The PI's laboratory has had extensive interest in mechanisms of diuretic resistance which can be dissected by first determining changes in pharmacokinetics of a diuretic in a given clinical condition and secondly by assessing the pharmacodynamics of response. His laboratory has demonstrated that an effective method to assess pharmacodynamics is by examining the relationship between urinary excretion rate of the loop diuretic and natriuretic response. These methods have been developed, validated, and employed by his laboratory to define the mechanisms of diuretic resistance in a variety of clinical conditions, and to develop logical therapeutic approaches to the patient with diuretic resistance. The studies currently proposed are extensions of this work. The current proposal seeks to address the following questions concerning clinically relevant issues pertaining to diuretic response: 1) Does displacement of furosemide from binding to urinary albumin in patients with nephrotic syndrome enhance diuretic response? 2) Does administration of albumin plus furosemide enhance diuretic response in hypoalbuminemic patients with nephrotic syndrome or cirrhosis? Is this effect different depending on the patient's serum albumin concentration? 3) Does """"""""renal dose"""""""" dopamine enhance response to a loop diuretic in patients with severe congestive heart failure? In addition he proposes to begin a series of studies of diuretic therapy, focusing on patients with congestive heart failure (CHF). Patients with CHF are common, many are heavy users of health care resources, and diuretics are a mainstay of therapy. He proposes that decompensation of many patients with CHF may be due to noncompliance with diuretics and/or diet. This proposal begins a long-term attempt to unravel these factors with an ultimate goal of designing therapeutic strategies in patients with CHF which decrease the frequency of decompensation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG007631-10
Application #
6055360
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Project Start
1988-04-01
Project End
2000-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Murray, Michael D; Young, James M; Morrow, Daniel G et al. (2004) Methodology of an ongoing, randomized, controlled trial to improve drug use for elderly patients with chronic heart failure. Am J Geriatr Pharmacother 2:53-65

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