Introduction to Pediatric Nephrology 2017-04-23 Introduction to Pediatric Nephrology Dr.Fahad Gadi, MD Pediatrics Demonstrator King Abdulaziz University Rabigh Medical School

2017-04-23 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.

2017-04-23 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.

After morphogenesis each kidney contains approx a million nephrons. 2017-04-23 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 Pronephros Przednercze Mesonephros Śródnercze 2017-04-23 Renal development aorta nefrotomy Pronephros Przednercze 3 t.ż. 4-8 t.ż. przewód Wolffa Mesonephros Śródnercze 5 t.ż. stek pączek moczowodowy Metanephros Nerka ostateczna blastema nerki ostatecznej

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

2017-04-23 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.

2017-04-23 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.

2017-04-23 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

2017-04-23 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

2017-04-23 Fetal kidney Angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists impair nephrogenesis and so are contraindicated in pregnancy

Production of urine starts at the age of 10-12 weeks of gestation: 2017-04-23 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) 2017-04-23 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.

2017-04-23 GFR

2017-04-23 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 2017-04-23 Creatinine Clearance Newborn: 40-65 ml/min/1.73 m2 <40 yrs: 97-137 ml/min/1.73 m2

Renal failure in the newborn 2017-04-23 Renal failure in the newborn Renal failure in the newborn: severe asphyxia, the majority suffered from nonoliguric renal failure

2017-04-23 CAKUT Congenital Anomalies of Kidney and Urogenital Tract

CAKUT Chronic renal failure (children): Obstructive nephropathy- 47% 2017-04-23 CAKUT Chronic renal failure (children): Obstructive nephropathy- 47% Reflux nephropathy- 18,5% Hypo/dysplasia 8,7%

bilateral fetal death- Potter syndrome 1:4000 pregnancies 2017-04-23 RENAL ABNORMALITIES Renal agenesis: bilateral fetal death- Potter syndrome 1:4000 pregnancies unilateral other organ- 1:2900 pregnancies abnormalites

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2017-04-23 Renal abnormalities Agenesis Aplasia Hypoplasia

2017-04-23 RENAL ABNORMALITIES Hydronephrosis

Obstractive uropathy: 2017-04-23 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

C. posterior urethral valve 2017-04-23 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

Posterior urethral valve 2017-04-23 Posterior urethral valve Type I – Type II Type III

Duplication of urinary tract 2017-04-23 Duplication of urinary tract Ureter Ureter Ureter duplex fissus

• Mothers with VUR in the past 60% 2017-04-23 Vesico-ureteral reflux 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%

autosomal dominant p.k.disease autosomal recessive p.k. disease 2017-04-23 RENAL ABNORMALITIES Polycystic kidney: autosomal dominant p.k.disease autosomal recessive p.k. disease

2017-04-23 Kidney ontogenesis

2017-04-23 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.

2017-04-23 Pronephros

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Vesico- ureteral reflux                                                                                       2017-04-23 Vesico- ureteral reflux Normal kidney, ureter, and bladder

Vesico- ureteral reflux 2017-04-23 Vesico- ureteral reflux Grade I Vesicoureteral Reflux: urine (shown in blue) refluxes part-way up the ureter

Vesico- ureteral reflux 2017-04-23 Vesico- ureteral reflux Grade II Vesicoureteral Reflux: urine refluxes all the way up the ureter

Vesico- ureteral reflux 2017-04-23 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 2017-04-23 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 2017-04-23 Vesico- ureteral reflux 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 2017-04-23 International Classification of VUR Io IIo IIIo IVo Vo