Estimating Nephron Number from Biopsies: Impact on Clinical Studies. Issue 1 (January 2022) - Morozov, Darya
Significance Statement: Total nephron number is a potentially important marker of susceptibility to kidney disease. This work demonstrates the effect of spatial variation in glomerular density on the estimation of whole-kidney nephron number from biopsy. We show here that a single needle biopsy does not accurately reflect whole-kidney nephron number on an individual level. However, in studies with a large number of subjects or samples, needle biopsies can reveal differences in nephron number between populations. There is a need for new technologies to directly measure nephron number at an individual level. Visual Abstract: Abstract : 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.