation of the efferent arteriole. Similarly, SGLT2i are believed to slow DKD progression predominantly by reducing glomerular capillary pressure via vasoconstriction of the afferent arteriole [11]. Therefore, RAS blockers and SGLT2i appears to have complementary positive effects on renal hemodynamic.…”
Section: Introductionmentioning
confidence: 99%
“…SGLT2 are low af inity and high capacity glucose co-transporters localized in the lumen of proximal tubular cells, exerting their action speci ically in the S1 segment of the proximal tubule; they conduct glucose and sodium inside the cells and are responsible for the reabsorption of 80% to 90% of the iltered glucose. The remaining 10% to 20% is reabsorbed by SGLT1, high af inity and low capacity glucose co-transporters, expressed in the distal part of the proximal tubule; they exert their action speci ically in the S2 and S3 segments of the proximal tubule [3,5,10,20,21]. The entry of sodium inside the cells through SGLT1 and 2 is driven by a concentration gradient of sodium generated by the sodium-potassium ATPase (Na-K ATPase) pump, located in the basolateral membrane.…”
Section: The Role Of the Kidney In Glucose Homeostasismentioning
confidence: 99%
“…Additionally, the reabsorption of proximal sodium produces a decrease in the availability of sodium in the distal tubules and the decrease in the sodium reaching the macular densa, leading to a reduction in the hydro-lysis of ATP and the production of adenosine. Adenosine is a potent vasoconstrictor, and its reduction, such as in the hyperglycemic state, causes vasodilatation of the afferent arteriole, increasing intra-glomerular pressure and iltration [3,5,20,22]. The previously mentioned changes at the glomerular level produce in lammation and oxidative stress, with an increase in the production of pro in lammatory cytokines and reactive oxygen species (ROS).…”
Section: Type 2 Diabetes and Renal Compromisementioning
confidence: 99%
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“…Moreover, the patients with ESRD often need hemodialysis or kidney transplantation to restore the normal kidney function [3]. At present, the therapies for DN mainly focus on controlling the blood pressure and glycemic, and regulating the renin-angiotensin system (RAS) to control the further development of DN [4]. Furthermore, DN is an extremely complicated pathophysiological process, in which multiple biological and pathological processes are involved [5].…”
Section: Introductionmentioning
confidence: 99%