Estimation of nephron number in living humans by combining unenhanced computed tomography with biopsy-based stereology

Abstract

Methods for estimating nephron number in a clinical setting may be useful for predicting renal outcomes. This study aimed to establish such a method using unenhanced computed tomography (CT) and biopsy-based stereology. Patients or living kidney donors simultaneously subjected to enhanced and unenhanced CT examinations were randomly assigned to development and validation groups. The enhanced CT-measured arterial phase and the venous phase images of kidneys were regarded as the true values for cortical volume and parenchymal volume, respectively. Linear multiple regression analysis was used to create models for estimating cortical volume using explanatory variables including unenhanced CT-measured parenchymal volume. Nephron number was determined as the product of cortical volume and the glomerular density in biopsies of donors. Five equations for estimating cortical volume were created and verified. In donors, estimated nephron number by unenhanced CT was consistent with that by enhanced CT, with minimal errors in all models (636–655 ± 210–219 vs. 648 ± 224 × 103/kidney). Clinical characteristics combined with parenchymal volume did not improve the equation over parenchymal volume alone. These results support the feasibility of estimating nephron number by a combination of unenhanced CT and biopsy-based stereology, with a possible application for renal disease patients who are often not suitable for contrast media.

Nephron Number and Time to Remission in Steroid-Sensitive Minimal Change Disease

“…To overcome this, we recently established an equation to accurately estimate kidney cortical volume from kidney parenchymal volume based on 3-dimensionally constructed unenhanced computed tomographic images. 23 In this study, we estimated the total number of nephrons per kidney in patients with MCD using unenhanced CT and biopsy-based stereology to examine the effects of individual differences in nephron number on the clinical phenotype, including the therapeutic response to corticosteroids.…”

Dietary Protein Intake and Single-Nephron Glomerular Filtration Rate

“…Finally, the study cohort included Japanese subjects with normal kidney function, and the generalization of the results require further studies. Recently, in our latest study, we proposed a new method to estimate nephron number using unenhanced computed tomography and biopsy-based stereology [45]. Therefore, further study on a larger number of subjects, including CKD patients who are often unsuitable for contrast media administration, is expected with this new method.…”

Magnetic resonance imaging accurately tracks kidney pathology and heterogeneity in the transition from acute kidney injury to chronic kidney disease

“…The large range in nephron number is present at birth 10 with considerable loss of nephrons over a lifetime 11,12 . Our knowledge of nephron number and loss is derived from studies at autopsy using unbiased estimates of glomerular number or from larger studies that use glomerular density from a kidney biopsy and cortical volume from imaging [12][13][14][15][16] . A barrier in clinical research is the lack of tools to assess nephron number and thereby stratify patients enrolling in AKI clinical trials.…”