T. Samuel

Determinants of Glomerular Volume in Different Cortical Zones of the Human Kidney

Enlarged glomerular size is a feature of focal segmental glomerulosclerosis, obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The distribution of glomerular volumes within different cortical zones and glomerular volume alterations with age and obesity may contribute to understanding the evolution of these diseases. We analyzed the distributions of volumes of individual glomeruli in the superficial, middle, and juxtamedullary cortex of normal human kidneys using the disector/Cavalieri method. Volumes (V(glom)) of 720 nonsclerotic glomeruli (30 per kidney, 10 per zone) were estimated in autopsy kidneys of 24 American men, 12 aged 20 to 30 yr and 12 aged 51 to 69 yr. Black and white individuals were represented equally. The range of individual V(glom) within subjects varied from two- to eight-fold. There were no significant zonal differences in V(glom) in the young or those with body surface area (BSA) < or = 2.11 m(2). In contrast, superficial glomeruli in the older age group, in those with BSA > 2.11 m(2), and in white subjects were significantly larger than juxtamedullary glomeruli. Black subjects tended toward larger V(glom) than white subjects, and this difference was significant and most marked in the juxtamedullary zone and independent of age, BSA, and glomerular number. There is a wide range in individual V(glom) in adults. BSA, race, and age independently influence V(glom) in different zones of the renal cortex. These findings might reflect processes of aging and susceptibility factors to renal disease.

Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index.

BACKGROUND Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). METHODS The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. RESULTS There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. DISCUSSION In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.

Glomerular Volume and Clinicopathologic Features Related to Disease Severity in Renal Biopsies of African Americans and Whites in the Southeastern United States

CONTEXT African Americans have a 4-fold greater risk than whites for developing end-stage renal disease. Glomerulomegaly, possibly related to obesity, has been identified in high-risk populations and is suggested to be a marker for end-stage renal disease risk. OBJECTIVE To investigate differences in glomerular size and patient clinical characteristics at the time of renal biopsy for the major diseases contributing to end-stage renal disease. DESIGN Mean glomerular tuft volumes were estimated by the Weibel-Gomez method (1964) in native renal biopsies of 203 African American and 100 white patients 18 years of age and older by point counting on a stereologic grid. Glomerulosclerosis was graded on individual glomeruli from 0 to 4, and a glomerular sclerosis index was calculated for each biopsy. Relationships between the mean volume of nonsclerotic glomeruli, age, sex, race, sclerosis index, cortical fibrosis, estimated glomerular filtration rate, body mass index, and disease diagnosis were analyzed. RESULTS Racial differences in mean volume of nonsclerotic glomeruli and body mass index were not significant in any disease category, and African Americans had more severe disease as determined by sclerosis index, cortical fibrosis, and estimated glomerular filtration rate only in focal segmental glomerulosclerosis. For all patients, increased sclerosis index and cortical fibrosis and lower estimated glomerular filtration rate were best predicted by increased age (P < .001). CONCLUSIONS For approximately the same severity of disease, African Americans were 10 years or more younger than whites with the difference being seen in all disease categories except membranous glomerulonephritis and diabetes. Glomerulomegaly relative to whites was not a distinguishing feature of African American renal biopsies.

Applicability of the glomerular size distribution coefficient in assessing human glomerular volume: the Weibel and Gomez method revisited

Changes in glomerular volume (Vglom) play an important role in the initiation and progression of various glomerulopathies. Estimation of Vglom in the normal kidney provides baseline values for studies of glomerular hypertrophy in disease. The traditional model‐based method of Weibel and Gomez is widely applied to estimate Vglom in clinical biopsy specimens. Assumptions of glomerular size distribution and shape required by this method are potential sources of bias that have not been verified. We evaluated the applicability of the glomerular size distribution coefficient in estimating Vglom in human kidneys. Vglom of 720 non‐sclerotic glomeruli in histologically normal kidneys of 24 males (20–69 years) was estimated by the unbiased disector/Cavalieri approach. Accurate glomerular diameters were calculated from Cavalieri estimates of Vglom assuming glomerular sphericity. The coefficients of variation (CV) of glomerular diameters were compared with the corresponding values of the size distribution coefficient predicted by the Weibel and Gomez method. Mean (SD) glomerular diameter was 201 (28) mm (range 110–276 mm). The CV of glomerular diameter within each kidney ranged from 4.9 to 14.6%. Corresponding glomerular size distribution coefficients predicted by the formula of Weibel and Gomez ranged from 1.00 to just 1.03. The value of the size distribution coefficient required by the Weibel and Gomez technique when estimating Vglom in normal human kidneys is remarkably constant. This is despite large variations in Vglom. Future studies should examine the extent of bias introduced by the glomerular shape assumptions of this method.

Distribution of volumes of different glomeruli within individuals: Findings in kidneys at coronial autopsy

Disease Jeff S Coombes, Amanda Crawford, Robert G Fassett, 3 Dale A Kunde, Iain K Robertson, Madeleine J Ball, Dominic P Geraghty School of Human Movement Studies, University of Queensland, Brisbane, Queensland, AUSTRALIA School of Human Life Sciences, University of Tasmania, Launceston, Tasmania, AUSTRALIA 3 Royal Brisbane and Womens Hospital, Brisbane, Queensland, AUSTRALIA Project funded by the Clifford Craig Medical Research Trust (C Prosser Green Endowment)