michigan hypertension core curriculum - State of Michigan

Use of Dihydropyridine Calcium Antagonist in Chronic Kidney Disease
270 Hypertension Core Curriculum
John M. Flack, MD, MPH
There has been substantial concern in the literature regarding the use of dihydropyridine (DHP)
calcium antagonists in patients with CKD, especially proteinuric kidney disease. The reason for this
concern has been studies showing that DHP calcium antagonists do not reliably reduce proteinuria,
or in some instances may increase proteinuria over and above baseline, when used as monotherapy.
Some, though not all, studies show that renin angiotensin system (RAS)-based antihypertensive drug
therapy preserves kidney function better than non-RAS containing antihypertensive drug regimens. 1,2
In both the African American Study of Kidney Disease (AASK) 2 and the Irbesartan Diabetes
Nephropathy Trial (IDNT) 1 DHP calcium antagonist-based antihypertensive drug therapy was a less
effect active comparator against RAS-based antihypertensive therapy for the preservation of kidney
function. There are physiologically plausible reasons for this observation.
The renal microcirculation auto-regulates glomerular flow and pressure largely by constriction
of the afferent arteriole when BP rises and dilation of the afferent arteriole when BP falls. DHP
calcium antagonists interfere with micro-circulatory autoregulation of glomerular flow and pressure by
preferentially dilating the afferent arteriole. Thus, when systemic pressure is not reduced to low levels,
there will be greater transmission of potentially injurous systemic arterial pressure into the glomerulus.
Nevertheless, the practitioner must interpret these studies as well as understand how well they
inform routing clinical practice. There are very few situations where RAS blockade will not be included
in the treatment regimen of patients with CKD given that virtually every authoritative hypertension
guideline recommends RAS blockade as preferred therapy in these patients. Given the proven
treatment resistance to pharmacological BP lowering in CKD, especially proteinuric CKD, the vast
majority of them will require multi-drug therapy – often times more than three drugs. The RENAAL
study provided insight into the how the combination of DHP calcium antagonists and RAS blockade
(with the ARB losartan) worked in patients with diabetic nephropathy; there was no diminution of the
renoprotective effect of losartan when used simultaneously with DHP calcium antagonists. 3 Also,
there are other likely more important reasons for choosing a DHP than a non-DHP calcium antagonist
in persons with CKD than their effects as monotherapy on proteinuria. For example, in a patient
also taking/requiring beta blockade, a commonly used antihypertensive drug class, the use of a DHP