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Abbreviations
BMP Bone morphogenetic protein
CM Cap mesenchyme
EE Embryonic ectoderm
FGF Fibroblast growth factor
GBM Glomerular basement membrane
GDNF Glial derived neutrophilic factor
hESC Human embryonic stem cell
IM Intermediate mesoderm
iPSC Induced pluripotent stem cell
MM Metanephric mesenchyme
PS Primitive streak RA retinoic acid
UB Ureteric bud
11.1 Introduction
The human kidney is a complex organ that serves a variety of physiological roles,
most of which are essential to sustain life. The functional unit of the kidney, the
nephron, consists of a glomerulus that filters the blood into a complex, highly organ-
ised tubule. The glomerulus is a capillary bundle supported by a mesangial stroma
and covered by a specialised epithelium of podocyte foot processes. The glomerular
capillary endothelium, the podocyte foot processes and the intervening glomerular
basement membrane (GBM) form the glomerular filtration barrier which filters the
blood with a precise selectivity. The tubule consists of multiple segments, including
the proximal tubule (segments 1–3), loop of Henle and distal tubule. Each segment
of the tubule contains unique combinations of specialised epithelial cell types capa-
ble of sensing the composition of the filtrate; responding to molecular signals from
other organs; processing this information to dynamically regulate electrolyte, water
and acid-base homeostasis; and excreting toxic, nitrogenous products of normal
metabolism (Fig. 11.1). The kidney also serves important endocrine functions, as
the primary site of erythropoietin production and 1α hydroxylation (and hence acti-
vation) of vitamin D precursors (Lacombe et al. 1991 ; Nykjaer et al. 1999 ).
Developmentally, the kidney is the third excretory organ to form in the human
embryo (the metanephros) and the only one to persist into postnatal life (Little
2015 ). Nephrons arise from a self-renewing population of nephron progenitor cells
called the cap mesenchyme (Little and McMahon 2012 ). In contrast to mice and rats
where nephrogenesis occurs postnatally, the human kidney generates all of its neph-
rons by 36-week gestation (Hinchliffe et al. 1991 ). Individual nephron endowment
is highly variable (between 0.2 and 2.7 × 10^6 nephrons per person) and positively
correlates with birth weight and gestational age (Keller et al. 2003 ; Hoy et al. 2003 ;
Hughson et al. 2003 ; McNamara et al. 2008 ). Nephron loss with age can be
M.H. Little et al.