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Reactive Oxygen Species in the Pathogenesis of Chronic Kidney Disease: Lessons Derived from Diabetic Nephropathy

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Systems Biology of Free Radicals and Antioxidants

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Abstract

Chronic kidney disease (CKD) is a major problem worldwide that adversely affects human health by increasing the cardiovascular disease (CVD) and reducing the life span and ultimately increases cost to the health-care system. One of the common disease processes that are a major contributing factor in increasing its incidence is diabetic nephropathy. The consensus at present is that oxidative stress may be the common denominator link for the major pathways involved in the development and progression of diabetic nephropathy progressing towards CKD. Despite heterogeneity in the oxidative stress levels in the CKD population, some studies show amelioration of oxidant stress following the administration of antioxidants. There are diverse sources from which reactive oxygen species (ROS) are derived, such as NADPH oxidase pathway, advanced glycation end products (AGE), polyol pathway, uncoupled nitric oxide synthase (NOS), and mitochondrial respiratory chain via oxidative phosphorylation. The excess ROS generated leads to the activation of redox-sensitive transcription factors, e.g., Nrf2, and a number of cellular signaling pathways, such as MAP kinase. Such activation leads to increased expression of extracellular matrix (ECM) genes with progression to fibrosis and CKD and end-stage renal disease (ESRD). The CKD injury is further compounded when there is concomitant endothelial dysfunction and activation of renin-angiotensin system (RAS). In this scenario, there is a precipitous worsening of renal injury and thereby acceleration in the progression of CKD. In this review various aspects of oxidative stress coupled with the damage induced by endothelial dysfunctions and RAS are discussed in the context of diabetic nephropathy that invariably progress to CKD. It is hoped that this discussion would give an impetus for development of new generation of specific antioxidants that could potentially decelerate the progression of CKD.

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Acknowledgments

Supported by NIH grant DK60635

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Authors and Affiliations

  1. Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan

    Naoki Kashihara & Minoru Satoh

  2. Departments of Pathology & Medicine, Northwestern University School of Medicine, 303 E. Chicago Ave, Chicago, 60611, IL, USA

    Yashpal S. Kanwar

Authors
  1. Naoki Kashihara
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  2. Minoru Satoh
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  3. Yashpal S. Kanwar
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Correspondence to Yashpal S. Kanwar .

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  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Kashihara, N., Satoh, M., Kanwar, Y.S. (2014). Reactive Oxygen Species in the Pathogenesis of Chronic Kidney Disease: Lessons Derived from Diabetic Nephropathy. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_185

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