Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
University of Cambridge, Cambridge, UK.
Health Technol Assess. 2024 May;28(24):1-54. doi: 10.3310/YTBT4172.
Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure.
To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency.
A prospective multicentre observational cohort study (the 'SONAR' study).
Seventeen haemodialysis centres in the UK.
Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created.
Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings.
Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months.
A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset ( = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data.
Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit.
This trial is registered as ISRCTN36033877 and ISRCTN17399438.
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in ; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.
动静脉瘘被认为是血液透析提供的最佳选择，但多达 30%的瘘管无法成熟或早期失败。
评估进行随机对照试验的可行性，该试验旨在检查通过早期有效的抢救干预措施来提高动静脉瘘的通畅率，即在瘘管失功之前进行多普勒超声监测，是否可以改善动静脉瘘的长期通畅率。
前瞻性多中心观察性队列研究（“SONAR”研究）。
英国 17 个血液透析中心。
计划进行动静脉瘘造瘘术的终末期肾病成年患者，且患者同意参与研究。
参与者在造瘘术后 2、4、6 和 10 周时接受多普勒超声监测其动静脉瘘，临床团队对超声监测结果不知情。
根据超声监测的代表性静脉直径和血流参数（腕部动静脉瘘：≥4mm 和>400ml/min；肘部动静脉瘘：≥5mm 和>500ml/min），判断造瘘术后第 10 周时瘘管是否成熟。采用早期超声扫描数据的多变量逻辑回归模型，预测 10 周内动静脉瘘未成熟和 6 个月内瘘管失败的情况。
研究期间共创建了 333 个动静脉瘘（47.7%为腕部，52.3%为肘部）。2 周时，37 个（11.1%）动静脉瘘已经闭塞（血栓形成），但到第 10 周时，333 个创建的动静脉瘘中有 219 个（65.8%）成熟（60.4%为腕部，67.2%为肘部）。未成熟的瘘管血流速度和静脉直径持续较低。在未能成熟的瘘管中，模型可以最优地使用第 4 周的扫描数据构建，影响腕部动静脉瘘成熟失败的最重要变量是瘘管静脉直径和血流速度（阳性预测值 60.6%，95%置信区间 43.9%至 77.3%），而肘部动静脉瘘的阻力指数和血流速度则最为重要（阳性预测值 66.7%，95%置信区间 48.9%至 84.4%）。与未成熟不同，这两种模型对瘘管成熟的预测都更可靠[腕部和肘部的阴性预测值分别为 95.4%（95%置信区间 91.0%至 99.8%）和 95.6%（95%置信区间 91.8%至 99.4%）]。对原始 SONAR 队列的一个子集（SONAR-12M 研究）进行的额外随访和建模表明，6 个月时原发性、辅助原发性和继发性动静脉瘘通畅率分别为 76.5%、80.7%和 83.3%。瘘管静脉大小、血流速度和阻力指数可识别 6 个月时的原发性通畅失败，其预测能力与 10 周时的动静脉瘘成熟失败相似，但腕部的置信区间较宽（阳性预测值 72.7%，95%置信区间 46.4%至 99.0%），肘部的阳性预测值（阳性预测值 57.1%，95%置信区间 20.5%至 93.8%）。此外，这些模型在识别辅助原发性和继发性通畅失败方面的表现不佳，可能是因为在超声监测中被认为有风险的一部分瘘管在没有使用早期超声数据的情况下，成功地进行了后续的抢救干预，而没有发生失功。
虽然早期超声可以非常有效地预测瘘管成熟和长期通畅率，但它对识别那些可能仍不成熟或在 6 个月内失败的瘘管的能力仅为中等。结合优于预期的瘘管通畅率（通过成功的抢救进一步提高），我们估计，一项比较早期超声引导干预与标准护理的随机对照试验需要至少 1300 个瘘管，只能给患者带来很小的益处。
该试验在英国临床试验注册中心注册（注册号：ISRCTN86062006），全文发表于；第 28 卷，第 24 期。有关进一步的奖励信息，请访问英国国家卫生与保健研究所（NIHR）资助和奖励网站。
