title: Calcium channel blocker inhibition of AGE and RAGE axis limits renal injury in nondiabetic patients with stage I or II chronic kidney disease.
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.
  
  
  OBJECTIVE
  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.
authors: Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Matsudo, Japan.
authors: Tsukasa
authors: T
authors: Nakamura
authors: Eiichi
authors: E
authors: Sato
authors: Nobuharu
authors: N
authors: Fujiwara
authors: Yasuhiro
authors: Y
authors: Kawagoe
authors: Hikaru
authors: H
authors: Koide
authors: Yoshihiko
authors: Y
authors: Ueda
authors: Masayoshi
authors: M
authors: Takeuchi
authors: Sho-ichi
authors: S
authors: Yamagishi
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002908:Chronic Disease; D004095:Dihydropyridines / Q000627:therapeutic use*; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007564:Japan; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000097:blood / Q000188:drug therapy; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D017311:Amlodipine; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine