Role for "uremic toxin" in the progressive loss of intact nephrons in chronic renal failure.
We studied the effect on the progression of glomerular sclerosis of two different experimental maneuvers, peritoneal dialysis and oral adsorbent, which remove circulating substances in different fashions. Munich-Wistar rats with established glomerular sclerosis, verified by renal biopsy analysis at seven weeks after subtotal nephrectomy, were treated for four weeks with either peritoneal dialysis (PD) or oral charcoal adsorbent (AST-120). Treatment was initiated at eight weeks. Rats were paired in treatment and control groups according to the similarity in the degree of sclerosis determined at biopsy with a minimum of 50 glomeruli analyzed. Systolic blood pressure and BUN and creatinine clearance, measured at seven to eight weeks, were not different among groups. In Group 2 rats, PD was performed with 1.5% dextrose for eight one-hour cycles, six days per week, while Group 1 control rats had zero indwelling time of the dialysate. Group 4 rats received AST-120, an oral adsorbent charcoal, mixed 5% by weight with standard rat chow and given ad libitum from 8 to 12 weeks after subtotal nephrectomy, while control Group 3 rats received only rat chow. Whole kidney GFR at 12 weeks was significantly higher in Group 2 PD versus Group 1 control (0.50 +/- 0.08 vs. 0.30 +/- 0.05 ml/min, P less than 0.05). There was no statistical difference for BUN and whole kidney creatinine or inulin clearance in Group 4 AST-120 treated versus Group 3 control rats. Light microscopic studies in autopsy specimens revealed that both PD and AST-120 attenuated progression of glomerular sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Motojima
M
M
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
Nishijima
F
F
Ikoma
M
M
Kawamura
T
T
Yoshioka
T
T
Fogo
A B
AB
Sakai
T
T
Ichikawa
I
I
D000818:Animals; D002244:Carbon / Q000627:therapeutic use; D016923:Cell Death; D003404:Creatinine / Q000378:metabolism; D006984:Hypertrophy; D007444:Inulin / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood / Q000473:pathology*; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D008657:Metabolic Clearance Rate; D009392:Nephrectomy; D009399:Nephrons / Q000473:pathology*; D010087:Oxides / Q000627:therapeutic use; D010530:Peritoneal Dialysis; D051381:Rats; D011919:Rats, Inbred Strains; D012598:Sclerosis; D016060:Sorption Detoxification; D014511:Uremia / Q000097:blood* / Q000628:therapy
D010087:Oxides; D002244:Carbon; D007444:Inulin; C040896:AST 120; D003404:Creatinine