UAMS, Yale Experts Advise International Scientists On Next Steps to Conquering Kidney Disease
| class="Default" style="margin: 0in 0in 0pt;">LITTLE ROCK – Sudhir Shah, M.D., of the University of Arkansas for Medical Sciences (UAMS) and a colleague at Yale University have issued advice to scientists worldwide on how to speed up research on acute renal failure, a problem that strikes about 5 percent of all hospital patients, killing half of them, and costs an estimated $10 billion a year.
Shah is a professor and director of nephrology in the Department of Internal Medicine in the UAMS College of Medicine and at Central Arkansas Veterans Healthcare System (CAVHS). He is internationally renowned for his pioneering research on the role of reactive oxygen metabolites in kidney disease.
At the request of the Journal of the American Society of Nephrology, he and Norman Siegel, M.D., at Yale University have summarized the next steps in research on acute renal failure (ARF). Their paper will appear in the journal in August.
ARF is the abrupt loss of kidney function that often happens in hospital patients. Half of the patients who develop the problem die from it. “After 50 years, the acute mortality rate is still at 50 percent. We must do better,” Shah says.
Shah has focused his research on novel mechanisms of the damage that occurs in ARF. The conventional wisdom was that ARF was necrotic and unstoppable – sudden death of tissue resulting from a catastrophic breakdown of homeostasis. However, Shah has shown in a series of papers in the Journal of Clinical Investigation and the Proceedings of the National Academy of Sciences that apoptic mechanisms (mechanisms not usually
associated with ischemic or toxic injury to the kidney) may play an important role in the renal injury, suggesting new therapeutic targets to treat and prevent acute renal failure.
In the upcoming journal article, Shah and Siegel emphasize studies to identify biomarkers “that could predict, reliably and sensitively, the development of significant renal insult. Such markers would aid not only in the early detection of ARF but would serve also to substantiate the diagnosis and provide uniformity in defining ARF.
Secondly, Shah and Siegel endorse observational studies to complement clinical trials that are limited by homogeneous patient populations. Data from a large-scale observational study will yield biomarkers and provide “important new insight concerning the natural history of ARF, vulnerability of specific groups of patients, and prognostic factors,” they wrote.
Thirdly, they call for a research consortium to sustain multiple clinical studies of new therapeutic interventions. “This effort will need to include our colleagues who have the primary responsibility for this patient population and must include experienced clinical investigators who will devote the time and effort required to carry out these intensive and critical investigations.” By storing data and biological samples, the consortium could help scientists identify possible biomarkers and evaluate new therapeutic interventions.
Shah’s first important contribution in the field of kidney disease was his study of the major category of diseases that cause chronic, as opposed to acute, renal failure – those that affect the glomerulus, the filtering part of the kidney. He was the first to recognize that resident glomerular cells may also generate oxidants and therefore play an important role in non-inflammatory models of glomerular disease, including diabetes. Karl A. Nath, MB, ChB, of Mayo Clinic has written that Shah “saw with clarity and prescience the commonality of … seemingly disparate disease processes [and] seamlessly wove that unbroken thread of oxidative stress that ran through and linked these areas.”
These novel mechanisms form the basis of a program project in the UAMS College of Medicine that is funded by the National Institutes of Health (NIH). Several investigators, in the Division of Nephrology and elsewhere in the College, are collaborating to better understand these mechanisms of injury. Shah’s leadership in this area led the American Society of Nephrology to invite him to chair a subcommittee on acute renal failure.