Low Nephron Number and Kidney Disease

Reduced nephron endowment and acquired nephron loss increase susceptibility to hypertension and chronic kidney disease (CKD). Low birth weight, prematurity, genetic factors, and adverse prenatal exposures can limit nephron development, whereas aging and kidney injury reduce the number of functioning nephrons after birth. Compensatory glomerular hypertrophy and increased single-nephron filtration can initially preserve overall glomerular filtration rate, but sustained glomerular stress may promote podocyte injury, proteinuria, and glomerulosclerosis. These changes can accelerate nephron loss and create a cycle of progressive kidney damage. Disease susceptibility depends on genetic background and additional metabolic, environmental, and hemodynamic stresses. This review examines the determinants of nephron number, the adaptive and potentially harmful consequences of nephron reduction, and approaches to preserving kidney function. Improving maternal health, reducing harmful exposures, and controlling hypertension and metabolic disease may reduce the long-term consequences of low nephron number.