title: Re-establishment of erythropoietin responsiveness in end-stage renal failure following renal transplantation.
abstract: Re-establishment of erythropoietin (EPO) secretion following renal transplantation is poorly understood. The development of sensitive EPO radioimmunoassay has enabled further study of this phenomenon. Forty-one adult patients were studied during the first 16 weeks following renal transplantation. Twenty six received cyclosporin monotherapy and 15 also received prednisolone and azathioprine. Serum creatinine, haemoglobin (Hb), ferritin and EPO were assayed pre-operatively, daily for 1 week, weekly for 1 month, and fortnightly to 16 weeks. An expected EPO value, for any Hb level, was derived by linear regression analysis in 144 patients with iron deficiency anemia. An observed to expected ratio (O/E) was calculated, a value of 1.0 implying appropriate responsiveness. Hb increased from 8.6 +/- 2.0 (SD) to 12.3 +/- 2.1 g/dl (p < 0.001) over 16 weeks, an increase unaffected by ferritin status. Mean EPO concentration increased during the first week with a peak at day 4 (22.1 +/- 13.3 to 44.6 +/- 40.0 mu/ml, p < 0.05), a change apparent only in patients with immediate graft function (24 cases). There was no correlation between EPO and Hb pre-operatively; however a significant inverse relationship was established by week 16 (r = -0.404, p < 0.02). The median O/E ratio (0.22) at baseline increased progressively to 1.0 at 16 weeks (p < 0.001); ratios were significantly greater in the immediate versus delayed function group throughout (p < 0.05). In the former group an O/E ratio of 1.0 was reached at 10 weeks when mean serum creatinine was 142 +/- 48 mumol/l. Patients with poor ongoing renal function (9 cases, serum creatinine > 250 mumol/l at 16 weeks) had impaired Hb recovery (10.1 +/- 1.6 vs 12.7 +/- 2.0 g/dl at 16 weeks, p < 0.05). EPO values were not different in those patients but median O/E ratios were significantly depressed (p < 0.05) throughout, the maximum O/E ratio being 0.75. Recovery of renal function is accompanied by a beneficial Hb response driven by EPO synthesis in the transplant. The O/E ratio provides a useful index to assess EPO responsiveness. Appropriate secretion was achieved during the first 4 months and optimized by immediate and satisfactory graft function.
authors.affiliation: Department of Renal Medicine, St. James's University Hospital, Leeds, UK.
authors.forename: R F
authors.initials: RF
authors.lastname: Jeffrey
authors.forename: R G
authors.initials: RG
authors.lastname: Kendall
authors.forename: P
authors.initials: P
authors.lastname: Prabhu
authors.forename: D R
authors.initials: DR
authors.lastname: Norfolk
authors.forename: E J
authors.initials: EJ
authors.lastname: Will
authors.forename: A M
authors.initials: AM
authors.lastname: Davison
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D005293:Ferritins / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011863:Radioimmunoassay
chemical_list: D006454:Hemoglobins; D007166:Immunosuppressive Agents; D004921:Erythropoietin; D005293:Ferritins; D003404:Creatinine