The cardio-renal-metabolic connection: a review of the evidence

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Abstract

Type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic kidney disease (CKD), are recognized among the most disruptive public health issues of the current century. A large body of evidence from epidemiological and clinical research supports the existence of a strong interconnection between these conditions, such that the unifying term cardio-metabolic-renal (CMR) disease has been defined. This coexistence has remarkable epidemiological, pathophysiologic, and prognostic implications. The mechanisms of hyperglycemia-induced damage to the cardio-renal system are well validated, as are those that tie cardiac and renal disease together. Yet, it remains controversial how and to what extent CVD and CKD can promote metabolic dysregulation. The aim of this review is to recapitulate the epidemiology of the CMR connections; to discuss the well-established, as well as the putative and emerging mechanisms implicated in the interplay among these three entities; and to provide a pathophysiological background for an integrated therapeutic intervention aiming at interrupting this vicious crosstalks.

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Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

Bernard Zinman, Christoph Wanner, John M. Lachin … (2015)

The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.

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Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

Stephen Wiviott, Itamar Raz, Marc Bonaca … (2018)

The cardiovascular safety profile of dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 that promotes glucosuria in patients with type 2 diabetes, is undefined.

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Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Boris Bikbov, Caroline A. Purcell, Andrew Levey … (2021)

Summary Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI. Funding Bill & Melinda Gates Foundation.

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Gian Paolo Fadini: gianpaolo.fadini@unipd.it

Journal

Journal ID (nlm-ta): Cardiovasc Diabetol

Journal ID (iso-abbrev): Cardiovasc Diabetol

Title: Cardiovascular Diabetology

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2840

Publication date (Electronic): 31 July 2023

Publication date PMC-release: 31 July 2023

Publication date Collection: 2023

Volume: 22

Electronic Location Identifier: 195

Affiliations

[1 ]GRID grid.5608.b, ISNI 0000 0004 1757 3470, Department of Medicine, Division of Metabolic Diseases, , University of Padova, ; Via Giustiniani 2, 35128 Padua, Italy

[2 ]GRID grid.428736.c, Veneto Institute of Molecular Medicine, ; 35129 Padua, Italy

Article

Publisher ID: 1937

DOI: 10.1186/s12933-023-01937-x

PMC ID: 10391899

PubMed ID: 37525273

SO-VID: 9014f526-bfa1-4f37-8489-f70e00db8c55

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 29 June 2023

Date accepted : 22 July 2023

Funding

Funded by: Italian Diabetes Society

Funded by: Università degli Studi di Padova

Open Access :

Open access funding provided by Università degli Studi di Padova within the CRUI-CARE Agreement.

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ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: metabolic syndrome,comorbidities,cardiorenal,cardiometabolic,pathophysiology,epidemiology

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ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: metabolic syndrome, comorbidities, cardiorenal, cardiometabolic, pathophysiology, epidemiology

The cardio-renal-metabolic connection: a review of the evidence

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Journal of the ASEAN Federation of Endocrine Societies

Most cited references 144

Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes

Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

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