He Xiang, Moore Jason, Shabir Shazia, Little Mark A, Cockwell Paul, Ball Simon, Liu Xiang, Johnston Atholl, Borrows Richard
Department of Clinical Pharmacology, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
Transplantation. 2009 Feb 15;87(3):384-92. doi: 10.1097/TP.0b013e31819004a1.
To date, efforts have focused on assessing estimated glomerular filtration rate (eGFR) formulae against measured GFR. However, a more appropriate clinical gold standard is one conveying a defined clinical disadvantage. In renal transplantation, these measures are mortality and graft failure.
The Long Term Efficacy and Safety Surveillance database was used to analyze 1344 renal transplant recipients. eGFR was assessed 6 months posttransplantation with the following formulae: Cockcroft-Gault; Walser; Nankivell; abbreviated modification of diet in renal disease (aMDRD); MDRD7; Rule's refitted MDRD; and Mayo Clinic. The outcome measures were mortality and graft failure.
Although eGFR was statistically associated with subsequent mortality and graft failure in the Cox model (irrespective of which eGFR formula was used), the clinical utility of eGFR was moderate at best in predicting subsequent mortality and graft failure. No clinically relevant or statistically significant difference was discernable between formulae, with a maximum area under the receiver operating characteristic curve of 0.63 and 0.61 for 3- and 5-year mortality, respectively, and 0.66 and 0.60 for 3- and 5-year graft failure, respectively. Serum creatinine used in isolation displayed similar predictive utility, and no improvement was seen by investigating the change in creatinine or eGFR between 6 and 12 months.
In summary, seven eGFR equations showed similar and limited utility in predicting mortality and graft failure after renal transplantation. This has important implications for the management of renal transplant recipients and the use of an eGFR as a surrogate endpoint in clinical trials.
迄今为止,相关工作主要集中在根据实测肾小球滤过率(GFR)评估估算肾小球滤过率(eGFR)公式。然而,一个更合适的临床金标准是反映明确临床劣势的指标。在肾移植中,这些指标是死亡率和移植失败。
利用长期疗效与安全性监测数据库分析了1344例肾移植受者。在移植后6个月使用以下公式评估eGFR:Cockcroft-Gault公式;Walser公式;Nankivell公式;简化肾病饮食(aMDRD)公式;MDRD7公式;Rule改良的MDRD公式;以及梅奥诊所公式。观察指标为死亡率和移植失败。
尽管在Cox模型中eGFR与随后的死亡率和移植失败存在统计学关联(无论使用哪种eGFR公式),但eGFR在预测随后的死亡率和移植失败方面的临床效用充其量只能说是中等。各公式之间未发现临床相关或统计学上的显著差异,3年和5年死亡率的受试者工作特征曲线下最大面积分别为0.63和0.61,3年和5年移植失败的受试者工作特征曲线下最大面积分别为0.66和0.60。单独使用血清肌酐显示出类似的预测效用,且研究6至12个月期间肌酐或eGFR的变化未见改善。
总之,七个eGFR方程在预测肾移植后死亡率和移植失败方面显示出相似且有限的效用。这对肾移植受者的管理以及在临床试验中使用eGFR作为替代终点具有重要意义。