[44] Although, Blantz et al. observed an increase in reactivity of TGF at both 2 and 12 hours after nephrectomy, they Lapatinib nmr did not observe a decrease in sensitivity of TGF at either time-point.[44] Together, these data suggest that there are temporal adaptations in TGF following a reduction in renal mass and alterations in TGF per se may be both an adaptation and a cause for the increase in SNGFR following nephron loss. The age at which nephron mass is reduced appears to affect the characteristics of the subsequent compensatory renal growth and hyperfiltration. GFR appears to increase to a maximal level of ∼70–80% of the value observed before nephrectomy, regardless of the age at which

renal mass is reduced. However, the rate of increase is faster in the young compared with the adult.[47,

48] The degree and duration of compensatory renal growth appears to be greater in the young compared with the adult. Nyengaard et al. showed a greater increase in number of glomerular capillaries and volume of glomeruli when uninephrectomy was performed in the rat neonate compared with the adult rat.[49] Additionally, following uninephrectomy in the rat at 10 days of age, weight of the remaining kidney increased until week 12 following uninephrectomy whereas in the adult rat, maximal growth was achieved by day 7.[50] The mechanisms underlying the greater degree of hypertrophy and the NSC 683864 more rapid increase in GFR in the young are unclear but perhaps Protein Tyrosine Kinase inhibitor a reduction in renal mass in the young ‘forces’ the kidney

to assume a more adult phenotype. Of importance, in human preterm neonates, in whom nephrogenesis has not reached completion owing to their premature birth, accelerated maturation of the kidney has also been observed as indicated by an increase in number of glomerular generations and a decrease in width of the nephrogenic zone.[51] Furthermore, Chevalier et al. demonstrated a greater increase in effective filtration pressure (the drive for glomerular ultrafiltration) between postnatal days 10 and 21 in neonatal guinea pigs that underwent uninephrectomy compared with guinea pigs with intact kidneys,[52] indicating accelerated functional maturation of the kidney with reduced renal mass. This shift towards a more adult phenotype may be compensatory to minimize disturbances in fluid and electrolyte homeostasis. Individuals born with a solitary functioning kidney are presumed to have a congenital nephron deficiency but the time course over which functional and structural adaptations occur is less well understood. In human fetuses, between gestational ages of 20–36 weeks, 11% increase in the volume of the solitary kidney has been observed in almost 90% of fetuses.[53] This increase in size of the solitary kidney is likely due to both hyperplasia and hypertrophy.