Does Diltiazem Decrease Proteinuria?
Yes, diltiazem does decrease proteinuria, as it is a non-dihydropyridine calcium channel blocker with substantially greater antiproteinuric effects compared to dihydropyridine calcium channel blockers. 1
Evidence for Antiproteinuric Effect
Non-dihydropyridine calcium channel blockers (including diltiazem and verapamil) have a greater antiproteinuric effect than other antihypertensive classes in hypertensive patients with diabetic kidney disease. 2 This effect translates into greater slowing of kidney disease progression and reduced cardiovascular event rates in patients with proteinuria greater than 300 mg/day. 1
Mechanism of Action
- Diltiazem improves glomerular size permselectivity, which is the mechanism by which it reduces proteinuria. 3
- In a randomized trial comparing diltiazem to nifedipine (a dihydropyridine), diltiazem reduced proteinuria by 57% over 21 months while improving glomerular size selectivity, whereas nifedipine showed no significant change in proteinuria despite similar blood pressure control. 3
- Diltiazem attenuates proteinuria and improves renal perfusion, which may help limit progression of renal injury. 4
Clinical Application in Diabetic Kidney Disease
- Non-dihydropyridine calcium channel blockers slow the progression of type 2 diabetic nephropathy with overt proteinuria almost to a similar extent as ACE inhibitors. 5
- One study demonstrated that diltiazem decreased proteinuria as effectively as lisinopril (an ACE inhibitor). 6
- Diltiazem is particularly indicated in patients with hypertension and concurrent chronic renal disease. 6
Combination Therapy Considerations
- The combination of diltiazem with enalapril (an ACE inhibitor) showed additive blood pressure effects and reduced proteinuria in patients with renal dysfunction. 7
- Calcium channel blockers may have an advantage when combined with ACE inhibitors and/or ARBs, as combination therapy is almost always required to attain sufficient blood pressure reduction in chronic nephropathy. 5
- When diltiazem is combined with ACE inhibitors, a reduction in creatinine clearance with coincident decrease in proteinuria has been observed. 7
Important Caveats
The BENEDICT trial showed that non-dihydropyridine calcium channel blockers used alone did not decrease the incidence of microalbuminuria relative to placebo in hypertensive patients with type 2 diabetes who had normal urinary albumin excretion at baseline. 2 This indicates that diltiazem's antiproteinuric benefit is most evident in patients who already have established proteinuria, not for primary prevention of microalbuminuria.