Jeffrey R F, Kendall R G, Prabhu P, Norfolk D R, Will E J, Davison A M
Department of Renal Medicine, St. James's University Hospital, Leeds, UK.
Clin Nephrol. 1995 Oct;44(4):241-7.
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.
肾移植后促红细胞生成素（EPO）分泌的重新建立情况目前了解甚少。灵敏的EPO放射免疫测定法的发展使得对这一现象能够进行进一步研究。对41例成年患者在肾移植后的头16周进行了研究。26例接受环孢素单一疗法，15例还接受了泼尼松龙和硫唑嘌呤。术前、术后第1周每天、第1个月每周以及直至第16周每两周测定血清肌酐、血红蛋白（Hb）、铁蛋白和EPO。通过对144例缺铁性贫血患者进行线性回归分析得出任何Hb水平对应的预期EPO值。计算观察值与预期值之比（O/E），该值为1.0表示反应性适当。16周内Hb从8.6±2.0（标准差）升至12.3±2.1 g/dl（p<0.001），这一升高不受铁蛋白状态的影响。EPO平均浓度在第1周升高，第4天达到峰值（从22.1±13.3升至44.6±40.0 μ/ml，p<0.05），这种变化仅在移植肾功能立即恢复的患者（24例）中明显。术前EPO与Hb之间无相关性；然而到第16周时建立了显著的负相关关系（r = -0.404，p<0.02）。基线时的O/E比值中位数（0.22）逐渐升至16周时的1.0（p<0.001）；整个过程中，移植肾功能立即恢复组的比值显著高于延迟恢复组（p<0.05）。在前一组中，当平均血清肌酐为142±48 μmol/l时，在第10周达到O/E比值1.0。移植肾功能持续不佳的患者（9例，16周时血清肌酐>250 μmol/l）Hb恢复受损（16周时为10.1±1.6 vs 12.7±2.0 g/dl，p<0.05）。这些患者的EPO值并无差异，但O/E比值中位数在整个过程中显著降低（p<0.05），最大O/E比值为0.75。肾功能的恢复伴随着移植中由EPO合成驱动的有益的Hb反应。O/E比值为评估EPO反应性提供了一个有用的指标。在头4个月内实现了适当的分泌，并通过移植肾功能立即且良好的恢复得以优化。
