The process of renal morphogenesis provides a basis for understanding
the causes of kidney aplasia, dysplasia, and hypoplasia, which together
are the second leading cause of chronic renal insufficiency in children.
It also may provide insight into congenital nephron underendowment,
which may not present as overt renal disease in childhood but has
been linked with adult-onset diseases such as hypertension and end-stage
The permanent mammalian kidney or metanephros forms following
the development of transient excretory precursors, the pronephros
and the mesonephros. The pronephros, the first urinary system in vertebrates,
appears at 22 days of human embryogenesis in the cervical region
(Fig. 464-1).3 Each pronephric nephron consists of
a simple glomus that filters the blood through tubular epithelial cords
called nephrotomes.4 While the pronephros is not functional
in mammals and eventually regresses, it must form or there will
be complete renal (metanephric) agenesis.5 The mesonephros,
the second urinary system in vertebrates, appears at about the fourth
week of human gestation, immediately caudal to the pronephric ducts
(Fig. 464-1).3 Unlike the pronephros,
the mesonephros is functional in mammals during embryogenesis. While most
of the mesonephros ultimately regresses, portions of the mesonephric
duct in males form the vas deferens, the seminal vesicle, and part
of the epididymis, while some mesonephric tubules persist as testicular
efferent ductules. In females, the mesonephros usually degenerates
completely due to the presence of müllerian inhibitory substance.
Mammalian embryonic kidney development. Mammalian kidney
development proceeds in a craniocaudal direction beginning with
formation of the pronephros, then the mesonephros, and finally the
metanephros, or the adult kidney. Although transitory, the pronephros
and mesonephros are necessary for development of the metanephros.
The metanephros begins when the ureteric bud invades the metanephric
The metanephros, the definitive kidney in mammals, first appears in
the fifth week of human gestation in the region of the hindlimb
(Fig. 464-1).3 Paired densities
of mesenchyme, termed metanephric mesenchyme, secrete molecules
that induce an epithelial outgrowth from the mesonephric duct called
the ureteric bud, which then invades the mesenchyme. Once these
2 tissues make contact, they begin a series of reciprocal signaling events
leading to formation of the metanephric kidney. The mesenchymal
cells induce the ureteric duct to elongate and branch fairly dichotomously
(Fig. 464-2) to
ultimately form the collecting ducts, pelvis, and ureter. Signals from
the ureteric bud tips in turn stimulate the mesenchymal cells to condense
and then convert into nephron epithelia (Fig.
the developing nephrons and ureteric bud tree is stromal mesenchyme,
which develops into the interstitial tissues of the adult kidney.
There is also an extensive vascular network that develops in the
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