Shih L Y, Huang J Y, Lee C T
Department of Internal Medicine, Chang Gung University, Chang Gung Memorial Hospital, Taipei, Taiwan.
J Am Soc Nephrol. 1999 Feb;10(2):315-22. doi: 10.1681/ASN.V102315.
Erythroid progenitor growth, the serum hormones that regulate erythropoiesis, and the effect of patient's serum on the growth of normal erythroid progenitors were assessed in eight patients with end-stage renal disease (ESRD) and erythrocytosis. All patients were male and had been on maintenance dialysis, they had a hematocrit >50% and/or a red blood cell count >6 x 10(12)/L and an arterial oxygen saturation >95%. Four had acquired cystic disease of the kidney (ACDK), and four other non-ACDK patients did not have known causes of secondary erythrocytosis after appropriate investigations and long-term follow-up. The methylcellulose culture technique was used to assay the erythroid progenitor (BFU-E/CFU-E) growth. Serum erythropoietin (EPO) and insulin-like growth factor I (IGF-I) levels were measured by RIA. Paired experiments were performed to determine the effects of 10% sera from ESRD patients and control subjects on normal marrow CFU-E growth. The numbers of EPO-dependent BFU-E in marrow and/or blood of patients with ESRD and erythrocytosis were higher than those of normal controls. No EPO-independent erythroid colonies were found. Serum EPO levels were constantly normal in one patient and elevated in three patients with ACDK; for non-ACDK patients, EPO levels were normal or low in two patients and persistently increased in one, but fluctuated in the remaining one on serial assays. There was no correlation between serum EPO levels and hematocrit values. The serum IGF-I levels in patients with ESRD and erythrocytosis were significantly increased compared with normal subjects or ESRD patients with anemia. We found an inverse correlation between serum EPO and IGF-I levels. Sera from patients with ESRD and erythrocytosis exhibited a stimulating effect on normal marrow CFU-E growth. The stimulating effect of sera from patients who had a normal serum EPO level and an elevated IGF-I level could be partially blocked by anti-IGF-I. The present study suggests that IGF-I plays an important role in the regulation of erythropoiesis in patients with ESRD and erythrocytosis who did not have an increased EPO production.
对8例终末期肾病（ESRD）合并红细胞增多症患者的红系祖细胞生长、调节红细胞生成的血清激素以及患者血清对正常红系祖细胞生长的影响进行了评估。所有患者均为男性，一直在接受维持性透析，其血细胞比容>50%和/或红细胞计数>6×10¹²/L，动脉血氧饱和度>95%。4例患有获得性肾囊肿病（ACDK），另外4例非ACDK患者在经过适当检查和长期随访后，没有已知的继发性红细胞增多症病因。采用甲基纤维素培养技术检测红系祖细胞（BFU-E/CFU-E）生长。通过放射免疫分析法测定血清促红细胞生成素（EPO）和胰岛素样生长因子I（IGF-I）水平。进行配对实验以确定ESRD患者和对照受试者的10%血清对正常骨髓CFU-E生长的影响。ESRD合并红细胞增多症患者骨髓和/或血液中依赖EPO的BFU-E数量高于正常对照组。未发现不依赖EPO的红系集落。1例患者血清EPO水平持续正常，3例ACDK患者血清EPO水平升高；对于非ACDK患者，2例患者EPO水平正常或降低，1例持续升高，但另1例在系列检测中波动。血清EPO水平与血细胞比容值之间无相关性。与正常受试者或贫血的ESRD患者相比，ESRD合并红细胞增多症患者的血清IGF-I水平显著升高。我们发现血清EPO与IGF-I水平呈负相关。ESRD合并红细胞增多症患者的血清对正常骨髓CFU-E生长具有刺激作用。血清EPO水平正常且IGF-I水平升高的患者血清的刺激作用可被抗IGF-I部分阻断。本研究表明，IGF-I在EPO产生未增加的ESRD合并红细胞增多症患者的红细胞生成调节中起重要作用。
