The body responds to diuretic drug therapy in several different ways that can lead to diuretic resistance. Some of these responses cause the body to retain sodium and water in the short term (rebound), and some increase sodium and water retention in the long term (the braking phenomenon).
Short-term responses: The half-life of a diuretic drug in the bloodstream determines how often it must be administered. Since the half-life of most loop diuretics is on the order of hours, and they are sometimes administered only once a day, their effectiveness can be gone before the patient receives the next dose. When one dose has worn off, the kidneys may respond by aggressively retaining sodium. This rebound effect can last several hours and may even counteract the diuretic effect of the previous dose.
The action of a diuretic drug to increase the elimination of sodium in one segment of the kidney may result in the delivery of an increased load of sodium to downstream portions of the kidney, which then increases sodium reabsorption.
Long-term responses: The effectiveness of loop diuretics may decline over time during their long-term administration, as the body slowly adapts to their effects. This complex process, called the "braking phenomenon," is due to changes in the structure and function of the kidney itself, activation of the sympathetic nervous system and changes in several hormone pathways. These are all ways that the body tries to counteract the effect of the loop diuretic.
Changes in structure and function of the kidney can occur in the portion downstream from the segment where loop diuretics act. These changes, caused by increased delivery of sodium in this area over a period of time, can result in decreased effectiveness of diuretics.
When treating diuretic resistance, it's important for the patient to restrict daily consumption of fluids, follow a low-sodium diet and avoid taking nonsteroidal anti-inflammatory drugs (NSAIDs).
Other approaches include changing the dose or the timing of diuretic therapy. Because of the short duration of loop diuretics, individual doses given at intervals can cause rebound sodium retention between doses. The continuous administration of loop diuretics by continuous infusion loop diuretic therapy may be more effective than individual doses -- this is an option for patients with moderate to severe heart failure.
Another way to overcome diuretic resistance is to use more than one type of diuretic (such as a combination of thiazide and loop diuretics), because different types of diuretic drugs act upon different parts of the kidney and their combination may produce an improved diuretic response. For many patients, however, despite these strategies, diuretics eventually stop working.
When diuretics fail to relieve the fluid overload, patients may receive a procedure known as ultrafiltration.
To learn more about diuretics, take a look at the links below.
- How Your Heart Works
- How Your Lungs Work
- How Your Kidneys Work
- How Blood Works
- How Ultrafiltration Works
- How Vasodilator Drugs Work
- How Fluid Overload and Edema Work
- How Orthopnea Works
- How Jugular Venous Distension Works
- How Heart Failure Affects Quality of Life
- How Inotropic Drugs Work
- How Low-Sodium Diets Work
More Great Links
- American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Acute Heart Failure Syndromes, Silvers SM, Howell JM, et al. Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with acute heart failure syndromes. Ann Emerg Med. 2007;49:627-669.
- Butler J, Forman DE, Abraham WT, et al. Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J. 2004; 147:331-338.
- Domanski M, Norman J, Pitt B, et al. Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 2003; 42:705-708.
- Ellison DH. The physiological basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991;114: 886-894.
- Eshaghian S, Horwich TB, Fonarow GC. Relation of loop diuretic dose to mortality in advanced heart failure. Am J Cardiol. 2006; 97: 1759-1764.
- Gupta S, Neyses L. Diuretic usage in heart failure: a continuing conundrum in 2005. Eur Heart J. 2005; 26:644-649.
- Iyengar S, Abraham WT. Diuretics for the treatment of acute decompensated heart failure. Heart Fail Rev. 2007; 12:125-130.
- Kramer BK, Schweda F, Riegger GA. Diuretic treatment and diuretic resistance in heart failure. Am J Med. 1999; 106:90-96.
- Mehta RL, Pascual MT, Soroko S, et al. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA. 2002; 288:2547-2553.
- Neuberg GW, Miller AB, O'Connor CM, et al. Diuretic resistance predicts mortality in patients with advanced heart failure. Am Heart J. 2002; 144:31-38.
- Taylor SH. Diuretic therapy in congestive heart failure. Cardiol Rev. 2000;8: 104-114.