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The Diabetic Kidney.

The Diabetic Kidney, edited by Pedro Cortes, MD, and Carl Erik Mogensen, MD

Totowa, NJ: Humana Press, 2006. Hardcover, 564 pp., $175.00.

Chronic hemodialysis is now nearing its 35th anniversary. In the early years of this now-common therapy, diabetic patients who developed end-stage renal disease were not considered candidates for chronic hemodialysis or peritoneal dialysis. In the past few decades, there has been a steady rise in diabetic renal disease due to several factors, including the better treatment and management of infectious diseases, diabetic ketoacidosis, and cardiovascular disease. Such medical care has enabled diabetic patients to survive long enough to develop diabetic nephropathy.

Diabetic nephropathy is now the leading cause of end-stage renal disease, accounting for approximately 45% of new patients requiring chronic dialysis. The 2005 US Renal Data System showed that only 25% of patients initiated on hemodialysis due to diabetes survived 5 years. These disturbing statistics have resulted in increasing basic and clinical research on this topic.

The editors of The Diabetic Kidney have brought together an amazing group of researchers and clinicians who present the recent progress that has been made to better understand the pathogenesis of diabetic nephropathy. With the increasing knowledge and understanding of the basic disease process have come new therapeutic interventions as well as preventive measures. The book is divided into two parts: The Basic Pathophysiology and Biochemistry of Diabetic Nephropathy (pp. 3-326) and The Clinical Aspects of Diabetic Nephropathy (pp. 327-548).

In the first part of the book, various authors discuss the pathophysiology of diabetic nephropathy. The nonhemodynamic effects of angiotensin II and its receptors are discussed, including stimulation of cytokines, activation of extracellular matrix synthesis, inhibition of extracellular matrix degradation, and generation of reactive oxygen species that may result in the changes seen with diabetic nephropathy. The role of glomerular protein ultrafiltration in the progression of interstitial fibrosis and diabetic nephropathy is discussed at length. The authors conclude that any method of limiting protein ultrafiltration, including improving blood pressure control, may decrease fibrosis.

The combination of angiotension-converting enzyme (ACE) inhibitor and angiotensin receptor blocker therapy is addressed. In theory, ACE inhibitor inhibition is not complete, as alternate pathways for angiotensin II generation exist. Accordingly, combination therapy should have an additive benefit. However, the data for the effectiveness of combination therapy are not yet convincing in humans, and such therapy may result in complications such as hyperkalemia.

Several chapters address the role of glucose transporters in the metabolism of glucose in the kidney. Hyperglycemia generates advanced glycation endproducts through nonenzymatic glycation and oxidation of proteins and lipids that appear to play a critical role in the pathogenesis of diabetic nephropathy. Studies in animal models have shown that inhibition of these pathways can decrease changes associated with diabetic nephropathy. Studies have also shown that hyperglycemia leads to changes in podocyte structure and function that result in increased albuminuria and glomerular damage.

The role of various growth factors, including connective tissue growth factor, vascular endothelial growth factor, and transforming growth factor, in the pathogenesis of diabetic nephropathy is explored. New technology, including the application of proteomics in diabetes research, is discussed in detail.

The second part of The Diabetic Kidney focuses on the clinical aspects of diabetic nephropathy. One of the initial chapters does an excellent job addressing the current strategies involved in identifying the genes potentially responsible for the development of diabetic nephropathy. Although a number of candidate genes are discussed, it is clear that more research is needed before this field will have clinical implications.

Multiple authors discuss the importance of strict glycemic control, normotension (defined as <130/80 mm Hg), and the blockade of the renin-angiotensin-aldosterone system. Studies have shown that progression of diabetic nephropathy can be halted and possibly even partially reversed with euglycemia. Several authors suggest screening for microalbuminuria with the goal of limiting any albuminuria.

Once a patient progresses to end-stage renal disease, options include hemodialysis, peritoneal dialysis, kidney transplantation, or kidney/pancreas transplant (for type 1 diabetics). Best outcomes have been seen with initial peritoneal dialysis followed by hemodialysis if necessary while the patient awaits a kidney or kidney/pancreas transplant. The early use of peritoneal dialysis may be beneficial because of the continued maintenance of residual renal function. In addition, vascular access for hemodialysis in diabetic patients is often challenging due to accelerated atherosclerotic disease and a subsequent higher vascular access failure rate. Many patients in the developing world are not candidates for dialysis or transplantation due to financial constraints. In some countries transplantation is not an option for religious reasons. As a result, the key in management is prevention or slowing of the development of end-stage renal disease.

One chapter provides an outstanding summary of the overall treatment of advanced renal disease in diabetics and discusses the importance of treating comorbid conditions such as hypertension, anemia, metabolic bone disease, cardiac disease, and hyperlipidemia.

This is an excellent book for both basic science researchers and clinicians. Since the textbook is a compilation of topics, the book becomes repetitive at times. A review of current guidelines in the treatment of diabetic nephropathy at various stages of chronic kidney disease would be very helpful for the clinician. Finally, perhaps due to space limitation, renal transplantation is only superficially discussed.

The reviewers, Andrew Z. Fenves, MD, and Jesse George, MD, are nephrologists on the medical staff at Baylor University Medical Center. Dr. Fenves is chief of the Division of Nephrology.
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Author:Fenves, Andrew Z.; George, Jesse
Publication:Baylor University Medical Center Proceedings
Article Type:Book review
Date:Jan 1, 2007
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