Is amlodipine (calcium channel blocker) renoprotective?

Is Amlodipine Renoprotective?

No, amlodipine is not renoprotective and is inferior to ACE inhibitors and ARBs for preventing kidney function decline in patients with chronic kidney disease, though it effectively controls blood pressure without significantly worsening renal function in most cases. 1

Evidence Against Renoprotection

Comparative Trial Data

• The African-American Study of Kidney Disease demonstrated that ramipril (an ACE inhibitor) was superior to amlodipine for slowing kidney function loss and preventing kidney-related clinical events in African Americans with nondiabetic CKD, despite virtually identical blood pressure control between groups 1

• In diabetic nephropathy, two major trials (IDNT and RENAAL) showed that angiotensin receptor blockers were superior to amlodipine for preventing progressive kidney function loss and reducing proteinuria in patients with type 2 diabetes and nephropathy 1

• The Japanese JLIGHT Study found that losartan significantly reduced 24-hour urinary protein excretion by approximately 24% in patients with proteinuric CKD, while amlodipine showed no significant change in proteinuria despite equivalent blood pressure reduction 2

Guideline Positioning

• The American Society of Nephrology explicitly states that amlodipine does not improve impaired kidney function and is inferior to ACE inhibitors/ARBs for renoprotection in patients with CKD 1

• For patients with CKD and proteinuria, ACE inhibitors or ARBs should be first-line therapy, not amlodipine 1

• The ABCD study in diabetics was stopped prematurely when nitrendipine (a dihydropyridine like amlodipine) was found inferior to lisinopril in reducing ischemic cardiac events 3

When Amlodipine May Be Appropriate

As Add-On Therapy

• Amlodipine is appropriate as second- or third-line therapy when blood pressure targets (<130/80 mmHg) are not achieved with ACE inhibitors/ARBs alone 1

• It can be safely used as an add-on agent for blood pressure control in CKD patients already on ACE inhibitors or ARBs 1

• The American College of Cardiology found that amlodipine combined with enalapril maintained stable renal function in adults with hypertension and nondiabetic nephropathies 1

Specific Clinical Scenarios

• In normotensive diabetics, the ABCD2 study showed nitrendipine was equivalent to lisinopril in stroke prevention and retardation of albuminuria development 3

• Calcium channel blockers may be useful in diabetics as part of combination therapy to control blood pressure and reduce cardiovascular events compared to placebo 3

• In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in decreased renal vascular resistance and increased glomerular filtration rate without change in filtration fraction or proteinuria 4

ALLHAT Study Findings: A Critical Nuance

Renal Function Outcomes

• ALLHAT data showed no significant differences in end-stage renal failure between chlorthalidone, amlodipine, and lisinopril arms 3

• Paradoxically, the decline in creatinine slope was less marked and estimated creatinine clearance was better preserved in the amlodipine arm compared to chlorthalidone and lisinopril 3, 5

• These results differ from expected evidence on ACE inhibitor renoprotection and can be explained by good blood pressure control (final BP approximately 135/75 mmHg), lower systolic BP control with the ACE inhibitor especially in Black patients, and relatively short-term treatment in patients with nephrosclerosis 3

Safety in Renal Impairment

Pharmacokinetics

• The pharmacokinetics of amlodipine are not significantly influenced by renal impairment, and patients with renal failure may receive the usual initial dose 4

• Serum concentration studies in patients with renal dysfunction showed no tendency for drug accumulation 6

Clinical Safety Data

• Amlodipine significantly decreased blood pressure while causing little or no aggravation of renal dysfunction in hypertensive patients with renal impairment 6

• In peritoneal dialysis patients, use of calcium channel blockers was associated with decreased loss of residual kidney function, defined as urine volume greater than 200 mL/day 3

Common Pitfalls to Avoid

• Do not use amlodipine as monotherapy in patients with proteinuric CKD expecting renoprotection—always prioritize ACE inhibitors or ARBs first 1

• Do not assume that blood pressure reduction alone provides renoprotection—the mechanism of ACE inhibitors/ARBs is partially independent of blood pressure effects 3

• Do not administer amlodipine to patients treated with polyacrylonitrile dialysis membranes due to potential anaphylactoid reactions 5

• Avoid using amlodipine as first-line therapy in diabetic nephropathy where ACE inhibitors/ARBs have proven superiority 1