Nephron number and its determinants in early life: a primer

Although there is wide variation, humans possess on average 900,000 nephrons per kidney. So far as is known, nephrons cannot regenerate; therefore, an individual’s nephron endowment has profound implications in determining his or her long-term risk of developing chronic kidney disease. Most of the variability in human nephron number is determined early in life. Nephrogenesis is a complex and carefully orchestrated process that occurs during a narrow time window until 36 weeks gestation in humans, and disruption of any part of this sequence may lead to reduced nephron number. In utero, genetic abnormalities, toxic insults, and nutritional deficiencies can each alter final nephron number. Infants born prematurely must continue nephrogenesis in an ex utero environment where there may be multiple threats to successful nephrogenesis. Once the nephron endowment is determined, postnatal factors (such as acute kidney injury or chronic illnesses) can only decrease nephron number. Current techniques for estimating nephron number require an invasive procedure or complete destruction of the tissue, making noninvasive means for counting nephron surgently needed. A better understanding of nephron number and its determinants, particularly during growth and maturation, could allow the development of therapies to support, prolong, or resume nephrogenesis.