title: Prospective randomized study of the tolerability and efficacy of combination therapy for hypertensive chronic kidney disease: results of the PROTECT-CKD study.
abstract: BACKGROUND
  We conducted a randomized, open-label trial to determine which of the antihypertensive drugs was most beneficial for CKD patients with hypertension in spite of treatment with an angiotensin receptor blocker (ARB).
  
  
  METHODS
  Patients 20-75 years of age who had CKD according to the definition in the K/DOQI Guidelines and hypertension (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg) with the usual dose of an ARB were randomly assigned to receive losartan 50 mg plus 5 mg of the calcium channel blocker amlodipine (CCB group, n = 37), 5 mg of the angiotensin-converting enzyme inhibitor enalapril (ACEI group, n = 36), or 12.5 mg of the thiazide diuretic hydrochlorothiazide (HCTZ group, n = 36). The primary endpoints were changes in blood pressure (BP), ratio of urinary excretion of protein to creatinine (UPCR), tolerability, and eGFR during the 12-month treatment period compared with control period.
  
  
  RESULTS
  There were no significant differences in BP and tolerability between the three groups. The percentage changes in UPCR at 12 months after start of the combination therapy were significantly different in the HCTZ group (-26.3 ± 11.1 %, mean ± SE) and CCB group (+46.7 ± 33.6 %, p < 0.05), while eGFR was significantly lower in the HCTZ group than in the ACEI group or CCB group at 4 months but not at 12 months.
  
  
  CONCLUSIONS
  Addition of diuretics, CCB, or ACEI to ARB was equally effective for the control of hypertension in CKD, while, in terms of urinary excretion of protein, diuretics may be better than CCB.
authors: Apheresis and Dialysis Center, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. matuhiko@z3.keio.jp.
authors: Matsuhiko
authors: M
authors: Hayashi
authors: School of Medicine, Teikyo University, Tokyo, Japan.
authors: Shunya
authors: S
authors: Uchida
authors: School of Medicine, The Jikei University, Tokyo, Japan.
authors: Tetsuya
authors: T
authors: Kawamura
authors: Shuwa General Hospital, Kasukabe, Japan.
authors: Michio
authors: M
authors: Kuwahara
authors: School of Medicine, The University of Tokyo, Tokyo, Japan.
authors: Masaomi
authors: M
authors: Nangaku
authors: Nippon Medical School, Tokyo, Japan.
authors: Yasuhiko
authors: Y
authors: Iino
mesh_terms: D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000009:adverse effects / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000209:etiology; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D006852:Hydrochlorothiazide; D017311:Amlodipine; D004656:Enalapril; D019808:Losartan
keywords: Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; Calcium channel blocker; Chronic kidney disease; Diuretics