Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo...
Transcript of Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo...
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www.philippelefevre.com
Acute Renal Failure
usually a consequence
Thursday, 10 February 2011
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•Definitions
•Pathogenisis
•Classification
•ICU Incidence/ Significance
•Treatments
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Prerenal Azotaemia
IntrarenalBaroreceptors
NaCl delivery to Macula Densa
CardiopulmonaryBaroreceptors
afferent vasodilatation
autoregulationRenin
RBFGRF
Blood Pressure
Sympathetic Drive
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Prerenal Azotaemia
IntrarenalBaroreceptors
NaCl delivery to Macula Densa
CardiopulmonaryBaroreceptors
afferent vasodilatation
autoregulationRenin
RBFGRF
Blood Pressure
Sympathetic Drive
GFR = permeability x surface area x net filtration pressure
Plasma Urea & Creatinine ∝ GFR
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Prerenal Azotaemia
IntrarenalBaroreceptors
NaCl delivery to Macula Densa
CardiopulmonaryBaroreceptors
afferent vasodilatation
autoregulationRenin
RBFGRF
Blood Pressure
Sympathetic Drive
Thursday, 10 February 2011
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ACE
angiotensinogen angiotensin I
angiotensin II
vasoconstriction
↓ noradrenalinreuptake
ADH &ACTH
aldosterone
Renin
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ACE
angiotensinogen angiotensin I
angiotensin II
vasoconstriction
↓ noradrenalinreuptake
ADH &ACTH
aldosterone
Salt Retention
Renin
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Prerenal Azotaemia
Prerenal Azotaemia
Urine Osmolality (mOsm/Kg) >500
Urine Sodium (mmol/l) <20
Urine/ Plasma Creatinine ratio >40
FENa <1%
FEUrea <35%
Urinary Sedimentoccasional hyaline or fine
granular casts
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Pathogenesis: Vascular Factors
Medulla30% O2 requirement10% Blood supply
Cortex70% O2 requirement90% Blood supply
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Pathogenesis: Vascular Factors
RenalBlood Flow
Oxygen Demand
Medulla30% O2 requirement10% Blood supply
Cortex70% O2 requirement90% Blood supply
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Pathogenesis: Vascular Factors
Ischaemia
RenalBlood Flow
Oxygen Demand
Medulla30% O2 requirement10% Blood supply
Cortex70% O2 requirement90% Blood supply
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Pathogenesis: Vascular Factors
Ischaemia
RenalBlood Flow
Oxygen Demand
Medulla30% O2 requirement10% Blood supply
Cortex70% O2 requirement90% Blood supply
Loss of Autoregulation
IntracellularCalcium
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Pathogenisis: Vascular Factors
Blood Pressure
IntrarenalBaroreceptorsRBF
GRF
CardiopulmonaryBaroreceptors
Sympathetic Drive
autoregulation
afferent vasodilatation
ReninNaCl delivery to Macula Densa
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Pathogenisis: Vascular Factors
Blood Pressure
IntrarenalBaroreceptorsRBF
GRF
CardiopulmonaryBaroreceptors
Sympathetic Drive
afferent vasoconstriction
ReninNaCl delivery to Macula Densa
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Prerenal Azotaemia
Urine Osmolality (mOsm/Kg) >500
Urine Sodium (mmol/l) <20
Urine/ Plasma Creatinine ratio >40
FENa <1%
FEUrea <35%
Urinary Sedimentoccasional hyaline or fine
granular casts
Acute Renal Failure
Thursday, 10 February 2011
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Prerenal Azotaemia Acute Renal failure
Urine Osmolality (mOsm/Kg) >500 <400
Urine Sodium (mmol/l) <20 >40
Urine/ Plasma Creatinine ratio >40 <40
FENa <1% >2%
FEUrea <35% >35%
Urinary Sedimentoccasional hyaline or fine
granular caststubular cells, coarse
granular casts
Acute Renal Failure
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Pathogenesis: Tubular Factors
Na/K ATPase
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Pathogenesis: Tubular Factors
Loss ofBrush Border
Loss ofPolarity
Na/K ATPase
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Pathogenesis: Tubular Factors
Loss ofBrush Border
Loss ofPolarity
Na/K ATPase
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Pathogenesis: Tubular Factors
Necrosis
Sloughing of Viable Epithelial Cells
Na/K ATPase
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Pathogenesis: Tubular Factors
Necrosis
Sloughing of Viable Epithelial Cells
Na/K ATPase
Inflammatory Infiltration
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Pathogenesis: Tubular Factors
Na/K ATPase
Adjacent tubule cells
Haematopoietic cells
Kidney stem cells
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Pathogenesis: Tubular Factors
Na/K ATPase
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Pathogenesis: Summary
Initiation
• Prerenal azotaemia• Loss of autoregulation• Intracellular calcium• ATD Depletion• Oxidative injury
Extension
• Loss of tubular cell polarity• Cell necrosis• Medullary congestion• GFR• Inflammatory infiltration
MaintenanceTubular histology is rebuilt by:• Adjacent tubule cells• Kidney stem cells• Haematopoietic cells
Repair Polarity and function restored
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Pathogenesis: Summary
Initiation
• Prerenal azotaemia• Loss of autoregulation• Intracellular calcium• ATD Depletion• Oxidative injury
Extension
• Loss of tubular cell polarity• Cell necrosis• Medullary congestion• GFR• Inflammatory infiltration
MaintenanceTubular histology is rebuilt by:• Adjacent tubule cells• Kidney stem cells• Haematopoietic cells
Repair Polarity and function restored
Thursday, 10 February 2011
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Pathogenesis: Summary
Initiation
• Prerenal azotaemia• Loss of autoregulation• Intracellular calcium• ATD Depletion• Oxidative injury
Extension
• Loss of tubular cell polarity• Cell necrosis• Medullary congestion• GFR• Inflammatory infiltration
MaintenanceTubular histology is rebuilt by:• Adjacent tubule cells• Kidney stem cells• Haematopoietic cells
Repair Polarity and function restored
Thursday, 10 February 2011
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Pathogenesis: Summary
Initiation
• Prerenal azotaemia• Loss of autoregulation• Intracellular calcium• ATD Depletion• Oxidative injury
Extension
• Loss of tubular cell polarity• Cell necrosis• Medullary congestion• GFR• Inflammatory infiltration
MaintenanceTubular histology is rebuilt by:• Adjacent tubule cells• Kidney stem cells• Haematopoietic cells
Repair Polarity and function restored
Thursday, 10 February 2011
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Pathogenesis: Tubular Factors
Maintenance PhaseExtension Phase
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RIFLE the Acute Dialysis Quality Initiative
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RIFLE
Indicator Classes
Risk
Injury
Failure
the Acute Dialysis Quality Initiative
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RIFLE
Indicator Classes
Risk
Injury
Failure
Outcome ClassesLoss
End-stage Kidney Disease
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004, 8:R204-R212
the Acute Dialysis Quality Initiative
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RIFLE: Classification
GFR (Serum Creatinine) Urine Output (ml/Kg/hr)
Risk x 1.5 < 0.5 for 6 hours
Injury 6.1% < 0.5 for 12 hours
Failure 4.4%< 0.3 for 24 hours
or anuria for 12 hours
Loss Complete loss of kidney disease > 4 weeksComplete loss of kidney disease > 4 weeks
End-stage Complete loss of kidney disease > 3 monthsComplete loss of kidney disease > 3 months
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RIFLE: In Practice
• n = 5383 patients
• Pittsburg University Hospital 2006
At Admission Ever Mortality (HR)
No ARF 78% 33%
Risk 8% 12% 1.0 (0.68 - 1.56)
Injury 7% 27% 1.4 (1.02 - 1.88)
Failure 7% 28% 2.7 (2.03 - 3.55)
E A Hoste, G Clermont, A Kersten et al: RIFLE critereria for acute kidney injury. Crit Care 2006, 10:R73
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RIFLE: In Practice
• n = 5383 patients
• Pittsburg University Hospital 2006
At Admission Ever Mortality (HR)
No ARF 78% 33%
Risk 8% 12% 1.0 (0.68 - 1.56)
Injury 7% 27% 1.4 (1.02 - 1.88)
Failure 7% 28% 2.7 (2.03 - 3.55)
E A Hoste, G Clermont, A Kersten et al: RIFLE critereria for acute kidney injury. Crit Care 2006, 10:R73
52%
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Preventions
• Cause Prevention
• Loop Diuretics
• Osmotic Diuretics
• Ca Channel Blockers
• N-Acetylcysteine
• Theophyllines
Treatments
• Loop Diuretics
• Natriuretic Peptides
• Dopamine/ Fenoldopam
• Dialysis Mode
• Dialysis Dosing
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Prevention & Treatment: Frusemide
• Inhibits Na/K/Cl channel in ascending Loop-of-Henley
• Reduced intracellular substrate for Na/K ATPase
• Reduced energy consumption in the critical outer medulla (by 45% in-vitro)
• Wash out tubular debris
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Prevention & Treatment: Frusemide
• 9 RCT
• n = 849
• In or at risk of ARF
• Heterogeneous selection criteria
• Many methodological problems
• Ototoxic
K M Ho, D J Sheridan: Meta-analysis of frusemide to prevent or treat acute renal failre. BMJ 2006, doi:10.1136/bmj.38902.605347.7C
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Prevention & Treatment: Frusemide
Prevention
Treatment
Renal Replacement Therapy Mortality
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Prevention: Ca Channel Blockers
Kribben, A, et al. Evidence for role of cytosolic free calcium in hypoxia-induced proximal tubule injury. J. Clin. Invest. 1994;93:1922–1929
Ca Blockade
Untreated
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Prevention: Ca Channel Blockers
V Riemsdijk, et al. Isradipine results in a beter renal function after kidney transplant. Transplantation. 2000;70:122–126
• n = 210
• Better serum creatinine at 3 months and 12 months post for patients receiving live or cadaveric kidney transplant
• Poor quality evidence.
• Adverse effects not reported.
• Other, trials (cumulatively larger) limited to cadaveric transplants have failed to find a benefit
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Treatment: Dopamine/ Fenoldopam
• Based on the vasomotor nephropathy model
• Correct aberrant vascular responses and improve renal blood supply
• Good in-vitro evidence to show improved RBF & GFR
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Treatment: Dopamine/ Fenoldopam
• 58 RCT
• n = 2149
• No difference from placebo in mortality or renal replacement therapy
• This review did not list adverse effects but we know dopamine can cause:
• Extravasation necrosis
• Arythmias
• Headaches
Kellum J A, Decker J M: The use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001;29:1526-1531
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Treatment: Dialysis Dose
• The biggest RCT
• n = 425
• CVVHF
• 20 / 30 / 45 (ml/Kg/hour)
• Low dose substantially inferior to higher two cohorts
• Three-way comparison:
• RR = 1.88 (1.14 - 1.67)
• NNT = 7 (4 - 16)
Ronco C, Bellomo R, Homel et al. Effects of different doses in continious veno-veno heamofiltration on outcomes of renal failure. Lancet 200;356:26-30
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Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
Thursday, 10 February 2011
![Page 45: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/45.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
Thursday, 10 February 2011
![Page 46: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/46.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
Thursday, 10 February 2011
![Page 47: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/47.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
Thursday, 10 February 2011
![Page 48: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/48.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
Thursday, 10 February 2011
![Page 49: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/49.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
Thursday, 10 February 2011
![Page 50: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/50.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
Thursday, 10 February 2011
![Page 51: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/51.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
↔
↔
↔
↔
✔ High dose
Thursday, 10 February 2011
![Page 52: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/52.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
↔
↔
↔
↔
✔ High dose
Thursday, 10 February 2011
![Page 53: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/53.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
↔
↔
↔
↔
✔ High dose
Thursday, 10 February 2011
![Page 54: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/54.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
↔
↔
↔
↔
✔ High dose
Thursday, 10 February 2011
![Page 55: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/55.jpg)
Interventions: Summary
Prevention
Cause Prevention
Loop Diuretics
Osmotic Diuretics
Ca Channel Blockers
N-Acetylcysteine
Theophyllines
Treatment
Loop Diuretics
Natriuretic Peptides
Dopamine
Dialysis Mode
Dialysis Dosing
✔ ✔
↔
↔
↔
✔
↔
↔
↔
↔
↔
✔ High dose
Thursday, 10 February 2011
![Page 56: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/56.jpg)
Questions
Thursday, 10 February 2011
![Page 57: Acute Renal Failure · 2019-11-18 · Failure Outcome Classes Loss End-stage Kidney Disease Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, the ADQI workgroup: Acute renal failure](https://reader033.fdocuments.in/reader033/viewer/2022042408/5f231f70a127b175cf2ebe2b/html5/thumbnails/57.jpg)
Key points
• RIFLE is the future of ARF research
• Preventing the causes of ARF is our best strategy
• Frusemide for fluid management only
Thursday, 10 February 2011