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What Role Do Nondihydropyridines Have in Patients With CKD?

Roughly 50%-75% of patients with chronic kidney disease (CKD) have high blood pressure. Therefore, it is important to know which antihypertensive interventions are associated with positive outcomes in these patients.[1,2] The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI™) practice guidelines address the pharmacotherapeutic management of this patient population, compiling the subanalyses of trials that focused on the use of antihypertensive agents in patients with CKD.[2-5]
In the setting of arrhythmias, angina, and high-risk cardiovascular disease (CVD), nondihydropyridine (non-DHP) calcium channel blockers (eg, diltiazem and verapamil) are the preferred antihypertensive agents.[2] Because all patients with CKD are classified as being at high risk for CVD, non-DHP calcium channel blockers are indicated along with other antihypertensives.[2] Non-DHPs have shown significant reductions in albuminuria, both alone and in combination with agents that act on the renin-angiotensin system (eg, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers), as well as reductions in blood pressure.[6-12] However, because there is strong evidence to support the use of both diuretics and renin-angiotensin system blockers in CKD, the use of non-DHP antihypertensives is limited to patients who require additional blood pressure lowering or cannot take or titrate the preferred agents.[1,13-15]
Beyond their efficacy, use of non-DHP calcium channel blockers is often limited by intolerable adverse effects and potential drug/drug interactions.[16] First, the clinician should confirm that all appropriate nonpharmacologic CVD prevention strategies have been implemented. If preferred pharmacologic agents for CVD prevention are not appropriate for use, the clinician should consider use of a non-DHP antihypertensive in patients with CKD to reduce risk for CVD and decrease albuminuria.
Patients who have had renal transplant present an additional set of issues. Small studies have shown the efficacy of non-DHP calcium channel blockers with respect to blood pressure reduction. Moreover, these agents do not kinetically pose an additional toxic threat to the kidney tissue.[17] Similar to CKD, the benefit of using a non-DHP antihypertensive would be most evident in patients with increased proteinuria after transplant.[5,17] However, excretion of immunosuppressant drugs may be diminished, warranting initiation at the lowest possible starting dose. Still, dihydropyridine (DHP) calcium channel blockers (eg, amlodipine and nifedipine) are efficacious and safe and continue to be widely used as post-transplant antihypertensives.[5]
In addition, DHP and non-DHP calcium channel blockers may have beneficial effects, such as allowing use of lower doses of cyclosporine; having fewer associated side effects; and dilating the afferent arteriole, which is often constricted as a side effect of antirejection medications.[5,17-21] Of note, the KDOQI guidelines specifically do not list any single antihypertensive as preferred for post-transplant patients.[5] As in CKD, use of non-DHP calcium channel blockers should be limited to patients who require additional blood pressure lowering or have contraindications to favored therapies.
In summary, non-DHP calcium channel blockers certainly have a role for treatment of hypertension in patients with CKD and patients who have had renal transplant. Specifically, clinicians should use non-DHP antihypertensives as indicated by the NKF-KDOQI guidelines when other preferred pharmacotherapy options are no longer effective or these agents are not tolerated by the patient.
The author wishes to acknowledge the assistance of Joseph P. Falinski, PharmD and Christine Chim, PharmD, PGY1 Residents, and Michael P. Conley, PharmD, and Nga T. Pham, PharmD, AE-C, Assistant Clinical Professors at Northeastern University -- School of Pharmacy and Harbor Health Services, Inc., Boston, Massachusetts.

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