A practical guide to antiproteinuric drugs in dogs - Veterinary Medicine
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A practical guide to antiproteinuric drugs in dogs
Appropriately treating a dog with glomerular disease prolongs the dog's survival; however, knowing what drug at what dosage is appropriate isn't as clear. Fortunately, this internist lays out the case for administering ACE inhibitors and angiotensin II-receptor blockers—and offers a suggested treatment protocol.


VETERINARY MEDICINE


ARBs

ARBs are competitive antagonists of angiotensin II. However, unlike ACE inhibitors, aldosterone escape does not blunt ARB-induced renin-angiotensin-aldosterone system blockade and reduction of the UPC ratio.

This class of drugs is commonly prescribed as first-line therapy in people with glomerular disease and appears to be equally effective as ACE inhibitors at reducing the severity of proteinuria, mean arterial blood pressure, and glomerular filtration rate decline.31,32 Available ARBs include losartan, irbesartan, olmesartan, candesartan, valsartan, azilsartan, and telmisartan. In people, these drugs vary in maximum achievable decreases in mean arterial pressure or reduction of the UPC ratio, with telmisartan in particular having more potent antiproteinuric effects than losartan has.33

Animal studies

Published information on ARB administration in dogs is limited to pharmacokinetic studies in healthy animals and effects on renal and systemic hemodynamics in animals with experimentally induced renal disease. Losartan has low oral bioavailability, and after gastrointestinal absorption, it undergoes enterohepatic recirculation and eventual biliary excretion.34 Intraglomerular hydrostatic pressure, systemic blood pressure, and end-organ damage are reduced in dogs with experimentally induced renal disease administered ARBs.35,36

Adjunctive administration

Based on the recognized benefits of ARB therapy in people with proteinuric nephropathies, many veterinary nephrologists consider adjunctive administration of these drugs to dogs with persistent proteinuria despite treatment with ACE inhibitors. First-line therapy with ARBs is not recommended as of yet, as it is still unknown whether long-term prognosis worsens, improves, or does not change in affected animals.

The generic formulation of losartan is affordable by most owners and has been used by many veterinary nephrologists as an adjunctive treatment in dogs with refractory proteinuria. An initial losartan dosage (0.125 to 0.25 mg/kg b.i.d.) can be administered as an adjunct to an ACE inhibitor (continued at the standard dosage discussed above) for four to seven days, followed by measurement of the serum creatinine concentration to confirm that azotemia has not markedly worsened. The losartan dosage can then be titrated up in a step-wise fashion, based on continued reduction of the UPC ratio, to a maximum of 0.5 to 2 mg/kg b.i.d., rechecking the serum creatinine concentration and UPC ratio after each dosage adjustment.

Reversible gastrointestinal side effects have anecdotally occurred in some dogs, although it is unclear whether this is due to concurrent use of losartan with an ACE inhibitor or due to the ARB alone. In people, concurrent use of ACE inhibitors and ARBs increases the risk of severe hyperkalemia.

Because of the limited literature regarding ARB therapy in dogs, I encourage you to discuss with a specialist whether administering an ARB in a particular patient may be indicated.

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Barrak Pressler, DVM, PhD, DACVIM
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
The Ohio State University
Columbus, OH 43210


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Source: VETERINARY MEDICINE,
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