Antihypertensive treatment of patients with proteinuric renal diseases: Risks or benefits of calcium channel blockers?

Abstract

In patients with proteinuric renal diseases the rate of progression of renal insufficiency is determined by the level of blood pressure and proteinuria. It has been demonstrated that strict blood pressure control with angiotensin converting enzyme (ACE)-inhibitors or beta-blockers, aimed at reaching values below 130/80 mm Hg, attenuates the deterioration of renal function. In general, the beneficial effects of these drugs are reflected in a parallel lowering of proteinuria. Calcium channel blockers are effective antihypertensive drugs, however, their safety in patients with proteinuric renal diseases and renal insufficiency may be questioned because of reported untoward effects on urinary protein excretion. The present review discusses the potential benefits and risks of calcium channel blockers (CCBs) in the treatment of patients with renal diseases. To this end we have evaluated the effects of these drugs in animal models of progressive renal injury. In these animal models adverse effects of CCBs have been reported which are attributed to an impairment of autoregulation. In patients with proteinuria, the dihydropyridine CCBs do not lower proteinuria despite a reduction of blood pressure. Studies on the effects on the course of renal function are limited, however, the available data do suggest that this class of CCBs may be less advantageous than other antihypertensive drugs, thus arguing against the use of these agents as first-line drugs in patients with proteinuric renal diseases. Information on the effects of the non-dihydropyridine CCBs is limited to a small number of studies in patients with diabetic renal disease. Although the data suggest that these classes of CCBs might be more beneficial, more studies are needed, particularly in patients with non-diabetic renal diseases, before founded conclusions can be reached.

Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms

“…Similar relationships between impaired renal autoregulation and increased renal susceptibility to hypertensive injury have been noted in the DOCA/salt model of hypertension (72,109), and in the nonclipped kidney of the 2K/1C model (124,133). Moreover, interventions that alter autoregulatory capacity, such as dietary protein restriction or calcium channel blockers, produce corresponding changes in susceptibility to hypertensive injury in models of CKD (57,60,62) and in the DOCA/ salt and 2K/1C models of hypertension (92,133).…”

Effect of calcium channels blockers and inhibitors of the renin-angiotensin system on renal outcomes and mortality in patients suffering from chronic kidney disease: systematic review and meta-analysis

“…However, the effects of CCBs on renal diseases drawn from current the available clinical data are quite contradictory: beneficial, neutral, even adverse. [6][7][8] To assess the action of CCBs on the progression of CKD, we undertook a systematic review and meta-analysis of clinical randomized controlled trials investigating the effects of CCBs on renal outcomes and all-cause mortality compared with ACEIs or ARBs.…”

T-type Ca2+channels and autoregulation of local blood flow

“…Inhibitors of L-type channels are often used in treatment of hypertension and it has been suggested that this leads to increased glomerular capillary pressure due to loss of renal autoregulation leading to increased proteinuria and glomerulosclerosis. 95,96 Therefore focus has increased on the role of T-type channels in renal protection 97,98 as they are hypothesized to reduce glomerular pressure.…”