Epidemiology and risk of cardiovascular disease in populations with chronic kidney disease

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(11), P. 696 - 707

Published: Sept. 14, 2022

Language: Английский

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Autophagy in metabolic disease and ageing

Nature Reviews Endocrinology, Journal Year: 2021, Volume and Issue: 17(11), P. 647 - 661

Published: Sept. 10, 2021

Language: Английский

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Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Dec. 20, 2021

Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i), or gliflozins, are a group of antidiabetic drugs that have shown improvement in renal and cardiovascular outcomes patients with kidney disease, without diabetes. In this review, we will describe the different proposed mechanisms action SGLT2i. Gliflozins inhibit glucose reabsorption by blocking SGLT2 cotransporters proximal tubules causing glucosuria. This reduces glycemia lowers HbA1c ~1.0%. The accompanying sodium excretion reverts tubuloglomerular feedback intraglomerular pressure, which is central to nephroprotective effects caloric loss weight, increases insulin sensitivity, lipid metabolism, likely lipotoxicity. Metabolism shifts toward gluconeogenesis ketogenesis, thought be protective for heart kidneys. Additionally, there evidence reduction tubular cell glucotoxicity through reduced mitochondrial dysfunction inflammation. SGLT2i reduce hypoxia reducing energy oxygen demand. improve blood pressure negative water balance possibly inhibiting sympathetic nervous system. These changes contribute function benefits also hepcidin levels, improving erythropoiesis anemia. Finally, other possible include inflammatory markers, fibrosis, podocyte injury, related mechanisms. significant highly consistent protection. complexity interconnectedness primary secondary make them most interesting exciting pharmacologic group.

Language: Английский

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Association of metabolic dysfunction-associated fatty liver disease with kidney disease

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(4), P. 259 - 268

Published: Jan. 10, 2022

Language: Английский

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Mapping the single-cell transcriptomic response of murine diabetic kidney disease to therapies

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(7), P. 1064 - 1078.e6

Published: June 15, 2022

Diabetic kidney disease (DKD) occurs in ∼40% of patients with diabetes and causes failure, cardiovascular disease, premature death. We analyzed the response a murine DKD model to five treatment regimens using single-cell RNA sequencing (scRNA-seq). Our atlas ∼1 million cells revealed heterogeneous all cell types both its treatment. Both monotherapy combination therapies targeted differing induced distinct non-overlapping transcriptional changes. The early effects sodium-glucose cotransporter-2 inhibitors (SGLT2i) on S1 segment proximal tubule suggest that this drug class induces fasting mimicry hypoxia responses. Diabetes downregulated spliceosome regulator serine/arginine-rich splicing factor 7 (Srsf7) was specifically rescued by SGLT2i. In vitro knockdown Srsf7 pro-inflammatory phenotype, implicating alternative as driver suggesting SGLT2i regulation potential mechanism action for class.

Language: Английский

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An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3651 - 3651

Published: March 26, 2022

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

Language: Английский

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Mechanisms of podocyte injury and implications for diabetic nephropathy

Clinical Science, Journal Year: 2022, Volume and Issue: 136(7), P. 493 - 520

Published: April 1, 2022

Abstract Albuminuria is the hallmark of both primary and secondary proteinuric glomerulopathies, including focal segmental glomerulosclerosis (FSGS), obesity-related nephropathy, diabetic nephropathy (DN). Moreover, albuminuria an important feature all chronic kidney diseases (CKDs). Podocytes play a key role in maintaining permselectivity glomerular filtration barrier (GFB) injury podocyte, leading to foot process (FP) effacement podocyte loss, unifying underlying mechanism glomerulopathies. The metabolic insult hyperglycemia paramount importance pathogenesis DN, while insults damage are poorly defined other However, shared mechanisms have been identified. Herein, we will review haemodynamic oxidative stress, inflammation, lipotoxicity, endocannabinoid (EC) hypertone, mitochondrial autophagic dysfunction damage, focussing particularly on their DN. Gaining better insight into may provide novel targets for treatment. strategies boosting repair open way regenerative medicine.

Language: Английский

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Glomerular hyperfiltration

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(7), P. 435 - 451

Published: April 1, 2022

Language: Английский

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Pathophysiologic Mechanisms and Potential Biomarkers in Diabetic Kidney Disease

Diabetes & Metabolism Journal, Journal Year: 2022, Volume and Issue: 46(2), P. 181 - 197

Published: March 25, 2022

Although diabetic kidney disease (DKD) remains the leading cause of end-stage eventually requiring chronic replacement therapy, prevalence DKD has failed to decline over past 30 years. In order reduce prevalence, extensive research been ongoing improve prediction onset and progression. most commonly used markers are albuminuria estimated glomerular filtration rate, their limitations have encouraged researchers search for novel biomarkers that could risk stratification. Considering is a complex process involves several pathophysiologic mechanisms such as hyperglycemia induced inflammation, oxidative stress, tubular damage, damage fibrosis, many capture one specific mechanism developed. Moreover, increasing use high-throughput omic approaches analyze biological samples include proteomics, metabolomics, transcriptomics emerged strong tool in biomarker discovery. This review will first describe recent advances understanding pathophysiology DKD, second, current clinical well status multiple potential with respect protein biomarkers, transcriptomics.

Language: Английский

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Kidney and heart failure outcomes associated with SGLT2 inhibitor use

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(5), P. 294 - 306

Published: Feb. 10, 2022

Language: Английский

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