Fehr Thomas, Ammann Peter, Garzoni Daniela, Korte Wolfgang, Fierz Walter, Rickli Hans, Wüthrich Rudolf P
Division of Nephrology, Institute of Clinical Chemistry and Hematology, Kantonsspital St. Gallen, Switzerland.
Kidney Int. 2004 Sep;66(3):1206-11. doi: 10.1111/j.1523-1755.2004.00880.x.
Chronic renal failure leads to hyporegenerative anemia due to erythropoietin deficiency. The creatinine clearance and hemoglobin levels, at which anemia treatment with recombinant erythropoietin should be started, are unclear. Interpretation of serum erythropoietin levels in the context of renal insufficiency remains controversial and was addressed in this study.
Three hundred and ninety-five patients were randomly chosen out of over 5000 consecutive patients investigated by coronary angiography at a single center between 1997 and 2001. Laboratory values and clinical information were prospectively collected in a central registry. Serum samples were frozen before angiography and now used to measure serum erythropoietin levels and evaluate the relationship between erythropoietin and hemoglobin levels in the context of various degrees of renal insufficiency.
The patients with the lowest renal function (creatinine clearance <20 mL/min) had significantly lower hemoglobin levels than the group with normal renal function. However, erythropoietin levels were identical indicating a lower set point for erythropoietin regulation. Above a creatinine clearance of 40 mL/min a significant inverse correlation between erythropoietin and hemoglobin levels was observed and described with the formula erythropoietin [U/L]= 2.5 x (140 - hemoglobin [g/L]) or alternatively Deltaerythropoietin (U/L) =-2.5 xDeltahemoglobin (g/L). Below 40 mL/min no significant correlation was found.
A cut-off level for an altered set point of erythropoietin regulation was determined at 40 mL/min creatinine clearance. Above this cut-off hemoglobin negatively regulates erythropoietin. Below the cut-off erythropoietin levels remain stable. Pathophysiologic concepts for this finding and clinical implications in patients with moderate renal failure are discussed.
慢性肾衰竭因促红细胞生成素缺乏导致再生障碍性贫血。开始用重组促红细胞生成素治疗贫血时的肌酐清除率和血红蛋白水平尚不清楚。在肾功能不全的情况下，血清促红细胞生成素水平的解读仍存在争议，本研究对此进行了探讨。
从1997年至2001年在单一中心接受冠状动脉造影检查的5000多名连续患者中随机选取395例患者。实验室值和临床信息前瞻性地收集于一个中央登记处。血清样本在血管造影术前冷冻，现在用于测量血清促红细胞生成素水平，并评估在不同程度肾功能不全情况下促红细胞生成素与血红蛋白水平之间的关系。
肾功能最差（肌酐清除率<20 mL/分钟）的患者血红蛋白水平明显低于肾功能正常的组。然而，促红细胞生成素水平相同，表明促红细胞生成素调节的设定点较低。肌酐清除率高于40 mL/分钟时，观察到促红细胞生成素与血红蛋白水平之间存在显著负相关，并用公式促红细胞生成素[U/L]= 2.5×(140 - 血红蛋白[g/L])或替代公式Δ促红细胞生成素(U/L)= -2.5×Δ血红蛋白(g/L)描述。低于40 mL/分钟时未发现显著相关性。
确定促红细胞生成素调节设定点改变的临界水平为肌酐清除率40 mL/分钟。高于此临界值时，血红蛋白对促红细胞生成素产生负调节。低于临界值时，促红细胞生成素水平保持稳定。讨论了这一发现的病理生理概念以及对中度肾衰竭患者的临床意义。
