Abstract
Chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular diseases (CVD) are complex disorders of partly unknown genesis and mostly known progression factors. CVD and DM are the risk factors of CKD and are strongly intertwined since DM can lead to both CKD and/or CVD, and CVD can lead to kidney disease. In recent years, our knowledge of CKD, DM, and CVD has been expanded and several important experimental, clinical, and epidemiological associations have been reported. The tight cellular and molecular interactions between the renal, diabetic, and cardiovascular systems in acute or chronic disease settings are becoming increasingly evident. However, the (patho-) physiological basis of the interactions of CKD, DM, and CVD with involvement of multiple endogenous and environmental factors is highly complex and our knowledge is still at its infancy. Not only single pathways and mediators of progression of these diseases have to be considered in these processes but also the mutual interactions of these factors are essential. The recent advances in proteomics and integrative analysis technologies have allowed rapid progress in analyzing complex disorders and clearly show the opportunity for new efficient and specific therapies. More than a dozen pathways have been identified so far, including hyperactivity of the renin–angiotensin (RAS)–aldosterone system, osmotic sodium retention, endothelial dysfunction, dyslipidemia, RAS/RAF/extracellular-signal-regulated kinase pathway, modification of the purinergic system, phosphatidylinositol 3-kinase (PI 3-kinase)-dependent signaling pathways, and inflammation, all leading to histomorphological alterations of the kidney and vessels of diabetic and non-diabetic patients. Since a better understanding of the common cellular and molecular mechanisms of these diseases may be a key to successful identification of new therapeutic targets, we review in this paper the current literature about cellular and molecular mechanisms of CKD.
Highlights
A healthy person could be defined as “a man with highly/tightly regulated and coordinated complex biological networks.” The crosstalk between the organs and the systems via molecular, cellular, paracrine, endocrine, and neuronal factors are essential in regulating these networks [1]
We reviewed the current incidence, pathways, and the mediators involved in these intricate diseases and made an attempt to compel the common risk factors from the current literature
Diabetes Mellitus Diabetes mellitus is a group of metabolic disorders resulting from hyperglycemia caused by genetic, molecular, or biochemical factors and activation of renin–angiotensin system (RAS), which eventually leads to the damage of end-organs like kidney [16]
Summary
A healthy person could be defined as “a man with highly/tightly regulated and coordinated complex biological networks.” The crosstalk between the organs and the systems via molecular, cellular, paracrine, endocrine, and neuronal factors are essential in regulating these networks [1]. Hypertension, cardiovascular diseases (CVD), and cigarette smoking are the common risk factors of chronic kidney disease (CKD) [9, 10]. A meta-analysis by Nitsch et al studied the association of GFR, albuminuria with mortality, and renal failure by sex, and observed that the increased risk of CKD is equal between both sexes [15]. Diabetes Mellitus Diabetes mellitus is a group of metabolic disorders resulting from hyperglycemia caused by genetic, molecular, or biochemical factors and activation of renin–angiotensin system (RAS), which eventually leads to the damage of end-organs like kidney [16]. Few studies have shown that the decrease in the kidney function and higher albuminuria are independent risk factors and not related to diabetes and hypertension [24, 25]. 7.4 million deaths were due to CHD and the rest were due to stroke, mostly observed in low-income and middle-income countries [22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
