Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy.
Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.
Sanaka
Tsutomu
T
Department of Nephrology and Blood Purification, Daini Hospital Medical Center, Tokyo Women's Medical University, Tokyo, Japan. sanakakc@dnh.twmu.ac.jp
Akizawa
Tadao
T
Koide
Keizou
K
Koshikawa
Shozo
S
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D005260:Female; D006400:Hematocrit; D006801:Humans; D007676:Kidney Failure, Chronic / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D010710:Phosphates / Q000097:blood; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood
D001798:Blood Proteins; D010087:Oxides; D010710:Phosphates; D014527:Uric Acid; D002244:Carbon; C040896:AST 120; D002784:Cholesterol; D003404:Creatinine