Long-term effects of calcium antagonists on augmentation index in hypertensive patients with chronic kidney diseases.

Abstract

Sir, In 2004, the Japanese Society of Hypertension recommended calcium channel blockers (CCBs) as second line drugs, with the renin–angiotensin (Ang) system (RAS) inhibitor as the first choice, for the treatment of hypertension associated with chronic kidney disease (CKD). We reported that augmentation index (AI) is related to proteinuria in CKD patients, and that RAS inhibition preserves arterial compliance in CKD [1,2]. However, the effects of CCBs on arterial stiffness remain unclear among CKD patients. A prospective comparative study was performed between 26 non-diabetic CKD patients treated with amlodipine and 27 patients on benidipine (supplemental methods). Patient backgrounds including the prescription of the RAS inhibitor did not differ between groups (supplemental table). Brachial blood pressure was controlled equally well in both groups for a year (supplemental figure). A year later, body weight (to 59 ± 11 kg, P < 0.05) and estimated glomerular filtration rate (eGFR) were decreased, and AI was increased without changes in proteinuria (Figure ​(Figure1)1) in the amlodipine group. However, in the benidipine group, either eGFR, body weight or AI was not altered, but proteinuria was reduced. Fig. 1 Annual changes in urinary protein (UP, left panel), estimated glomerular filtration rate (eGFR, middle panel) and augmentation index (AI, right panel). *P < 0.05 from zero. Significant decreases in UP (116 ± 93 to 82 ± 67 mg/g ... In renal tissue, L-type calcium channels are only found in afferent arterioles, while N-type and T-type calcium channels are localized in both afferent and efferent arterioles [3]. Amlodipine blocks L-type and N-type calcium channels and dilates afferent arterioles much more than efferent arterioles. In contrast, benidipine that inhibits L-type and T-type calcium channels, dilates both afferent and efferent arterioles and reduces glomerular pressure. We have demonstrated that efferent arteriolar constriction is mediated by inositol trisphosphate-induced calcium mobilization and calcium entry through transient receptor potential (TRP) channels [4]. T-type CCBs inhibited AngII-induced calcium mobilization rather than calcium entry in efferent arterioles [3]. TRP channels possess molecular similarity with voltage-dependent calcium channels, but they lack the structure of voltage-sensor, gating independently of voltage. It is possible that some CCBs including benidipine inhibit calcium entry through TRP channels into efferent arteriole. Increasing AI elevates central blood pressure, worsening glomerular hypertension, proteinuria, renal and cardiovascular prognosis [1,2]. Although we would not deny the other possibilities (supplemental discussion), benidipine could reduce oxidative stress on arterial wall by decreasing proteinuria. Albumin passed through slit diaphragm is absorbed by proximal tubular cells. Although a small amount of protein is cleaved by acidification [5], oxidative process is involved in dealing a large amount of protein, generating reactive oxygen species that appear to leak from the kidney. This escalation of AI should worsen glomerular hypertension further, forming a vicious circle of progressive kidney damage [1,2]. Our results provided the evidence that benidipine may be superior to amlodipine in renoprotection as the antihypertensive additional to the RAS inhibitor when similar blood pressure levels are attained. Furthermore, the present data suggest that the influence on AI differs among types of CCBs in patients with CKD. Conflict of interest statement. None declared.