Several studies have shown that total nephron (glomerular) number varies widely in normal human kidneys. Whereas the studies agree that average nephron number is approximately 900,000 to 1 million per kidney, numbers for individual kidneys range from approximately 200,000 to >2.5 million. Several studies have shown loss of glomeruli due to age-related glomerulosclerosis. The rates of loss vary among individuals depending upon blood pressure, diseases affecting the kidney, and other attributes of health, but most of the variation in nephron number is present at birth and is therefore developmentally determined. For example, in a relatively small study of nephron number in 15 children <3 months of age, we found that nephron number ranged from approximately 250,000 to 1.1 million. Given that no new nephrons are formed in human kidneys after approximately 36 weeks' gestation, much interest has focused on renal function and health in individuals born with relatively low nephron endowment. Several studies have reported a direct correlation between birth weight and nephron number and an indirect association between nephron number and blood pressure. Associations between low birth weight and cardiovascular disease, including hypertension, have also been widely reported. This report provides an update on our current knowledge of human nephron number and the associations with adult health and disease.

Data from several human populations indicate that the quantitative microanatomy of the human kidney varies considerably: total glomerular number varies at least 13-fold, mean glomerular volume varies up to seven-fold and the volumes of individual glomeruli within single kidneys can vary as much as eight-fold. Human glomerular number, size and size distribution are being found to correlate with risk factors for kidney disease. The genetic and fetal environmental regulators of nephrogenesis, and thereby nephron endowment, are being rapidly identified and will provide the bases for future clinical interventions. In contrast, the molecular regulation of glomerular size remains unclear.

Despite similar nephron numbers, a common genetic constitution, and even in relation to current body size, African Americans have larger V(glom) than Senegalese subjects. This may mark exposure to environmental stressors or hereditary traits concentrated in the population's relocation to North America.

There was a considerable variation in IGV within kidneys of Senegalese males at autopsy. The heterogeneity of IGV was increased in association with low nephron number and increased BSA, with more pronounced effects in older subjects.

We have demonstrated considerable variability in the volumes of different glomeruli in given individuals (individual glomerular volume: IGV) in a stereologic study of kidneys at forensic autopsy performed to investigate sudden or unexpected death in people without manifest kidney disease. We review some important associations of IGV by subject characteristics and by ethnic groups. IGVs were measured by the Cavalieri method in 30 glomeruli in each of 111 adult males who belonged to 4 ethnic groups, i.e. US Whites, African-Americans, Africans from Senegal, and Australian Aborigines. Correlations of pooled IGV values with certain subject characteristics were evaluated in the US Whites. Pooled IGV data were compared in subjects across the 4 ethnic groups. In US Whites, mean IGV and its variance were greater with higher age, lower nephron number, lower birth weight, and with gross obesity, hypertension and cardiovascular death. In comparisons by ethnic group, mean IGV and IGV ranges were higher in African-Americans and Australian Aborigines than in US Whites and African Senegalese subjects. We conclude that glomerular enlargement with volume heterogeneity marks more advanced age, relative nephron deficiency, lower birth weight, obesity, hypertension, and advanced cardiovascular disease. The findings in African-Americans and Australian Aborigines suggest that larger IGVs and volume heterogeneity might mark populations with accentuated susceptibility to hypertension and kidney disease, but the data need to be further examined in the context of the determining characteristics defined in the US Whites.