#8 Ameliorate gastrointestinal signs. Dogs and cats with stage 3 or 4 chronic kidney disease may have gastrointestinal complications including reduced appetite, nausea, vomiting, uremic stomatitis and halitosis, gastrointestinal hemorrhage, diarrhea, and hemorrhagic colitis. Treatment for these gastrointestinal signs largely focuses on ameliorating uremic gastritis (evidence grade 4) by

1. Limiting gastric acidity with H₂ blockers (ranitidine, famotidine)

2. Suppressing nausea and vomiting with antiemetics (metoclopramide, 5-HT₃ receptor antagonists such as ondansetron hydrochloride or dolasetron mesylate, or the neurokinin-1 receptor antagonist maropitant [Cerenia—Pfizer]) or low doses of phenothiazine tranquilizers (prochlorperazine)

Of these treatments, H₂ blockers are most commonly used, and few adverse effects have been attributed to their use. Antiemetics are typically added when anorexia, nausea, or vomiting persist despite the use of an H₂ blocker. Sucralfate is added when gastrointestinal ulcers and hemorrhage are suspected.

PROVIDE RENOPROTECTIVE THERAPY TO SLOW DISEASE PROGRESSION

#9 Reduce the magnitude of proteinuria. Glomerular proteinuria should be reduced in dogs and cats with chronic kidney disease stages 1 through 4. Intervention is indicated when the urine protein/creatinine ratio exceeds 2 in dogs and cats with stage 1 disease and when it exceeds 0.5 in dogs and 0.4 in cats with stage 2 through 4 disease.¹¹

Proteinuria has been shown to adversely affect outcomes in people, dogs, and cats with chronic kidney disease, presumably because proteinuria itself appears to injure the renal tubules, thereby promoting progression of chronic kidney disease.^11-13 In people, it is well-established that reducing proteinuria by suppressing the renin-angiotensin system ameliorates the adverse effects of proteinuria on the kidneys. Although qualitatively similar, evidence in dogs and cats is far less compelling.^14,15 Studies on the long-term effects of angiotensin-converting enzyme (ACE) inhibitors on survival outcome in proteinuric dogs have not been reported, and although such studies have been reported in cats, they have failed to yield statistically significant evidence of enhanced survival. Nonetheless, an ACE inhibitor such as enalapril, benazepril, or lisinopril is recommended in patients with chronic kidney disease that meet the above criteria (evidence grade 4).¹¹ Ideally, proteinuria should be reduced below the therapeutic target. However, this is typically difficult and may require higher doses of the ACE inhibitor or the addition of angiotensin II receptor blocking drugs (e.g. losartan or irbesartan). Losartan may be administered at a dose of 0.25 to 0.5 mg/kg/day while monitoring for any changes in serum creatinine concentration. Dosages may be increased as needed up to 1 mg/kg every 12 hours.

Initially monitor a urine protein/creatinine ratio monthly to ascertain whether the treatment target of normalizing or at least halving the urine protein/creatinine ratio has been achieved. Once therapeutic targets have been attained, monitor the urine protein/creatinine ratio every three to four months to ensure continued compliance and therapeutic success at maintaining the target.

#10 Minimize systemic hypertension. Drug therapy to lower blood pressure is indicated in dogs and cats with chronic kidney disease stages 2 through 4 when the pressure exceeds 160/100 mm Hg and in dogs and cats with chronic kidney disease stage 1 when blood pressure exceeds 180/120 mm Hg.¹⁶ Unless hypertensive retinopathy or central nervous system signs are present or the systolic blood pressure remains above 200 mm Hg, determine blood pressure values on at least three separate clinic visits before establishing the need for therapeutic intervention. The goal of therapy is to reduce blood pressure to below 160/100 mm Hg.

Amlodipine is the first-choice drug for managing elevated blood pressure in cats with chronic kidney disease (evidence grade 2).¹⁷ It is typically highly effective in reducing blood pressure in cats, often by as much as 20 to 50 mm Hg. Amlodipine is administered at a dose of 0.625 mg/cat in cats less than 11 lb (5 kg) and 1.25 mg/cat in cats 11 lb or greater. The dose may be doubled if response fails to meet treatment goals.