The metanephric human kidney precursor forms 28 days after fertilization when ureteric bud (UB) branches from the mesonephric duct (MD).
In the next few days, renal mesenchyme (RM) condenses from intermediate mesoderm around the ureteric bud tip, or ampulla.
Ultimately, the ureteric bud lineage will form urothelium, from the renal pelvis to bladder trigone, and collecting ducts.
Some renal mesenchyme cells undergo an epithelial conversion, through aggregation and lumen formation to form nephrons, whereas others form interstitial fibroblasts.
The first 6 to 10 ureteric bud branch generations remodel, forming the pelvis and calyces, whereas the final 6 to 9 generations form collecting ducts.
In humans, early ureteric bud divisions are not associated with nephrogenesis. The first nephrons are formed at 8 weeks.
As the ampullae divide between 8 and 15 weeks, one branch continues to be associated with the already-attached nephron, whereas the other induces a new nephron.
Although weeks branching decelerates after 15 weeks, nephrons are induced up to 32 to 36 wk.
Between 15 and 20 weeks, four to seven nephrons are serially induced by each nondividing ampulla; each nephron is transiently attached to an ampulla but then shifts its linkage to the connecting piece of the next-formed nephron. This results in "arcades" of nephrons.
From 20 until 32 to 36 weeks, elongating ampullae induce nephrons in series.
Formation of a nephron always occurred near an ampulla, and murine RM did not form nephrons in organ culture when the UB was physically removed.
It is now clear that renal mesenchyme and ureteric bud induction and differentiation depend on mutual interactions mediated by growth factors and matrix molecules, with transcription factors controlling expression of these genes.
Potter estimated that a human kidney contained 35 x 104 nephrons at 20 weeks gestation and 82 x 104 at 40 weeks. More recent human studies suggest, however, that the majority of nephrons form in the final third of gestation and that final nephron number can be highly variable: Mean numbers range between 64 x 104 and 130 x 104.
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