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Introduction to Pediatric Nephrology

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Introduction to
Pediatric Nephrology
Dr.Fahad Gadi, MD
Pediatrics Demonstrator
King Abdulaziz University
Rabigh Medical School
Kidney ontogenesis
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The embryological development of the
kidney is a long and continuous
process which begins in the 3rd week
and is completed by about 34-35
weeks of fetal life.
Kidney organogenesis is
characterised by 3 distinct and
linked stages: pronephros,
mesonephros and metanephros.
Kidney ontogenesis
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In humans, the first two are
transient structures with
little excretory capacity but
they are important for the
appropriate development of the
metanephros, which is the
direct precursor of the adult
kidney.
METANEPHROS
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The final stage of the kidney is the
differentation of the metanephros and
arise from the ureteric bud and the
metanephric blastema (mesenchyme).
The renal pelvis, major and minor
calyces and terminal collecting duct
are formed by the 10-13th wks of ges.
After morphogenesis each kidney
contains approx a million nephrons.
Renal development
Pronephros
aorta
nefrotomy
Przednercze
3 t.Еј.
4-8 t.Еј.
Mesonephros
przewГіd
Wolffa
ЕљrГіdnercze
5 t.Еј.
Metanephros
stek
pД…czek
moczowodowy
blastema nerki
ostatecznej
Nerka
ostateczna
Antenatal Period
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The most common cause is physiologic
dilation.
Metanephric urine production begins at 8
weeks, even before ureteral canalization is
complete.
Transient obstruction with hydronephrosis
occurs.
Embryology
MOLECULAR ASPECT
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The development of the metanephric
kidney depends on inductive
interaction between the ureteric
bud (UB) and the metanephric
mesenchyme (MM).
A large number of genes have been
found to be crucial during kidney
development.
Nephrons
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In the fetus at 36 weeks’ gestation there is an
adult complement of nephrons- approx. one
million
All further growth of the kidney is via
hyperplasia mainly in the tubules.
Fetal kidney
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Nephrogenesis is completed between the
28 and 36th gestational week in the human,
the renal tissue and particularly the tubular
cells continue to develop postnatally.
Several of the major transporters in the
tubular epithelial cells undergo postnatal
maturation
Fetal kidney
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Outer cortical glomeruli are relatively
underperfused compared with inner
cortical glomeruli.
Following birth, renal perfusion to
superficial cortical nephrons rises
compared with deeper glomeruli
Fetal kidney
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Angiotensin-converting enzyme inhibitors
and angiotensin-receptor antagonists impair
nephrogenesis and so are contraindicated in
pregnancy
Production of urine
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Production of urine starts at the age of
10-12 weeks of gestation:
1. very dilute urine
2. small amount of urine
Fetal urine is a major constituent of
amniotic fluid and urinary flow rate
increases from 12ml/hr at 32
weeks’gestation to 28ml/hr at 40
weeks’gestation.
Similar increases are described during
the maturation of premature newborns.
Glomerular Filtration Rate (GFR)
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Glomerular filtration begins between
the 9th and 12th week of gestation in
humans.
The GFR is relatively low at birth
especially in the premature infant.
The values of GFR nearly double
between 3 and 7 days and thereafter
GFR continues to increase, by 1 to 2
yrs of age the GFR is the same as in
an older child- 80% of mature kidney.
GFR
A ge
P rem atu re
< 30w ks
3034w ks
F u ll term
< 24 h rs
3 d ays to 3 w ks
1-2 m on th s
3-4 m on th s
6m on th s to 1 yr
A d u lts
2
G F R (m l/m in /1,73m )
S eru m creatin in e (m g/d l)
5-8m l
5-10 m l
< 1,6
< 1,2
15-25 m l
30-50 m l
60-70 m l
70-80 m l
80-100 m l
0,6-1,0
0,5-0,6
0,4-0,5
0,3-0,4
0,4-0,5
0,6-1,1 (f)
0,6- 1,4 (m )
120п‚± 20
Kidney of newborn
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The kidney of the newborn infant has a
limited capacity to regulate the excretion of
fluid and electolytes.
The high sodium excretion during the first 2
to 3 weeks often results in a negative sodium
balance and predisposes to hyponatremia.
Creatinine Clearance
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Newborn: 40-65 ml/min/1.73 m2
<40 yrs: 97-137 ml/min/1.73 m2
Renal failure in the
newborn
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Renal failure in the newborn:
severe asphyxia,
the majority suffered from
nonoliguric renal failure
CAKUT
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Congenital
Anomalies of
Kidney and
Urogenital
Tract
CAKUT
Chronic renal failure (children):
Obstructive nephropathy- 47%
Reflux nephropathy- 18,5%
Hypo/dysplasia 8,7%
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RENAL ABNORMALITIES
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Renal agenesis:
bilateralп‚® fetal death- Potter syndrome
1:4000 pregnancies
unilateralп‚® other organ- 1:2900
pregnancies abnormalites
Renal abnormalities
Agenesis
Aplasia
Hypoplasia
RENAL ABNORMALITIES
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Hydronephrosis
RENAL ABNORMALITIES
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Obstractive uropathy:
A. ureteropelvic junction
obstruction- dilated renal
pelvis with/ without
caliectasis and no dilation
of the ureter
B. ureterovesical junction
obstruction (megaureter)pelviectasis and caliectasis
with significant ureter
dilation
RENAL ABNORMALITIES
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C. posterior urethral valve
D. ureterocele- cystic dilatation of the
distal ureter that protrudes into the
urinary bladder, may extend past the
bladder into urethra
E. ectopic ureters
F. constriction (stenosis)of urethra
Posterior urethral valve
Type I –
Type II
Type III
Duplication of urinary tract
Ureter
duplex
Ureter
fissus
Ureter
Vesico-ureteral reflux
Frequency of VUR
• Isolated
• UTI in the past
• Siblings with VUR
• Mothers with VUR in the past
1% (0.4-4%)
29-50%
32-45%
60%
RENAL ABNORMALITIES
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Polycystic kidney:
autosomal dominant p.k.disease
autosomal recessive p.k. disease
Kidney
ontogenesis
PRONEPHROS
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Pronephros is a transitory nonfunctional kidney, the first tubules
appear the middle of the 3rd week and
arise from intermediate mesodermal
cells.
The pronephric tubules persist for
only a short time and undergo
degeneration by the 5th week.
At the time the pronephros is
degenerating the mesonephric tubules
and duct are developing.
Pronephros
Vesico- ureteral reflux
Normal kidney, ureter, and bladder
Vesico- ureteral reflux
Grade I Vesicoureteral Reflux:
urine (shown in blue) refluxes part-way up the ureter
Vesico- ureteral reflux
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Grade II
Vesicoureteral
Reflux:
urine refluxes
all the way up
the ureter
Vesico- ureteral reflux
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Grade III
Vesicoureteral
Reflux:
urine refluxes all the
way up the ureter
with dilatation of the
ureter and calyces
(part of the kidney
where urine
collects)
Vesico- ureteral reflux
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Grade IV
Vesicoureteral
Reflux:
urine refluxes
all the way up
the ureter with
marked
dilatation of
the ureter and
calyces
Vesico- ureteral reflux
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Grade V
Vesicoureteral
Reflux:
massive reflux of
urine up the ureter
with marked
tortuosity and
dilatation of the
ureter and calyces
International Classification of VUR
Io
IIo
IIIo
IVo
Vo
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