Carbonic adsorbent AST-120 retards progression of renal failure by additive effect with ACEI and protein restriction diet.
BACKGROUND
In order to slow the progression of chronic renal failure (CRF), a multimodal approach should be applied if the efficacy is proved. Although compelling evidence of a beneficial effect exists for the use of angiotensin-converting enzyme inhibitors (ACEIs) and low-protein diets, there is little evidence on whether carbon adsorbent has an effect on retardation of the progression of CRF.


METHODS
In experiment 1, we examined whether the oral carbon adsorbent, AST-120, conferred an additive effect with captopril and an 80% restriction diet on the survival rate of 3/4 nephrectomized rats (3/4 NX). The 3/4 NX rats were divided into three groups (C, control, n = 7; AD, captopril (an ACEI) +80% restriction diet (RD), n = 8; and ADK, ACEI + RD + AST-120, n = 8) and survival was observed for 72 weeks. In experiment 2, 3/4 NX rats were divided into four groups (C, control, n = 4; D, 80% restriction diet, n = 4; AD, temocapril + RD, n = 9; and ADK, temocapril + RD + AST-120, n = 9) for the examination of renal function, blood pressure, hematocrit (Ht), serum albumin, and proteinuria every month. We analyzed morphological changes in the kidney at 48 weeks.


RESULTS
In experiment 1, ADK did not improve the survival rate compared with AD, although ADK prolonged the survival significantly compared with C (C vs AD, P = 0.24; C vs ADK, P = 0.0007; AD vs ADK, P = 0.073). In experiment 2, renal function and proteinuria were significantly ameliorated in the ADK group compared with AD at 48 weeks. Concomitantly with the preservation of renal function, pathological indices, including the glomerular sclerosis index and the interstitial fibrosis index, were significantly improved in ADK compared with AD. In the ADK group, Ht and serum albumin did not change over the 48 weeks.


CONCLUSIONS
Administration of AST-120 in addition to an ACEI and a restriction diet preserves renal function independently of blood pressure control, angiotensin II inhibition, and protein restriction in 3/4 NX rats at 48 weeks, but does not improve the survival significantly.
Imai
Enyu
E
Division of Nephrology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. imai@medone.med.osaka-u.ac.jp
Takenaka
Masaru
M
Isaka
Yoshitaka
Y
Moriyama
Toshiki
T
Akagi
Yoshitaka
Y
Kakuchi
Jyunji
J
Fujii
Takashi
T
Ito
Takahito
T
Hori
Masatsugu
M
Horio
Masaru
M
Syoji
Tatsuya
T
Tsubakihara
Yoshiharu
Y
D000327:Adsorption; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure; D002216:Captopril / Q000627:therapeutic use*; D002244:Carbon / Q000378:metabolism / Q000627:therapeutic use*; D018753:Diet, Protein-Restricted; D004359:Drug Therapy, Combination; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000628:therapy*; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D010087:Oxides / Q000378:metabolism / Q000627:therapeutic use*; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
D000806:Angiotensin-Converting Enzyme Inhibitors; D010087:Oxides; D002244:Carbon; C040896:AST 120; D002216:Captopril