Introduction to Pediatric Nephrology

Dr.Fahad Gadi, MD

Pediatrics Demonstrator

King Abdulaziz University

Rabigh Medical School

Kidney ontogenesis

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

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

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

3 t.ż.

4-8 t.ż.

5 t.ż.

nefrotomy

przewód Wolffa

Przednercze

Śródnercze

Nerka ostateczna

stek

aorta

pączek moczowodowy

blastema nerki ostatecznej

Pronephros

Mesonephros

Metanephros

Antenatal Period

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

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

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

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

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

Angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists impair nephrogenesis and so are contraindicated in pregnancy

Production of urine

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)

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

Age GFR (ml/min/1,73m2) Serum creatinine (mg/dl)Premature<30wks30-34wks

5-8ml5-10 ml

<1,6<1,2

Full term<24 hrs3 days to 3 wks1-2 months3-4 months6months to 1 yr

15-25 ml30-50 ml60-70 ml70-80 ml80-100 ml

0,6-1,00,5-0,60,4-0,50,3-0,40,4-0,5

Adults 12020 0,6-1,1 (f)0,6- 1,4 (m)

Kidney of newborn

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

Newborn: 40-65 ml/min/1.73 m2 <40 yrs: 97-137 ml/min/1.73 m2

Renal failure in the newborn

Renal failure in the newborn: severe asphyxia, the majority suffered from nonoliguric renal failure

CAKUT

Congenital Anomalies of Kidney and Urogenital Tract

CAKUT

Chronic renal failure (children):

Obstructive nephropathy- 47%

Reflux nephropathy- 18,5%

Hypo/dysplasia 8,7%

RENAL ABNORMALITIES

Renal agenesis:

bilateral fetal death- Potter syndrome 1:4000 pregnancies

unilateral other organ- 1:2900 pregnancies abnormalites

Agenesis Aplasia Hypoplasia

Renal abnormalities

RENAL ABNORMALITIES

Hydronephrosis

RENAL ABNORMALITIES

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

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

Type I – Type II Type III

Posterior urethral valve

Duplication of urinary tract

Ureter Ureter Ureter

duplex fissus

Frequency of VUR

• Isolated 1% (0.4-4%)

• UTI in the past 29-50%

• Siblings with VUR 32-45%

• Mothers with VUR in the past 60%

Vesico-ureteral reflux

RENAL ABNORMALITIES

Polycystic kidney:

autosomal dominant p.k.disease

autosomal recessive p.k. disease

Kidney ontogenesis

PRONEPHROS

Pronephros is a transitory non-functional 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

Grade II Vesicoureteral Reflux:urine refluxes all the way up the ureter

Vesico- ureteral reflux

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

Grade IV Vesicoureteral Reflux:urine refluxes all the way up the ureter with marked dilatation of the ureter and

calyces

Vesico- ureteral reflux

Grade V Vesicoureteral Reflux:massive reflux of urine up the ureter with marked tortuosity and dilatation of the ureter and calyces

Io IIo IIIo IVo Vo

International Classification of VUR