Diuretic Use Linked to End-Stage Renal Disease

Laurie Barclay, MD

May 16, 2003

May 15, 2003 -- A comparison of drug use and disease occurrence showed an association between the use of diuretics and the development of end-stage renal disease (ESRD), according to a presentation on May 15 at the American Society of Hypertension annual meeting.

"Our concern is that most prospective clinical trials in hypertension are only four to five years in duration, which doesn't allow analysis of many of the long-term complications such as ESRD," coauthor Mark C. Houston, MD, from St. Thomas Hospital in Nashville, Tennessee, told Medscape. "Findings from this study, as well as animal models, suggest that thiazide diuretics, and especially hydrochlorothiazide, may be nephrotoxic in the long-term."

By merging concurrent observations of the same total population using different measurement tools, the investigators compared cardiovascular disease mortality, stroke mortality, hypertensive nephrosclerosis incidence, and ESRD incidence in national databases with a commercial database (IMS Health) reflecting U.S. distribution of antihypertensive drugs from 1990 to 2001.

Based on the assumption that the annual percentage change in manufacturer supply reflected the annual percentage change in medication use by the U.S. population at large, the investigators compared annual variations in disease behaviors and in drug category use.

Annual changes in prescription diuretic supply fluctuated in tandem with the annual variability in ESRD incidence, except for a time delay of two years. Over time, there was a direct relationship between these variables ( P = .0001). From 1990 to 2001, changes in diuretic supply and use were directly associated with changes in ESRD incidence two years later.

Because new diuretic prescriptions in the U.S. are still on the increase, the investigators suggest a prospective randomized controlled trial to demonstrate the nephrotoxic effects of prolonged diuretic exposure. In the meantime, they suggest that deliberately minimizing diuretic use might decrease ESRD incidence rates.

"We're concerned that there could be a long time lag between use of thiazide diuretics and ESRD, even as long as 10 to 15 years," Dr. Houston said.

This study was conducted independently by Dr. Houston and first author Ralph G. Hawkins, without any specific financial support from pharmaceutical companies or other industry sources. Both authors are now receiving or have previously received research funding from Pfizer, Merck, Bristol-Myers Squibb, and Boehringer Ingelheim.

ASH 18th Annual Meeting: Abstract OR-23. Presented May 15, 2003.

Reviewed by Gary D. Vogin, MD