INSIGNEO Institute for In Silico Medicine, The University of Sheffield, Sheffield, UK.
Department of Mechanical Engineering, The University of Sheffield, Sheffield, UK.
Ann Biomed Eng. 2024 Nov;52(11):3098-3112. doi: 10.1007/s10439-024-03573-2. Epub 2024 Jul 5.
Early diagnosis of kidney disease remains an unmet clinical challenge, preventing timely and effective intervention. Diabetes and hypertension are two main causes of kidney disease, can often appear together, and can only be distinguished by invasive biopsy. In this study, we developed a modelling approach to simulate blood velocity, volumetric flow rate, and pressure wave propagation in arterial networks of ageing, diabetic, and hypertensive virtual populations. The model was validated by comparing our predictions for pressure, volumetric flow rate and waveform-derived indexes with in vivo data on ageing populations from the literature. The model simulated the effects of kidney disease, and was calibrated to align quantitatively with in vivo data on diabetic and hypertensive nephropathy from the literature. Our study identified some potential biomarkers extracted from renal blood flow rate and flow pulsatility. For typical patient age groups, resistive index values were 0.69 (SD 0.05) and 0.74 (SD 0.02) in the early and severe stages of diabetic nephropathy, respectively. Similar trends were observed in the same stages of hypertensive nephropathy, with a range from 0.65 (SD 0.07) to 0.73 (SD 0.05), respectively. Mean renal blood flow rate through a single diseased kidney ranged from 329 (SD 40, early) to 317 (SD 38, severe) ml/min in diabetic nephropathy and 443 (SD 54, early) to 388 (SD 47, severe) ml/min in hypertensive nephropathy, showing potential as a biomarker for early diagnosis of kidney disease. This modelling approach demonstrated its potential application in informing biomarker identification and facilitating the setup of clinical trials.
早期肾脏病的诊断仍然是一个未满足的临床挑战,无法实现及时有效的干预。糖尿病和高血压是肾脏病的两个主要病因,常同时出现,只能通过有创活检来区分。在这项研究中,我们开发了一种建模方法来模拟衰老、糖尿病和高血压虚拟人群的动脉网络中的血流速度、容积流量和压力波传播。通过将我们对压力、容积流量和波形衍生指标的预测与文献中关于衰老人群的体内数据进行比较,验证了该模型。该模型模拟了肾脏病的影响,并通过定量校准与文献中关于糖尿病和高血压肾病的体内数据相匹配。我们的研究从肾血流率和血流脉动中提取了一些潜在的生物标志物。对于典型的患者年龄组,糖尿病肾病的早期和严重阶段的阻力指数值分别为 0.69(SD 0.05)和 0.74(SD 0.02)。在高血压肾病的相同阶段也观察到了类似的趋势,范围分别为 0.65(SD 0.07)至 0.73(SD 0.05)。单个患病肾脏的平均肾血流率在糖尿病肾病的早期为 329(SD 40)至 317(SD 38)ml/min,严重阶段为 329(SD 40)至 317(SD 38)ml/min,高血压肾病的早期为 443(SD 54)至 388(SD 47)ml/min,具有作为肾脏病早期诊断的生物标志物的潜力。这种建模方法证明了其在生物标志物识别和临床研究设计中的潜在应用。