SGLT-2 inhibitors in Diabetic Kidney Disease: What Lies Behind their Renoprotective Properties?
Curr Med Chem
; 26(29): 5564-5578, 2019.
Article
em En
| MEDLINE
| ID: mdl-29792136
ABSTRACT
BACKGROUND:
Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensinaldosterone- system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD.METHODS:
A systematic literature search of bibliographic databases was conducted to identify preclinical studies and randomized trials evaluating the effects SGLT-2 inhibitors on DKD.RESULTS:
Preclinical studies performed in animal models of DKD support the renoprotective action of SGLT-2 inhibitors showing that these agents exert albuminuria-lowering effects and reverse glomerulosclerosis. The renoprotective action of SGLT-2 inhibitors is strongly supported by human studies showing that these agents prevent the progression of albuminuria and retard nephropathy progression to ESRD. This beneficial effect of SGLT-2 inhibitors is not fully explained by their glucose-lowering properties. Attenuation of glomerular hyperfiltration and improvement in a number of surrogate risk factors, including associated reduction in systemic blood pressure, body weight, and serum uric acid levels may represent plausible mechanistic explanations for the cardio-renal protection offered by SGLT-2 inhibitors. Furthermore, the tubular cell metabolism seems to be altered towards a ketone-prone pathway with protective activities.CONCLUSION:
SGLT-2 inhibition emerges as a novel therapeutic approach of diabetic with anticipated benefits towards cardio-renal risk reduction. Additional research efforts are clearly warranted to elucidate this favorable effect in patients with overt DKD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Substâncias Protetoras
/
Nefropatias Diabéticas
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Transportador 2 de Glucose-Sódio
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Inibidores do Transportador 2 de Sódio-Glicose
/
Hipoglicemiantes
/
Nefropatias
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
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Risk_factors_studies
/
Systematic_reviews
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Med Chem
Ano de publicação:
2019
Tipo de documento:
Article