Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disease caused by defects in the PKD1 and PKD2 genes. Diagnosis involves ultrasound imaging of the kidneys which is used to identify multiple bilateral cysts, with MRI used if ultrasound is equivocal. Genetic testing may be needed in some cases. Treatment focuses on general measures like blood pressure and diet control. The drug tolvaptan can slow cyst growth and kidney function decline but requires close monitoring due to side effects. Ongoing trials are exploring targeting the altered cellular metabolism in cysts through metabolic reprogramming.

1. Autosomal Dominant Polycystic
Kidney Disease (ADPKD)
Emerging Concepts
and Management Update
Mohammed Abdel Gawad
Nephrology Consultant - Alexandria
MD Nephrology - Mansoura University
drgawad@gmail.com

2. Visit
www.NephroTube.com
for more lectures

4. Talk Outline
• Genetics and Pathogenesis
• Diagnosis
o Imaging
o Genetic Testing
• Treatment

5. Talk Outline
• Genetics and Pathogenesis
• Diagnosis
o Imaging
o Genetic Testing
• Treatment

6. 2004;350:151-64
2016 May ; 67(5): 792–810

7. 2016 May ; 67(5): 792–810
Normally:
form complex with
each other →
↑ intracellular Ca

8. Vol 2 | Iss 2 | March/April 2020
G protein
& adenylate cyclase 6

9. Vol 2 | Iss 2 | March/April 2020
G protein
& adenylate cyclase 6
Normally (cyst
growth inhibition)

10. Vol 2 | Iss 2 | March/April 2020
G protein
& adenylate cyclase 6
ADPKD

11. Vol 2 | Iss 2 | March/April 2020
G protein
& adenylate cyclase 6
ADPKD

12. Vol 2 | Iss 2 | March/April 2020
G protein
& adenylate cyclase 6
ADPKD
Mitogen activated protein kinase
Dual threonine & tyrosine
recognition kinase
protein kinase A
Play an important role in the
generation and persistence of
the fluid-filled cysts in ADPKD

13. 2016 May ; 67(5): 792–810
Normally:
form complex with
each other →
↑ intracellular Ca

14. www.cjasn.org Vol 16 May, 2021

15. Talk Outline
• Genetics and Pathogenesis
• Diagnosis
o Imaging
o Genetic Testing
• Treatment

16. 2015 Jul;88(1):17-27
In patients with family history of ADPKD

17. 2015 Jul;88(1):17-27
In patients with family history of ADPKD

18. www.cjasn.org Vol 16 May, 2021
In patients with family history of ADPKD
MRI indication
If US is equivocal
MRI criteria
Age No. of cysts

19. 2016 May ; 67(5): 792–810
In patients with
no family history
of ADPKD

20. Talk Outline
• Genetics and Pathogenesis
• Diagnosis
o Imaging
o Genetic Testing
• Treatment

21. www.cjasn.org Vol 16 May, 2021

22. www.cjasn.org Vol 16 May, 2021
Up to 8 % of patients
with suspected ADPKD
do not have mutations
in genes despite a
comprehensive screen
JASN. 2016 Sep;27(9):2872-84

23. Talk Outline
• Genetics and Pathogenesis
• Diagnosis
o Imaging
o Genetic Testing
• Treatment

24. Vol 13 November, 2018
To asses risk of rapid progression

25. October 2018, 29 (10) 2458-2470

26. Vol 13 November, 2018
Risk of rapid progression

27. Criteria to identify rapidly progressive ADPKD
(rather than Mayo classification)
October 2018, 29 (10) 2458-2470

28. Criteria to identify rapidly progressive ADPKD
(rather than Mayo classification)
October 2018, 29 (10) 2458-2470
Can J Kidney Health Dis. 2017 Mar, Volume 4: 1–12

29. Vol 13 November, 2018
Risk of rapid progression

30. Vol 13 November, 2018
Risk of rapid progression

31. Vol 13 November, 2018
Risk of rapid progression

32. Vol 13 November, 2018
Risk of rapid progression
Tolvaptan
Drugs with no
benefit on
kidney function
Ongoing Trials

33. Vol 13 November, 2018
Risk of rapid progression
Tolvaptan
Drugs with no
benefit on
kidney function
Ongoing Trials

34. N Engl J Med 2012;367:2407-18
N Engl J Med 2017;377:1930-42
Tolvaptan slowed the increase in
total kidney volume and
the decline in kidney function

35. Vol 2 | Iss 2 | March/April 2020
G protein
& adenylate cyclase 6
ADPKD
Mitogen activated protein kinase
Dual threonine & tyrosine
recognition kinase
protein kinase A
Play an important role in the
generation and persistence of
the fluid-filled cysts in ADPKD

36. www.cjasn.org Vol 16 May, 2021

37. October 2018, 29 (10) 2458-2470

38. October 2018, 29 (10) 2458-2470

39. October 2018, 29 (10) 2458-2470
USD $13,000 for a 28-day supply

41. Vol 13 November, 2018
Risk of rapid progression
Tolvaptan
Drugs with no
benefit on
kidney function
Ongoing Trials

42. Vol 2 | Iss 2 | March/April 2020
• ↓ kidney & liver cyst fluid
accumulation
• They have not been shown
to slow the progression of
kidney function decline
• They produce a variety of
prohibitive adverse effects
JAMA. 2018;320(19):2010

43. Vol 2 | Iss 2 | March/April 2020
• It stabilized cyst growth at six
months
• No benefit on kidney function
JASN. 2010;21(6):1031
N Engl J Med. 2010;363(9)
• ↓ kidney & liver cyst fluid
accumulation
• They have not been shown
to slow the progression of
kidney function decline
• They produce a variety of
prohibitive adverse effects
JAMA. 2018;320(19):2010

44. Vol 13 November, 2018
Risk of rapid progression
Tolvaptan
Drugs with no
benefit on
kidney function
Ongoing Trials

45. 2018, vol. 11, Suppl 1, i27–i38
Cysts in PKD exhibit an altered energy metabolism
characterized by a high rate of glycolysis and a low
rate of mitochondrial oxidative phosphorylation

46. 2018, vol. 11, Suppl 1, i27–i38
Cysts in PKD exhibit an altered energy metabolism
characterized by a high rate of glycolysis and a low
rate of mitochondrial oxidative phosphorylation
2020 Apr 7;15(4):577-584

47. Home Messages
• ADPKD is genetic disease due to defect of PKD1 (the commonest and
PKD2
• Other rare genetic inheritances may be the cause of the disease
(GANAB, DNAJB12)

48. Home Messages
• US is the first imaging tool to be used for diagnosis
• MRI may be used if US is equivocal
• Genetic test may be needed in certain situations

49. Home Messages
• General treatment measures (BP control, diet control, ….etc.) must be applied to
all ADPKD cases
• Assess risk of rapid progression (Mayo Classification) before considering disease
modifying treatment
• Tolvaptan slowed the increase in total kidney volume and the decline in kidney
function
• Tolvaptan use needs close monitoring because of its side effects and interactions
• There are ongoing trials testing the metabolic reprogramming in ADPKD