The document provides an overview of acute renal failure, including the structure and function of the kidneys, nephron components, and mechanisms of glomerular filtration. It defines acute renal failure, distinguishing between oliguric and non-oliguric forms, and outlines diagnostic approaches focusing on pre-renal causes and renal blood flow regulation. Key factors influencing renal function, such as the renin-angiotensin system and various vasoactive substances, are also discussed regarding their role in renal pathophysiology.

1. Acute Renal Failure
Acute Renal Failure

2. Structure and Function of the
Structure and Function of the
Kidney
Kidney
 Primary unit of the
Primary unit of the
kidney is the nephron
kidney is the nephron
 1 million nephrons per
1 million nephrons per
kidney
kidney
 Composed of a
Composed of a
glomerulus and a
glomerulus and a
tubule
tubule
 Kidneys receive 20%
Kidneys receive 20%
of cardiac output
of cardiac output
Renal Lecture Required Picture #1

3. Renal blood flow
Renal blood flow
 Aorta
Aorta 
 Renal artery
Renal artery 

interlobar arteries
interlobar arteries 

interlobular arteries
interlobular arteries 

afferent arterioles
afferent arterioles 

glomerulus
glomerulus 
 efferent
efferent
arterioles
arterioles
 In the cortex
In the cortex 

peritubular capillaries
peritubular capillaries
 In the juxtamedullary
In the juxtamedullary
region
region 
vasa recta
vasa recta
 Back to the heart through
Back to the heart through
the interlobular
the interlobular 

intralobar
intralobar 
 renal veins
renal veins

4. Glomerular Filtration Rate
Glomerular Filtration Rate
 Determined by the hydrostatic and oncotic
Determined by the hydrostatic and oncotic
pressure within the nephron
pressure within the nephron
 Hydrostatic pressure in the glomerulus is
Hydrostatic pressure in the glomerulus is
higher than in the tubule, so you get a net
higher than in the tubule, so you get a net
outflow of filtrate into the tubule
outflow of filtrate into the tubule
 Oncotic pressure in the glomerulus is the
Oncotic pressure in the glomerulus is the
result of non-filterable proteins
result of non-filterable proteins

Greater oncotic pressure as you progress through
Greater oncotic pressure as you progress through
the glomerulus
the glomerulus
 GFR = Kf (hydrostatic – oncotic pressure)
GFR = Kf (hydrostatic – oncotic pressure)

6. Glomerular Filtration Rate
Glomerular Filtration Rate
 The capillary endothelium is surrounded
The capillary endothelium is surrounded
by a basement membrane and podocytes
by a basement membrane and podocytes
 Foot processes of the podocytes form
Foot processes of the podocytes form
filtration slits that :
filtration slits that :

Allow for ultrafiltrate passage
Allow for ultrafiltrate passage

Limit filtration of large negatively charged
Limit filtration of large negatively charged
particles
particles
• Less than 5,000 daltons = freely filtered
Less than 5,000 daltons = freely filtered
• Large particles (albumin 69,000 daltons) not
Large particles (albumin 69,000 daltons) not
filtered
filtered

7. Tubular Function
Tubular Function
 Proximal
Proximal

Most of reabsorption occurs here
Most of reabsorption occurs here

Fluid is isotonic with plasma
Fluid is isotonic with plasma

66-70% of sodium presented is reabsorbed
66-70% of sodium presented is reabsorbed

Glucose and amino acids are completely
Glucose and amino acids are completely
reabsorbed
reabsorbed

8. Tubule Function
Tubule Function
 Loop of Henle
Loop of Henle

Urine concentration and dilution via changes
Urine concentration and dilution via changes
in oncotic pressure in the vasa recta
in oncotic pressure in the vasa recta

Descending tubule – permeable to water,
Descending tubule – permeable to water,
impermeable to sodium
impermeable to sodium

Ascending tubule – actively reabsorbs
Ascending tubule – actively reabsorbs
sodium, impermeable to water
sodium, impermeable to water

9. Tubular Function
Tubular Function
 Medullary thick ascending limb – critical
Medullary thick ascending limb – critical
for urinary dilution and most often
for urinary dilution and most often
damaged in ARF
damaged in ARF

ADH stimulates Na re-absorption in this area
ADH stimulates Na re-absorption in this area

Most sensitive to ischemia
Most sensitive to ischemia
• Low oxygen tension, high oxygen consumption
Low oxygen tension, high oxygen consumption

Lasix use here inhibits the Na-K-2Cl ATPase
Lasix use here inhibits the Na-K-2Cl ATPase
which in the face of ARF, may decrease
which in the face of ARF, may decrease
oxygen consumption and ameliorate the
oxygen consumption and ameliorate the
severity of the ARF
severity of the ARF

10. Tubular Function
Tubular Function
 All of those studies done in an in vitro
All of those studies done in an in vitro
model
model

In vivo, if you drop oxygen concentration even
In vivo, if you drop oxygen concentration even
sub-atmospheric you do not get tubular
sub-atmospheric you do not get tubular
damage even with increased tubular workload
damage even with increased tubular workload

In vivo models exist where you do see that
In vivo models exist where you do see that
damage, but appears to need a “second hit”
damage, but appears to need a “second hit”

11. Tubule Function
Tubule Function
 Distal Tubule
Distal Tubule

Re-absorption of another ~12% of NaCl
Re-absorption of another ~12% of NaCl

Proximal segment – impermeable to water
Proximal segment – impermeable to water

Distal segment is the cortical collecting duct
Distal segment is the cortical collecting duct
and secretes K and HCO3
and secretes K and HCO3

12. Tubular Function
Tubular Function
 Collecting Duct
Collecting Duct

Aldosterone acts here to increase Na
Aldosterone acts here to increase Na
reuptake and K wasting
reuptake and K wasting

ADH enhances water re-absorption
ADH enhances water re-absorption

Urea re-absorption to maintain the medullary
Urea re-absorption to maintain the medullary
interstitial concentration gradient
interstitial concentration gradient

13. Acute Renal Failure - Definitions
Acute Renal Failure - Definitions
 Renal failure
Renal failure is defined as the cessation
is defined as the cessation
of kidney function with or without changes
of kidney function with or without changes
in urine volume
in urine volume
 Anuria
Anuria – UOP < 0.5 cc/kg/hour
– UOP < 0.5 cc/kg/hour
 Oliguria
Oliguria – UOP “more than 1 cc/kg/hour”
– UOP “more than 1 cc/kg/hour”

Less than?
Less than?

14. Acute Renal Failure - Definitions
Acute Renal Failure - Definitions
 70% Non-oliguric , 30% Oliguric
70% Non-oliguric , 30% Oliguric
 Non-oliguric associated with better
Non-oliguric associated with better
prognosis and outcome
prognosis and outcome
 “
“Overall, the critical issue is maintenance
Overall, the critical issue is maintenance
of adequate urine output and prevention of
of adequate urine output and prevention of
further renal injury.”
further renal injury.”

Are we converting non-oliguric to oliguric with
Are we converting non-oliguric to oliguric with
our hemofilters?
our hemofilters?

15. Acute Renal Failure - Diagnosis
Acute Renal Failure - Diagnosis
 Pre-renal
Pre-renal
• Decrease in RBF
Decrease in RBF 
constriction of afferent arteriole
constriction of afferent arteriole
which serves to increase systemic blood pressure
which serves to increase systemic blood pressure
by reducing the “shunt” through the kidney, but
by reducing the “shunt” through the kidney, but
does so at a cost of decreased RBF
does so at a cost of decreased RBF
• At the same time, efferent arteriole constricts to
At the same time, efferent arteriole constricts to
attempt to maintain GFR
attempt to maintain GFR
• As GFR decreases, amount of filtrate decreases.
As GFR decreases, amount of filtrate decreases.
Urea is reabsorbed in the distal tubule, leading to
Urea is reabsorbed in the distal tubule, leading to
increased tubular urea concentration and thus
increased tubular urea concentration and thus
greater re-absorption of urea into the blood.
greater re-absorption of urea into the blood.

Creatinine cannot be reabsorbed, thus leading to a
Creatinine cannot be reabsorbed, thus leading to a
BUN/Cr ratio of > 20
BUN/Cr ratio of > 20

16. Pre-Renal vs. Renal Failure
Pre-Renal vs. Renal Failure
Prerenal
Prerenal Renal
Renal
BUN/Cr
BUN/Cr >20
>20 <20
<20
FENa
FENa <1%
<1% >2%
>2%
Renal Failure Index
Renal Failure Index <1%
<1% >1%
>1%
U
UNa
Na <20 mEq/L
<20 mEq/L >40 mEq/L
>40 mEq/L
Specific Gravity
Specific Gravity >1.020
>1.020 <1.010
<1.010
U
Uosm
osm >500 mOsm/L
>500 mOsm/L <350 mOsm/L
<350 mOsm/L
U
Uosm
osm/P
/Posm
osm >1.3
>1.3 <1.3
<1.3
Renal Lecture Required Picture #3

17. Acute Renal Failure - Diagnosis
Acute Renal Failure - Diagnosis
 Diagnosis
Diagnosis

Ultrasound
Ultrasound
• Structural anomalies – polycystic, obstruction, etc.
Structural anomalies – polycystic, obstruction, etc.
• ATN –
ATN –

poor corticomedullary differentiation
poor corticomedullary differentiation

Increased Doppler resistive index
Increased Doppler resistive index
• (Systolic Peak – Diastolic peak) / systolic peak
(Systolic Peak – Diastolic peak) / systolic peak

Nuclear medicine scans
Nuclear medicine scans
• DMSA – Static - anatomy and scarring
DMSA – Static - anatomy and scarring
• DTPA/MAG3 – Dynamic – renal function, urinary
DTPA/MAG3 – Dynamic – renal function, urinary
excretion, and upper tract outflow
excretion, and upper tract outflow

18. Acute Renal Failure
Acute Renal Failure
 Overall, renal vasoconstriction is the major
Overall, renal vasoconstriction is the major
cause of the problems in ARF
cause of the problems in ARF

Suggested ARF be replaced with vasomotor
Suggested ARF be replaced with vasomotor
nephropathy
nephropathy
 Insult to tubular epithelium causes release
Insult to tubular epithelium causes release
of vasoactive agents which cause the
of vasoactive agents which cause the
constriction
constriction

Angiotensin II, endothelin, NO, adenosine,
Angiotensin II, endothelin, NO, adenosine,
prostaglandins, etc.
prostaglandins, etc.

19. Regulation of Renal Blood Flow
Regulation of Renal Blood Flow
 In adults auto-regulated over a range of
In adults auto-regulated over a range of
MAP’s 80-160
MAP’s 80-160
 Developmental changes
Developmental changes

Doubling of RBF in first 2 weeks of life
Doubling of RBF in first 2 weeks of life

Triples by 1 year
Triples by 1 year

Approaches adult levels by preschool
Approaches adult levels by preschool
 Renal blood flow regulation is complex
Renal blood flow regulation is complex

No one system accounts for everything…..
No one system accounts for everything…..

20. Renin-Angiotensin Axis
Renin-Angiotensin Axis
 For the one millionth time….
For the one millionth time….
 Hypovolemia leads to decreased afferent
Hypovolemia leads to decreased afferent
arteriolar pressure which leads to decreased
arteriolar pressure which leads to decreased
NaCl re-absorption which leads to decreased Cl
NaCl re-absorption which leads to decreased Cl
presentation to the macula densa which
presentation to the macula densa which
increases the amount of renin secreted from the
increases the amount of renin secreted from the
JGA which increases conversion
JGA which increases conversion
angiotensinogen to AGI to AGII which increases
angiotensinogen to AGI to AGII which increases
Aldosterone secretion from the adrenal cortex
Aldosterone secretion from the adrenal cortex
and ADH which leads to increased sodium and
and ADH which leads to increased sodium and
thus water re-absorption from the tubule which
thus water re-absorption from the tubule which
increases your blood pressure……whew…
increases your blood pressure……whew…

21. Renin Angiotensin Axis
Renin Angiotensin Axis
Renal Lecture Required
Picture #4

22. Renin Angiotensin Axis
Renin Angiotensin Axis
 Renin’s role in pathogenesis of ARF
Renin’s role in pathogenesis of ARF

Hyperplasia of JGA with increased renin
Hyperplasia of JGA with increased renin
granules seen in patients and experimental
granules seen in patients and experimental
models of ARF
models of ARF

Increased plasma renin activity in ARF
Increased plasma renin activity in ARF
patients
patients

Changing intra-renal renin content modifies
Changing intra-renal renin content modifies
degree of damage
degree of damage
• Feed animals high salt diet (suppress renin
Feed animals high salt diet (suppress renin
production)
production) 
 renal injury
renal injury 
 less renal injury than
less renal injury than
those fed a low sodium diet
those fed a low sodium diet

23. Renin Angiotensin Axis
Renin Angiotensin Axis
 Not the only thing going on though
Not the only thing going on though

You can also ameliorate renal injury by
You can also ameliorate renal injury by
induction of solute diuresis with mannitol or
induction of solute diuresis with mannitol or
loop diuretics (neither affect the RAS)
loop diuretics (neither affect the RAS)

No change in renal injury in animals given
No change in renal injury in animals given
ACE inhibitors, competitive antagonist to
ACE inhibitors, competitive antagonist to
angiotensin II
angiotensin II
 Overall, role of RAS in ARF is uncertain
Overall, role of RAS in ARF is uncertain

24. Prostaglandins
Prostaglandins
 PGE 2 and PGI
PGE 2 and PGI

Very important for renal vasodilation,
Very important for renal vasodilation,
especially in the injured kidney
especially in the injured kidney

Act as a buffer against uncontrolled A2
Act as a buffer against uncontrolled A2
mediated constriction
mediated constriction
• If you constrict the afferent arteriole, you will
If you constrict the afferent arteriole, you will
decrease GFR
decrease GFR
 The RAS and Prostaglandin pathways
The RAS and Prostaglandin pathways
account for ~60% of RBF auto-
account for ~60% of RBF auto-
regulation…
regulation…

25. Adenosine
Adenosine
 Potent renal vasoconstrictor
Potent renal vasoconstrictor

Peripheral vasodilator
Peripheral vasodilator
 Infusion of methylxanthines (adenosine
Infusion of methylxanthines (adenosine
receptor blockers) inhibits the decrease in
receptor blockers) inhibits the decrease in
GFR that is seen with tubular damage
GFR that is seen with tubular damage
 Some animal models show that infusion of
Some animal models show that infusion of
methylxanthines lessen renal injury in ARF
methylxanthines lessen renal injury in ARF

26. Adenosine
Adenosine
 But…. Likely not a major factor in ARF
But…. Likely not a major factor in ARF

Methylxanthines have lots of other actions
Methylxanthines have lots of other actions
besides adenosine blockade
besides adenosine blockade

Adenosine is rapidly degraded after
Adenosine is rapidly degraded after
production
production

Intra-renal adenosine levels diminish very
Intra-renal adenosine levels diminish very
rapidly after reperfusion, but the
rapidly after reperfusion, but the
vasocontriction remains for a longer period
vasocontriction remains for a longer period

Finally, if you block ADA, creating higher
Finally, if you block ADA, creating higher
tissue adenosine levels, and then create
tissue adenosine levels, and then create
ischemia
ischemia 
 you actually get an enhancement
you actually get an enhancement
of renal recovery
of renal recovery

27. Endothelin
Endothelin
 21 amino acid peptide that is one of the most
21 amino acid peptide that is one of the most
potent vasoconstrictors in the body
potent vasoconstrictors in the body

Can be used as a pressor
Can be used as a pressor
 Its role in unclear in normal state
Its role in unclear in normal state
 In ARF, overproduction by cells (both in and
In ARF, overproduction by cells (both in and
outside of the kidney) leads to decreased
outside of the kidney) leads to decreased
afferent flow and thus decreased RBF and GFR
afferent flow and thus decreased RBF and GFR

Endothelin increases mesangial cell contraction which
Endothelin increases mesangial cell contraction which
reduces glomerular ultrafiltration
reduces glomerular ultrafiltration
 Stimulates ANP release at low doses and can
Stimulates ANP release at low doses and can
increase UOP
increase UOP
 Anti-endothelin antibodies or endothelin receptor
Anti-endothelin antibodies or endothelin receptor
antagonists decrease ARF in experimental
antagonists decrease ARF in experimental
models
models

28. Nitric Oxide
Nitric Oxide
 Produced by multiple iso-enzymes of NOS
Produced by multiple iso-enzymes of NOS
 In addition to its role in vasodilation, likely
In addition to its role in vasodilation, likely
has a role in sodium re-absorption
has a role in sodium re-absorption

Give a NOS blocker and you get naturesis
Give a NOS blocker and you get naturesis
 Important in the overall homeostasis of
Important in the overall homeostasis of
RBF
RBF
 Exact mechanisms not worked out
Exact mechanisms not worked out
completely…at least when Rogers was
completely…at least when Rogers was
written….
written….

29. Obligatory Incomprehensible
Pathway for Jim #1

30. Nitric Oxide
Nitric Oxide
 Confusing results
Confusing results

Ischemic rat kidney model – inducing NOS
Ischemic rat kidney model – inducing NOS
causes increasing injury
causes increasing injury

Hypoxic tubular cell culture model – inducing
Hypoxic tubular cell culture model – inducing
NOS causes increasing injury
NOS causes increasing injury

But if you block NOS production, you get
But if you block NOS production, you get
worsening of renal function and severe
worsening of renal function and severe
vasoconstriction
vasoconstriction

31. Nitric Oxide
Nitric Oxide
 So stimulation of NO in the renal
So stimulation of NO in the renal
vasculature will modulate vasoconstriction
vasculature will modulate vasoconstriction
and lead to lesser injury…but…
and lead to lesser injury…but…
 That same induction of NO in the tubular
That same induction of NO in the tubular
cells will cause increased cytotoxic effects
cells will cause increased cytotoxic effects

32. Dopamine
Dopamine
 Dopamine receptors in the afferent
Dopamine receptors in the afferent
arteriole
arteriole
 Dilation of renal vasculature at low doses,
Dilation of renal vasculature at low doses,
constriction at higher doses
constriction at higher doses
 Also causes naturesis (? Reason for
Also causes naturesis (? Reason for
increased UOP after starting)
increased UOP after starting)
 Renal dose dopamine controversy……….
Renal dose dopamine controversy……….

33. Renal Hemodynamics and ARF
Renal Hemodynamics and ARF
 Conclusions….
Conclusions….

Renal vasoconstriction is a well documented
Renal vasoconstriction is a well documented
cause of ARF
cause of ARF

Renal vasodilation does not consistently
Renal vasodilation does not consistently
reduce ARF once established
reduce ARF once established

Although renal hemodynamic factors play a
Although renal hemodynamic factors play a
large role in initiating ARF, they are not the
large role in initiating ARF, they are not the
dominant determinants of cell damage
dominant determinants of cell damage

34. ARF - Pathophysiology
ARF - Pathophysiology
 Damage is caused mostly by renal
Damage is caused mostly by renal
perfusion problems and tubular
perfusion problems and tubular
dysfunction
dysfunction
 Usual causes
Usual causes

Hypo-perfusion and ischemia
Hypo-perfusion and ischemia

Toxin mediated
Toxin mediated

Inflammation
Inflammation

35. ARF – Pathophysiology
ARF – Pathophysiology
 Hypo-perfusion
Hypo-perfusion

Well perfused kidney – 90% of blood to cortex
Well perfused kidney – 90% of blood to cortex

Ischemia – increased blood flow to medulla
Ischemia – increased blood flow to medulla

Outcome may be able to be influenced by
Outcome may be able to be influenced by
restoration of energy/supply demands
restoration of energy/supply demands
• Lasix example
Lasix example

Leads to tubular damage
Leads to tubular damage

36. ARF - Pathophysiology
ARF - Pathophysiology
 Oxidative damage
Oxidative damage

Especially during reperfusion injuries
Especially during reperfusion injuries

Main players
Main players
• Super-oxide anion, hydroxyl radical – highly
Super-oxide anion, hydroxyl radical – highly
ionizing
ionizing
• Hydrogen peroxide, hypochlorous acid – not as
Hydrogen peroxide, hypochlorous acid – not as
reactive, but because of that have a longer half life
reactive, but because of that have a longer half life
and can travel farther and cause injury distal to the
and can travel farther and cause injury distal to the
site of production
site of production

37. ARF - Pathophysiology
ARF - Pathophysiology
 Ischemia
Ischemia

Damage to mitochondrial membrane and
Damage to mitochondrial membrane and
change of xanthine dehydrogenase (NAD
change of xanthine dehydrogenase (NAD
carrier) to xanthine oxidase (produces O2
carrier) to xanthine oxidase (produces O2
radicals)
radicals)

Profound utilization of ATP
Profound utilization of ATP 
 5-10 minutes of
5-10 minutes of
ischemia you use ~90% of your ATP
ischemia you use ~90% of your ATP
• Make lots of adenosine, inosine, hypoxanthine
Make lots of adenosine, inosine, hypoxanthine

38. ATP
ADP
AMP
Adenylosuccinate Adenosine
Inosine
IMP Hypoxanthine
Xanthine
Uric Acid
Allantoin
H20 ∙ O2
H20 ∙ O2
H20 ∙ O2
H2O2
H2O2
CO2

39. ARF - Pathophysiology
ARF - Pathophysiology
 Once you get reperfusion, the hypoxanthine gets
Once you get reperfusion, the hypoxanthine gets
metabolized to xanthine and uric acid – each
metabolized to xanthine and uric acid – each
creating one H
creating one H2
2O
O2
2 and one super-oxide radical
and one super-oxide radical
intermediate
intermediate
 Reactive oxygen species oxidize cellular proteins
Reactive oxygen species oxidize cellular proteins
resulting in:
resulting in:

Change in function/inactivation/activation
Change in function/inactivation/activation

Loss of structural integrity
Loss of structural integrity

Lipid peroxidation (leads to more radical formation)
Lipid peroxidation (leads to more radical formation)

Direct DNA damage
Direct DNA damage

40. ARF Pathophysiology
ARF Pathophysiology
 Amount of damage depends on ability to
Amount of damage depends on ability to
replete ATP stores
replete ATP stores

Continued low ATP leads to disruption of cell
Continued low ATP leads to disruption of cell
cytoskeleton, increased intracellular Ca,
cytoskeleton, increased intracellular Ca,
activation of phospholipases and
activation of phospholipases and
subsequently the apoptotic pathways
subsequently the apoptotic pathways

41. Obligatory
Incomprehensible Pathway
for Jim #2

42. ARF Pathophysiology
ARF Pathophysiology
 Amount of damage depends on ability to
Amount of damage depends on ability to
replete ATP stores
replete ATP stores

Continued low ATP leads to disruption of cell
Continued low ATP leads to disruption of cell
cytoskeleton, increased intracellular Ca,
cytoskeleton, increased intracellular Ca,
activation of phospholipases and
activation of phospholipases and
subsequently the apoptotic pathways
subsequently the apoptotic pathways
 This endothelial cell injury sparks an
This endothelial cell injury sparks an
immune response….that can’t be good….
immune response….that can’t be good….

44. ARF - Prevention
ARF - Prevention
 Maintenance of blood flow
Maintenance of blood flow

Cardiac output, isovolemia, etc
Cardiac output, isovolemia, etc
 Avoidance of toxins
Avoidance of toxins

Aminoglycosides, amphoteracin, NSAIDs
Aminoglycosides, amphoteracin, NSAIDs
 Easy on paper….difficult in practice
Easy on paper….difficult in practice

45. ARF - Prevention
ARF - Prevention
 Lasix
Lasix

May have uses early in ARF
May have uses early in ARF
 Mannitol
Mannitol

May work by
May work by
• Increasing flow through tubules, preventing
Increasing flow through tubules, preventing
obstruction
obstruction
• Osmotic action, decreasing endothelial swelling
Osmotic action, decreasing endothelial swelling
• Decreased blood viscosity with increased renal
Decreased blood viscosity with increased renal
perfusion (???)
perfusion (???)
• Free radical scavenging
Free radical scavenging

46. ARF - Prevention
ARF - Prevention
 Renal dose dopamine….
Renal dose dopamine….
 Endothelin antibodies
Endothelin antibodies

No human trials
No human trials
 Thyroxine
Thyroxine

More rapid improvement of renal function in
More rapid improvement of renal function in
animals
animals

Increased uptake of ADP to form ATP or cell
Increased uptake of ADP to form ATP or cell
membrane stabilization as a possible cause
membrane stabilization as a possible cause

47. ARF - Prevention
ARF - Prevention
 ANP
ANP

Improve renal function and decrease renal
Improve renal function and decrease renal
insufficiency
insufficiency

? Nesiritide role
? Nesiritide role
 Theophyline
Theophyline

Adenosine antagonist – prevents reduction in GFR.
Adenosine antagonist – prevents reduction in GFR.
 Growth Factors
Growth Factors

After ischemic insult, infusion of IGF-I, Epidermal GF,
After ischemic insult, infusion of IGF-I, Epidermal GF,
Hepatocyte GF improved GFR, diminished
Hepatocyte GF improved GFR, diminished
morphologic injury, diminished mortality
morphologic injury, diminished mortality
 None of these things are well tested…..
None of these things are well tested…..

48. ARF – Prevention in Specific Cases
ARF – Prevention in Specific Cases
 Hemoglobinuria/Myoglobinuria
Hemoglobinuria/Myoglobinuria

Mechanism of toxicity
Mechanism of toxicity
• Disassociation to ferrihemate, a tubular toxin, in
Disassociation to ferrihemate, a tubular toxin, in
acidic urine
acidic urine
• Tubular obstruction
Tubular obstruction
• Inhibition of glomerular flow by PGE inhibition or
Inhibition of glomerular flow by PGE inhibition or
increased renin activation
increased renin activation

Treatments (?)
Treatments (?)
• Aggressive hydration to increase UOP
Aggressive hydration to increase UOP
• Alkalinization of urine
Alkalinization of urine
• Mannitol/Furosemide to increase UOP
Mannitol/Furosemide to increase UOP
• ?Early Hemofiltration
?Early Hemofiltration

49. ARF – Prevention in Specific Cases
ARF – Prevention in Specific Cases
 Uric Acid Nephropathy
Uric Acid Nephropathy

A thing of the past thanks to Rasburicase?
A thing of the past thanks to Rasburicase?

Treatments
Treatments
• Aggressive hydration to drive UOP
Aggressive hydration to drive UOP
• Alkalinization of the urine
Alkalinization of the urine
• Xanthine oxidase inhibitors
Xanthine oxidase inhibitors

50. ARF - Management
ARF - Management
 Electrolyte management
Electrolyte management

Sodium
Sodium
• Hyponatremia – fluid restriction first, 3% NaCl if
Hyponatremia – fluid restriction first, 3% NaCl if
AMS or seizing
AMS or seizing

Potassium
Potassium
• Calcium/Bicarb/Glucose/Insulin/Kayexalate
Calcium/Bicarb/Glucose/Insulin/Kayexalate
• Hemodialysis
Hemodialysis

51. ARF - Management
ARF - Management
 Nutrition management
Nutrition management

Initially very catabolic
Initially very catabolic

Goals:
Goals:
• Adequate calories
Adequate calories
• Low protein
Low protein
• Low K and Phos
Low K and Phos
• Decreased fluid intake
Decreased fluid intake

52. Renal Replacement Therapy
Renal Replacement Therapy
 Peritoneal Dialysis
Peritoneal Dialysis
 Acute Intermittent Hemodialysis
Acute Intermittent Hemodialysis
 Continuous Hemofiltration
Continuous Hemofiltration

CAVH
CAVH

SCUF
SCUF

CVVH, CVVHD
CVVH, CVVHD

And others….
And others….

53. Peritoneal dialysis
Peritoneal dialysis
 Simple to set up &
Simple to set up &
perform
perform
 Easy to use in infants
Easy to use in infants
 Hemodynamic stability
Hemodynamic stability
 No anti-coagulation
No anti-coagulation
 Bedside peritoneal access
Bedside peritoneal access
 Treat severe hypothermia
Treat severe hypothermia
or hyperthermia
or hyperthermia
 Unreliable ultrafiltration
Unreliable ultrafiltration
 Slow fluid & solute removal
Slow fluid & solute removal
 Drainage failure & leakage
Drainage failure & leakage
 Catheter obstruction
Catheter obstruction
 Respiratory compromise
Respiratory compromise
 Hyperglycemia
Hyperglycemia
 Peritonitis
Peritonitis
 Not good for
Not good for
hyperammonemia or
hyperammonemia or
intoxication with dialyzable
intoxication with dialyzable
poisons
poisons
Advantages Disadvantages

54. Intermittent Hemodialysis
Intermittent Hemodialysis
 Maximum solute
Maximum solute
clearance of 3
clearance of 3
modalities
modalities
 Best therapy for severe
Best therapy for severe
hyperkalemia
hyperkalemia
 Limited anti-coagulation
Limited anti-coagulation
time
time
 Bedside vascular
Bedside vascular
access can be used
access can be used
 Hemodynamic instability
Hemodynamic instability
 Hypoxemia
Hypoxemia
 Rapid fluid and
Rapid fluid and
electrolyte shifts
electrolyte shifts
 Complex equipment
Complex equipment
 Specialized personnel
Specialized personnel
 Difficult in small infants
Difficult in small infants
Advantages Disadvantages

55. Continuous Hemofiltration
Continuous Hemofiltration
 Easy to use in PICU
Easy to use in PICU
 Rapid electrolyte correction
Rapid electrolyte correction
 Excellent solute clearances
Excellent solute clearances
 Rapid acid/base correction
Rapid acid/base correction
 Controllable fluid balance
Controllable fluid balance
 Tolerated by unstable pts.
Tolerated by unstable pts.
 Early use of TPN
Early use of TPN
 Bedside vascular access
Bedside vascular access
routine
routine
 Systemic
Systemic
anticoagulation
anticoagulation
(except citrate)
(except citrate)
 Frequent filter clotting
Frequent filter clotting
 Vascular access in
Vascular access in
infants
infants
Advantages Disadvantages

56. Indications for RRT
Indications for RRT
 Still evolving….Generally accepted
Still evolving….Generally accepted

Oliguria/Anuria
Oliguria/Anuria

Hyperammonemia
Hyperammonemia

Hyperkalemia
Hyperkalemia

Severe acidemia
Severe acidemia

Severe azotemia
Severe azotemia

Pulmonary Edema
Pulmonary Edema

Uremic complications
Uremic complications

Severe electrolyte abnormalities
Severe electrolyte abnormalities

Drug overdose with a filterable toxin
Drug overdose with a filterable toxin

Anasarca
Anasarca

Rhabdomyolysis
Rhabdomyolysis