1.
Calcium channel blocker inhibition of AGE and RAGE axis limits renal injury in nondiabetic patients with stage I or II chronic kidney disease.
Nakamura, T, Sato, E, Fujiwara, N, Kawagoe, Y, Koide, H, Ueda, Y, Takeuchi, M, Yamagishi, S
Clinical cardiology. 2011;(6):372-7
Abstract
BACKGROUND There is a growing body of evidence that advanced glycation end products (AGE) and their receptor (RAGE) system are implicated in chronic kidney disease (CKD). We have previously found that a long-acting calcium channel blocker, azelnidipine, but not amlodipine, improves renal injury in CKD patients. However, little is known about the effect of azelnidipine on the AGE-RAGE axis in humans. In this study, we examined whether azelnidipine addition could have renoprotective properties in hypertensive CKD patients by reducing serum levels of AGE and soluble form of RAGE (sRAGE). Thirty nondiabetic stage I or II CKD patients who had already been treated with angiotensin II receptor blockers were enrolled in this study. HYPOTHESIS We hypothesized that azelnidipine treatment could limit renal injury partly by blocking the AGE-RAGE axis. METHODS Patients were randomly divided into 2 groups; one group was treated with 16 mg azelnidipine and the other with 5 mg amlodipine once daily. They were followed up for 6 months. RESULTS Proteinuria was positively correlated with circulating AGE and sRAGE levels in our subjects. Both drugs exhibited comparable and significant blood pressure (BP)-lowering effects. Although neither of them affected glucose, glycated hemoglobin, lipid levels, and estimated glomerular filtration rate, treatment with azelnidipine, but not amlodipine, decreased circulating AGE, sRAGE, proteinuria, and urinary levels of liver-type fatty acid binding protein, a marker of tubular injury, in a BP-lowering-independent manner. CONCLUSIONS Our present results suggest that azelnidipine may exert renoprotective properties in nondiabetic hypertensive CKD patients via its unique inhibitory effects on the AGE-RAGE axis.
2.
Comparative effects of benidipine and amlodipine on proteinuria, urinary 8-OHdG, urinary L-FABP, and inflammatory and atherosclerosis markers in early-stage chronic kidney disease.
Nakamura, T, Sato, E, Fujiwara, N, Kawagoe, Y, Ueda, Y, Sugaya, T, Yamagishi, S, Yamada, S, Koide, H
The American journal of the medical sciences. 2010;(2):157-63
Abstract
INTRODUCTION We examined the effects of 2 calcium channel blockers, benidipine (T-, L-, and N-type) and amlodipine (L- and N-type), on renal, inflammatory, oxidative, and atherosclerosis markers in hypertensive patients with mild chronic kidney disease (CKD). METHODS Forty hypertensive patients with CKD were assigned randomly to either of the 2 treatments: 8 mg benidipine once daily (n = 20, group A) or 5 mg amlodipine once daily (n = 20, group B). Treatment was continued for 12 months. Blood pressure, serum creatinine, estimated glomerular filtration rate, urinary protein excretion, urinary liver-type fatty acid-binding protein, interleukin-6, high mobility group box-1 protein, urinary 8-hydroxy-2'-deoxyguanosine, pulse wave velocity, intima-media thickness, and blood asymmetric dimethylarginine were monitored. RESULTS Blood pressure decreased equally in both groups (P < 0.001, at 6 and 12 months versus before treatment). Serum creatinine and estimated glomerular filtration rate changed little during the experimental period in each group. However, urinary protein excretion (P < 0.001), urinary liver-type fatty acid-binding protein (P < 0.001), urinary 8-hydroxy-2'-deoxyguanosine (P < 0.001), blood interleukin-6 (P < 0.001), blood high mobility group box-1 (P < 0.05), and pulse wave velocity (P < 0.01) decreased more in group A than in group B with 12 months of treatment. The percent reductions in intima-media thickness and blood asymmetric dimethylarginine were significantly greater in group A than in group B (P < 0.001). CONCLUSIONS Benidipine is more effective than amlodipine for protecting renal function and potentially for ameliorating atherosclerosis in hypertensive patients with mild CKD. T-type calcium channel blockers may be effective in patients with CKD.