Renoprotective effects of angiotensin II receptor blocker, candesartan cilexetil, in patients with stage 4-5 chronic kidney disease.
BACKGROUND
To investigate the renoprotective effects and safety of angiotensin II receptor blocker (ARB) for patients with stage 4-5 chronic kidney disease.


METHODS
An ARB, candesartan cilexetil, was administered to 13 patients (ARB group, n = 7; control group, n = 6) with a serum creatinine level of 2.52-5.95 mg/dl whose blood pressure had been maintained below 140/90 mmHg by the use of drugs other than ARBs. Routine measurements were conducted for 48 weeks, and renal survival analysis was observed for up to 3 years with the endpoints being doubling of the serum creatinine level, entry to hemodialysis, or death. The results were compared with those of the control group that was not treated with ARB.


RESULTS
No significant changes were observed in the blood pressure in either group. Proteinuria significantly decreased from 0.95 +/- 0.51 to 0.39 +/- 0.12 g/day (paired t test, P = 0.033) in the ARB group, but did not change in the control group. Creatinine clearance in the control group decreased significantly from 16.2 +/- 5.7 to 10.4 +/- 4.8 ml/min per 1.73 m2 (paired t test, P = 0.011), but did not change in the other group. Thus, the slopes of the reciprocal serum creatinine values became less steep in the ARB group as compared with the control (-0.002 +/- 0.015 vs. -0.025 +/- 0.015 dl/mg per month; unpaired t test, P = 0.019). Kaplan-Meier analysis revealed that ARB exhibited more favorable renal outcome at 3 years (log-rank, P = 0.025). No serious adverse events were noted in the study.


CONCLUSIONS
These results show that ARB reduces proteinuria and protects renal function even in the advanced renal failure.
Tamura
Yoshifuru
Y
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan. xaa@mwe.biglobe.ne.jp.
Kosuga
Masahiro
M
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Yamashita
Masahiro
M
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Tomioka
Satoru
S
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Sasaki
Michiko
M
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Hikita
Tomoyuki
T
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Nakajima
Hideaki
H
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Kojima
Kenichiro
K
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
Uchida
Shunya
S
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan.
D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003404:Creatinine; C077793:candesartan cilexetil