Kidney structural characteristics based on a kidney biopsy and contrast‐enhanced computed tomography in healthy living kidney donors

Abstract

The demands for kidney transplantations are increasing, and so is the number of live kidney donors (LKDs). Recent studies show that LKDs have an increased risk of developing end‐stage renal disease compared with healthy non‐donors. However, the knowledge about factors predicting renal disease in kidney donors is sparse. Some evidence points to increased glomerular sclerosis and kidney fibrosis, as well as a low number of glomeruli as associated with a worse renal outcome. This methodological study investigated that which estimates are obtainable with a standard kidney biopsy taken from the donated kidney during the transplantation, and a standard contrast‐enhanced computed tomography (CT) in kidney donors. CT‐scans were used to obtain total volume of the kidney and kidney cortex using the Cavalieri estimator and 2D‐nucleator. Glomerular number density in the biopsies was estimated by a model‐based method, and was multiplied by total cortex volume in order to estimate the total number of glomeruli in the kidney. Glomerular volume was estimated by the 2D‐nucleator and a model‐based stereological technique. Kidney fibrosis (point‐counting), glomerular sclerosis (evaluation of glomerular profiles), and arteriole dimensions (2D‐nucleator) were also estimated in the biopsy sections from the donated kidney. Various studies have attempted to identify predictors of renal outcome in LKDs. There is no consensus yet, and further studies are needed to elucidate if and how the estimates described in this study are associated with renal outcome in LKDs.

Prediction of Renal Function in Living Kidney Donors and Recipients of Living Donor Kidneys Using Quantitative Histology

“…20 Cortex volume (V cortex ) was then determined using the Cavalieri estimator based on the slice thickness and number of images between the sampled images as previously explained in detail. 21 Determination of cortex volume was performed in the same way in CT- and MRI-based angiographies. The volumes of both the donated and nondonated kidney cortices were calculated with the donated kidney representing the recipient and the nondonated kidney representing the donor at the time of follow-up.…”

“…Approximately 15 serial sections were cut at 2-μm thickness and stained with hematoxylin and eosin, periodic acid-Schiff, and Masson trichrome. The quantitative histological evaluation was used to evaluate the biopsies as described previously in detail 21 using an Olympus BX50 light microscope (Olympus Denmark, Ballerup, Denmark) equipped with a prior motorized stage, an Olympus DP70 digital camera interfaced to a PC with commercially available newCAST software (Visiopharm, Hørsholm, Denmark). Patient characteristics were unknown to the investigator analyzing the biopsies.…”

Introduction to a special issue on kidney development and disease

“…Some of these stereological techniques are described in step‐by‐step detail in a review article authored by myself and John's long‐standing collaborator and Monash colleague Prof. Jane Black, with the aim of making these gold standard quantitative approaches accessible to a wider group of researchers (Sutherland, Vojisavljevic, & Black, 2020). Stereology collaborator Prof. Jens Nyengaard presents in this issue a proof‐of‐concept application of the design‐based nucleator technique for estimating nephron number in human kidneys, using CT scanning and biopsy samples (Nielsen et al, 2020). Collaborator Prof. Norbert Gretz also reports on a new technique, with a description of ethyl cinnamate‐based tissue clearing protocols for the optimization of 3D imaging of paraffin‐embedded tissue (Brenna et al, 2020); great potential to bring old tissue archives back to life.…”

Filtering the good from the bad: A focus on kidney development and disease to celebrate John Bertram's long‐standing career in anatomy and renal research

“…In this Special Issue, Megan Sutherland, Danica Vojisavljevic, and I have written a step‐by‐step guide to stereological analyses of glomeruli that we routinely use in our laboratories (Sutherland, Vojisavljevic, & Black, 2020); these techniques we have developed in close collaboration with John Bertram and the members of his research group. John's close colleague Jens Nyengaard, also internationally recognized for his expertise in stereology and a regular contributor to The Anatomical Record , has also contributed an article to this Special Issue (Nielsen et al, 2020).…”

“…The development of these techniques has the potential to make a big impact on the fields of renal biology and clinical medicine, especially as accurate in vivo techniques are developed. Recent advances in these methodologies, feature highly in this Special Issue, with contributions from Norbert Gretz (Brenna et al, 2020), Kevin Bennett (Parvin, Charlton, Baldelomar, Derakhshan, & Bennett, 2020), and Jens Nyengaard (Nielsen et al, 2020) specifically relating to contemporary kidney imaging and quantitation.…”