Research Updates in Kidney and Urologic Health

New DKUHD Programs for 2003

Through its Division of Kidney, Urologic, and Hematologic Diseases (DKUHD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) provides leadership for a national research program in kidney and urologic diseases. Each year, DKUHD works with NIDDK's Advisory Council—representing a broad range of non-Federal scientific, educational, and medical institutions—to plan and develop a set of program initiatives designed to yield fundamental, innovative, and valuable contributions to human health. The following 2003 DKUHD initiatives demonstrate the division's commitment to maintaining the recent progress in understanding the biological processes that result in kidney and urologic diseases. The initiatives also demonstrate a continuing commitment to clinical research and epidemiology.

Prospective Study of Chronic Kidney Disease in Children

The NIDDK has issued a request for applications (RFA) for a Coordinating Center to design and implement an epidemiological study of the longitudinal aspects of pediatric kidney disease. Although an RFA was issued recently to study chronic renal insufficiency in adults, DKUHD is now planning a separate study in the pediatric population because some issues in children differ substantively from those in adults. Numerous metabolic derangements occur in chronic kidney disease (CKD) and have significant effects on the overall well-being of affected children. Some negative effects of pediatric renal disease, such as growth impairment, are well documented and well studied. Many other impairments, however, have a marked paucity of information on both the etiology and the magnitude of the specific problems—for example, the incidence and risk of cardiovascular disease, and the incidence of and risk factors for impaired neurocognitive development.

The primary goals of the epidemiological study in children with mildly to moderately reduced renal function are to prospectively define factors that affect the well-being of these children and to delineate the disease progression. Some specific goals are to determine

• risk factors for accelerated decline in renal function



• incidence of and risk factors for impaired neurocognitive development and function



• long-term implications of growth failure and its treatment



• incidence of and risk factors for cardiovascular disease

The Coordinating Center investigators will develop testable hypotheses for the study to address. The study outcomes will aid in setting future research policy for the Institute and drive future interventional research by evaluating the magnitude of specific problems affecting children with CKD.

The deadline for applications is February 21, 2003. The RFA is available at http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-03-012.html on the NIH website.

Basic Research in Interstitial Cystitis

DKUHD has issued an RFA to attract new and established investigators from related research areas to apply their knowledge to the study of interstitial cystitis (IC). Such related areas are inflammation, epithelial biology, cellular biology, molecular genetics, neuropathology and neurophysiology, the biology and physiology of pain, diagnostic radiology and nuclear medicine, genomics, proteomics, the development of genetic animal models, autoimmunity, and so on. Productive research collaboration among investigators with diverse scientific backgrounds is another relevant aim of this RFA, which is a part of NIDDK's commitment to encourage and support innovative, high-quality basic and translational studies that will provide insights into this chronic, painful, and disabling disorder.

Research areas of special interest include

• Etiology and pathogenesis of IC. Critical areas for basic IC research are the identification of the causes and the factors that influence the course of the disease. Examples of relevant topics include bladder permeability and immunologic and neurogenic factors related to cause and progression of IC. Studies in these areas, as well as new and novel areas of IC cause and pathology, are especially encouraged.



• Disease markers and molecular biology of IC. Identification of molecular markers for IC is a critical area of basic research. Finding disease markers in blood and urine is encouraged, although studies of markers from biopsy samples are also appropriate. These studies may involve a variety of molecular methodologies such as microarray and mass-spectroscopy assessment of gene expression and identification of protein type and levels. Markers that can be used in sensitive, specific tests for IC may be valuable for accurate diagnosis and even early prediction of disease. Studies that further describe already reported markers, as well as identify new ones, are encouraged.



• Neurological aspects of IC. Studies that investigate the neural properties of relevant cell types, such as bladder urothelium, and how these properties are altered in IC are encouraged. Studies of bladder afferent neurons would also be significant. Other strongly encouraged areas of study include analysis of relevant neurologic cells/tissues and bladder innervation through molecular and imaging strategies, neurophysiology and neuropathology studies, and factors that influence pelvic pain pathways. Investigations in these areas should provide insight into many particularly debilitating IC symptoms such as urgency, pain associated with bladder filling and urination, and generalized pelvic pain.



• Genetics of IC susceptibility, causality, and disease progression. Evidence suggests a possible genetic basis for IC susceptibility. Studies of existing cohorts of twins are especially encouraged.



• The application of established and innovative diagnostic and imaging techniques to the study of IC. One example would be developing and using radiological and nuclear medicine techniques to diagnose IC by visualizing the affected urinary bladder.

The deadline for applications is February 21, 2003. The RFA is available at http://grants1.nih.gov/grants/guide/rfa-files/RFA-DK-03-010.html on the NIH website.

NIDDK/VA Cooperative Study in Acute Renal Failure

NIDDK and the Department of Veterans Affairs (VA) are planning a multicenter, prospective, randomized, parallel-group trial of two strategies for managing renal support in critically ill acute renal failure (ARF) patients. The primary hypothesis is that intensive renal support decreases mortality in critically ill ARF patients compared with conventional management of renal replacement therapy. Secondary hypotheses are that intensive renal support will shorten the duration of ARF in critically ill patients with acute renal failure and decrease the incidence and duration of non-renal complications compared with conventional management. The projected enrollment is 1,164 patients. The study will be conducted at approximately 25 VA Medical Centers (8 to 10 patients a year from each center) and 7 to 8 NIDDK-funded university medical center sites (28 to 30 patients a year from each center).

Patients will be randomized to receive either intensive renal support or conventional management of renal replacement therapy for their ARF. In both arms of the study, dialysis will be initiated using the same criteria. In the intensive therapy arm, renal support will be intermittent hemodialysis six times a week, compared with three times a week in the conventional therapy arm. In both arms, hemodynamically unstable patients will receive continuous venovenous hemodiafiltration or sustained, low-efficiency dialysis (SLED), with different target doses or schedules for the intensive and standard therapy arms. Protocol therapy will be continued until renal function recovers or until day 28. Patients who remain dialysis dependent when they are ready to be discharged from acute care or after day 28, whichever comes first, will be taken off protocol treatment and prescribed further dialysis at the discretion of their treating physician. The primary study end-point will be 60-day all-cause mortality. Secondary end-points will include all-cause hospital mortality, 1-year all-cause mortality, and recovery of renal function. Recruitment for the study is scheduled to begin in the summer of 2003.

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