Abstract
The number of nephrons is a key determinant of blood pressure regulation and chronic kidney disease (CKD) progression. Although traditional estimates suggest approximately one million nephrons per kidney, modern stereological approaches reveal substantial variability, that is influenced by ethnicity, birth weight, and other early life factors. This review evaluates the century-long evolution of nephron number research, variations across racial and ethnic groups, and explores how factors, such as body size, aging, and lifestyle risks, influence nephron endowment. Techniques for nephron quantification, from design-based stereology to emerging in vivo imaging, are also discussed. Recent research suggests markedly lower nephron counts in Japanese populations, especially among individuals with hypertension or CKD. The autopsy-based investigation in the present study included 27 middle-aged to older Japanese men (9 normotensive, 9 hypertensive, and 9 participants with CKD) who underwent dissector-fractionator stereology to quantify non-sclerosed glomeruli. Normotensive men had an average of approximately 640,399 non-sclerosed glomeruli. In contrast, the hypertensive participants had approximately 392,108 non-sclerosed glomeruli and those with CKD had only 268, 043. These findings underscore the potential influence of limited nephron reserves on hypertension and CKD in Japan. Current evidence suggests that nephron number estimates can guide therapeutic decisions and predict CKD outcomes, while advancements in real-time imaging offer potential avenues for non-invasive nephron assessment. Collectively, these developments highlight the central importance of nephron quantity in nephrology and enable targeted interventions aimed at preserving kidney function and mitigating the CKD burden.