Nephron endowment at birth and the pathogenesis of hypertension and chronic renal failure

Summary: It is well established that extensive ablation of renal mass initiates a cycle of accelerated, progressive glomerular injury in remnant kidneys. This process is associated with extreme nephron hypertrophy and hyperfiltration and systemic hypertension. Severe congenital deficiencies in nephron number are also associated with adverse effects on the kidney. In rodents, more subtle reductions in nephron supply are known to advance age‐related glomerular injury. Since intra‐uterine growth retardation is associated with formation of fewer nephrons, the recent observation that low birthweight is associated with increased risk of hypertension in later life raises the possibility that comparatively modest reductions in nephron complement may predispose to hypertension and renal injury over 4–5 decades. the finding of an association between short stature, a marker of low birthweight and nephropathy among type I diabetics also implies that a modest congenital nephron underendowment predisposes to glomerular injury. the numbers of viable nephrons supplied to renal allograft recipients may be critical determinants of late allograft success or failure, since unique circumstances combine to lower the nephron complement to levels akin to those seen in patients with surgical reduction of a solitary kidney, in whom predisposition to hypertension and glomerulosclerosis is evident. This article summarizes recent findings that suggest that congenital nephron endowment is a significant and overlooked factor in the pathogenesis of chronic renal disease and hypertension.