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**18** 

*Spain* 

**Novel Strategies in** 

**Drug-Induced Acute Kidney Injury** 

*Renal Physiopathology Laboratory, Department of Nephrology, Hospital General Universitario Gregorio Marañón, Madrid,* 

Alberto Lázaro, Sonia Camaño, Blanca Humanes and Alberto Tejedor

Renal toxicity associated with commonly prescribed drugs lengthens hospital stay, worsens prognosis, and limits the potential benefits obtained from therapy (Peracella, 2011; Servais et

Proximal tubule preservation is a clue in strategies aimed to prevent nephrotoxicity. The proximal tubule is a target for filtered drugs that are reabsorbed by solvent drag or

Proximal tubules recover more than 60% of total filtered load, i.e., a single molecule of toxin that is filtered and reabsorbed will pass through the proximal tubule cell more than 50 times per day. Such a high degree of exposure implies a risk of cell damage causing a variety of clinical syndromes, from proximal acidosis and acquired Fanconi syndrome to tubular cell necrosis (Oh, 2010). This spectrum of diseases is known as acute kidney injury (AKI), which also includes cell death by apoptosis, anoikis, necrosis, or cell dysfunction (Lorz et al., 2006). Nephrotoxicity can often be expected with certain drugs, such as vancomycin, gentamicin, foscarnet, cisplatin, cyclosporine A (CsA), and tacrolimus. Less often, the toxic effect is unexpected and not predictable, as is the case with iodinated contrast agents and

Intrinsic pathway–mediated apoptosis and extrinsic pathway–mediated apoptosis are both involved in toxic proximal tubule cell death (Pabla & Dong, 2008; Servais et al., 2008; Xiao et al., 2011). With most of toxins, cell death is followed by detachment and anoikis. Paracetamol is a notable exception to this behavior. Caspases activation, mitochondrial depolarization, release of cytochrome C from mitochondria, cell membrane modification, and nucleosome formation are all hallmarks of apoptosis that are regularly observed in toxin-damaged proximal tubules (Camano et al., 2010). Nitric oxide, soluble oxygen radicals, and proinflammatory cytokines are released by damaged proximal tubules, thus amplifying

pinocytosis, but also for drugs that are secreted into the luminal side.

**1. Introduction 1.1 Renal toxicity** 

al., 2008).

paracetamol.

the lesion.

**1.2 Cell death mediation** 

methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity, *Journal of Medical Toxicology*, Vol.6:327–330.

