What are the recommended initial dosages of Angiotensin Receptor Blocker (ARB) medications for a patient with Chronic Kidney Disease (CKD) stage 3b and impaired renal function?

From the Guidelines

For patients with chronic kidney disease stage 3b (eGFR 30-44 ml/min/1.73m²), the recommended starting ARB dosages should be lower than standard doses, such as losartan 25 mg daily, valsartan 80 mg daily, irbesartan 75 mg daily, or candesartan 4 mg daily, as stated in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. These reduced initial doses help minimize the risk of acute kidney injury or hyperkalemia while still providing renoprotective benefits. After starting therapy, monitor serum creatinine, potassium, and blood pressure within 1-2 weeks, then periodically thereafter. If well-tolerated, doses can be gradually titrated upward to target doses (losartan 50-100 mg daily, valsartan 160-320 mg daily, irbesartan 300 mg daily, or candesartan 16-32 mg daily) as tolerated. Some key points to consider when using ARBs in patients with CKD include:

• Avoid using ARBs in combination with ACE inhibitors or direct renin inhibitors, as this increases adverse effect risks without providing additional benefits 1.
• Monitor for hyperkalemia, especially in patients with CKD or those on K+ supplements or K-sparing drugs 1.
• Be cautious when using ARBs in patients with severe bilateral renal artery stenosis, as there is a risk of acute renal failure 1. ARBs are beneficial in CKD as they reduce intraglomerular pressure by blocking angiotensin II effects on the efferent arteriole, thereby decreasing proteinuria and slowing CKD progression. However, the most recent and highest quality study, which is the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, should be prioritized when making decisions about ARB dosages in patients with CKD. The guideline provides a comprehensive overview of the management of high blood pressure in adults, including the use of ARBs in patients with CKD. It is essential to follow the guideline recommendations and monitor patients closely to minimize the risk of adverse effects and maximize the benefits of ARB therapy. In addition to the guideline, other studies, such as those published in Circulation 1, also provide valuable information on the use of ARBs in patients with CKD. However, when making decisions about ARB dosages, it is crucial to prioritize the most recent and highest quality study, which is the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.

From the FDA Drug Label

The usual recommended starting dose of candesartan cilexetil is 16 mg once daily when it is used as monotherapy in patients who are not volume depleted. Use in Renal Impairment: Dosing recommendations for candesartan cilexetil and hydrochlorothiazide tablets in patients with creatinine clearance < 30 mg/min cannot be provided

The best ARB medication dosage to start for CKD 3b is not explicitly stated in the label, as CKD 3b corresponds to a creatinine clearance of 30-44 ml/min, and the label only provides dosing recommendations for patients with creatinine clearance < 30 mg/min or does not specify recommendations for CKD 3b. However, considering the usual recommended starting dose is 16 mg once daily for patients who are not volume depleted, a conservative approach would be to start with this dose and monitor the patient's response. 2

From the Research

Angiotensin-Receptor Blockers (ARBs) for CKD 3b

• The optimal dosage of ARBs for patients with CKD 3b is not clearly established, but studies suggest that higher doses may be more effective in reducing proteinuria and slowing disease progression 3, 4.
• A study comparing the efficacy of ACEi and ARB in patients with early CKD (stage 1 to 3) found that ARB (losartan 50 mg) may reduce eGFR rate of decline, presence of proteinuria, and blood pressure, but the certainty of the evidence is very low 3.
• Another study found that ACEi in combination with ARB was superior to low-dose ACEi or ARB in reducing urine albumin excretion, urine protein excretion, and blood pressure, but was associated with decreased GFR and increased rates of hyperkalemia and hypotension 4.

Starting Dosages for ARBs

• The starting dosage for losartan is 50 mg once daily, which can be increased to 100 mg once daily if necessary 5.
• The starting dosage for telmisartan is 20-40 mg once daily, which can be increased to 80 mg once daily if necessary 5.
• The starting dosage for valsartan is 80-160 mg once daily, which can be increased to 320 mg once daily if necessary 5.

Combination Therapy with ARBs

• Combination therapy with ARB and calcium channel blocker (CCB) or diuretic may be effective in reducing blood pressure and proteinuria in patients with CKD 6.
• A study found that combination therapy with losartan and controlled-release nifedipine was superior to fixed-dose combination of losartan-hydrochlorothiazide in terms of blood pressure control and renal function 6.

Dosage Optimization

• Maximizing the ARB dose before adding additional therapies or another renal-protecting agent may be superior to adding another class of antihypertensive, even if similar blood pressures can be achieved 7.
• ARB dosage optimization or the addition of a second renoprotective agent (ACE inhibitor or non-dihydropyridine calcium-channel blocker) may be important for optimal renoprotection, although further research is clearly needed in this area 7.