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Estimating Nephron Number from Biopsies: Impact on Clinical Studies
Journal of the American Society of Nephrology ( IF 10.3 ) Pub Date : 2022-01-01 , DOI: 10.1681/asn.2021070998
Darya Morozov 1 , Neda Parvin 1 , Mark Conaway 2 , Gavin Oxley 3 , Edwin J Baldelomar 1 , Aleksandra Cwiek 4 , Kim deRonde 5 , Scott C Beeman 6 , Jennifer R Charlton 5 , Kevin M Bennett 1
Affiliation  

Background

Accumulating evidence supports an association between nephron number and susceptibility to kidney disease. However, it is not yet possible to directly measure nephron number in a clinical setting. Recent clinical studies have used glomerular density from a single biopsy and whole kidney cortical volume from imaging to estimate nephron number and single nephron glomerular filtration rate. However, the accuracy of these estimates from individual subjects is unknown. Furthermore, it is not clear how sample size or biopsy location may influence these estimates. These questions are critical to study design, and to the potential translation of these tools to estimate nephron number in individual subjects.

Methods

We measured the variability in estimated nephron number derived from needle or virtual biopsies and cortical volume in human kidneys declined for transplantation. We performed multiple needle biopsies in the same kidney, and examined the three-dimensional spatial distribution of nephron density by magnetic resonance imaging. We determined the accuracy of a single-kidney biopsy to predict the mean nephron number estimated from multiple biopsies from the same kidney.

Results

A single needle biopsy had a 15% chance and virtual biopsy had a 60% chance of being within 20% of the whole-kidney nephron number. Single needle biopsies could be used to detect differences in nephron number between large cohorts of several hundred subjects.

Conclusions

The number of subjects required to accurately detect differences in nephron number between populations can be predicted on the basis of natural intrakidney variability in glomerular density. A single biopsy is insufficient to accurately predict nephron number in individual subjects.



中文翻译:


从活组织检查中估计肾单位数量:对临床研究的影响


 背景


越来越多的证据支持肾单位数量与肾脏疾病易感性之间的关联。然而,目前还不可能在临床环境中直接测量肾单位数量。最近的临床研究使用单次活检的肾小球密度和成像的全肾皮质体积来估计肾单位数量和单肾单位肾小球滤过率。然而,这些来自个体受试者的估计的准确性尚不清楚。此外,尚不清楚样本量或活检位置如何影响这些估计。这些问题对于研究设计以及这些工具估计个体受试者肾单位数量的潜在转化至关重要。

 方法


我们测量了来自针或虚拟活检的估计肾单位数量的变异性,并且人肾的皮质体积因移植而下降。我们对同一个肾脏进行了多次穿刺活检,并通过磁共振成像检查了肾单位密度的三维空间分布。我们确定了单肾活检的准确性,以预测根据同一肾脏的多次活检估计的平均肾单位数量。

 结果


单针活检有 15% 的机会,虚拟活检有 60% 的机会出现在全肾肾单位数量的 20% 以内。单针活检可用于检测数百名受试者的大群体之间肾单位数量的差异。

 结论


准确检测人群之间肾单位数量差异所需的受试者数量可以根据肾小球密度的自然肾内变异性进行预测。单次活检不足以准确预测个体受试者的肾单位数量。

更新日期:2021-12-31
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