Janmaat Cynthia J, van Diepen Merel, Krediet Raymond T, Hemmelder Marc H, Dekker Friedo W
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden.
Department of Nephrology, Academic Medical Center, Amsterdam.
Clin Epidemiol. 2017 Apr 10;9:217-230. doi: 10.2147/CLEP.S127695. eCollection 2017.
Current clinical guidelines recommend to initiate dialysis in the presence of symptoms or signs attributable to kidney failure, often with a glomerular filtration rate (GFR) of 5-10 mL/min/1.73 m. Little evidence exists about the optimal kidney function to start dialysis. Thus far, most observational studies have been limited by lead-time bias. Only a few studies have accounted for lead-time bias, and showed contradictory results. We examined the effect of GFR at dialysis initiation on survival in chronic kidney disease patients, and the role of lead-time bias therein. We used both kidney function based on 24-hour urine collection (measured GFR [mGFR]) and estimated GFR (eGFR).
A total of 1,143 patients with eGFR data at dialysis initiation and 852 patients with mGFR data were included from the NECOSAD cohort. Cox regression was used to adjust for potential confounders. To examine the effect of lead-time bias, survival was counted from the time of dialysis initiation or from a common starting point (GFR 20 mL/min/1.73 m), using linear interpolation models.
Without lead-time correction, no difference between early and late starters was present based on eGFR (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.81-1.3). However, after lead-time correction, early initiation showed a survival disadvantage (HR between 1.1 [95% CI 0.82-1.48] and 1.33 [95% CI 1.05-1.68]). Based on mGFR, the potential survival benefit for early starters without lead-time correction (HR 0.8, 95% CI 0.62-1.03) completely disappeared after lead-time correction (HR between 0.94 [95% CI 0.65-1.34] and 1.21 [95% CI 0.95-1.56]). Dialysis start time differed about a year between early and late initiation.
Lead-time bias is not only a methodological problem but also has clinical impact when assessing the optimal kidney function to start dialysis. Therefore, lead-time bias is extremely important to correct for. Taking account of lead-time bias, this controlled study showed that early dialysis initiation (eGFR >7.9, mGFR >6.6 mL/min/1.73 m) was not associated with an improvement in survival. Based on kidney function, this study suggests that in some patients, dialysis could be started even later than an eGFR <5.7 and mGFR <4.3 mL/min/1.73 m.
当前临床指南建议在出现肾衰竭相关症状或体征时开始透析，此时肾小球滤过率（GFR）通常为5 - 10 mL/min/1.73 m²。关于开始透析的最佳肾功能，几乎没有证据。到目前为止，大多数观察性研究都受到领先时间偏倚的限制。只有少数研究考虑了领先时间偏倚，且结果相互矛盾。我们研究了透析开始时的GFR对慢性肾病患者生存的影响，以及领先时间偏倚在其中的作用。我们同时使用了基于24小时尿液收集的肾功能（实测GFR [mGFR]）和估算GFR（eGFR）。
从NECOSAD队列中纳入了1143例透析开始时具有eGFR数据的患者和852例具有mGFR数据的患者。采用Cox回归对潜在混杂因素进行校正。为了研究领先时间偏倚的影响，使用线性插值模型从透析开始时间或一个共同起点（GFR 20 mL/min/1.73 m²）计算生存情况。
在未校正领先时间的情况下，基于eGFR，早期和晚期开始透析的患者之间没有差异（风险比[HR] 1.03，95%置信区间[CI] 0.81 - 1.3）。然而，在校正领先时间后，早期开始透析显示出生存劣势（HR在1.1 [95% CI 0.82 - 1.48]和1.33 [95% CI 1.05 - 1.68]之间）。基于mGFR，未校正领先时间时早期开始透析的潜在生存获益（HR 0.8, 95% CI 0.62 - 1.03）在校正领先时间后完全消失（HR在0.94 [95% CI 0.65 - 1.34]和1.21 [95% CI 0.95 - 1.56]之间）。早期和晚期开始透析的时间相差约一年。
领先时间偏倚不仅是一个方法学问题，在评估开始透析的最佳肾功能时也具有临床影响。因此，校正领先时间偏倚极其重要。考虑到领先时间偏倚，这项对照研究表明早期透析开始（eGFR >7.9，mGFR >6.6 mL/min/1.73 m²）与生存改善无关。基于肾功能，本研究表明在某些患者中，透析甚至可以在eGFR <5.7和mGFR <4.3 mL/min/1.73 m²时更晚开始。
