Dosing of Antihypertensive Medications in Patients with Renal Insufficiency

Abstract

The use of antihypertensive agents in patients with renal insufficiency necessitates careful consideration of dosages, titration, and monitoring. Renal function must be estimated to appropriately make dosage adjustments for antihypertensives that exhibit extensive renal elimination. Thiazide diuretics are useful in mild degrees of renal insufficiency but loop diuretics become necessary as renal function deteriorates further. With either class, low dosages should be used to prevent hypovolemia, hyponatremia, and hypokalemia which may worsen renal blood flow. Angiotensin-converting enzyme (ACE) inhibitors have become popular because they may have unique renal protective properties. All ACE inhibitors except fosinopril require reduced dosages and/or less frequent administration in patients with renal insufficiency. It is often necessary to use a diuretic with an ACE inhibitor and special dosing considerations are important. Due to demographic and physiologic characteristics of patients with renal insufficiency, beta blockers are often reserved for patients with other indications for beta blockers such as ischemic heart disease. Several beta blockers are eliminated primarily by the kidney and dosage reductions are necessary for these agents. Calcium antagonists may also have renal protective effects. Because calcium antagonists are metabolized extensively, significant dosage adjustments are not necessary. Data suggest that antihypertensives may slow the decline in renal insufficiency. The pharmacokinetics of several antihypertensives change with renal impairment because of reduced elimination. Therefore, dosage adjustments, slower titration, and less frequent administration are often necessary.

Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study

“…In the present survey, age ≥75 years and concomitant diuretic use were risk factors for volume depletion-related ADRs. The relationship between diuretic use and volume depletion was expected because higher doses of loop diuretics may cause hypovolemia in patients with renal insufficiency [19], and volume depletion is a frequent adverse reaction to diuretics [20,21]. These findings are consistent with those of a pooled analysis of patients treated with 100 mg canagliflozin, 300 mg canagliflozin, or placebo/active comparators [22], where volume depletion-related AEs occurred in 4.9%, 8.7%, and 2.6% of 8949 patients aged ≥75 years, respectively, compared with 2.2%, 3.1%, and 1.4% of 490 patients aged <75 years.…”

Is Dose Titration Required for Antihypertensive Agents in Geriatric Diabetic Patients?

“…Metoprolol dose appeared to be higher in geriatrics (60 vs. 55 mg), whereas atenolol dose lower in geriatrics (42 vs. 43 mg) which was statistically and clinically insignificant. Hydrophilic beta-blockers (e.g., atenolol, bisoprolol, nadolol, and acebutolol) are eliminated renally and dosing adjustments are expected in patients with chronic kidney disease [17]; however, in our study, there was no reduction in the atenolol dose probably because there was only a mild renal impairment (Crcl < 90 ml/min) in the geriatric population.…”

Principles of Drug Therapy, Dosing, and Prescribing in Chronic Kidney Disease and Renal Replacement Therapy

“…Antihypertensives should be used cautiously according to clinical response to avoid renal hypoperfusion. 78 Hypotension from hemodialysis may require antihypertensives to be withheld or delayed on dialysis days.…”