Calcium Antagonists and Renal Failure Progression

Abstract

Although tighter blood pressure control is considered the main mechanism for preventing the progression of chronic renal failure, angiotensin-converting enzyme inhibitors and angiotensin receptors blockers seem to have an additional organ protective role. The effects of calcium antagonists in renal disease are not so clearly defined. Calcium antagonists have pleiotropic effects that might contribute to protect the kidney, such as attenuating mesangial entrapment of macromolecules, countervailing the mitogenic effect of platelet-derived growth factors and platelet-activating factors, and suppressing mesangial cell proliferation. They could also act as free radical scavengers and inhibit the renal effects of endothelin. Some evidence has been accumulated demonstrating that certain new dihydropyridinic calcium antagonists may affect postglomerular as well as preglomerular vessels, resulting in decreased filtration fraction and nephroprotective effect as renin-angiotensin axis-blocking drugs. Though there are few reports on the clinical renal effects of new calcium antagonists, they have rendered promising results. Manidipine does not increase proteinuria as do some classic calcium antagonists, and lercanidipine combined with renin-angiotesin axisblocking drugs reduce proteinuria. Both drugs have been shown to decrease microalbuminuria when administered alone.

Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicity

“…Review of animal and human data show conflicting results as to the effects of dihydropyridine calcium channel blockers on renal hemodynamics. [21][22][23][24][25] In general, although dihydropyridine calcium channel blockers decrease afferent arteriole resistance, they also fully impair renal autoregulation, resulting in glomerular hypertension. 22,23,[26][27][28] The class has variable effects on progression of proteinuria or renal disease, with no clear benefit.…”

Treatment of proteinuria with lercanidipine associated with reninangiotensin axis-blocking drugs

“…По другим данным, преимущественное действие этих препаратов на афферентные артериолы может приводить к клубочковой гипертензии и прогрессированию патологии почек [31][32][33][34]. В последнее время появляется все больше доказательств того, что отдельные АК (лерканидипин) влияют как на афферентные, так и на эфферентные артериолы почечных клубочков [6]. Таким образом, новые дАК могут обладать антипротеинурическим эффектом, в пользу чего свидетельствуют данные выполненных in vitro исследований о влиянии этих препаратов на эфферентные клубочковые артериолы.…”

“…БРАС более эффективно, чем традиционные АК уменьшают ПУ и предотвращают прогрессирование поражения почек. Однако новые АК, оказывающие вазодилатирующее действие как на афферентные, так и на эфферентные артериолы почечных клубочков, могут обладать специфическим ренопротективным эффектом [6]. Одним из представителей новых дигидропиридиновых АК (дАК) является лерканидипин.…”

Treatment of Proteinuria with Lercanidipine Associated with Renin-Angiotensin Axis-Blocking Drugs

“…[31][32][33][34] In contrast with this effect of classic calcium antagonists, a growing body of evidence has been accumulated demonstrating that certain types of these agents (i.e., lercanidipine) may act on postglomerular as well as preglomerular vessels. [6] Thus, new-generation dihydropyridine calcium channel blockers may have antiproteinuric effects, as suggested by its in vitro effects on postglomerular arterioles.…”

“…Renin-angiotensin axis-blocking drugs are more effective than classic calcium channel blockers to reduce proteinuria and prevent renal disease progression; however, new generation calcium antagonists, with the property of vasodilator action on afferent and efferent glomerular arterioles, might have special renoprotective effects. [6] Lercanidipine is one of these new dihydropyridine calcium antagonists with high lipophilicity and high vascular selectivity, which confers upon it a gradual and prolonged antihypertensive effect and a good tolerability as compared with other dihydropyridine calcium channel blockers. [7,8] It can induce vasodilatation of glomerular efferent arterioles [9] and reduce microalbuminuria in type II diabetic patients.…”