From Nephron Number to Global Health

In 1988, in a seminal paper, Brenner and colleagues proposed that the numbers of nephrons acquired in utero may be a factor that determines an individual's lifelong risk of kidney disease. The hypothesis posited that a kidney with fewer nephrons would have a reduced filtration surface, a reduced capacity to excrete sodium, and a limited capacity to compensate for additional kidney injury and nephron loss. These factors increase the risk of high blood pressure and kidney dysfunction. Potential clinical markers for such risk include preterm birth, small-for-gestational-age birth and low birth weight, which have been associated with reduced nephron numbers and with population-level risk of kidney disease and kidney failure. As such, these birth circumstances are now recognized in mainstream guidelines on the identification of individuals at risk of kidney disease. Importantly, these circumstances depend to a large degree on maternal health in pregnancy, which, in turn, depends on many social and structural determinants of health. Optimization of maternal, fetal, and child health through achievement of the sustainable development goals therefore offers an opportunity to mitigate the growing global burden of kidney disease through supporting healthy fetal kidney development and minimizing the accumulation of additional kidney stressors throughout life. Awareness of the importance of nephron number for individual kidney health could translate into strategies to promote global kidney health.