Using diuretics to help relieve the failing heart

Photo: RubenPH/Adobe Stock

Diuretics wield their physiologic magic along various channels within the kidneys to create a thriving spillway that expels excess water. This lightens the load on the diseased heart, and prevents pooling in the lungs and beyond.

The cornerstone of therapy for congestive heart failure (CHF)¹, diuretics block sodium reabsorption in the renal tubules, and the water that tags along. The result: boosted water excretion into the urine and reduced fluid burden on the heart.

“Different diuretic classes exert their activity at different parts of the ducts,” cardiologist Gordon Peddle, VMD, DACVIM, said in a lecture at the 2025 Unique Seminar Destinations Annual Winter Seminar in Cancun, Mexico.¹

Renal physiology

Blood enters the kidneys for filtration of toxins and rebalancing of water, electrolytes and other components.^2-3 First, it strains through the renal glomerulus, a nest of capillaries that filters out various elements into these ducts, or renal tubules. Here, passive substance exchange occurs within the renal epithelial cells lining the tubules, creating urine.

This exchange starts in the proximal convoluted tubule (PCT), where 60% of filtered sodium is reabsorbed into the renal epithelial cells. As much as 35% gets sopped up in the thick ascending loop of Henle (TAL), up to 10% in the distal convoluted tubule (DCT), and 2%to 5% in the collecting ducts. When the kidneys take up sodium, water follows.

If a compromised heart can’t handle the vascular fluid volume, it spills over into the lungs.^2,4 Diuretics curtail this flooding.

Diuretic classes

PCT diuretics

Carbonic anhydrase inhibitors (CAIs)—acetazolamide and dorzolamide ophthalmic—tweak the sodium-hydrogen passive exchange system in the PCT by reducing available hydrogen, which cuts sodium reabsorption.⁴ Because there are ample downstream sites for sodium uptake, CAIs have weak diuretic action, and are primarily used to manage glaucoma.

Osmotic diuretics like mannitol bring hyperosmolarity to the PCT and descending loop of Henle, thereby deterring water reabsorption.⁴ Best suited for treating glaucoma and cerebral edema, osmotic diuretics can elevate venous pressures in CHF patients, limiting its utility for managing heart disease.

Loop diuretics

The loop diuretics furosemide (Lasix), torsemide and bumetanide target the sodium-potassium-chloride transport system in the TAL.^3-5 Known as ‘high ceiling’ diuretics, these short-acting drugs induce natriuresis and corresponding diuresis in a steep dose-response fashion.

A powerful pulmonary vasodilator, furosemide administered intravenously quickly improves oxygenation in CHF patients.⁶ Furosemide doesn’t clear pulmonary edema.Rather, Peddle explained, “it drops pulmonary pressure to reduce further pulmonary flooding.”

Furosemide also produces bronchodilation⁴, aiding patients with reactive airway disease.A positive clinical response in a dyspneic dog or cat can confound differentiation between cardiac and respiratory etiology.

Experts spar over the use of furosemide in patients with renal insufficiency. “Lasix in kidneys equals bad, right?” Peddle said, “Well, sort of. There are some qualities of furosemide that are renoprotective.”

In the short term, furosemide enhances renal blood flow and slows cellular metabolism in the kidneys.⁵ But over time, it may worsen azotemia by impairing renal blood flow, and deplete important electrolytes.

“If blood flow is already bad in the kidneys,” Peddle cautioned, “then how will furosemide even get there?”

But every patient is trial and error, he emphasized. He preaches a measured tolerance for furosemide-wrought azotemia “when they are still eating and clinically healthy because you got them there slowly.”

DCT diuretics (thiazides)

Similar in chemical structure to CAIs, thiazide diuretics curb sodium and chloride reabsorption in the DCT and other segments.^4,7 Its’ efficacy in diluting the urine is limited, however, due to numerous other tubular sites of sodium reabsorption.

Collecting tubule diuretics

These diuretics block sodium reabsorption either directly (amiloride, triamterene) or indirectly (spironolactone) via competitive receptor antagonism of the sodium-retentive hormone aldosterone.² Because they act at the terminal portion of the nephron, where minimal sodium uptake occurs, these drugs have weak diuretic activity and are mainly utilized as part of a cocktail6. A “potassium-sparing” diuretic, spironolactone may cause hyperkalemia, particularly if used as a sole diuretic.

Diuretic resistance

Sometimes diuretics are the architects of their own undoing: Successful diuretic therapy diminishes extracellular fluid over time, causing chronic activation of the renin-angiotensin-aldosterone system (RAAS).^3,4 The kidneys respond by holding onto sodium and water, boosting blood volume.

By the ‘braking phenomenon,’ a slightly different mechanism, diuretic administration activates RAAS with successivedoses, provided there was a sufficient drop in extracellular fluid early on.

Lastly, increased downstream delivery of NaCl causes hypertrophy and hyperplasia of distal tubular segments, which expands the capacity for distal NaCl reabsorption.^2-4

Diuretic resistance can be countered by combination therapy.² For instance, adding a thiazide to a loop diuretic suppresses NaCl transport in the TAL, PCT and DCT.⁷Likewise, adding angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs) to diuretics can alleviate CHF signs by downregulating rebound RAAS surges.

Diuretic strategies for dogs and cats in CHF

Peddle named loop diuretics as the first drugs to reach for when managing CHF in dogand cats. In dogs, furosemide administered intravenously has a rapid onset (5-20 minutes), and a duration of about 2 hours; peak activity occurs within 45 minutes.^4,5

Peddle cautioned against impulsive re-dosing. “Don’t panic and give more furosemide if it doesn’t work instantly. You can’t take away what you’ve given, but you can always give more,” he said.

Typical pulsed intravenous dosing starts at 2 mg/kg q1-4h, and should be lowered to q6-12h once breathing improves. According to Peddle, it is usually unnecessary to exceed 8-12 mg/kg total dosing over the first 24-hour period in hospitalized dogs.

Oral furosemide has a 30-60-minute onset of action⁵, a peak effect of 90 minutes or less, and a 4-6-hour duration. But dose efficacy in any one dog is difficult to predict, as oral absorption varies from 10% to 100%.

Cats are particularly sensitive to furosemide. Compared to dogs, they have a quicker and stronger response.⁵ Peddle recommended an initial intravenous dose of 2 mg/kg, followed by serial 1 mg/kg dosing on a schedule similar to that for dogs. Cats should max out at 4-8 mg/kg over 24 hours.

Once a dog or cat is stabilized and eupneic, oral furosemide administration can be initiated (2 mg/kg q12h). Patients with active respiratory signs may benefit from q6-8h dosing for 2-3 days, then twice daily. Peddle advocated careful monitoring of resting respiratory rates at home, plus renal/electrolyte checks within the first week of therapy.For patients with kidney disease, these numbers are particularly relevant.

Furosemide dosages can be bumped up to manage recurrent CHF episodes, but exceeding 12 mg/kg/day in dogs and 6-8 mg/kg/day in cats offers little incremental benefit, he noted. When adding additional diuretic classes to a loop diuretic, the dosage for the latter should not be reduced.

The oral loop diuretic torsemide has greater potency and duration than furosemide.^8,9 The latter feature provides a smoother diuretic effect and enables once-daily dosing, but delays peak activity to at least 10 days following start of therapy.

In dogs, torsemide may be ten times more potent than furosemide, with dose-related factor increases at or above 0.2mg/kg/day thought to be up to twenty times stronger.⁹Dosing of torsemide appears similar in cats, but is not yet well established.

Torsemide is mostly recruited following poor response to escalating furosemide dosages¹⁰, but Peddle shared that he finds it useful as first-line therapy in dogs and cats with chronic cavity effusions caused by CHF. When using torsemide as first-line therapy, an initial dose of 0.1-0.2 mg/kg q24h is appropriate.

When transitioning from furosemide to torsemide, potency factors must be weighed in setting dosages; Peddle considers a division factor of twenty as a safe starting point for patients with kidney disease or on high-dosage furosemide therapy. Ideally, furosemide should be discontinued.

Loop diuretic resistance can also be met with hydrochlorothiazide as an add-on drug that incites significant diuresis⁷, and excretion of sodium, potassium and chloride. Although it can alleviate cardiogenic congestion, it may worsen azotemia and deplete electrolytes.Peddle initiates hydrochlorothiazide at 0.5-1 mg/kg PO q24h, with slow titration upward as needed. “A little goes a long way,” Peddle said.

Spironolactone cannot control CHF when used alone, but works well in tandem with others.⁶ It is dosed at 2-4 mg/kg q24h in dogs and cats. Spironolactone-induced hyperkalemia is rare because concurrent loop and/or thiazide diuretics produce kaliuresis.

Monitoring diuretic therapy

Baseline renal and electrolyte values should be obtained before beginning diuretic treatment, and reassessed within two weeks afterward and following dosage increases.With all diuretic therapies, close monitoring of renal function via measurement of blood urea nitrogen (BUN), creatinine (+/- SDMA), electrolytes and hematocrit is key; in patients with preexisting kidney disease, some degree of azotemia is expected.

References

1. Peddle G. Bailing out the ship: diuretic therapy. Presented at: Unique Seminar Destinations; Cancun, Mexico. February 8-15, 2025.
2. Wile D. Diuretics: a review. Ann Clin Biochem. 2012;49:419-431. doi:10.1258/acb.2011.011281
3. Bernstein PL, Ellison DH. Diuretics and salt transport along the nephron. Semin Nephrol. 2011;31(6):475-482. doi:10.1016/j.semnephrol.2011.09.002
4. Felker GM, Ellison DH, Mullens W, et al. Diuretic therapy for patients with heart failure. J Am CollCardiol. 2020;75(10):1178-1195. doi:10.1016/j.acc.2019.12.059
5. Abbott LM, Kovacic J. The pharmacologic spectrum of furosemide. J Vet Emerg Crit Care.2008;18(1):24-39. doi:10.1111/j.1476-4431.2007.00267.x
6. Coffman M, Guillot E, Blondel T, et al. Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The Benazepril Spironolactone Study (BESST). J Vet Intern Med. 2021;35(4):1673-1687. doi:10.1111/jvim.16155
7. Iwanaga K, Araki R, Isaka M. A retrospective study of 14 dogs with advanced heart failure treated with loop diuretics and hydrochlorothiazide. Open Vet J.2021;11(3):342-345. doi:10.5455/OVJ.2021.v11.i3.2
8. Besche B, Blondel T, Guillot E, et al. Efficacy of oral torsemide in dogs with degenerative mitral valve disease and new onset of congestive heart failure: The CARPODIEM study. J Vet Intern Med. 2020;34(5):1746-1758. doi:10.1111.jvim.15864
9. Potter BM, Ames MK, Hess A, et al. Comparison between the effects of torsemide and furosemide on the renin-angiotensin-aldosterone system of normal dogs. J Vet Cardiol.2019;26:51-62. doi:10.1016/jvc.2019.11.003
10. Chetboul V, Pouchelon JL, Menard J, et al. Short-term efficacy and safety of torasemide and furosemide in 366 dogs with degenerative mitral valve disease: the TEST study. J Vet Intern Med. 2017;31:1629-1642. doi:10.1111/jvim.14841