ReviewThe cardiorenal syndrome in diabetes mellitus
Introduction
The appreciation of the interaction between heart and kidney during dysfunction of each or both organs has major clinical implications for the practical prevention and treatment strategies in a spectrum of acute and chronic situations. Such interactions represent the pathophysiological basis for an emerging clinical entity called the cardiorenal syndrome (CRS). Recently, the definition of CRS was expanded to better reflect the dual and reciprocal heart–kidney interactions [1]. The new definition was restated as ‘a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ’. To further stress the complicated interactions between these organ systems, a classification was introduced with four types in which the etymology reflects the presumptive primary and secondary abnormality and their chronologies and a fifth subtype that includes systemic conditions that cause both cardiac and renal dysfunction, with diabetes mellitus being the typical example of the latter subtype (Table 1). There is limited systematic information on type 5 CRS, although there is an appreciation that as more organs fail in this setting, mortality increases. There is limited insight, also, into how combined renal and cardiovascular failure may differentially affect such an outcome. It is clear, however, that diabetes can affect both organs simultaneously and that the disease induced in one can affect the other and vice versa (Fig. 1).
Section snippets
Diabetes and the kidney
According to a recent report by the International Diabetes Federation diabetes currently affects nearly 250 million people worldwide and this number is expected to reach 380 million by year 2025 [2]. The high prevalence of diabetes will further burden the health care system by its long-term complications particularly the macrovascular and the microvascular associated diseases. Diabetic nephropathy is the most common chronic kidney disease in the industrialized world and is the leading cause of
Diabetes and the heart
In addition to increased morbidity, diabetic patients suffer high mortality rate, with cardiovascular disease (CVD) being the major cause of death accounting for some 50% of all diabetes fatalities [2]. Identification of diabetes as a high-risk condition for macrovascular diseases is based on the fact that there is a high long-term risk for developing CVD. Various studies showed that the risk for cardiovascular events increase two to fourfold in patients with type 2 diabetes compared to
Micro- and macroalbuminuria and risk of CVD in diabetes
Microalbuminuria is a common complication of diabetes and has been long known to be a strong predictor of subsequent development of overt nephropathy. Of patients with type 1 diabetes 50% of childhood onset and 35% of adult onset will develop microalbuminuria after almost 20 years [10], [11]. In addition, 15% of patients in both groups will have macroalbuminuria by then. In newly diagnosed type 2 diabetes, 28% of patients will develop microalbuminuria and 7% will have macroalbuminuria after 15
CKD and CVD in diabetes
Various studies have shown that CVD risk factors, CVD surrogates, and clinical CVD are more prevalent in patients with reduced glomerular filtration rate (GFR). For example, the HOPE study, the Cardiovascular Health Study (CHS), the Hypertension Optimal Treatment (HOT) Study, the Framingham and Framingham Offspring Studies, and the Atherosclerosis Risk In Communities (ARIC) Study, have shown that higher systolic blood pressure and total cholesterol are associated with decreased GFR. In
Pathogenesis
The mechanisms by which the diabetic milieu causes kidney injury have been extensively studied. The associated hyperglycemia, glycated proteins, and oxidative stress cause hemodynamic stress and activate metabolic pathways that induce a group of growth factors in the kidney. It is widely believed that the fibrogenic cytokine transforming growth factor-beta (TGF-β) and the vascular endothelial growth factor (VEGF) are implicated in the development of the cardinal features of diabetic
Treatment
Both microvascular and macrovascular complications contribute to the increased morbidity and mortality in diabetes. Although microvascular complications predispose to premature mortality, CVD is the leading cause of death in diabetes. In addition to the defined role of hyperglycemia, other modifiable risk factors for late complications in patients with diabetes, including hypertension and dyslipidemia, increase the risk of a poor outcome. Results from randomized controlled trials have
Conclusions
Cardiorenal syndrome in diabetes refers to pathophysiologic conditions where the heart and the kidneys are simultaneously affected by a systemic disorder leading to injury and/or dysfunction of both organ systems. The presence of nephropathy in diabetic patients appears to be a significant independent contributing factor in the tally of overall risks for and outcomes from vascular complications and mortality. As such, the pathogenesis of the accelerated course of CVD in diabetic patients with
Conflict of interest
None.
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2022, European Journal of Internal MedicineCitation Excerpt :Patients with advanced HF and DM had the highest rate of CKD. In an advanced diabetic state, progressive fibrosis and proteinuria worsen as a result of many factors related to endothelial dysfunction [22], which are also implicated in the progression of heart disease. Therefore, this association could be useful for determining advanced disease in these patients.
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2016, Chinese Journal of Natural MedicinesDiabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications
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2013, Clinica Chimica ActaCitation Excerpt :Diabetic patients have a 2- to 4-fold increased risk of heart disease and stroke than people without diabetes. Cardiovascular complications are the leading cause of morbidity and mortality among diabetic patients, accounting for some 50% of all diabetes fatalities [2,3]. Diabetic nephropathy is the most common cause of end stage renal disease (ESRD), contributing to approximately 45% of new cases, and is an independent risk factor for cardiovascular disease [3].
Over-nutrition and metabolic cardiomyopathy
2012, Metabolism: Clinical and ExperimentalCitation Excerpt :In recent years, a lot of attention has been focused on the cardiorenal metabolic syndrome as a pre-existing condition to the development of diabetes and cardiovascular disease [16]. The cardiorenal metabolic syndrome can be summarized as a loosely defined group of risk factors, such as insulin resistance, dyslipidemia, high blood pressure and the main feature of central or abdominal obesity, that predispose to well-characterized medical conditions such as diabetes and cardiovascular disease [16,17]. The central feature of abdominal obesity may predispose to the development of the other characteristics of the cardiorenal metabolic syndrome, which may develop later [16–18].