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The Aging Kidney 
Why it is more vulnerable for injury? 
Applied clinical physiology 
Mohammed Abdel Gawad 
Nephrology Spe...
To download the lecture contact 
me at 
drgawad@gmail.com 
For more lectures visit 
www.NephroTubeCNE.com
Why aging kidney 
is an important topic? 
Aging kidney in its own is a risk factor 
for most of renal problems
Pathological & Physiological 
Changes of Aging Kidney
Pathological & Physiological 
Changes of Aging Kidney
Pathological & Physiological 
Changes of Aging Kidney
Glomerular changes 
The proportion of functioning glomeruli decreases with aging 
The percentage of hyaline and sclerotic ...
Glomerular changes 
Brenner’s Hyperfiltration Theory
Glomerular changes 
Brenner’s Hyperfiltration Theory
Glomerular changes 
GFR and Aging Kidney 
Mean rate of decline in creatinine clearance 
0.75-1 mL/min per year
Glomerular changes 
CKD Classification and Aging Kidney 
Will you tell this man that he is a CKD patient? 
Is he really a ...
Community CKD (cCKD) vs 
Referred CKD (rCKD) 
cCKD rCKD 
Older people Younger 
rCKD versus cCKD (El Nahas M, Comprehensive...
Community CKD (cCKD) vs 
Referred CKD (rCKD) 
cCKD rCKD 
Older people Younger 
rCKD versus cCKD (El Nahas M, Comprehensive...
Community CKD (cCKD) vs 
Referred CKD (rCKD)
Pathological & Physiological 
Changes of Aging Kidney
Tubulo-Interstitial changes 
Increased Interstitial Volume 
Normal Tubules Aging Tubules
Tubulo-Interstitial changes 
Increased Interstitial Volume 
Normal Tubules Aging Tubules
Tubulo-Interstitial changes 
Tubular atrophy and tubular diverticula
Tubulo-Interstitial changes 
Tubular atrophy and tubular diverticula 
Diverticula of the DCT 
or the collecting duct 
Simp...
Tubulo-Interstitial changes 
Tubulo-Interstitial changes will affect: 
- Electrolyte balance 
- Acid Base balance 
- Water...
Tubulo-Interstitial changes 
Normal Tubules Aging Tubules 
Distal fractional 
reabsorption of sodium 
is reduced 
Elderly ...
Tubulo-Interstitial changes 
Aging Tubules 
Distal fractional 
reabsorption of sodium 
is reduced 
Elderly people more 
vu...
Tubulo-Interstitial changes 
Normal Tubules Aging Tubules 
Decreased activity of 
distal Na-K ATPase 
activity 
Elderly pe...
Tubulo-Interstitial changes 
Normal Tubules Aging Tubules 
Capacity of generating 
ammonia is clearly 
impaired 
Elderly p...
Tubulo-Interstitial changes 
Normal Tubules Aging Tubules 
downregulation of 
vasopressin-2 receptors
Tubulo-Interstitial changes 
Normal Tubules Aging Tubules 
downregulation of 
vasopressin-2 receptors 
reduced expression ...
Tubulo-Interstitial changes 
Aging Tubules 
downregulation of 
vasopressin-2 receptors 
reduced expression of 
urea transp...
Pathological & Physiological 
Changes of Aging Kidney
Vascular Changes 
Normal Kidney
Vascular Changes 
Aging Kidney
Vascular Changes 
Aging Kidney 
The injured older kidney is less likely to recover 
from acute insult.
Vascular Changes 
Aging Kidney 
Albuminuria
Vascular Changes 
Aging Kidney 
Albuminuria
Vascular Changes 
Aging Kidney & CKD Classification
Vascular Changes 
Aging Kidney & CKD Classification 
Will you prescribe ACEi/ARBS for 
this man? 
Will you tell this man t...
Vascular Changes 
Intimal and medial hypertrophy, with overt 
atherosclerotic lesions 
Reduction in both total renal plasm...
Vascular Changes
Vascular Changes 
El Nahas, KI 2010
Vascular Changes 
Normal Kidney 
Afferent Arteriole Efferent Arteriole
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
↓ 
Afferent Arteriole Efferent Arteriole 
...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
↓ 
Afferent Arteriole Efferent Arteriole 
...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
Ang...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
Ang...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
Ang...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
Ang...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
Ang...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
ACE...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
ACE...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
ACE...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
ACE...
Vascular Changes 
Aging Kidney 
Atherosclerosis & decrease both and RPF & ERPF 
Afferent Arteriole Efferent Arteriole 
ACE...
Vascular Changes 
Aging Kidney 
Take care of prescribing ACEi/ARBs in 
Old Age group & in Atherosclerosis 
Atherosclerosis...
Vascular Changes 
RPF is 40% lower in healthy 
normotensive older men than in 
young men
Vascular Changes 
RPF is 40% lower in healthy 
normotensive older men than in 
young men 
Vasodilating prostaglandins are ...
RPF is 40% lower in healthy 
normotensive older men than in 
young men 
Vasodilating prostaglandins are 
increased 
Vasodi...
RPF is 40% lower in healthy 
normotensive older men than in 
young men 
Vasodilating prostaglandins are 
increased 
Vasodi...
RPF is 40% lower in healthy 
normotensive older men than in 
young men 
Vasodilating prostaglandins are 
increased 
Vasodi...
Pathological & Physiological 
Changes of Aging Kidney 
Endocrinal Changes
Take Home Messages
Aging kidney in its own is a risk factor 
for most of renal problems
Take Home Messages
Take Home Messages 
The proportion of functioning glomeruli 
decreases with aging 
The percentage of hyaline and sclerotic...
Take Home Messages 
Mean rate of decline in creatinine 
clearance 
0.75-1 mL/min per year
Take Home Messages 
Community CKD (cCKD) vs 
Referred CKD (rCKD)
Take Home Messages 
Increased Interstitial Volume 
Tubular atrophy and tubular diverticula 
Tubulo-Interstitial changes wi...
Take Home Messages 
The injured older kidney is less likely to 
recover from acute insult.
Take Home Messages
Take Home Messages 
Take care of prescribing ACEi/ARBs in 
Old Age group & in Atherosclerosis
Take Home Messages 
NSAIDs 
Increased (roughly doubled) risk 
of renal injury
Take Home Messages 
Are we missing AGE as a parameter??
Thank You 
Mohammed Abdel Gawad
The Aging Kidney - Why it is more vulnerable for injury? - Applied clinical physiology - Dr. Gawad
The Aging Kidney - Why it is more vulnerable for injury? - Applied clinical physiology - Dr. Gawad
The Aging Kidney - Why it is more vulnerable for injury? - Applied clinical physiology - Dr. Gawad
The Aging Kidney - Why it is more vulnerable for injury? - Applied clinical physiology - Dr. Gawad
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The Aging Kidney - Why it is more vulnerable for injury? - Applied clinical physiology - Dr. Gawad

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The Aging Kidney - Why it is more vulnerable for injury? - Applied clinical physiology - Dr. Gawad

  1. 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. 2. To download the lecture contact me at drgawad@gmail.com For more lectures visit www.NephroTubeCNE.com
  3. 3. Why aging kidney is an important topic? Aging kidney in its own is a risk factor for most of renal problems
  4. 4. Pathological & Physiological Changes of Aging Kidney
  5. 5. Pathological & Physiological Changes of Aging Kidney
  6. 6. Pathological & Physiological Changes of Aging Kidney
  7. 7. Glomerular changes The proportion of functioning glomeruli decreases with aging The percentage of hyaline and sclerotic glomeruli increases
  8. 8. Glomerular changes Brenner’s Hyperfiltration Theory
  9. 9. Glomerular changes Brenner’s Hyperfiltration Theory
  10. 10. Glomerular changes GFR and Aging Kidney Mean rate of decline in creatinine clearance 0.75-1 mL/min per year
  11. 11. 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?
  12. 12. 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.
  13. 13. 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.
  14. 14. Community CKD (cCKD) vs Referred CKD (rCKD)
  15. 15. Pathological & Physiological Changes of Aging Kidney
  16. 16. Tubulo-Interstitial changes Increased Interstitial Volume Normal Tubules Aging Tubules
  17. 17. Tubulo-Interstitial changes Increased Interstitial Volume Normal Tubules Aging Tubules
  18. 18. Tubulo-Interstitial changes Tubular atrophy and tubular diverticula
  19. 19. Tubulo-Interstitial changes Tubular atrophy and tubular diverticula Diverticula of the DCT or the collecting duct Simple renal cyst
  20. 20. Tubulo-Interstitial changes Tubulo-Interstitial changes will affect: - Electrolyte balance - Acid Base balance - Water balance
  21. 21. Tubulo-Interstitial changes Normal Tubules Aging Tubules Distal fractional reabsorption of sodium is reduced Elderly people more vulnerable to volume depletion and AKI
  22. 22. 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
  23. 23. Tubulo-Interstitial changes Normal Tubules Aging Tubules Decreased activity of distal Na-K ATPase activity Elderly people higher risk of hyperkalemia
  24. 24. Tubulo-Interstitial changes Normal Tubules Aging Tubules Capacity of generating ammonia is clearly impaired Elderly people develop acidosis in response to acid load
  25. 25. Tubulo-Interstitial changes Normal Tubules Aging Tubules downregulation of vasopressin-2 receptors
  26. 26. Tubulo-Interstitial changes Normal Tubules Aging Tubules downregulation of vasopressin-2 receptors reduced expression of urea transporters impair urinary concentration
  27. 27. 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
  28. 28. Pathological & Physiological Changes of Aging Kidney
  29. 29. Vascular Changes Normal Kidney
  30. 30. Vascular Changes Aging Kidney
  31. 31. Vascular Changes Aging Kidney The injured older kidney is less likely to recover from acute insult.
  32. 32. Vascular Changes Aging Kidney Albuminuria
  33. 33. Vascular Changes Aging Kidney Albuminuria
  34. 34. Vascular Changes Aging Kidney & CKD Classification
  35. 35. 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?
  36. 36. Vascular Changes Intimal and medial hypertrophy, with overt atherosclerotic lesions Reduction in both total renal plasma flow and effective renal plasma flow
  37. 37. Vascular Changes
  38. 38. Vascular Changes El Nahas, KI 2010
  39. 39. Vascular Changes Normal Kidney Afferent Arteriole Efferent Arteriole
  40. 40. Vascular Changes Aging Kidney Atherosclerosis & decrease both and RPF & ERPF Afferent Arteriole Efferent Arteriole
  41. 41. Vascular Changes Aging Kidney Atherosclerosis & decrease both and RPF & ERPF ↓ Afferent Arteriole Efferent Arteriole Intraglomerular Pressure
  42. 42. Vascular Changes Aging Kidney Atherosclerosis & decrease both and RPF & ERPF ↓ Afferent Arteriole Efferent Arteriole Intraglomerular Pressure
  43. 43. 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
  44. 44. 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
  45. 45. 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
  46. 46. 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
  47. 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 Protective Mechanism
  48. 48. 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
  49. 49. 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
  50. 50. 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
  51. 51. 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
  52. 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. 53. 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
  54. 54. Vascular Changes RPF is 40% lower in healthy normotensive older men than in young men
  55. 55. 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
  56. 56. 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
  57. 57. 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
  58. 58. 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
  59. 59. Pathological & Physiological Changes of Aging Kidney Endocrinal Changes
  60. 60. Take Home Messages
  61. 61. Aging kidney in its own is a risk factor for most of renal problems
  62. 62. Take Home Messages
  63. 63. Take Home Messages The proportion of functioning glomeruli decreases with aging The percentage of hyaline and sclerotic glomeruli increases
  64. 64. Take Home Messages Mean rate of decline in creatinine clearance 0.75-1 mL/min per year
  65. 65. Take Home Messages Community CKD (cCKD) vs Referred CKD (rCKD)
  66. 66. Take Home Messages Increased Interstitial Volume Tubular atrophy and tubular diverticula Tubulo-Interstitial changes will affect: - Electrolyte balance - Acid Base balance - Water balance
  67. 67. Take Home Messages The injured older kidney is less likely to recover from acute insult.
  68. 68. Take Home Messages
  69. 69. Take Home Messages Take care of prescribing ACEi/ARBs in Old Age group & in Atherosclerosis
  70. 70. Take Home Messages NSAIDs Increased (roughly doubled) risk of renal injury
  71. 71. Take Home Messages Are we missing AGE as a parameter??
  72. 72. Thank You Mohammed Abdel Gawad
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