This observation suggests initial hyperfiltration in the smaller kidneys, which could not be sustained after 7 years, likely due to on-going nephron loss, as reflected in more proteinuria, more antihypertensive drug use, a greater degree of glomerulosclerosis, and a 55% increased risk for transplant failure by 2 years in the low DKW/RBW group. The authors conclude that

incompatibility between graft and recipient weight is an independent predictor of long-term graft BI 6727 survival. These data strongly support the contention that nephron “dose”, relative to the recipient’s needs, should be an important consideration Inhibitors,research,lifescience,medical in organ allocation. Strategies for Optimization of Nephron Number Evidence is emerging that clinically feasible interventions, Inhibitors,research,lifescience,medical at a critical period of nephron development, can rescue nephron number and impact later life blood pressure. In rats, adequate postnatal nutrition, achieved by cross-fostering growth-restricted pups onto normal lactating females at birth, was found to restore nephron Inhibitors,research,lifescience,medical number and abrogate development of subsequent

hypertension.73 Similarly, supplementation of maternal low-protein diet with glycine, urea, or alanine during gestation normalized nephron number in all rat offspring, although blood pressure was only normalized in those supplemented with glycine.71 Postnatal hypernutrition in normal rats was found to increase nephron number by 20%, but these rats went on to develop hypertension and glomerulosclerosis with age, likely Inhibitors,research,lifescience,medical as a result of obesity.72 Vitamin A deficiency has been shown to reduce nephron number in a dose-dependent manner, but encouragingly a single dose of retinoic acid, administered during early nephrogenesis,

was enough to restore nephron numbers to levels of control Inhibitors,research,lifescience,medical rats in pups exposed to a low-protein diet in utero.30,161 Interestingly, administration of ouabain was also found to abrogate the effect of serum starvation and low-protein diet on nephron development in vitro and in vivo again in rats.162 Although still preliminary, taken together, these studies suggest possible all mechanisms whereby nephron numbers could be rescued if at-risk fetuses were identified early enough. Likewise, avoidance or judicious use of drugs during pregnancy, that are known to impact kidney development as described above, are another means to optimize fetal nephron number.21–30,32–34,36,163–165 CONCLUSION The idea that low nephron number may have a long-term impact on an individual’s later life risk of hypertension and renal disease has now entered the main stream. Until we learn more about developmental programming in nephrology, LBW should be used as the most useful current clinical surrogate for low nephron number and inborn risk of hypertension and renal disease. It is not surprising that nephron number and LBW are not the whole story, however.