http://www.mdpi.com/journal/toxins/special_issues/renal-toxicity/ Dear Colleagues, A wide variety of drugs and environmental chemicals are known to cause nephrotoxicity. The mammalian kidney is particularly susceptible to the toxic effects of noxious chemicals, in part, due to the unique physiologic and anatomic features of this organ. The excretory and metabolic functions of the kidneys place them at high risk following exposure to toxicants. Xenobiotics in the systemic circulation are delivered to the kidney in relatively high amounts because this organ receives about 25% of the resting cardiac output. Toxicants are also concentrated in the tubular fluid via the normal processes of urine concentration. For this reason, a nontoxic plasma concentration may achieve toxic concentrations within the kidney. Furthermore, the biotransformation of xenobiotics to toxic intermediates within the tubular epithelium also contributes to this increased renal susceptibility to toxic injury. Over the past decade, research into the pathophysiologic and molecular basis of renal disease has grown tremendously with the ultimate goal of assessing human health risk. This special journal issue provides a review of mechanisms of acute renal failure with examples of renal toxicity from a variety of agents including mycotoxins, herbicides, heavy metals, solvents, therapeutic agents and plants. Chemically induced α2u-globulin nephropathy is also reviewed. Dr. Susan A. Elmore Guest Editor Submission All manuscripts should be submitted to toxins@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website. Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed Open Access monthly journal published by MDPI.   Please visit the Instructions for Authors page before submitting a manuscript. Article Processing Charges (APC) for publication in this Open Access journal will be waived for well-prepared manuscripts submitted before 30 June 2010. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections. http://www.mdpi.com/2072-6651/2/11/2490/ Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. One of the limiting side effects of cisplatin use is nephrotoxicity. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatin-induced renal cell death. It has also become apparent that inflammation provoked by injury to renal epithelial cells serves to amplify kidney injury and dysfunction in vivo. This review summarizes recent advances in our understanding of cisplatin nephrotoxicity and discusses how these advances might lead to more effective prevention. http://www.mdpi.com/2072-6651/2/11/2490/ Tue, 26 Oct 2010 00:00:00 CEST Toxins 2010-10-26 2 11 Review 2490 2518 2072-6651 Mechanisms of Cisplatin Nephrotoxicity 2010-10-26 doi: 10.3390/toxins2112490 Ronald P. Miller Raghu K. Tadagavadi Ganesan Ramesh William Brian Reeves http://www.mdpi.com/2072-6651/2/10/2340/ Patients with end-stage renal disease (ESRD), whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-a. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation. http://www.mdpi.com/2072-6651/2/10/2340/ Mon, 11 Oct 2010 00:00:00 CEST Toxins 2010-10-11 2 10 Review 2340 2358 2072-6651 Genomic Damage in Endstage Renal Disease—Contribution of Uremic Toxins 2010-10-11 doi: 10.3390/toxins2102340 Nicole Schupp August Heidland Helga Stopper http://www.mdpi.com/2072-6651/2/8/2083/ Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat. http://www.mdpi.com/2072-6651/2/8/2083/ Mon, 09 Aug 2010 00:00:00 CEST Toxins 2010-08-09 2 8 Article 2083 2097 2072-6651 Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate 2010-08-09 doi: 10.3390/toxins2082083 Peter G. Mantle Katharine M. McHugh John E. Fincham http://www.mdpi.com/2072-6651/2/8/2055/ In the present review we have attempted to assess the involvement of the organic anion transporters OAT1, OAT2, OAT3, and OAT4, belonging to the SLC22 family of polyspecific carriers, in drug-induced renal damage in humans. We have focused on drugs with widely recognized nephrotoxic potential, which have previously been reported to interact with OAT family members, and whose underlying pathogenic mechanism suggests the participation of tubular transport. Thus, only compounds generally believed to cause kidney injury either by means of direct tubular toxicity or crystal nephropathy have been considered. For each drug, or class of agents, the evidence for actual transport mediated by individual OATs under in vivo conditions is discussed. We have then examined their role in the context of other carriers present in the renal proximal tubule sharing certain substrates with OATs, as these are critical determinants of the overall contribution of OAT-dependent transport to intracellular accumulation and transepithelial drug secretion, and thus the impact it may have in drug-induced nephrotoxicity. http://www.mdpi.com/2072-6651/2/8/2055/ Mon, 09 Aug 2010 00:00:00 CEST Toxins 2010-08-09 2 8 Review 2055 2082 2072-6651 Assessment of the Role of Renal Organic Anion Transporters in Drug-Induced Nephrotoxicity 2010-08-09 doi: 10.3390/toxins2082055 Yohannes Hagos Natascha A. Wolff