Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: a randomized crossover study.
BACKGROUND
Indoxyl sulfate (IS) suppresses erythropoietin (EPO) activity and exerts renal damage. The oral adsorbent AST-120 reduces IS load and has antioxidant and renoprotective properties; however, its roles in the treatment of anemia remain unclear in chronic kidney disease (CKD) patients.


METHODS
Fifty-one Stage 5 predialysis CKD patients with hemoglobin <10 g/dL were randomly assigned to receive two period treatments with AST-120 plus once-monthly administration of continuous EPO receptor activator (CERA, A) and CERA alone (B), with a 4-week washout period in between. Mean changes of serum creatinine, estimated glomerular filtration rate (eGFR) and hemoglobin levels from the baseline were compared between two treatments.


RESULTS
The baseline and postintervention mean creatinine levels were 5.48 and 5.36 mg/dL in the Treatment A, and 5.14 mg/dL and 5.61 g/dL in the Treatment B group, respectively (treatment effect P = 0.025, period effect P = 0.467, carryover effect P = 0.384). The baseline and postintervention mean hemoglobin levels were 9.27 and 10.47 g/dL in the Treatment A, and 9.63 g/dL and 9.54 g/dL in the Treatment B group, respectively (treatment effect P = 0.039, period effect P = 0.001, carryover effect P = 0.060). Use of AST-120 significantly reduced IS and p-cresyl sulfate (PCS) levels. Hierarchical regression showed that eGFR was an independent predictor for hemoglobin after adjustment of serum free IS and PCS levels (B = 0.049, P = 0.005).


CONCLUSIONS
Use of adjuvant AST-120 may improve renal function and hemoglobin levels than use of CERA alone in late-stage CKD patients. The change of eGFR might play an intermediate role between serum IS/PCS and improve hemoglobin levels. The finding offered insight into novel therapeutic strategies of anemia for late-stage CKD patients.
Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan College of Medicine, Chang Gung University, Taoyuan, Taiwan.
I-Wen
IW
Wu
Laboratory for Epidemiology, Department of Health Care Management, Chang Gung University, Taoyuan, Taiwan Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
Kuang-Hung
KH
Hsu
Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chio-Yin
CY
Sun
Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chi-Jen
CJ
Tsai
Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan Division of Nephrology, Taipei Medical University Hospital, Taipei, Taiwan School of Medicine, Taipei Medical University, Taipei, Taiwan.
Mai-Szu
MS
Wu
Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chin-Chan
CC
Lee
D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D002244:Carbon / Q000494:pharmacology* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004357:Drug Synergism; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007200:Indican / Q000037:antagonists & inhibitors; D007668:Kidney / Q000737:chemistry / Q000187:drug effects*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D010087:Oxides / Q000494:pharmacology* / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins
D006454:Hemoglobins; D010087:Oxides; D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols; D000068817:Epoetin Alfa; D002244:Carbon; C040896:AST 120; D007200:Indican
anemia; carbonaceous adsorbents; chronic kidney disease; uremic toxins