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1. The Aging Kidney
Why it is more vulnerable for injury?
Applied clinical physiology
Mohammed Abdel Gawad
Nephrology Specialist
Alexandria – EGY
Fellow of Global Kidney Online Academy
NephroTube Chairman
drgawad@gmail.com
7th KUC Club – May 2014

2. To download the lecture contact
me at
drgawad@gmail.com
For more lectures visit
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3. Why aging kidney
is an important topic?
Aging kidney in its own is a risk factor
for most of renal problems

8. Pathological & Physiological
Changes of Aging Kidney

9. Pathological & Physiological
Changes of Aging Kidney

10. Pathological & Physiological
Changes of Aging Kidney

11. Glomerular changes
The proportion of functioning glomeruli decreases with aging
The percentage of hyaline and sclerotic glomeruli increases

12. Glomerular changes
Brenner’s Hyperfiltration Theory

13. Glomerular changes
Brenner’s Hyperfiltration Theory

14. Glomerular changes
GFR and Aging Kidney
Mean rate of decline in creatinine clearance
0.75-1 mL/min per year

15. Glomerular changes
CKD Classification and Aging Kidney
Will you tell this man that he is a CKD patient?
Is he really a CKD patient?
Is KDIGO 2012 CKD Classification missing Age as a parameter?

16. Community CKD (cCKD) vs
Referred CKD (rCKD)
cCKD rCKD
Older people Younger
rCKD versus cCKD (El Nahas M, Comprehensive Clinical Nephrology, 2014)
Underlying co-morbidities (e.g.
CVD)
Glomerulonephritis, Pyelonephritis,
Vasculitis and LN, as well as PKD
and
hereditary nephropathies.
Decreased eGFR but no significant
proteinuria or hematuria.
Associated with faster decline in
eGFR and more markers of renal
damage
They seldom end up on dialysis.
Tend to die from old age and co-morbidities
before reaching ESRD.
Mainly end up on RRT/dialysis.

17. Community CKD (cCKD) vs
Referred CKD (rCKD)
cCKD rCKD
Older people Younger
rCKD versus cCKD (El Nahas M, Comprehensive Clinical Nephrology, 2014)
Underlying co-morbidities (e.g.
CVD)
Glomerulonephritis, Pyelonephritis,
Vasculitis and LN, as well as PKD
and
hereditary nephropathies.
Decreased eGFR but no significant
proteinuria or hematuria.
Associated with faster decline in
eGFR and more markers of renal
damage
They seldom end up on dialysis.
Tend to die from old age and co-morbidities
before reaching ESRD.
Mainly end up on RRT/dialysis.
Older 75 year old
longstanding
hypertension history of
CVD
T2DM
He is unlikely to
progress to ESRD but
will die from their co-morbidities:
CVD, HTN,
and Insulin
resistance/T2DM.
T1DM give rise to a
young and early onset
progressive
nephropathy with
severe proteinuria
leading to ESRD.

18. Community CKD (cCKD) vs
Referred CKD (rCKD)

19. Pathological & Physiological
Changes of Aging Kidney

20. Tubulo-Interstitial changes
Increased Interstitial Volume
Normal Tubules Aging Tubules

21. Tubulo-Interstitial changes
Increased Interstitial Volume
Normal Tubules Aging Tubules

22. Tubulo-Interstitial changes
Tubular atrophy and tubular diverticula

23. Tubulo-Interstitial changes
Tubular atrophy and tubular diverticula
Diverticula of the DCT
or the collecting duct
Simple renal cyst

24. Tubulo-Interstitial changes
Tubulo-Interstitial changes will affect:
- Electrolyte balance
- Acid Base balance
- Water balance

25. Tubulo-Interstitial changes
Normal Tubules Aging Tubules
Distal fractional
reabsorption of sodium
is reduced
Elderly people more
vulnerable to volume
depletion and AKI

26. Tubulo-Interstitial changes
Aging Tubules
Distal fractional
reabsorption of sodium
is reduced
Elderly people more
vulnerable to volume
depletion and AKI
Aging Tubules
a relative inability to
excrete sodium excess in
response to salt load
salt retention and
hypertension

27. Tubulo-Interstitial changes
Normal Tubules Aging Tubules
Decreased activity of
distal Na-K ATPase
activity
Elderly people higher
risk of hyperkalemia

28. Tubulo-Interstitial changes
Normal Tubules Aging Tubules
Capacity of generating
ammonia is clearly
impaired
Elderly people develop
acidosis in response to
acid load

29. Tubulo-Interstitial changes
Normal Tubules Aging Tubules
downregulation of
vasopressin-2 receptors

30. Tubulo-Interstitial changes
Normal Tubules Aging Tubules
downregulation of
vasopressin-2 receptors
reduced expression of
urea transporters
impair urinary
concentration

31. Tubulo-Interstitial changes
Aging Tubules
downregulation of
vasopressin-2 receptors
reduced expression of
urea transporters
impair urinary
concentration
Aging Tubules
In the opposite direction
the aging kidney has
impaired urine diluting
capacity

32. Pathological & Physiological
Changes of Aging Kidney

33. Vascular Changes
Normal Kidney

34. Vascular Changes
Aging Kidney

35. Vascular Changes
Aging Kidney
The injured older kidney is less likely to recover
from acute insult.

36. Vascular Changes
Aging Kidney
Albuminuria

37. Vascular Changes
Aging Kidney
Albuminuria

38. Vascular Changes
Aging Kidney & CKD Classification

39. Vascular Changes
Aging Kidney & CKD Classification
Will you prescribe ACEi/ARBS for
this man?
Will you tell this man that he is a CKD patient?
Is he really a CKD patient?
Is KDIGO 2012 CKD Classification missing Age as a parameter?

40. Vascular Changes
Intimal and medial hypertrophy, with overt
atherosclerotic lesions
Reduction in both total renal plasma flow and
effective renal plasma flow

41. Vascular Changes

42. Vascular Changes
El Nahas, KI 2010

43. Vascular Changes
Normal Kidney
Afferent Arteriole Efferent Arteriole

44. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole

45. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
↓
Afferent Arteriole Efferent Arteriole
Intraglomerular
Pressure

46. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
↓
Afferent Arteriole Efferent Arteriole
Intraglomerular
Pressure

47. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↓
Intraglomerular
Pressure

48. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↓
Intraglomerular
Pressure

49. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↑
Intraglomerular
Pressure

50. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↑
Intraglomerular
Pressure

51. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↑
Intraglomerular
Pressure
Protective
Mechanism

52. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
ACE-I & ARBs
Protective
Mechanism
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↑
Intraglomerular
Pressure

53. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
ACE-I & ARBs
Protective
Mechanism
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↑
Intraglomerular
Pressure

54. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
ACE-I & ARBs
Protective
Mechanism
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↓
Intraglomerular
Pressure

55. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
ACE-I & ARBs
Protective
Mechanism
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↓
Intraglomerular
Pressure

56. Vascular Changes
Aging Kidney
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
ACE-I & ARBs
Protective
Mechanism
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↓
Intraglomerular
Pressure

57. Vascular Changes
Aging Kidney
Take care of prescribing ACEi/ARBs in
Old Age group & in Atherosclerosis
Atherosclerosis & decrease both and RPF & ERPF
Afferent Arteriole Efferent Arteriole
ACE-I & ARBs
Protective
Mechanism
Angiotensin II
(N.B. low serum renin
& aldosterone in old
age)
↓
Intraglomerular
Pressure

58. Vascular Changes
RPF is 40% lower in healthy
normotensive older men than in
young men

59. Vascular Changes
RPF is 40% lower in healthy
normotensive older men than in
young men
Vasodilating prostaglandins are
increased
Vasodilation to compensate for
loss of vasculature

60. RPF is 40% lower in healthy
normotensive older men than in
young men
Vasodilating prostaglandins are
increased
Vasodilation to compensate for
loss of vasculature
NSAIDs
Vascular Changes

61. RPF is 40% lower in healthy
normotensive older men than in
young men
Vasodilating prostaglandins are
increased
Vasodilation to compensate for
loss of vasculature
NSAIDs
Vascular Changes

62. RPF is 40% lower in healthy
normotensive older men than in
young men
Vasodilating prostaglandins are
increased
Vasodilation to compensate for
loss of vasculature
NSAIDs
Increased
(roughly
doubled) risk
of renal injury
Vascular Changes

63. Pathological & Physiological
Changes of Aging Kidney
Endocrinal Changes

64. Take Home Messages

65. Aging kidney in its own is a risk factor
for most of renal problems

66. Take Home Messages

67. Take Home Messages
The proportion of functioning glomeruli
decreases with aging
The percentage of hyaline and sclerotic
glomeruli increases

68. Take Home Messages
Mean rate of decline in creatinine
clearance
0.75-1 mL/min per year

69. Take Home Messages
Community CKD (cCKD) vs
Referred CKD (rCKD)

70. Take Home Messages
Increased Interstitial Volume
Tubular atrophy and tubular diverticula
Tubulo-Interstitial changes will affect:
- Electrolyte balance
- Acid Base balance
- Water balance

71. Take Home Messages
The injured older kidney is less likely to
recover from acute insult.

72. Take Home Messages

73. Take Home Messages
Take care of prescribing ACEi/ARBs in
Old Age group & in Atherosclerosis

74. Take Home Messages
NSAIDs
Increased (roughly doubled) risk
of renal injury

75. Take Home Messages
Are we missing AGE as a parameter??

76. Thank You
Mohammed Abdel Gawad