Abstract
The Toxicology of the Kidney, 3rd edition, edited by Tarloff and Lash continues the tradition of the two earlier editions of this Target Organ Series, but offers some new approaches and insights. It is a multiauthored volume, consistent with the earlier editions, and as such suffers from some unevenness in the writing and organization. There is some unnecessary duplication of some of the material, e.g., Chapter 14 and subsequent chapters dealing with some specific nephrotoxicants. Although a molecular biology emphasis is present in some of the individual chapters, there is no overall thrust related to the molecular biology of nephrotoxicity. This is not a significant shortcoming, however, because molecular science including molecular biology is presented chapter by chapter where appropriate.
In terms of style, it was disappointing to find no color figures. This, as always, is problematic when examining photographs of tissue histology. No doubt this was an editorial issue related to the cost of the volume (significant at $160), but even so, the absence of color is disappointing in the year 2005.
The encyclopedic nature of the volume may be useful in some ways, but potentially detrimental in others. It would have been valuable for the editors and authors to select among the “hot topics” (the foreword notes the explosion of new information in the past 10 years), and eliminate or reduce in coverage some of the older materials. The addition of Section IV clearly was a move in the direction of adding new material and this is commendable. A critical look at the topics in Sections II and III might have allowed for an important reduction in volume leaving room for new topics. In general, the referencing of the individual chapters is detailed and appropriate. The title of Section III is confusing at best. Mostly, it is focused on specific toxicants, not on clinical nephrotoxicology. The fact that some of the information on the individual toxicants comes from humans doesn’t warrant the use of “Clinical Nephrotoxicology” in the title. Finally, in terms of general organization, it would have been helpful to list the authors’ names by the chapter titles in the Table of Contents. As it is now, the first perusal of the book is inconvenient by having to go from the Contents to each chapter to see who the authors are.
The book is organized into four sections, each with multiple chapters. The material covered is broad ranging, all inclusive and, except for one instance, nonduplicative. The volume starts with a variety of background information important for understanding nephrotoxic events. There is an extensive discussion of potential mechanisms of toxicity followed by an examination of the effects of a variety of individual nephrotoxicants. The book concludes with material on risk and safety assessment applied specifically to renal toxicology.
The five chapters of Section I, entitled “Basic Principles,” contain the background information needed to study and assess a nephrotoxic response. The topics presented here are common to most books on nephrotoxicity, e.g., earlier target organ series. This section begins with a brief presentation of renal anatomy and physiology to give the naïve reader minimal, but essential, information. For the experienced renal physiologist or toxicologist, this chapter serves as a “refresher course.” Three chapters are devoted to an analysis of the techniques available for assessment of nephrotoxicity. These include cellular and subcellular techniques, isolated organs, renal slices, nephron segments, and whole-animal procedures. Chapter 2 is focused on assessment of nephrotoxicity with an emphasis on the newer, potentially important renal biomarkers. It is in this area that major strides have been made in the recent past and this new information is well summarized here. Finding new, predictive biomarkers for a nephrotoxic event is important for assessing the human response to potentially harmful chemicals, and some of the markers discussed here may prove to be clinically useful, e.g., KIM-1, MAPK family members.
The eight chapters of Section II present an interesting mix of old and new mechanisms of toxicity. The detailed, well-organized, and clearly presented discussion of mechanisms of renal cell death pulls together a variety of information and clarifies often confusing terminology (Chapter 7). Chapter 8 on signal transduction and cellular repair contains, in general, new information in the context of renal toxicology. Cell signaling has been prominent in understanding pharmacological actions of drugs and is now being demonstrated to be important in some toxicological events. Chapter 12 on adhesion molecules also contains new toxicological material that may prove important for furthering an understanding of biomarkers as well as mechanisms of toxicity. The material in this chapter compliments that presented in Chapter 2. The chapter on endocytosis is valuable because it brings together a large amount of information in a well organized presentation. The chapters on xenobiotic metabolism, cellular energetics, and oxidant mechanisms related to nephrotoxicity do not offer any new views on the acute nephrotoxic response, but do appropriately update these important fields. Xenobiotic metabolism could have been expanded somewhat by adding the relevant parts of Chapter 23 on glutathione S-conjugate formation. Because glutathione S-conjugate formation is an expression of xenobiotic metabolism-induced nephrotoxicity, inclusion in Chapter 6 would be appropriate. The chapter devoted to cancer focuses on the Eker rat as a model system for studying hydroquinone induced renal carcinogenesis. The chapter is well written and clearly presented. Unfortunately, because of its relatively narrow focus it does not blend well with the other chapters in this book. Carcinogenesis is such a huge topic it could command a book of its own, and the Eker rat model would be an outstanding chapter in a book on mechanisms of carcinogenesis.
The third section, presented in 10 chapters, deals with the effects of numerous, often well-studied, nephrotoxicants. As noted earlier, inclusions of “clinical nephrotoxicity” in the title seems at least unnecessary, if not inappropriate. This section contains “all the usual suspects,” i.e., all of the well-studied and well-recognized classes of nephrotoxic agents. The first chapter in this section, Chapter 14, presents a lot of background information on the renin-angiotensin system, endothelin, NO, etc., and then examines the effects of selected nephrotoxicants. Unfortunately, much of the material on specific nephrotoxicants overlaps significantly with other chapters in this section and the presentations in the subsequent chapters offer more detailed and specific information. The chapters on antibiotics, cyclosporine and related substances, radiocontrast media, and nonsteroidal anti-inflammatory drugs (NSAIDs) are all very thorough, detailed, and up to date. In addition, the chapter NSAIDs on contains a broad review of prostaglandin physiology and chemistry so the potential NSAID nephrotoxicity is put in the appropriate context. The chapters on radiocontrast medium nephrotoxicity and analgesic nephrotoxicity update important new information for these two long-standing clinical problems. The material on cisplatin is detailed and up to date, as is the chapter on mycotoxins. Although the material on metal nephrotoxicity is covered in detail, especially cadmium and mercury, the absence of any mention of chromium is noteworthy. Finally, the chapter on glutathione S-conjugate formation is well presented. However, as noted above, this material mainly highlights a mechanism of toxicity and could easily have been covered in Chapter 6 on xenobiotic metabolism.
The fourth section deals with issues of risk and safety assessment as related to nephrotoxic responses. Although aspects of this material have been reviewed elsewhere, the present collection offers a new approach to this study of nephrotoxicity.
One chapter summarizes epidemiological studies related to analgesic nephropathy, cadmium exposure, etc., and stresses the strength and importance of the discipline in addressing potential nephrotoxicity problems. A second chapter examines the age-, sex-, and species-related differences in renal function and structure that could have an impact on the susceptibility of nephrotoxicity. The last two chapters bring forth risk assessment analyses for selected metals and therapeutic agents. The latter focuses on obstructive nephropathy and cyclooxygenase-2 (COX-2) inhibitors.
In summary, this book makes a substantial contribution to our understanding of nephrotoxity. It will be useful for selected readings in a graduate course in renal toxicology or an advanced course in general toxicology. Because the referencing is so detailed, this book will probably find its place as a reference work rather than textbook.