Research Updates in Kidney and Urologic Health

NIDDK Identifies Risks, Measures Burden of Kidney and Urologic Diseases

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) provides funding and support for a wide range of biomedical research projects, from animal studies to clinical trials of new drugs. NIDDK's Division of Kidney, Urologic, and Hematologic Diseases (KUH) focuses on the areas of end-stage renal disease (ESRD) and chronic renal insufficiency; urinary tract diseases, including infections, stones, erectile dysfunction, and voiding disorders; and disorders of the blood and blood-forming organs. Many of these diseases increase with age, and the aging of the U.S. population means that the prevalence of these diseases is rising. In recent years, KUH has placed special emphasis on epidemiology and cohort studies to track and understand these trends.

Prospective cohort studies have played an important role in defining risk factors for a wide range of diseases. In 1948, when little was known about the causes of heart disease and stroke, scientists recruited more than 5,000 people in Framingham, MA, to undergo extensive physical examinations and lifestyle interviews every 2 years. Researchers would later analyze these data to discover the major risk factors for cardiovascular disease (CVD), that is, high blood pressure, high blood cholesterol, smoking, obesity, diabetes, and physical inactivity. The Framingham cohort is primarily white, but other studies such as the San Antonio Family Heart Study have confirmed the universal importance of the major CVD risk factors, even though distribution patterns may vary among different racial and ethnic groups.

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Figure 2: ESRD prevalent rates per million population, White

The concept of risk factors has had a major influence on medical research in the past 50 years. Another concept that has evolved out of population-based studies is burden of disease, which now encompasses quality of life issues as well as population counts and the economic costs of treatment. For example, Framingham data have been used to estimate and compare the cost- effectiveness of various cholesterol-lowering and antihypertensive drugs. A drug that costs $4,000 for each year it extends the life of one patient is considered more cost-effective than one that costs $6,000 for the same benefit.

Scientists have used knowledge derived from cohort studies to develop lifestyle interventions that reduce risk and medications that counter the effects of chronic disease. Through a series of epidemiologic programs, KUH researchers are establishing the knowledge base that may help scientists find ways to prevent kidney failure or urinary tract infections.

United States Renal Data System

Since its creation in 1988, the United States Renal Data System (USRDS) has established and managed a comprehensive database on ESRD. Under NIDDK's direction, the USRDS has produced major studies aimed at improving outcomes for patients with kidney disease.

The USRDS has six major goals:

• to characterize the ESRD population in terms of age, racial and gender makeup, and regional variations
  
  
• to describe the prevalence and incidence of ESRD, along with trends in mortality and disease rates
  
  
• to investigate relationships among patient demographics, treatment modalities, and morbidity
  
  
• to identify new areas for special renal studies and to support investigator-initiated research
  
  
• to conduct cost-effectiveness studies and other economic studies of ESRD
  
  
• to provide data sets and samples of national data to support research by the Special Studies centers
  
  

The USRDS has documented some alarming trends in the ESRD population. Although this population has grown continually since the beginning of Medicare coverage in 1973, the 1990s saw a doubling of the number of U.S. residents needing renal replacement therapy—either dialysis or transplantation—to stay alive. The point prevalence of ESRD rose from 156,461 at the end of 1989 to 340,261 at the end of 1999. The annual incidence—the number of people who begin to need treatment in a given year—rose from 44,569 in 1989 to 88,091 a decade later. The incidence rate rose from 181 per million in 1989 to 317 per million in 1999, far exceeding growth that could be explained by population growth and aging. USRDS data support the theory that the diabetes epidemic is contributing to the rising incidence and prevalence of ESRD. The number of deaths from ESRD rose from 28,970 in 1989 to 66,964 in 1999.

Also, USRDS data help point out racial health disparities. For African Americans, the incidence rate for ESRD is 953 per million, four times the rate for whites. Further, researchers use USRDS data to compare survival rates among patients receiving hemodialysis, peritoneal dialysis, and transplantation or among patients in different parts of the country. These data help administrators identify the most cost-effective and efficient treatments and point out areas where further research or quality control is needed.

Chronic Renal Insufficiency Cohort Study

The USRDS answers many questions about people who have ESRD, but it raises many more about the people who have kidney disease now and may develop ESRD in the future. Few studies have focused on patients with chronic renal disease before they reach ESRD. Further research is needed to increase our knowledge about the factors that contribute to the decline in renal function and the development of CVD in patients with chronic renal insufficiency.

NIDDK is establishing the Chronic Renal Insufficiency Cohort Study (CRICS), a 7-year prospective, multiethnic, multiracial study of approximately 3,000 patients. The data and patient specimens from this study will serve as a national resource for investigating chronic renal disease and CVD. 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.

Centers participating in the study are Case Western Reserve University in Cleveland, Johns Hopkins University in Baltimore, Tulane University in New Orleans, the University of Michigan in Ann Arbor, and the University of Pennsylvania in Philadelphia.

The study officially began in September 2001. The first 6 months of the study will be devoted to protocol development. Recruitment will begin around March 2002 and continue for 18 months. The main part of the study will consist of followup and monitoring through regular clinic visits 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 reach ESRD will be performed after they start renal replacement therapy (renal transplantation, hemodialysis, peritoneal dialysis), with modification of data collection, measurements, and followup visit schedule as necessary and as described in the study protocol. The last followup visit will be scheduled during the final 4 months of this phase. Data collection for persons who previously reached ESRD will also be terminated at that time. Final data analysis and closeout are scheduled for 2008.

Pediatric Nephrology Planning Committee

The original plan for CRICS included a pediatric nephrology protocol, parallel to the one for adults. Since kidney failure in children has different causes and different consequences, however, planners decided to move forward with a complete new initiative. To pursue this strategy, a Pediatric Nephrology Planning Committee will capitalize on the experience gained in CRICS to help review and identify issues that are crucial to furthering our understanding of the epidemiology of chronic renal insufficiency in children.

Urologic Diseases in America

NIDDK is establishing a program to develop a Urologic Diseases in America (UDA) compendium that will describe and evaluate the scope of urology as a practice, including practice patterns and the incidence, morbidity, mortality, outcomes, and economic health impact of the diseases involved. The UDA compendium will consist of data tables and analyses, as well as narrative descriptive chapters that amplify the analyses. This project will, for the first time, lead to realistic estimates of the extent of these diseases and their effect on minority populations, the health care expenditures involved, and the variations in treatment.

The compendium will analyze retrospectively over a 10-year period the changes in the epidemiology and practice patterns for each of the diseases within the practice of urology. Project objectives will include data collection and analyses of the following specific topics:

• changes in the overall health care burden for individual urologic diseases
  
  
• changes in physician practice patterns for each disease
  
  
• demographic changes in people with urologic diseases
  
  
• the impact of specific urologic diseases, especially diseases of the prostate, on minority populations in the United States
  
  
• the documentation of new and evolving therapies for urologic diseases and their potential impact on treatment outcomes and health care costs
  
  

Chronic Prostatitis Collaborative Research Network

The Chronic Prostatitis Collaborative Research Network (CPCRN) is the first large, multicenter study designed to gather well-defined, detailed clinical information on chronic abacterial prostatitis, which leads to pain in the genital area and lower back, usually accompanied by urgent and frequent urination. Other symptoms may include burning or pain during voiding or ejaculation.

Unlike bacterial prostatitis, which can be readily diagnosed by the presence of infection, the abacterial form produces no signs of infection that can be detected using routine clinical methods. Abnormalities in prostatic secretions provide the only objective sign of the condition. Chronic pelvic pain is the main subjective symptom.

The study began with a prospective cohort study phase in which the researchers documented symptoms, possible risk factors, and medical histories over time. In this phase, researchers examined blood, prostate fluid, semen, and urine. One goal of this phase was to explore possible relationships between chronic prostatitis, urethral and bladder inflammation, and other chronic pain disorders. The second phase is a randomized controlled clinical trial of Cipro and Flomax. Results are anticipated in late 2002.

Epidemiology of Urologic Disorders in Minority Men

As men age, increasing numbers of them experience benign prostatic hyperplasia and erectile dysfunction. Younger men are also vulnerable to prostatitis and hypogonadism. The NIDDK is funding a 5-year epidemiologic study of urologic disorders in a random sample of 3,000 men in the Boston area, ages 40 to 79, divided evenly among African Americans, European Americans, and Hispanic Americans. Investigators will collect blood samples and conduct in-home interviews to obtain in-depth health background information from each of the participants. Data will be used to estimate and compare the age-specific prevalence of urologic conditions in the three racial groups, as well as to measure the relative contribution of social and behavioral factors.

With a fuller understanding of national trends in kidney and urologic diseases, scientists can direct their research efforts toward those diseases that cause the most suffering and have the greatest economic impact. As cause-and-effect patterns become clearer, scientists will be able to identify more risk factors for problems like kidney stones and interstitial cystitis. Knowing the risks will help people make lifestyle choices that help them avoid kidney and urologic problems.

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