Glomerular number and size in autopsy kidneys: The relationship to birth weight

Background. In the Southeast United States, African Americans have an estimated incidence of hypertension and end-stage renal disease (ESRD) that is five times greater than Caucasians. Higher rates of low birth weight (LBW) among African Americans is suggested to predispose African Americans to the higher risk, possibly by reducing the number of glomeruli that develop in the kidney. This study investigates the relationships between age, race, gender, total glomerular number (N-glom), mean glomerular volume (V-glom), body surface area (BSA), and birth weight. Methods. Stereologic estimates of N-glom and V-glom were obtained using the physical disector/fractionator combination for autopsy kidneys from 37 African Americans and 19 Caucasians. Results. N-glom was normally distributed and ranged from 227,327 to 1,825,380, an 8.0-fold difference. A direct linear relationship was observed between N-glom and birth weight (r=0.423, P=0.0012) with a regression coefficient that predicted an increase of 257,426 glomeruli per kilogram increase in birth weight (alpha=0.050:0.908). Among adults there was a 4.9-fold range in V-glom , and in adults, V-glom was strongly and inversely correlated with N-glom (r=-0.640, P=0.000002). Adult V-glom showed no significant correlation with BSA for males (r=-0.0150, P=0.936), although it did for females (r=0.606, P=0.022). No racial differences in average N-glom or V-glom were observed. Conclusion. Birth weight is a strong determinant of N-glom and thereby of glomerular size in the postnatal kidney. The findings support the hypothesis that LBW by impairing nephron development is a risk factor for hypertension and ESRD in adulthood.

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) <= 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 different zones of the renal cortex. These findings might reflect processes of aging and susceptibility factors to renal disease.

How many glomerular profiles must be measured to obtain reliable estimates of mean glomerular areas in human renal biopsies?

The objective of this study was to investigate the number of glomerular profiles that are required for accurate estimates of mean profile area in a renal biopsy series. Slides from 384 renal biopsies from one center were reviewed. They contained a median of seven glomerular profiles or of four profiles without sclerosis. Profile areas were measured using stereologic point counting. The true individual mean for each biopsy was calculated and the true population mean for groups of biopsies derived. Individual and population random sample means then were calculated from a random sampling of profiles in each biopsy and were compared with true means for the same biopsies. The effect on the true population means of the entire group of biopsies was also assessed, as the minimum number of glomerular profiles that were required for inclusion was changed. In a single biopsy, random sampling of >= 10 profiles without exclusions and of eight profiles or more without sclerosis reliably estimated the true mean areas. In a group of 30 biopsies, random sampling of five or more glomeruli per biopsy reliably estimated the true population mean. In the aggregate series, inclusion of all 384 biopsies produced the most robust true population mean; the reliability of the estimates decreased as the numbers of eligible biopsies diminished with increasing requisite minimum numbers of profiles per biopsy. We conclude that, while >= 10 profiles might be needed for reliable area estimates in a single biopsy, far fewer profiles per biopsy can suffice when groups of biopsies are studied. In analyses of groups of biopsies, all available biopsies should be used without consideration of the number of glomerular profiles in each. Stipulation of a specific minimum number of glomeruli in each biopsy for inclusion reduces the power of analyses because fewer biopsies are available for evaluation.

Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States

Low nephron number has been related to low birth weight and hypertension. In the southeastern United States, the estimated prevalence of chronic kidney disease due to hypertension is five times greater for African Americans than white subjects. This study investigates the relationships between total glomerular number (N-glom), blood pressure, and birth weight in southeastern African Americans and white subjects. Stereological estimates of N-glom were obtained using the physical disector/fractionator technique on autopsy kidneys from 62 African American and 60 white subjects 30-65 years of age. By medical history and recorded blood pressures, 41 African Americans, and 24 white subjects were identified as hypertensive and 21 African Americans and 36 white subjects as normotensive. Mean arterial blood pressure ( MAP) was obtained on 81 and birth weights on 63 subjects. For African Americans, relationships between MAP, N-glom, and birth weight were not significant. For white subjects, they were as follows: MAP and N-glom ( r = -0.4551, P = 0.0047); Nglom and birth weight ( r = 0.5730, P = 0.0022); MAP and birth weight ( r = -0.4228, P = 0.0377). For African Americans, average N-glom of 961 840 +/- 292 750 for normotensive and 867 358 +/- 341 958 for hypertensive patients were not significantly different ( P = 0.285). For white subjects, average N-glom of 923 377 +/- 256 391 for normotensive and 754 319 +/- 329 506 for hypertensive patients were significantly different ( P = 0.03). The data indicate that low nephron number and possibly low birth weight may play a role in the development of hypertension in white subjects but not African Americans.

Alveolar haemorrhage in anti-glomerular basement membrane disease without detectable antibodies by conventional assays

Anti-glomerular basement membrane (anti-GBM) disease represents the spectrum of disease attributable to circulating anti-GBM antibodies. While active anti-GBM disease in the absence of circulating anti-GBM antibodies has been described, it is considered rare with the use of current routinely available assays. We report four subjects with features consistent with active anti-GBM antibody disease without detectable antibodies by routinely available enzyme linked immunosorbent assay (ELISA) and immunoblot techniques. All were smokers who presented with diffuse alveolar haemorrhage, minimal renal involvement, and undetectable anti-GBM antibodies. Seronegative anti-GBM disease with predominant pulmonary involvement may be more common than previously appreciated and should be part of the differential diagnosis for otherwise unexplained diffuse alveolar haemorrhage. Renal biopsy with immunofluorescent studies should be considered in the diagnostic evaluation of such subjects, including those with idiopathic pulmonary haemosiderosis.