Combination therapy with angiotensin-converting enzyme inhibitor and oral adsorbent of uremic toxins can delay the appearance of glomerular sclerosis and interstitial fibrosis in established renal failure.
OBJECTIVE
Angiotensin II plays a central role in the progression of chronic renal failure (CRF), and administration of angiotensin-converting enzyme inhibitor (ACEI) in rats delays the progression of CRF. However, ACEI has little effect on CRF progression in rats with established CRF. We therefore examined whether combination therapy with ACEI and oral adsorbent for uremic toxins in the gastrointestinal tract has the desired effect.


METHODS
Rats subjected to subtotal nephrectomy were given enalapril at 20 mg/kg (n = 10, group E), AST-120 at 5 g (n = 10, group A), enalapril and AST-120 together at the same doses (n = 10, group EA), or no treatment (n = 10, group C) 8 weeks after the operation. The substances were administered in 100 g rat chow. All animals were pair-fed, and all were killed after 8 weeks of pair-feeding.


RESULTS
Body weight did not differ between groups during the study. Blood pressure at week 8 was significantly lower in groups E and EA than in groups C and A (p < 0.05). Urinary protein excretion level and renal plasma flow rate at week 8 were significantly less in groups E and EA than in group C (p < 0.05, p < 0.01). The glomerular filtration rate at week 8 was significantly higher in group EA than in group C (p < 0.05). The glomerular sclerosis index and interstitial fibrosis area at week 8 were significantly less in group EA than in group C (p < 0.01).


CONCLUSIONS
ACEI and AST-120 in combination can delay progression of established CRF in rats by inhibiting the appearance of glomerular sclerosis and interstitial fibrosis.
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. kokada@med.nihon-u.ac.jp
Kazuyoshi
K
Okada
Erina
E
Okawa
Hiroshi
H
Shibahara
Takashi
T
Maruyama
Noriaki
N
Maruyama
Koichi
K
Matsumoto
Susumu
S
Takahashi
D000327:Adsorption; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001806:Blood Urea Nitrogen; D002244:Carbon / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology*; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000517:prevention & control; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000517:prevention & control; D010087:Oxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016060:Sorption Detoxification; D014511:Uremia / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010087:Oxides; D004656:Enalapril; D002244:Carbon; C040896:AST 120; D003404:Creatinine