Hsu Chi-Yuan, Xie Dawei, Waikar Sushrut S, Bonventre Joseph V, Zhang Xiaoming, Sabbisetti Venkata, Mifflin Theodore E, Coresh Josef, Diamantidis Clarissa J, He Jiang, Lora Claudia M, Miller Edgar R, Nelson Robert G, Ojo Akinlolu O, Rahman Mahboob, Schelling Jeffrey R, Wilson Francis P, Kimmel Paul L, Feldman Harold I, Vasan Ramachandran S, Liu Kathleen D
University of California, San Francisco, San Francisco, California, USA; Kaiser Permanente Northern California, Oakland, California, USA.
University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kidney Int. 2017 Jan;91(1):196-203. doi: 10.1016/j.kint.2016.09.003. Epub 2016 Oct 28.
Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.
很少有研究评估肾小管损伤生物标志物对改善慢性肾脏病（CKD）进展预测的额外作用。因此，我们在前瞻性慢性肾功能不全队列研究的2466名参与者中，在高度标准化的条件下测量了尿肾损伤分子-1、中性粒细胞明胶酶相关脂质运载蛋白、N-乙酰-β-D-氨基葡萄糖苷酶和肝脂肪酸结合蛋白。在9433人年的随访期间，有581例CKD进展病例，定义为新发终末期肾病或估计肾小球滤过率减半。在未调整的Cox比例风险模型中，以尿肌酐标准化的尿损伤生物标志物水平与CKD进展密切相关，最高五分位数与最低五分位数相比，风险比在7至15之间。然而，在控制了基于血清肌酐的估计肾小球滤过率和尿白蛋白/肌酐比值后，没有一个标准化的生物标志物与CKD进展独立相关。没有一个生物标志物能提高基础临床模型的高（0.89）C统计量。因此，在CKD患者中，在基于血清肌酐的估计肾小球滤过率和尿白蛋白/肌酐比值的临床模型中加入肾小管损伤生物标志物并不能改善风险预测。
