Skupien Jan, Warram James H, Smiles Adam M, Stanton Robert C, Krolewski Andrzej S
Research Division, Joslin Diabetes Center, Boston, MA
Department of Medicine, Harvard Medical School, Boston, MA.
Diabetes Care. 2016 Dec;39(12):2262-2269. doi: 10.2337/dc16-0950. Epub 2016 Sep 19.
The patterns of estimated glomerular filtration rate (eGFR) decline to end-stage renal disease (ESRD) in patients with type 1 diabetes has not been conclusively described. Decline could be linearly progressive to ESRD but with a variable rate. Conversely, decline may be linear but interrupted by periods of plateaus or improvements.
This observational study included 364 patients with type 1 diabetes attending the Joslin Clinic who developed ESRD between 1991 and 2013. We retrieved serum creatinine measurements from clinic visits or research examinations up to 24 years (median 6.7 years) preceding the onset of ESRD. Using serial measurements of serum creatinine to estimate renal function (eGFR), we used regression-based spline methods and a data smoothing approach to characterize individual trajectories of eGFR over time for the 257 patients with five or more data points.
The rate of eGFR decline per year ranged widely, from -72 to -2 mL/min/1.73 m (median -8.5). The trajectories, as characterized with linear regression-based spline models, were linear or nearly so for 87% of patients, accelerating for 6%, and decelerating for 7%. Smoothed trajectories evaluated by a Bayesian approach did not significantly depart from a linear fit in 76%.
The decline of eGFR in type 1 diabetes is predominantly linear. Deviations from linearity are small, with little effect on the expected time of ESRD. A single disease process most likely underlies renal decline from its initiation and continues with the same intensity to ESRD. Linearity of renal decline suggests using slope reduction as the measure of effectiveness of interventions to postpone ESRD.
1型糖尿病患者估计肾小球滤过率（eGFR）下降至终末期肾病（ESRD）的模式尚未得到确切描述。下降可能呈线性进展至ESRD，但速率可变。相反，下降可能是线性的，但会被平台期或改善期打断。
这项观察性研究纳入了364例在1991年至2013年间于乔斯林诊所就诊并发展为ESRD的1型糖尿病患者。我们从ESRD发病前长达24年（中位数6.7年）的门诊就诊或研究检查中获取血清肌酐测量值。利用血清肌酐的系列测量值来估计肾功能（eGFR），我们采用基于回归的样条方法和数据平滑方法来描述257例有五个或更多数据点的患者eGFR随时间的个体轨迹。
每年eGFR下降速率差异很大，从-72至-2 mL/min/1.73 m²（中位数-8.5）。基于线性回归的样条模型所描述的轨迹，87%的患者呈线性或近乎线性，6%的患者加速下降，7%的患者减速下降。采用贝叶斯方法评估的平滑轨迹在76%的情况下与线性拟合无显著差异。
1型糖尿病患者eGFR的下降主要是线性的。与线性的偏差很小，对ESRD的预期时间影响不大。单一疾病过程很可能是肾脏从发病开始下降的基础，并以相同强度持续至ESRD。肾脏下降的线性表明可将斜率降低作为衡量干预措施推迟ESRD有效性的指标。
