Introduction to Pediatric Nephrology

1. Introduction to Pediatric Nephrology Dr.Fahad Gadi, MD Pediatrics Demonstrator King Abdulaziz University Rabigh Medical School

2. 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.

3. 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.

4. 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.

5. Renal development aorta nefrotomy Pronephros Przednercze 3 t.ż. 4-8 t.ż. przewód Wolffa Mesonephros Śródnercze 5 t.ż. stek pączek moczowodowy Nerka ostateczna Metanephros blastema nerki ostatecznej

6. 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.

7. Embryology

10. 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.

11. 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.

12. 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

13. 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

14. Fetal kidney • Angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists impair nephrogenesis and so are contraindicated in pregnancy

15. 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.

16. 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.

17. GFR

18. 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.

19. Creatinine Clearance • Newborn: 40-65 ml/min/1.73 m2 • <40 yrs: 97-137 ml/min/1.73 m2

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

21. CAKUT • Congenital • Anomalies of • Kidney and • Urogenital • Tract

22. CAKUT • Chronic renal failure (children): Obstructive nephropathy- 47% Reflux nephropathy- 18,5% Hypo/dysplasia 8,7%

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

25. Renal abnormalities Agenesis Aplasia Hypoplasia

26. RENAL ABNORMALITIES • Hydronephrosis

27. 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

28. 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

29. Posterior urethral valve Type I – Type II Type III

30. Duplication of urinary tract UreterUreterUreter duplex fissus

31. Vesico-ureteral reflux Frequency of VUR • Isolated1% (0.4-4%) • UTI in the past 29-50% • Siblings with VUR 32-45% • Mothers with VUR in the past 60%

32. RENAL ABNORMALITIES • Polycystic kidney: autosomal dominant p.k.disease autosomal recessive p.k. disease

33. Kidney ontogenesis

34. 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.

35. Pronephros

37. Vesico- ureteral reflux Normal kidney, ureter, and bladder

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

39. Vesico- ureteral reflux • Grade II Vesicoureteral Reflux:urine refluxes all the way up the ureter

40. 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)

41. Vesico- ureteral reflux • Grade IV Vesicoureteral Reflux:urine refluxes all the way up the ureter with marked dilatation of the ureter and calyces

42. Vesico- ureteral reflux • Grade V Vesicoureteral Reflux:massive reflux of urine up the ureter with marked tortuosity and dilatation of the ureter and calyces

43. International Classification of VUR Io IIo IIIo IVo Vo