acute and chronic renal-failure discussion.ppt

RN discussion on renal failure

1. Acute Renal FailureAcute Renal Failure

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

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

4. Glomerular Filtration RateGlomerular Filtration Rate
Determined by the hydrostatic and oncotic Determined by the hydrostatic and oncotic
pressure within the nephronpressure 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 tubuleoutflow of filtrate into the tubule
Oncotic pressure in the glomerulus is the Oncotic pressure in the glomerulus is the
result of non-filterable proteinsresult of non-filterable proteins

Greater oncotic pressure as you progress through Greater oncotic pressure as you progress through
the glomerulusthe glomerulus
GFR = Kf (hydrostatic – oncotic pressure)GFR = Kf (hydrostatic – oncotic pressure)

6. Glomerular Filtration RateGlomerular Filtration Rate
The capillary endothelium is surrounded The capillary endothelium is surrounded
by a basement membrane and podocytesby 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 passageAllow for ultrafiltrate passage

Limit filtration of large negatively charged Limit filtration of large negatively charged
particlesparticles
•Less than 5,000 daltons = freely filteredLess than 5,000 daltons = freely filtered
•Large particles (albumin 69,000 daltons) not Large particles (albumin 69,000 daltons) not
filteredfiltered

7. Tubular FunctionTubular Function

ProximalProximal

Most of reabsorption occurs hereMost of reabsorption occurs here

Fluid is isotonic with plasmaFluid is isotonic with plasma

66-70% of sodium presented is reabsorbed66-70% of sodium presented is reabsorbed

Glucose and amino acids are completely Glucose and amino acids are completely
reabsorbed reabsorbed

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

9. Tubular FunctionTubular 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 ARFdamaged in ARF

ADH stimulates Na re-absorption in this areaADH stimulates Na re-absorption in this area

Most sensitive to ischemiaMost sensitive to ischemia
•Low oxygen tension, high oxygen consumptionLow 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 ARFseverity of the ARF

10. Tubular FunctionTubular Function

All of those studies done in an in vitro All of those studies done in an in vitro
modelmodel

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 workloaddamage 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 FunctionTubule Function

Distal TubuleDistal Tubule

Re-absorption of another ~12% of NaClRe-absorption of another ~12% of NaCl

Proximal segment – impermeable to waterProximal segment – impermeable to water

Distal segment is the cortical collecting duct Distal segment is the cortical collecting duct
and secretes K and HCO3and secretes K and HCO3

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

13. Acute Renal Failure - DefinitionsAcute Renal Failure - Definitions

Renal failureRenal 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 volumein urine volume

AnuriaAnuria – UOP < 0.5 cc/kg/hour – UOP < 0.5 cc/kg/hour

OliguriaOliguria – UOP “more than 1 cc/kg/hour” – UOP “more than 1 cc/kg/hour”

Less than?Less than?

14. Acute Renal Failure - DefinitionsAcute Renal Failure - Definitions

70% Non-oliguric , 30% Oliguric70% Non-oliguric , 30% Oliguric

Non-oliguric associated with better Non-oliguric associated with better
prognosis and outcomeprognosis 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 - DiagnosisAcute Renal Failure - Diagnosis

Pre-renalPre-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 RBFdoes 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 GFRattempt 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 FailurePre-Renal vs. Renal Failure
PrerenalPrerenal RenalRenal
BUN/CrBUN/Cr >20>20 <20<20
FENaFENa <1%<1% >2%>2%
Renal Failure IndexRenal Failure Index <1%<1% >1%>1%
UU
NaNa <20 mEq/L<20 mEq/L >40 mEq/L>40 mEq/L
Specific GravitySpecific Gravity >1.020>1.020 <1.010<1.010
UU
osmosm >500 mOsm/L>500 mOsm/L<350 mOsm/L<350 mOsm/L
UU
osmosm/P/P
osmosm >1.3>1.3 <1.3<1.3
Renal Lecture Required Picture #3

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

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

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

20. Renin-Angiotensin AxisRenin-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 AxisRenin Angiotensin Axis
Renal Lecture Required
Picture #4

22. Renin Angiotensin AxisRenin Angiotensin Axis
Renin’s role in pathogenesis of ARFRenin’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 ARFmodels of ARF

Increased plasma renin activity in ARF Increased plasma renin activity in ARF
patientspatients

Changing intra-renal renin content modifies Changing intra-renal renin content modifies
degree of damagedegree 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 dietthose fed a low sodium diet

23. Renin Angiotensin AxisRenin Angiotensin Axis

Not the only thing going on thoughNot 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 IIangiotensin II

Overall, role of RAS in ARF is uncertainOverall, role of RAS in ARF is uncertain

24. ProstaglandinsProstaglandins
PGE 2 and PGIPGE 2 and PGI

Very important for renal vasodilation, Very important for renal vasodilation,
especially in the injured kidneyespecially in the injured kidney

Act as a buffer against uncontrolled A2 Act as a buffer against uncontrolled A2
mediated constrictionmediated constriction
•If you constrict the afferent arteriole, you will If you constrict the afferent arteriole, you will
decrease GFRdecrease 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. AdenosineAdenosine

Potent renal vasoconstrictorPotent renal vasoconstrictor

Peripheral vasodilatorPeripheral 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 damageGFR 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 ARFmethylxanthines lessen renal injury in ARF

26. AdenosineAdenosine
But…. Likely not a major factor in ARFBut…. Likely not a major factor in ARF

Methylxanthines have lots of other actions Methylxanthines have lots of other actions
besides adenosine blockadebesides adenosine blockade

Adenosine is rapidly degraded after Adenosine is rapidly degraded after
productionproduction

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 periodvasocontriction 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 recoveryof renal recovery

27. EndothelinEndothelin

21 amino acid peptide that is one of the most 21 amino acid peptide that is one of the most
potent vasoconstrictors in the bodypotent vasoconstrictors in the body

Can be used as a pressorCan be used as a pressor

Its role in unclear in normal stateIts 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 GFRafferent flow and thus decreased RBF and GFR

Endothelin increases mesangial cell contraction which Endothelin increases mesangial cell contraction which
reduces glomerular ultrafiltrationreduces glomerular ultrafiltration

Stimulates ANP release at low doses and can Stimulates ANP release at low doses and can
increase UOPincrease UOP

Anti-endothelin antibodies or endothelin receptor Anti-endothelin antibodies or endothelin receptor
antagonists decrease ARF in experimental antagonists decrease ARF in experimental
modelsmodels

28. Nitric OxideNitric Oxide
Produced by multiple iso-enzymes of NOSProduced 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-absorptionhas a role in sodium re-absorption

Give a NOS blocker and you get naturesisGive a NOS blocker and you get naturesis
Important in the overall homeostasis of Important in the overall homeostasis of
RBFRBF
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 OxideNitric Oxide

Confusing resultsConfusing results

Ischemic rat kidney model – inducing NOS Ischemic rat kidney model – inducing NOS
causes increasing injurycauses increasing injury

Hypoxic tubular cell culture model – inducing Hypoxic tubular cell culture model – inducing
NOS causes increasing injuryNOS 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
vasoconstrictionvasoconstriction

31. Nitric OxideNitric 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 effectscells will cause increased cytotoxic effects

32. DopamineDopamine

Dopamine receptors in the afferent Dopamine receptors in the afferent
arteriolearteriole

Dilation of renal vasculature at low doses, Dilation of renal vasculature at low doses,
constriction at higher dosesconstriction 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 ARFRenal Hemodynamics and ARF

Conclusions….Conclusions….

Renal vasoconstriction is a well documented Renal vasoconstriction is a well documented
cause of ARFcause of ARF

Renal vasodilation does not consistently Renal vasodilation does not consistently
reduce ARF once establishedreduce 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 damagedominant determinants of cell damage

34. ARF - PathophysiologyARF - Pathophysiology

Damage is caused mostly by renal Damage is caused mostly by renal
perfusion problems and tubular perfusion problems and tubular
dysfunctiondysfunction

Usual causesUsual causes

Hypo-perfusion and ischemiaHypo-perfusion and ischemia

Toxin mediatedToxin mediated

InflammationInflammation

35. ARF – PathophysiologyARF – Pathophysiology

Hypo-perfusionHypo-perfusion

Well perfused kidney – 90% of blood to cortexWell perfused kidney – 90% of blood to cortex

Ischemia – increased blood flow to medullaIschemia – 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 demandsrestoration of energy/supply demands
•Lasix exampleLasix example

Leads to tubular damageLeads to tubular damage

36. ARF - PathophysiologyARF - Pathophysiology

Oxidative damageOxidative damage

Especially during reperfusion injuriesEspecially during reperfusion injuries

Main playersMain 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 productionsite of production

37. ARF - PathophysiologyARF - Pathophysiology

IschemiaIschemia

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 ATPischemia you use ~90% of your ATP
•Make lots of adenosine, inosine, hypoxanthineMake lots of adenosine, inosine, hypoxanthine

38. ATP
ADP
AMP
Adenylosuccinate
Adenosine
InosineIMP
Hypoxanthine
Xanthine
Uric Acid
Allantoin
H
2
0 ∙ O
2
H
2
0 ∙ O
2
H
2
0 ∙ O
2
H
2
O
2
H
2
O
2
CO
2

39. ARF - PathophysiologyARF - 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 Hcreating one H
22OO
22 and one super-oxide radical and one super-oxide radical
intermediateintermediate

Reactive oxygen species oxidize cellular proteins Reactive oxygen species oxidize cellular proteins
resulting in:resulting in:

Change in function/inactivation/activationChange in function/inactivation/activation

Loss of structural integrityLoss of structural integrity

Lipid peroxidation (leads to more radical formation)Lipid peroxidation (leads to more radical formation)

Direct DNA damageDirect DNA damage

40. ARF PathophysiologyARF Pathophysiology

Amount of damage depends on ability to Amount of damage depends on ability to
replete ATP storesreplete 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 pathwayssubsequently the apoptotic pathways

41. Obligatory
Incomprehensible Pathway
for Jim #2

42. ARF PathophysiologyARF Pathophysiology

Amount of damage depends on ability to Amount of damage depends on ability to
replete ATP storesreplete 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 pathwayssubsequently 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 - PreventionARF - Prevention

Maintenance of blood flowMaintenance of blood flow

Cardiac output, isovolemia, etcCardiac output, isovolemia, etc

Avoidance of toxinsAvoidance of toxins

Aminoglycosides, amphoteracin, NSAIDsAminoglycosides, amphoteracin, NSAIDs

Easy on paper….difficult in practiceEasy on paper….difficult in practice

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

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

47. ARF - PreventionARF - Prevention
ANPANP

Improve renal function and decrease renal Improve renal function and decrease renal
insufficiencyinsufficiency

? Nesiritide role? Nesiritide role
TheophylineTheophyline

Adenosine antagonist – prevents reduction in GFR.Adenosine antagonist – prevents reduction in GFR.
Growth FactorsGrowth 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 mortalitymorphologic injury, diminished mortality
None of these things are well tested…..None of these things are well tested…..

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

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

50. ARF - ManagementARF - Management

Electrolyte managementElectrolyte management

SodiumSodium
•Hyponatremia – fluid restriction first, 3% NaCl if Hyponatremia – fluid restriction first, 3% NaCl if
AMS or seizingAMS or seizing

PotassiumPotassium
•Calcium/Bicarb/Glucose/Insulin/KayexalateCalcium/Bicarb/Glucose/Insulin/Kayexalate
•HemodialysisHemodialysis

51. ARF - ManagementARF - Management

Nutrition managementNutrition management

Initially very catabolicInitially very catabolic

Goals:Goals:
•Adequate caloriesAdequate calories
•Low proteinLow protein
•Low K and PhosLow K and Phos
•Decreased fluid intakeDecreased fluid intake

52. Renal Replacement TherapyRenal Replacement Therapy

Peritoneal DialysisPeritoneal Dialysis

Acute Intermittent HemodialysisAcute Intermittent Hemodialysis

Continuous HemofiltrationContinuous Hemofiltration

CAVHCAVH

SCUFSCUF

CVVH, CVVHDCVVH, CVVHD

And others….And others….

53. Peritoneal dialysisPeritoneal dialysis

Simple to set up & Simple to set up &
performperform

Easy to use in infantsEasy to use in infants

Hemodynamic stabilityHemodynamic stability

No anti-coagulationNo anti-coagulation

Bedside peritoneal accessBedside peritoneal access

Treat severe hypothermia Treat severe hypothermia
or hyperthermiaor hyperthermia

Unreliable ultrafiltrationUnreliable ultrafiltration

Slow fluid & solute removalSlow fluid & solute removal

Drainage failure & leakageDrainage failure & leakage

Catheter obstructionCatheter obstruction

Respiratory compromiseRespiratory compromise

HyperglycemiaHyperglycemia

PeritonitisPeritonitis

Not good for Not good for
hyperammonemia or hyperammonemia or
intoxication with dialyzable intoxication with dialyzable
poisonspoisons
Advantages Disadvantages

54. Intermittent HemodialysisIntermittent Hemodialysis

Maximum solute Maximum solute
clearance of 3 clearance of 3
modalitiesmodalities

Best therapy for severe Best therapy for severe
hyperkalemiahyperkalemia

Limited anti-coagulation Limited anti-coagulation
timetime

Bedside vascular Bedside vascular
access can be usedaccess can be used

Hemodynamic instabilityHemodynamic instability

HypoxemiaHypoxemia

Rapid fluid and Rapid fluid and
electrolyte shiftselectrolyte shifts

Complex equipmentComplex equipment

Specialized personnelSpecialized personnel

Difficult in small infantsDifficult in small infants
Advantages Disadvantages

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

56. Indications for RRTIndications for RRT

Still evolving….Generally acceptedStill evolving….Generally accepted

Oliguria/AnuriaOliguria/Anuria

HyperammonemiaHyperammonemia

HyperkalemiaHyperkalemia

Severe acidemiaSevere acidemia

Severe azotemiaSevere azotemia

Pulmonary EdemaPulmonary Edema

Uremic complicationsUremic complications

Severe electrolyte abnormalitiesSevere electrolyte abnormalities

Drug overdose with a filterable toxinDrug overdose with a filterable toxin

AnasarcaAnasarca

RhabdomyolysisRhabdomyolysis