From the Guidelines
Calcium channel blockers can exacerbate proteinuria, particularly dihydropyridine calcium channel blockers such as amlodipine and nifedipine, which not only have little impact on proteinuria but may also increase it 1.
Key Points
- Dihydropyridine calcium channel blockers are less efficacious than ACE inhibitors, ARBs, and nondihydropyridine calcium channel blockers in reducing albuminuria in diabetic kidney disease (DKD) 1.
- Nondihydropyridine calcium channel blockers have substantially greater antiproteinuric effects than dihydropyridine calcium channel blockers, which can translate into greater slowing of kidney disease progression and reduced cardiovascular event rates in those with proteinuria greater than 300 mg/d 1.
- In patients with increasing proteinuria on dihydropyridine calcium channel blockers, discontinuation and/or substitution with another antihypertensive should be considered prior to concluding that immunosuppression is necessary 1.
- The combination of an ACE inhibitor and an ARB can reduce proteinuria more than either agent alone, and may be considered for patients with controlled blood pressure but persistent high-level macroalbuminuria or ACR greater than 500 mg/g 1.
Management Considerations
- Counsel patients to hold ACEi or ARB and diuretics when at risk for volume depletion to avoid hemodynamic- and volume-related acute kidney injury (AKI) 1.
- Consider a systolic blood pressure goal even lower than 130 mm Hg to slow the progression of DKD, as lower blood pressure levels are associated with lower levels of proteinuria 1.
From the Research
Effects of Calcium Channel Blockers on Proteinuria
- The effects of calcium channel blockers (CCBs) on proteinuria are variable and depend on the type of CCB and the presence of other medications, such as angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin 2 receptor blockers (ARB) 2, 3, 4.
- Dihydropyridine CCBs may have an adverse effect on renal protein handling, which depends on the severity of hypertension and is minimized by ACE-I therapy or tight blood pressure control 3, 4.
- Non-dihydropyridine CCBs, such as diltiazem and verapamil, may slow the progression of type 2 diabetic nephropathy with overt proteinuria to a similar extent as observed with ACE-I 2, 5.
- The use of dihydropyridine CCBs in children with chronic kidney disease is associated with higher levels of proteinuria, unless used concomitantly with ACEi and ARB therapy 6.
Factors Influencing the Effects of CCBs on Proteinuria
- Blood pressure control: Tight blood pressure control can minimize the adverse effects of dihydropyridine CCBs on proteinuria 3, 4.
- Type of CCB: Non-dihydropyridine CCBs may have a more beneficial effect on proteinuria than dihydropyridine CCBs 2, 5.
- Concomitant medication use: The use of ACEi and ARB therapy can modify the effects of CCBs on proteinuria 3, 6.
Clinical Implications
- CCBs may be used as antihypertensive agents in patients with renal disease, but their effects on proteinuria should be carefully monitored 2, 3, 4.
- The choice of CCB and concomitant medication use should be individualized based on the patient's specific clinical characteristics and response to treatment 2, 3, 4, 5, 6.