title: Effects of erythropoietin and aminoguanidine on red blood cell deformability in diabetic azotemic and uremic patients.
abstract: Impaired red blood cell-deformability (RBC-df) is noted in patients with diabetes and may play a role in the pathogenesis of microvasculopathy and nephropathy. We report the effects of erythropoietin (EPO) alone and combined with aminoguanidine (AG) for 1 year on RBC-df in predialysis patients (P-DPs) with renal insufficiency and in end-stage renal disease (ESRD) patients on maintenance hemodialysis (DPs). Nine P-DPs who received EPO 50 U/kg by subcutaneous injection 3 times per week are compared with 5 P-DPs treated without EPO (mean serum creatinine 4.1 +/- 0.1 versus 4.2 +/- 0.6 mg/dL, respectively). Twelve DPs (Kt/V = 1.5 +/- 0.1) were studied. Six DPs received AG 200 mg/every other day by mouth and EPO 50 U/kg by intravenous (IV) injection, and 6 DPs received EPO (50 U/kg) and placebo and served as control. RBC-df improved significantly in 9 P-DPs treated with EPO at 6 months (from 2.7 +/- 0.1 to 1.6 +/- 0.2, P = 0.005). This positive effect was sustained at 12 months (P = 0.005); there was no change in RBC-df in P-DPs receiving usual care without EPO. RBC-df improved significantly and progressively at 6 and 12 months in DPs treated with EPO and AG (from 2.2 +/- 0.2 to 1.8 +/- 0.2; P = 0.01; 1.2 +/- 0.1; P = 0.001, respectively); there was limited improvement in RBC-df in DPs treated with EPO and placebo. We conclude that EPO treatment significantly improved RBC-df in diabetic P-DPs, but EPO alone has no significant effect on RBC-df after 12 months in diabetic DPs. The combination of EPO and AG restores RBC-df to near-normal levels in diabetic DPs. We speculate that the effect of EPO on RBC-df seen in P-DPs and DPs is related to increased synthesis and influx of new and younger RBCs. AG may confer protection of RBCs in DPs by blocking advanced glycosylated end-product (AGE) formation.
authors.affiliation: Renal Diseases Division, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA. crownbrown@aol.com
authors.forename: C D
authors.initials: CD
authors.lastname: Brown
authors.forename: Z H
authors.initials: ZH
authors.lastname: Zhao
authors.forename: L L
authors.initials: LL
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: deGroof
authors.forename: E A
authors.initials: EA
authors.lastname: Friedman
mesh_terms: D019540:Area Under Curve; D003928:Diabetic Nephropathies / Q000097:blood / Q000628:therapy*; D004359:Drug Therapy, Combination; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006146:Guanidines / Q000008:administration & dosage*; D006400:Hematocrit; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood / Q000628:therapy*
chemical_list: D006146:Guanidines; D004921:Erythropoietin; C004479:pimagedine