Research Updates in Kidney and Urologic Health

Clinical Trials in Kidney and Urologic Disease Set for Recruitment

Focus on Chronic Renal Insufficiency, BPH Therapies, and Dialysis Access

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research on many of the most serious diseases affecting public health. NIDDK's Division of Kidney, Urologic, and Hematologic Diseases (KUH) provides research funding and support for basic science and clinical research studies of the kidney and urinary tract and disorders of the blood and blood-forming organs.

John Kusek, Ph.D., directs the Clinical Trials Program, which works in concert with other KUH programs to develop and manage cooperative clinical trials to prevent or retard major chronic kidney, urologic, and hematologic diseases. The program coordinates and monitors patient recruitment and adherence to interventions.

Three new clinical trials have begun recruiting patients at participating centers around the country. CRIC, MIST, and DAC are the acronyms that stand for the new programs in chronic renal insufficiency (also called chronic kidney disease), treatments for benign prostatic hyperplasia (BPH), and vascular access for hemodialysis, respectively.

Chronic Renal Insufficiency Cohort (CRIC) Study

End-stage renal disease (ESRD) is an important medical and public health problem in the United States, and it disproportionately affects racial and ethnic minority groups, particularly African Americans, American Indians, and Hispanics. African Americans and American Indians are four times as likely as whites, and Hispanics are twice as likely as whites, to develop kidney failure, which requires dialysis or kidney transplantation for survival.

In 2000, almost 100,000 people with chronic kidney disease entered ESRD, with the result that approximately 300,000 people were sustained on hemodialysis while 80,000 had functioning transplants. These numbers have doubled since 1990, and they are expected to nearly double again by 2010. The increase in the number of Americans with ESRD is directly proportional to the increase in the number of Americans with type 2 diabetes, a major cause of chronic renal insufficiency. Another major cause is hypertension. The leading cause of death in patients with ESRD is cardiovascular disease.

The factors that contribute to the decline in kidney function and the development of cardiovascular disease in people with chronic renal insufficiency are unknown, and further research is needed before interventions can be evaluated and implemented. To date, few studies have focused on people whose chronic kidney disease has not yet developed into ESRD. Only a small number of studies have been conducted, and all have had significant methodological shortcomings.

One type of study that has played an important role in defining risk factors for a wide range of diseases is the prospective cohort study. To determine the risk factors for rapid decline in kidney function and development of cardiovascular disease, the NIDDK established the CRIC Study, a 7-year prospective, multiethnic, multiracial study of approximately 3,000 patients with chronic renal insufficiency. Participants will reflect the racial, ethnic, and gender composition of the U.S. ESRD population. The data and specimens obtained from people in this study will serve as a national resource for investigating chronic renal as well as cardiovascular disease. Establishing this cohort of patients and following them prospectively will also provide an opportunity to examine genetic, environmental, behavioral, nutritional, quality-of-life, and health resource utilization factors in this population.

Seven clinical centers are participating in the study: University of Pennsylvania, Philadelphia; University of Maryland-Johns Hopkins, Baltimore; University of Illinois at Chicago Clinical Centers; University of Michigan, Ann Arbor; University of California, Kaiser Permanente of Northern California/University of California, San Francisco; Tulane University, New Orleans; and Case Western Reserve University, Cleveland.

Protocol development for the CRIC study began in September 2001. The recruitment stage, begun in 2003, will continue into early 2005. The main part of the study will consist of regular clinic visits for followup and monitoring of patients so that renal function can be measured and cardiovascular studies and laboratory tests can be performed. In addition, participants will answer questionnaires to assess various demographic, nutritional, and quality-of-life factors. Followup and data collection on cohort study participants who develop ESRD will be performed after they start renal replacement therapy (renal transplantation, hemodialysis, or peritoneal dialysis), with modification of data collection, measurements, and followup visits as necessary and as described in the protocol. Final data analysis and closeout are scheduled for 2008. Thomas Hostetter, M.D., is the project officer.

Minimally Invasive Surgical Therapies (MIST) Treatment Consortium for BPH

KUH has had a substantial and longstanding interest in evaluating the effectiveness of strategies for treating BPH. For many years, transurethral resection of the prostate (TURP) has been the surgical standard for this condition; however, over the past decade, a number of technical innovations have allowed the development of new surgical treatments that aim to achieve the same long-term outcomes as TURP but with less morbidity, lower cost, shorter hospital stay, and more rapid recovery. These new, minimally invasive surgical approaches funded by the NIDDK include laser therapy, hyperthermia and thermotherapy, transurethral electrovaporization, microwave therapy, and transurethral needle ablation. New techniques are appearing regularly. The quality of published reports on the outcomes of these minimally invasive therapies are highly variable, and rigorous randomized clinical trials have only rarely been conducted.

To assess the long-term safety and effectiveness of these new therapies, the NIDDK has formed a group of seven collaborative Prostate Evaluation Treatment Centers and a Biostatistical Coordinating Center to develop and conduct randomized, controlled clinical trials that will give a clearer picture of the benefits and risks of these methods. The first trial to be conducted by the MIST consortium will evaluate the safety and effectiveness of transurethral needle ablation (TUNA), transurethral microwave therapy (TUMT), and medical therapy with an alpha-blocker and finasteride combined. The results of this first trial will provide both physicians and patients with the knowledge needed to make the most appropriate choices for long-term management of BPH. Leroy Nyberg, Ph.D., M.D., is the project officer.

Dialysis Access Consortium (DAC)

Maintenance of vascular access for hemodialysis is one of the major challenges in caring for the hemodialysis patient. Access-related problems are among the most frequent reasons for hospitalization in the ESRD population, and the cost of vascular access placement and repair in the United States exceeds $700 million per year. In fiscal year 2000, NIDDK established the Dialysis Access Consortium, which consists of seven clinical centers and a data coordinating center, to undertake interventional clinical trials to improve outcomes in patients with fistulas and grafts. Two randomized placebo-controlled clinical trials have been designed and have begun recruiting patients. The first trial will evaluate the effects of the antiplatelet agent clopidogrel on prevention of early fistula failure. A second clinical trial will study Aggrenox, with the goal of preventing access stenosis in hemodialysis patients with grafts. Catherine Meyers, M.D., is the project officer.

For more information about these trials, call KUH at 301–594–7717 and ask to speak with the project officer or Dr. Kusek.

[Top]