What are the post-medication options for hypertension in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

For patients with chronic kidney disease (CKD) and hypertension, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the first-line medications of choice, with a target blood pressure of less than 130/80 mmHg, as recommended by the most recent guidelines 1. The choice of ACEI or ARB should be based on the patient's specific clinical characteristics and comorbidities. Common ACEIs include lisinopril (starting at 5-10 mg daily) and enalapril (5-10 mg daily), while ARBs include losartan (25-50 mg daily) and valsartan (80-160 mg daily). These medications not only lower blood pressure but also reduce proteinuria and slow CKD progression by decreasing intraglomerular pressure. Some key points to consider when treating hypertension in patients with CKD include:

• Starting RASi (ACEi or ARB) for people with high BP, CKD, and severely increased albuminuria (G1–G4, A3) without diabetes, as recommended by the KDIGO 2021 clinical practice guideline 1
• Avoiding any combination of ACEi, ARB, and direct renin inhibitor (DRI) therapy in patients with CKD, with or without diabetes, due to the increased risk of adverse effects 1
• Monitoring blood pressure regularly and adjusting therapy as needed to achieve the target blood pressure of less than 130/80 mmHg
• Checking kidney function and electrolytes, particularly potassium, within 1-2 weeks of starting or adjusting ACEI/ARB therapy, as these medications can cause acute kidney injury or hyperkalemia in some patients. If blood pressure targets aren't achieved with an ACEI or ARB alone, a calcium channel blocker like amlodipine (5-10 mg daily) or a diuretic appropriate for the patient's kidney function can be added. For advanced CKD (stages 4-5), thiazide diuretics become less effective, so loop diuretics like furosemide (20-80 mg once or twice daily) are preferred. Beta-blockers such as metoprolol (25-100 mg twice daily) can be added as third-line agents, especially in patients with concurrent heart disease.

From the FDA Drug Label

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose In hypertensive patients with normal renal function treated with lisinopril alone for up to 24 weeks, the mean increase in serum potassium was approximately 0.1 mEq/L; however, approximately 15% of patients had increases greater than 0.5 mEq/L and approximately 6% had a decrease greater than 0. 5 mEq/L.

Hypertension PO medication options for CKD:

• Amlodipine: can be used in patients with renal impairment, as its pharmacokinetics are not significantly influenced by renal impairment 2.
• Lisinopril: can be used in patients with hypertension and normal renal function, but patients with CKD should be monitored for changes in serum potassium levels 3. Key considerations:
• Monitor serum potassium levels in patients with CKD taking lisinopril.
• Amlodipine may be a suitable option for patients with CKD, but its use should be individualized based on patient-specific factors.

From the Research

Hypertension Medication Options for CKD

• The primary goal in managing hypertension in patients with chronic kidney disease (CKD) is to reduce blood pressure to <130/80 mmHg 4, 5, 6.
• Angiotensin-converting enzyme (ACE) inhibitors are recommended as the first-line treatment for hypertension in CKD patients, due to their ability to reduce proteinuria and slow the decline in kidney function 4, 5, 6.
• Angiotensin II receptor blockers (ARBs) are recommended as an alternative to ACE inhibitors if they are not tolerated, as they have similar benefits in reducing proteinuria and slowing kidney function decline 4, 5, 6.
• Non-dihydropyridine calcium channel blockers (CCBs) can reduce albuminuria and slow kidney function decline, while dihydropyridine CCBs should not be used as monotherapy in proteinuric CKD patients, but rather in combination with a renin-angiotensin-aldosterone system (RAAS) blocker 4, 5.
• Diuretics are commonly used in CKD patients and represent a cornerstone in their management, with the addition of other agents as needed to achieve blood pressure goals 4, 7.
• The choice of antihypertensive medication in CKD patients should be individualized, taking into account patient comorbidities and the potential for drug removal with dialysis 7.

Comparison of ACE Inhibitors and ARBs

• A comparison of ACE inhibitors and ARBs found no difference in total mortality, total cardiovascular events, or cardiovascular mortality, but ARBs had a slightly lower incidence of withdrawals due to adverse effects (WDAEs) 8.
• The evidence for total mortality and cardiovascular outcomes was limited by possible publication bias, and the quality of the evidence was judged to be moderate to low 8.
• While ACE inhibitors have shown efficacy in reducing mortality and morbidity in placebo-controlled trials, the evidence for ARBs is weaker, and their use should be considered in the context of their tolerability and potential benefits 8.