Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
MD Anderson Cancer Center, Houston, TX.
Am J Kidney Dis. 2018 Jan;71(1):91-101. doi: 10.1053/j.ajkd.2017.08.010. Epub 2017 Nov 16.
In clinical practice and clinical trials, changes in serum creatinine concentrations are used to evaluate changes in kidney function. It has been assumed that these changes follow a linear pattern when serum creatinine concentration is converted to estimated glomerular filtration rate (eGFR). However, the paradigm that kidney function declines linearly over time has been questioned by studies showing either linear or nonlinear patterns. To verify how this impacts on kidney end points in intervention trials, we analyzed eGFR trajectories in multiple clinical trials of patients with and without diabetes.
Longitudinal observational study.
SETTING & PARTICIPANTS: 6 clinical trials with repeated measurements of serum creatinine.
Patient demographic and clinical parameters.
Probability of nonlinear eGFR function trajectory calculated for each patient from a Bayesian model of individual eGFR trajectories.
The median probability of a nonlinear eGFR decline in all trials was 0.26 (interquartile range, 0.13-0.48). The median probability was 0.28 in diabetes versus 0.09 in nondiabetes trials (P<0.01). The percentage of patients with a >50% probability of nonlinear eGFR decline was generally low, ranging from 19.3% to 31.7% in the diabetes trials and from 15.1% to 21.2% in the nondiabetes trials. In the pooled data set, multivariable linear regression showed that higher baseline eGFR, male sex, diabetes status, steeper eGFR slope, and non-renin-angiotensin-aldosterone-system antihypertensives were independently associated with a greater probability of a nonlinear eGFR trajectory.
Relatively short follow-up and no measured GFR.
In both diabetes and nondiabetes trials, the majority of patients show a more or less linear eGFR decline. These data support the paradigm that in diabetic and nondiabetic kidney disease, eGFR decline progresses linearly over time during a clinical trial period. However, in diabetes, one should take the nonlinearity proportion into account in the design of a clinical trial.
在临床实践和临床试验中，血清肌酐浓度的变化用于评估肾功能的变化。当血清肌酐浓度转换为估算肾小球滤过率（eGFR）时，人们一直认为这些变化呈线性模式。然而，一些研究表明，肾功能随时间的下降呈线性或非线性模式，这一模式受到了质疑。为了验证这如何影响干预试验中的肾脏终点，我们分析了伴有和不伴有糖尿病的患者的多个临床试验中的 eGFR 轨迹。
纵向观察性研究。
6 项具有重复血清肌酐测量的临床试验。
患者的人口统计学和临床参数。
从个体 eGFR 轨迹的贝叶斯模型为每位患者计算非线性 eGFR 函数轨迹的概率。
所有试验中，非线性 eGFR 下降的中位数概率为 0.26（四分位距，0.13-0.48）。糖尿病试验中的中位数概率为 0.28，非糖尿病试验中的中位数概率为 0.09（P<0.01）。具有非线性 eGFR 下降>50%概率的患者百分比通常较低，在糖尿病试验中为 19.3%至 31.7%，在非糖尿病试验中为 15.1%至 21.2%。在汇总数据集中，多变量线性回归显示，较高的基线 eGFR、男性、糖尿病状态、eGFR 斜率较陡和非肾素-血管紧张素-醛固酮系统降压药与非线性 eGFR 轨迹的概率更大独立相关。
随访时间相对较短，且未测量 GFR。
在糖尿病和非糖尿病试验中，大多数患者的 eGFR 下降或多或少呈线性。这些数据支持在糖尿病和非糖尿病肾脏疾病中，eGFR 下降在临床试验期间随时间呈线性进展的模式。然而，在糖尿病中，在临床试验设计中应考虑到非线性的比例。
