Mini Review: Reappraisal of Uric Acid in Chronic Kidney Disease

Goldberg, Avi; García, Gabriela; Sasai, Fumihiko; Rodríguez‐Iturbe, Bernardo; Sánchez‐Lozada, Laura G.; Lanaspa, Miguel A.; Johnson, Richard J.

doi:10.1159/000519491

Cited by 21 publications

(12 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Uric acid has been associated with CV diseases and with inflammation and oxidative stress. In addition, the majority of these studies showed that elevated levels of uric acid are a potential contributor risk factor in the development and progression of CKD [ 186 , 187 ].…”

Section: Improvement Of Conventional CV and Renal Risk Factors By Sgl...mentioning

confidence: 99%

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Salvatore

Galiero

Caturano

et al. 2022

IJMS

128

View full text Add to dashboard Cite

Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection.

show abstract

Section: Improvement Of Conventional CV and Renal Risk Factors By Sgl...mentioning

confidence: 99%

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Salvatore

Galiero

Caturano

et al. 2022

IJMS

128

View full text Add to dashboard Cite

show abstract

“… 75 Finally, elevated uric acid levels have been associated with increased renal inflammation and oxidative stress and, in this context, SGLT2i would promote an increased glycosuria-associated uricosuric action. 76 …”

Section: Reviewmentioning

confidence: 99%

Emerging concepts in heart failure treatment and management: focus on SGLT2 inhibitors in heart failure with preserved ejection fraction

Lorenzi¹,

Kaplinsky²,

Zambrano³

et al. 2023

DIC

View full text Add to dashboard Cite

The role of sodium–glucose cotransporter 2 inhibitors (SLTG2i), developed initially as glucose-lowering agents, has represented a novelty in patients with heart failure (HF) and reduced ejection fraction (HFrEF) since dapagliflozin (DAPA-HF study) and empagliflozin (EMPEROR-Reduced study) were able to reduce morbidity and mortality in this setting regardless of the presence or absence of diabetes. In previous large clinical trials (EMPA-REG OUTCOME study, CANVAS, DECLARE-TIMI 58), SGLT2i have been shown to attenuate HF progression expressed by reducing the risk of HF hospitalizations in patients with type 2 diabetes mellitus mostly without HF at baseline. This benefit was then corroborated with positive results in HF outcomes (cardiovascular mortality and HF hospitalizations) in patients with HF with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved (empagliflozin) and DELIVER (dapagliflozin) trials. Several biological mechanisms apart from the glycosuria are attributed to these agents in this last context, including anti-inflammatory effects, reduction of fibrosis and apoptosis, improvement of myocardial metabolism, mitochondrial function optimization, and oxidative stress protection. Moreover, SGLT2i can also improve ventricular loading conditions by forcing diuresis and natriuresis, and by enhancing vascular and renal function. In addition, SGLT2i can reduce myocardial passive stiffness (diastolic function) by enforcing the phosphorylation of myofilament modulatory proteins. This article provided an overview of the main pathophysiological characteristics of HFpEF and of the diverse mechanisms of action of SGLT2i in this setting. The supporting clinical evidence of SGLT2i in HFpEF (EMPEROR-Preserved and DELIVER trials) is also reviewed. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment

show abstract

“…11 Although recent studies are mixed as to whether urate lowering is actually renally protective, evidence suggests that some patient subsets, including those with gout, may be more likely to benefit. 33 Overall, when choosing among multiple antihypertensive agents, the selection of losartan, particularly over other agents that can raise sU levels, can significantly affect a patient's sU level and may have additional benefits. For this reason, the 2020 ACR gout treatment guideline conditionally recommends "choosing losartan preferentially as an antihypertensive agent for patients with gout."…”

Section: Antihypertensivesmentioning

confidence: 99%