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Mitochondria and Kidney Disease

  • Kenneth E. McMartin
Chapter

Abstract

The kidney maintains body homeostasis by regulating the excretion and/or conservation of nutrients such as glucose and amino acids, of electrolytes such as sodium and potassium, and of xenobiotics such as drugs or toxic compounds. Reabsorption and secretion of these compounds utilize transport pathways that rely on the energy produced by mitochondrial oxidative phosphorylation, which generates ATP. Because of the high demand for ATP, renal tubule cells contain a large number of mitochondria, particularly the proximal tubule cells, where most of the transporter pathways are located. Damage to the kidney is generally classified as either chronic kidney disease (CKD) or acute kidney injury (AKI), where CKD is a slow loss of kidney function over an extended period of time, while AKI is a sudden loss of kidney function in hours to days. Both CKD and AKI are associated with damage to tubular cells, which is likely to result from a loss of mitochondrial function. Some drugs and toxic compounds, such as cisplatin, gentamycin, tenofovir, heavy metals and contrast media, are well known to induce mitochondrial damage leading to cell death and eventually to AKI. This chapter will however focus on two less known compounds, ethylene glycol and diethylene glycol that both induce AKI and can result in complete loss of kidney function. Neither compound itself is nephrotoxic, rather they are metabolized to oxalic acid and diglycolic acid, respectively, which in turn damage proximal tubule cells. Both oxalate, in its crystalline form calcium oxalate monohydrate, and diglycolate produce mitochondrial dysfunction, either by direct inhibition of mitochondrial respiration or by increasing reactive oxygen species production.

Keywords

Proximal tubular necrosis Acute kidney injury Ethylene glycol Diethylene glycol Oxalate crystals Diglycolic acid 

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Authors and Affiliations

  1. 1.Department of Pharmacology, Toxicology, and NeuroscienceLouisiana State University Health Sciences CenterShreveportUSA

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