Ifudu Onyekachi
Renal Disease Division, SUNY Downstate Medical Center, Brooklyn, New York 11203, USA.
Nephrol Dial Transplant. 2002;17 Suppl 5:38-41. doi: 10.1093/ndt/17.suppl_5.38.
Suboptimal response to recombinant human erythropoietin (rHuEPO) is common in a substantial percentage of patients with chronic kidney disease. Consequently, a higher dose of rHuEPO is needed to attain target haematocrit (Hct) in such patients. Variables that affect rHuEPO dose requirements can be broadly divided into modifiable and immutable characteristics. To date, most of the scientific studies on rHuEPO hyporesponsiveness have focused on modifiable variables that affect rHuEPO response, such as iron status and dialysis adequacy, while exploration of immutable variables has received less attention. This review addresses the key immutable variables that have been suggested as potential determinants of rHuEPO dose requirement. Several investigators, on the basis of analysis of large patient databases, have suggested that diabetic individuals, women, and Black patients on haemodialysis (HD) require a higher dose of rHuEPO than their respective counterparts to attain target Hct. It is unclear whether the observed differences in achieved Hct are due to inherent biological differences in responsiveness to rHuEPO or failure of the investigators to account for modifiable variables that affect rHuEPO dose requirement. Protocol studies with specific a priori hypotheses have failed to confirm some of the findings from these large database analyses. Factors, such as nutritional status, pregnancy, duration of end-stage renal disease, and type of HD vascular access can all potentially modulate response to rHuEPO and should also be considered.
在相当比例的慢性肾脏病患者中,对重组人促红细胞生成素(rHuEPO)反应欠佳很常见。因此,这类患者需要更高剂量的rHuEPO才能达到目标血细胞比容(Hct)。影响rHuEPO剂量需求的变量大致可分为可改变和不可改变的特征。迄今为止,大多数关于rHuEPO低反应性的科学研究都集中在影响rHuEPO反应的可改变变量上,如铁状态和透析充分性,而对不可改变变量的探索则较少受到关注。本综述阐述了一些关键的不可改变变量,这些变量被认为是rHuEPO剂量需求的潜在决定因素。一些研究人员在分析大型患者数据库的基础上提出,糖尿病患者、女性以及接受血液透析(HD)的黑人患者,为达到目标Hct,需要比各自的对照组更高剂量的rHuEPO。目前尚不清楚观察到的Hct差异是由于对rHuEPO反应的内在生物学差异,还是研究人员未能考虑到影响rHuEPO剂量需求的可改变变量。具有特定先验假设的方案研究未能证实这些大型数据库分析中的一些发现。营养状况、妊娠、终末期肾病持续时间以及HD血管通路类型等因素都可能潜在地调节对rHuEPO的反应,也应予以考虑。