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Cellular and Molecular Mechanisms of Chronic Kidney Disease with Diabetes Mellitus and Cardiovascular Diseases as Its Comorbidities.

Gajjala PR, Sanati M, Jankowski J - Front Immunol (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Cardiovascular Research, Universitätsklinikum RWTH Aachen , Aachen , Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of clinical link between chronic kidney disease, diabetes mellitus, and cardiovascular disease.
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Figure 3: Schematic representation of clinical link between chronic kidney disease, diabetes mellitus, and cardiovascular disease.

Mentions: Epidemiological studies have so far confirmed and reported that there is an association between CKD and CVD (190). Go et al. (191) conducted a study on the relationship between GFR and cardiovascular events in a large group who had not undergone dialysis or transplantation and demonstrated an inverse relationship. The key mechanisms accounting for cardiovascular events apart from the traditional risk factors could be disturbances in mineral metabolism, anemia, ADMA (asymmetric omega NG, NG-dimethylarginine), inflammation, and oxidative stress, which are observed even in CKD. Whether CKD causes CVD or acts as a marker is still controversial (192). Due to disturbances in the metabolism in diabetes, the most effected cells are endothelial and β cells. Since the micro and macro vessels are lined with endothelial cells, the whole vascular system is damaged leading to CKD and CVD. Therefore, disturbance in one of these diseases will affect the other. Figure 3 shows how these diseases are interlinked with each other in a clinical perspective.


Cellular and Molecular Mechanisms of Chronic Kidney Disease with Diabetes Mellitus and Cardiovascular Diseases as Its Comorbidities.

Gajjala PR, Sanati M, Jankowski J - Front Immunol (2015)

Schematic representation of clinical link between chronic kidney disease, diabetes mellitus, and cardiovascular disease.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495338&req=5

Figure 3: Schematic representation of clinical link between chronic kidney disease, diabetes mellitus, and cardiovascular disease.
Mentions: Epidemiological studies have so far confirmed and reported that there is an association between CKD and CVD (190). Go et al. (191) conducted a study on the relationship between GFR and cardiovascular events in a large group who had not undergone dialysis or transplantation and demonstrated an inverse relationship. The key mechanisms accounting for cardiovascular events apart from the traditional risk factors could be disturbances in mineral metabolism, anemia, ADMA (asymmetric omega NG, NG-dimethylarginine), inflammation, and oxidative stress, which are observed even in CKD. Whether CKD causes CVD or acts as a marker is still controversial (192). Due to disturbances in the metabolism in diabetes, the most effected cells are endothelial and β cells. Since the micro and macro vessels are lined with endothelial cells, the whole vascular system is damaged leading to CKD and CVD. Therefore, disturbance in one of these diseases will affect the other. Figure 3 shows how these diseases are interlinked with each other in a clinical perspective.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecular Cardiovascular Research, Universitätsklinikum RWTH Aachen , Aachen , Germany.

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.

No MeSH data available.


Related in: MedlinePlus