Evaluation of Short-Term Changes in Serum Creatinine Level as a Meaningful End Point in Randomized Clinical Trials

被引:52
作者
Coca, Steven G. [1 ]
Zabetian, Azadeh [3 ]
Ferket, Bart S. [2 ]
Zhou, Jing [2 ]
Testani, Jeffrey M. [3 ]
Garg, Amit X. [4 ]
Parikh, Chirag R. [3 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, Inst Healthcare Delivery Sci, New York, NY 10029 USA
[3] Yale Univ, Sch Med, Dept Internal Med, Program Appl Translat Res, New Haven, CT 06510 USA
[4] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2016年 / 27卷 / 08期
基金
美国国家卫生研究院;
关键词
ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; SODIUM-SENSITIVE HYPERTENSION; ATRIAL-NATRIURETIC-PEPTIDE; RECEPTOR BLOCKER USE; HEART-FAILURE; CARDIAC-SURGERY; URINARY BIOMARKERS; ISCHEMIC-INJURY; DISEASE;
D O I
10.1681/ASN.2015060642
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Observational studies have shown that acute change in kidney function (specifically, AKI) is a strong risk factor for poor outcomes. Thus, the outcome of acute change in serum creatinine level, regardless of underlying biology or etiology, is frequently used in clinical trials as both efficacy and safety end points. We performed a meta-analysis of clinical trials to quantify the relationship between positive or negative short-term effects of interventions on change in serum creatinine level and more meaningful clinical outcomes. After a thorough literature search, we included 14 randomized trials of interventions that altered risk for an acute increase in serum creatinine level and had reported between-group differences in CKD and/or mortality rate >= 3 months after randomization. Seven trials assessed interventions that, compared with placebo, increased risk of acute elevation in serum creatinine level (pooled relative risk, 1.52; 95% confidence interval, 1.22 to 1.89), and seven trials assessed interventions that, compared with placebo, reduced risk of acute elevation in serum creatinine level (pooled relative risk, 0.57; 95% confidence interval, 0.44 to 0.74). However, pooled risks for CKD and mortality associated with interventions did not differ from those with placebo in either group. In conclusion, several interventions that affect risk of acute, mild to moderate, often temporary elevation in serum creatinine level in placebo-controlled randomized trials showed no appreciable effect on CKD or mortality months later, raising questions about the value of using small to moderate changes in serum creatinine level as end points in clinical trials.
引用
收藏
页码:2529 / 2542
页数:14
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