Glomerular number and size variability and risk for kidney disease

PURPOSE OF REVIEW: This review discusses current understandings of variability in glomerular number and size, and the implications for renal health. RECENT FINDINGS: The quantitative microanatomy of the normal human kidney varies widely. Of greatest significance, total nephron number varies at least 13-fold, and several genes and environmental factors that regulate human nephron endowment have been identified. Full or partial deletion of more than 25 genes in mice has been shown to result in renal hypoplasia and, when measured, reduced nephron endowment. Many more will likely be identified. As would be expected, some gene abnormalities increase nephron endowment above that found in control mice. Glomerular volume also varies widely, both between and within kidneys, and increased heterogeneity of glomerular volume within kidneys is associated with risk factors for kidney disease, including birth weight, age, race, body size and hypertension. SUMMARY: 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.