Clinical and Pathology Findings Associate Consistently with Larger Glomerular Volume

Abstract

Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities. We studied kidney biopsy specimens from living kidney donors (=2453) and patients who underwent radical nephrectomy for a renal tumor (=780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel-Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen. Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli (<0.001). In both populations, male sex, taller height, obesity, hypertension, and proteinuria associated with larger nonsclerosed glomeruli to a similar extent. In patients with tumors, diabetes, glomerulosclerosis >25%, and interstitial fibrosis >25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume. Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity.

Glomerular Volume and Glomerulosclerosis at Different Depths within the Human Kidney

“…The study sample was an expansion of previously described patients that had undergone a radical nephrectomy for a renal tumor at Mayo Clinic Minnesota from 2000 to 2012. 16 We only studied patients who underwent a complete unilateral nephrectomy for a renal tumor (usually renal cancer) with no metastatic lesions or positive lymph nodes at the time of surgery. Comorbidities do not generally exclude patients from radical nephrectomy unless severe enough to make the surgical risks outweigh the benefits of treating cancer.…”

“…stereological model) 25 and the percentage globally sclerotic glomeruli (%GSG) for each region as previously described (Figure 1). 5,16 The %GSG in each region was classified into four levels (0: ,10%, 1: 10%-25%, 2: 26%-50%, and 3: .50%). 26 Ischemic-appearing (but not sclerosed) glomeruli were identified by capsule thickening, pericapsular fibrosis, and a wrinkled (deflated) tuft.…”

“…26 Ischemic-appearing (but not sclerosed) glomeruli were identified by capsule thickening, pericapsular fibrosis, and a wrinkled (deflated) tuft. 16 The percentage of nonsclerotic glomeruli that were ischemic-appearing (%ischemic glomeruli) was calculated for each region and dichotomized at #5% or .5%. The mean nonsclerotic glomerular volume (referred to as glomerular volume) was calculated using nonischemic and ischemic-appearing glomeruli.…”

“…Further, compensation for age-related glomerulosclerosis is not clearly evident in living humans as glomerular volume, single nephron GFR, and glomerular filtration capacity do not increase with healthy aging. 16,[17][18][19] To investigate the intricate relationship between glomerular volume and glomerulosclerosis across different depths of cortex in living humans, we studied wedge sections of the renal parenchyma in patients who underwent a radical nephrectomy. We had three objectives: to determine whether glomerular volume and its associated clinical characteristics differ by depth of cortex, to determine whether glomerulosclerosis and its associated clinical characteristics differ by depth of cortex, and to determine the association between glomerular pathology at different depths with other biopsy pathology.…”

Nephron Number as Predictor of Corticosteroid Response in Adult Minimal Change Disease

“…Recent seminal work by Denic et al 11 proposed a method to estimate total nephron number by multiplying cortical volume (mm 3 ) measured using contrast-enhanced computed tomography (CT) and glomerular density (number per mm 3 of cortex) measured in a kidney biopsy ( Fig 1 ). The method was applied on images from CT and biopsy material from a large cohort of living kidney donors in the United States.…”