Effects of manidipine vs. amlodipine on intrarenal haemodynamics in patients with arterial hypertension

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Dihydropyridine calcium channel blockers (CCBs) are widely used antihypertensive drugs. Evidence from animal studies indicates there are differences between CCBs in their renal haemodynamic effects suggesting that manidipine reduces, whereas amlodipine increases intraglomerular pressure but data from humans are scarce. WHAT THIS STUDY ADDS• In this study amlodipine was found to increase significantly intraglomerular pressure whereas manidipine decreased intraglomerular pressure in people with essential hypertension. This difference was attributed to significant vasodilation of the afferent arteriole with amlodipine compared with manidipine. This study for the first time has confirmed in humans data from experimental models on the different action of CCBs on dilatory capacity on efferent and afferent arterioles. AIMSIntraglomerular pressure is one of the main drivers of progression of renal failure. Experimental data suggest that there are important differences between calcium channel blockers (CCBs) in their renal haemodynamic effects: manidipine reduces, whereas amlodipine increases intraglomerular pressure. The aim of this study was to investigate the effects of manidipine and amlodipine treatment on intragomerular pressure (Pglom) in patients with mild to moderate essential hypertension. METHODSIn this randomized, double-blind, parallel group study, hypertensive patients were randomly assigned to receive manidipine 20 mg (n = 54) or amlodipine 10 mg (n = 50) for 4 weeks. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined by constant-infusion input-clearance technique with p-aminohippurate (PAH) and inulin. Pglom and resistances of the afferent (RA) and efferent (RE) arterioles were calculated according to the model established by Gomez. RESULTSPglom did not change in the manidipine group (P = 0.951), whereas a significant increase occurred in the amlodipine group (P = 0.009). There was a significant difference in the change of Pglom by 1.2 mmHg between the manidipine and amlodipine group (P = 0.042). In both treatment arms, RA was reduced (manidipine P = 0.018; amlodipine P < 0.001). The reduction of RA was significantly more pronounced with amlodipine compared with manidipine treatment (P < 0.001). RE increased in both treatment arms (manidipine P = 0.012; amlodipine P = 0.002), with no difference between the treatment arms. Both CCBs significantly reduced systolic and diastolic blood pressure (BP) (both P < 0.001). However, amlodipine treatment resulted in a significantly greater decrease of BP compared with manidipine (P < 0.001). CONCLUSIONSIn accordance with experimental data after antihypertensive treatment of 4 weeks, intraglomerular pressure was significantly lower with the CCB manidipine than with amlodipine, resulting and explaining their disparate effects on albuminuria.

Several Conventional Risk Markers Suggesting Presence of Albuminuria Are Weak Among Rural Africans With Hypertension

“…On the other hand, another finding in this study was that treatment with CCBs was associated with albuminuria. A recent study has demonstrated that the CCB, amlodipine, increased albuminuria by decreasing the resistance of the afferent arteriole in the glomerulus, leading to increased intraglomerular pressure . Even though the CCB used among the participants in this study was predominantly nifedipine, the mechanism that explains the association with albuminuria may be similar.…”

Plasma uric acid effects on glomerular haemodynamic profile of patients with uncomplicated Type 1 diabetes mellitus

“…Indirect intraglomerular haemodynamic parameters were estimated using equations derived by Gomez based on data from animal studies . These equations were successfully used in a similar manner to evaluate patients with conditions such as hypertension, endocrine disorders and Type 1 diabetes . Assumptions imposed by Gomez's equations were the following: (1) intrarenal vascular resistances are divided into afferent, post‐glomerular and efferent; (2) hydrostatic pressures within the renal tubules, venules, Bowman's space and interstitium ( P Bow ) are in equilibrium of 10 mmHg; (3) glomerulus is in filtration disequilibrium; and (4) the gross filtration coefficient ( K FG ) is 0.0867 ml/s/mmHg given a normal kidney physiology (GFR = 130 ml/min, oncotic pressure π G is 25 mmHg and P GLO = 60 mmHg, given Winton's indirect estimates in dogs that glomerular pressure is roughly two‐thirds of the mean arterial pressure (MAP) ).…”

Renal resistance and long-term blood pressure in individuals genetically predisposed for essential hypertension

“…Instead we utilized the model developed by Gomez [21] and later adapted by other research groups [28][29][30]. The reliability of the estimates rests on several assumptions as outlined in previous studies [29,31,32], and the most consistent results are probably achieved in individuals with two functionally normal and similar kidneys as it likely applies to the DHyPP cohort. In accordance with previous findings, we found that angiotensin II blockade selectively reduces R A without affecting P glom or R E [31].…”