For medical students

1. Cystic Diseases of Kidney
Dr. Usman Shams

2. CYSTIC
DISEASES
OF KIDNEY

3. CYSTIC
DISEASES
OF KIDNEY

4. Dysplasia
may involve
all or part of
the kidney

5. AUTOSOMAL DOMINANT

6. ADPKD

7. • One of the most common inherited genetic diseases
• Estimated prevalence: 0.1% in general population
• 1 of every 400 to 1000 live births
• Ten times more common than sickle cell disease
• Fifteen times more common than cystic fibrosis.
ADPKD

8. ADPKD
• May start in utero or right after birth
• Approximately 5% of nephrons affected
• May involve any part of nephron
CYST FORMATION

9. ADPKD
GENES
PKD1 Chromosome 16 (16p.13.3)
PKD2 Chromosome 4 (4q13-23)
The disease due to PKD2 mutation is milder and
clinically presents later in life.
The gene product polycystin 1 and 2 play a crucial role in
controlling cell proliferation and differentiation.

10. APKD Gene
PKD1 PKD2
Mutations 85% 15%
Mean age of onset
ESRD
53 years 69 years
Function Receptor Calcium channel
Distal nephron All parts, even extrarenal
Severe Less severe

11. Polycystin 1 and 2
Control of cell proliferation
by modulating Ca level

12. Proliferation
Secretion

13. ADPKD

15. ADPKD
• Starts as hematuria
• Pain (expanding kidney)
• CKD … Hypertension (children 40%, adults 60%),
Proteinuria (glomerulopathy), Polyuria
• Renal Failure
45% by age 60
RENAL MANIFESTATIONS

16. ADPKD
• Cysts in pancreas, liver (40%), ovary
• Cardiovascular manifestations
Mitral valve prolapse
Cerebral vascular aneurysms (10%)
Gastrointestinal tract
Colonic diverticuli
EXTRA-RENAL MANIFESTATIONS

17. ADPKD
• Coronary or hypertensive heart disease, 40%
• Infection, 25%
• Ruptured berry aneurysm or hypertensive
intracerebral hemorrhage, 15%
• Other causes, 20%
CAUSE OF DEATH

18. AUTOSOMAL RECESSIVE
• Perinatal
• Neonatal
• Infantile
• Juvenile

19. ARPKD

20. ARPKD

21. Polycystic Kidney Disease

22. ARPKD
The gene mutated in ARPKD is the PKHD1 gene on
chromosome 6.
The gene product, fibrocystin-polyductin, is a
member of a class of proteins that is involved in the
regulation of cell proliferation and cell adhesion.

23. Primary
Cilia

24. The kidneys are reniform and have a
relatively smooth external surface with
numerous, round cysts beneath the
capsule
ARPKD

25. ARPKD
Fusiform cysts in the cortex, arranged perpendicular to the
capsule, producing a radial pattern.

26. ARPKD

27. ARPKD
Markedly enlarged kidneys compress the thorax
resulting in pulmonary hypoplasia
May also interfere with the delivery.

28. ARPKD
ARPKD is much less frequent than the ADPKD.
Occurs in 1 in 10,000 to 50,000 live births.
Most infants are stillborn or die in the perinatal period, usually
because of respiratory insufficiency.
Infants who survive into the neonatal period are at risk for
developing uremia after varying intervals.

29. ARPKD
Prolonged survival may be complicated by:
• Renal failure with hypertension,
• Hepatic fibrosis with portal hypertension
• Chronic lung disease (pulmonary hypoplasia)

30. ARPKD
Clinical Course
Depends on percentage of tubules involved
>75%
Perinatal death. Minimal liver involvement
25-50%
Patients survive for several months Have mild hepatic
fibrosis.
<25%
Patients survive longer, develop moderate to
severe hepatic fibrosis.

31. MEDULLARY CYSTS
Medullary Sponge kidney
Cysts within the renal papillae
Nephronophthiasis-medullary cystic complex
Cysts at the cortico medullary junction
Two very different diseases

32. Medullary Sponge Kidney Nephronophthiasis-Medullary
Cystic Disease Complex

33. A congenital disorder characterized by dilatation of collecting tubules in one or
more renal papillae, affecting one or both kidneys.
A benign condition, and patients can remain asymptomatic.
Usually diagnosed until the second or third decade of life or later.
ESRD … 10%
Medullary Sponge Kidney

34. Nephronophthiasis - Medullary Cystic Complex
NPH presents in infancy, childhood or adolescence with
progressive renal failure
There may be extrarenal manifestations:
Retinitis pigmentosa
Hepatic fibrosis
Skeletal defects
Cerebellar aplasia.

35. Primary
Cilia

36. Nephronophthiasis - Medullary
Cystic Complex

37. Acquired Renal Cystic Disease
Development of numerous fluid-filled cysts in both
kidney in individuals who have no history of
hereditary cystic disease.
Usually does not produce symptoms, discovered
incidentally during imaging
Hemodialysis is an important causative factor

38. Acquired Cystic Disease
Renal size not increased

39. Acquired Renal Cystic Disease
Acquired cystic disease occurs in 35% of long-term
dialysis patients; of these, 6% develop carcinoma.
Risk for renal carcinoma (12-18x)

40. “SIMPLE” CYSTS
•Cortical
•Also called “retention” cysts
•Also “acquired”
•Incidental, asymptomatic
•VERY very very common

41. Simple Cyst

42. Simple Cyst
Up to 50% of individuals >50 years of age may have simple renal
cysts.

43. Aplastic
Multicystic (most common)
Obstructive
Bilateral
Unilateral
Segmental
Renal Dysplasia

44. May mimic renal
agenesis
Aplastic Dysplasia

45. Multicystic Renal Dysplasia

47. Ureteric obstruction during active
nephrogenesis results in cystic renal
dysplasia
The earlier and longer the
obstruction the more severe the
histopathological changes of
dysplasia
Obstructive Renal Dysplasia

48. SUMMARY

49. Dysplasia
may involve
all or part of
the kidney