Uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats.
BACKGROUND
Uremic toxins have been shown to promote glomerular hypertrophy. The present study was performed to elucidate the relation between uremic toxins and tubulointerstitial changes.


METHODS
Sixty male Sprague-Dawley rats underwent 2/3 nephrectomy (Nx; n = 30) and 4/5 Nx (n = 30). Experiments were initiated 2 weeks after surgery, and were performed over an 8-week period. Half of each group (Nx-A) was administered 1 g/day of an oral carbonaceous adsorbent, AST-120, with pair-feeding, and the other half (Nx-C) served as controls. All rats were sacrificed at week 8 after a clearance study.


RESULTS
The shortest diameter of proximal tubules (PTD) and interstitial fibrosis area (IFA) at week 8 in 2/3 Nx-A rats was significantly decreased compared to that in 2/3 Nx-C rats (similar body weights, systolic blood pressures, glomerular filtration rates, and urinary protein excretion levels). The values of PTD and IFA, glomerular filtration rate and urinary protein excretion level at week 8 in 4/5 Nx-A rats were significantly decreased compared to those in 4/5 Nx-C rats (similar body weights and systolic blood pressures).


CONCLUSIONS
Administration of AST-120 minimized the appearance of proximal tubular hypertrophy and interstitial fibrosis, and subsequently prevented the occurrence of proteinuria and decreased renal function. The present study indicates that uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats.
Okada
Kazuyoshi
K
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. kokada@med.nihon-u.ac.jp
Matsumoto
Koichi
K
Takahashi
Susumu
S
D000818:Animals; D002244:Carbon / Q000008:administration & dosage*; D005355:Fibrosis / Q000473:pathology; D005919:Glomerular Filtration Rate; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010087:Oxides / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014118:Toxins, Biological / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism* / Q000473:pathology
D010087:Oxides; D014118:Toxins, Biological; D002244:Carbon; C040896:AST 120