Dr. Osama El-ShahatConsultant Nephrologist

Head of Nephrology department-NMGH (Egypt)

ObjectivesObjectives

Treatment Non- dialytic support Dialytic support

DiagnosisIncidence Mortality Biomarkers

DefinatinonARF AKI

ARF AKI

1802: Ischuria Renalis (William Heberden)

1909: Acute Bright’s Disease (William Osler)

W.W.I: War Nephritis

W.W.II: Acute Kidney Insufficiency (Bywaters & Beall)

1951: Acute Renal Failure (Homer W. Smith)

2006 : Acute Kidney Injury (AKI Network)

By AKI we actually mean “loss of small solute clearance” (urea/creatinine increase in blood)

This implies loss of GFR

So…clinically we actually mean

“acute decrease in GFR”

What do we mean by AKI?What do we mean by AKI?

Lameire N, Van BW, Vanholder R. Nat Clin Pract Nephrol 2006; 2: 364–377.

Can we do staging for AKI?

AKIN Classification

RIFLE Versus AKINRIFLE Versus AKIN

Nephrology Self-Assessment Program - Vol 10, No 3, May 2011

The use of the RIFLE system resulted in a higher detection

rate of AKI during the first 48 hours of ICU stay.

What is the advantages of RIFLE Criteria ?

Applying the RIFLE criteria revealed new insights.

Firstly,the RIFLE classification is feasible and fairly straightforward.

Secondly, the patients categorized as RIFLE-F had a far higher mortality than RIFLE-I and -R patients.

Max Bell et al; Nephrol Dial Transplant 2005 20:354 –360

Number of ARF Hospitalizations: Number of ARF Hospitalizations: 19791979 to to 20022002Rates per 1,000 personsRates per 1,000 persons

0.0

0.5

1.0

1.5

2.0

2.5

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002

Source: National Center for Health Statistics, National Hospital Discharge Survey

Mortality in Sepsis and RIFLE

Critical Care 2007; 11:411

Causes of AKICauses of AKI

Pre renal Intrinsic renal Post renal

Decrease in effective

blood volume.Arterial

occlusionOr

stenosis.Homodynamic

Form.

VascularVasculitis.Malignant

hypertension

Acute Glomerulonephritis

AcuteInterstitialnephritis

Acute Tubularnecrosis

Ischemic. Nephrotoxic.

ObstructionOf

CollectingSystem

OrExtra renaldrainage

ExogenousAntibiotic

Radio contrastcisplatin

EndogenousIntra tubular pigmentIntra tubular protein.Intra tubular crystal.

CAUSES OF AKI

Post-OP, sepsis, shock,multi-organ

failure 70%

Post-OP, sepsis, shock,multi-organ

failure 70%

Obstructive uropathy 15%

Obstructive uropathy 15%

Glomerulonephritis 5%Glomerulonephritis 5%

Nephrotoxic agents 10%Nephrotoxic agents 10% reduced blood flowreduced blood flow

ischemiaischemia

acute tubular necrosisacute tubular necrosis

Findings that suggest prerenal causes:Volume depletionCongestive heart failureSevere liver disease or other edematous states

Findings that suggest postrenal causes:Palpable bladder or hydronephrotic kidneysEnlarged prostateAbnormal pelvic examinationLarge residual bladder urine volumeHistory of renal calculi,

Findings that suggest intrinsic renal disease:

Exposure to nephrotoxic drugs or hypotensiveRecent radiographic procedures with contrast

Examine the urine sediment:

•If no abnormalities: suspect prerenal or postrenal azotemia•If eosinophils: suspect acute interstitial nephritis•If red blood cell casts: suspect glomerulonephritis or vasculitis•If renal tubular epithelial cells and muddy brown casts: suspect acute tubular necrosis

Findings that suggest prerenal azotemia :

Urinary sodium concentration <20 mEq/LUrine : plasma creatinine ratio >30Renal failure index <1Renal failure index Renal failure index = (urinary sodium concentration × plasma creatinine concentration)/urinary creatinine concentrationUrine osmolality >500 mOsm/kg

Findings that suggest acute tubular necrosis or postrenal azotemia: Urinary sodium concentration >40 mEq/LUrine:plasma creatinine ratio <20Renal failure index >1Urine osmolality <400 mOsm/kg

Timing nephrology consultationTiming nephrology consultation (Mehta, Am J Med 2002)

In-hospital mortalityEarlyEarly

consult

Delayed Delayed

consultP

40%67%<0,001

Early nephrologist involvement in patients with AKI may reduce the risk of a further decrease in kidney function.

Am J Kidney Dis. 2011;57(2):228-234

New urinary biomarkers for the early detection of acute kidney disease

Han, Bonventre,Current Opin Crit Care 2004, 10:476–482

Neutrophil gelatinase associated lipocalin

Early detection of AKI by Cystatin C

Definition of AFArea under the ROC

Day - 2Day - 1Day 0

≥ 50 % increase0.820.970.99

≥ 100 % increase0.920.980.98

≥ 200 % increase0.970.990.99

•Changes in cystatin C were able to detect the onset of AKI one to two days earlier than comparable changes in serum creatinine

1. RIFLE- R ( ≥ 50 % increase ): 1.5 ± 0.6 days earlier2. RIFLE- I ( ≥ 100 % increase): 1.2 ± 0.9 days earlier3. RIFLE- F ( ≥ 200 % increase): 1.0 ± 0.6 days earlier

Herget-Rosenthal et al, Kidney Int 2004, 66: 1115- 1122

Loop diuretics in AKI

Diuretics, particularly high doses of loop diuretics, are frequently administered to patients with acute renal failure. This is done in part in an attempt to convert oliguric to nonoliguric acute renal failure.

However, a retrospective observational report found that the use of diuretics in this setting may increase the risk of death and no recovery of renal

function.

3.4.13.4.1: We recommend not using diuretics to prevent AKI. (1B1B)

3.4.23.4.2: We suggest not using diuretics to treat AKI, except in the

management of volume overload. (2C2C)

There is insufficient evidence that the low-There is insufficient evidence that the low-dose dopamine improves survival or obviates the dose dopamine improves survival or obviates the

need for dialysis in persons with acute renal failure. need for dialysis in persons with acute renal failure. The routine use of low-dose dopamine should be The routine use of low-dose dopamine should be

discouraged until a prospective, randomized, discouraged until a prospective, randomized, placebo-controlled trial establishes its safety and placebo-controlled trial establishes its safety and

efficacy.efficacy.

Is the administration of dopamine associated with adverse or favorable outcomes in acute renal failure? Auriculin Anaritide Acute Renal

Failure Study Group.

Low Dose Dopamine in Low Dose Dopamine in AKIAKI

3.5.13.5.1: We recommend not using low-dose dopamine to prevent or treat AKI. (1A)

IV Fluids in AKI

3.1.13.1.1: In the absence of hemorrhagic shock, we

suggest using isotonic crystalloids rather than

colloids (albumin or starches) as initial

management for expansion of intravascular

volume in patients at risk for AKI or with AKI.

(2B2B)

Contrast Induced AKI

4.4.14.4.1 :We recommend i.v. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no i.v.

volume expansion, in patients at increased risk for CI-AKI. (1A1A)

4.5.14.5.1 :We suggest not using prophylactic intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast-media removal in patients at

increased risk for CI-AKI. (2C2C)

4.4.34.4.3 :We suggest using oral NAC, together with i.v. isotonic

crystalloids, in patients at increased risk of CI-AKI. (2D2D)

4.3.24.3.2: We recommend using either iso-osmolar or low-osmolar iodinated contrast media, rather than high-osmolar iodinated contrast

media in patients at increased risk of CI-AKI. (1B1B)

Bicarbonate or Saline

Among the large

randomized trials there was

no evidence of benefit for

hydration with sodium

bicarbonate compared with

sodium chloride for the

prevention of CI-AKI.

Contrast Induced AKI

Stage-based management

General Principles

Stage 1 (RiskRisk)

Risk for more severe AKI

Monitor (prevent progression)

Stage 2 (InjuryInjury)

Risk of AKI-related mortality/morbidi

ty highConservative therapy)

Stage 3 (FailureFailure)

Highest risk of death

Consider RRT Avoid subclavian catheters if possible

Discontinue all nephrotoxic agents when possible

Consider invasive diagnostic workup

Consider Renal Replacement Therapy

1 2 3

Non-invasive diagnostic workup

Ensure volume status and perfusion pressure

Check for changes in drug dosing

AKI Stage

Consider functional hemodynamic monitoring

Monitoring Serum creatinine and urine output

Consider ICU admission

Avoid hyperglycemia

Consider alternatives to radiocontrast procedures

Risk InjuryFailure

High Risk

Indications for RRT in critically ill AKI patients

Renal Indications

Life-threatening indications

Hyperkalemia Metabolic Acidosis Pulmonary edema Uremic omplications

Gibney et al, Clin J Am Soc Nephrol 2008

5.1.15.1.1: InitiateInitiate RRTRRT emergentlyemergently when life-threatening changes in fluid, electrolyte, and acid-base balance exist.(Not Graded)

5.1.25.1.2: Consider the broaderbroader clinicalclinical contextcontext, the presence of conditions that can be modified with RRT, and trendstrends ofof laboratorylaboratory tests—rather than single BUN and creatinine thresholds alone—when making the decision to start RRT. (Not Graded)

Dialysis Interventions for Treatment of Dialysis Interventions for Treatment of AKI

KDIGO® AKI Guideline March 2012

When to start RRTWhen to start RRT? ?

Crit Care Med 2008, Vol. 36, No 4 )suppl.)

Early RRT seems betterEarly RRT seems better

What What ModalityModality ??

1. Peritoneal dialysis (PD)

2. Intermittent Hemodialysis (IHD)

3. Slow Low-Efficiency Daily Dialysis (SLED)

4. Continuous Renal Replacement Therapy (CRRT)

• Slow Continuous Ultrafiltration (SCUFSCUF)

• Continuous Venovenous Hemofiltration (CVVHCVVH)

• Continuous Venovenous Hemodialysis (CVVHDCVVHD)

• Continuous Venovenous Diafiltration (CVVHDFCVVHDF)

AdvantagesHemodynamic stability 

Slow correction  

Easy access placement 

No Anticoagulation

Tolerated in children

Peritoneal Dialysis )PD) In AkI

DisadvantagesRisk of infectionsDifficulty to use with abdominals surgeryLogestics

Potential Advantages of CRRTCRRT

Homodynamic stability

Recovery of renal function

Brain edema

Biocompatibility

Removal of cytokines

Nutritional support

Correction of metabolic acidosis

CVVHCVVH Avoids Hypertensive Episodes

Ronco C et al Kidney Int 56 ) suppl 72 ) s-8-s-14 , 1999Ronco C et al Kidney Int 56 ) suppl 72 ) s-8-s-14 , 1999

5.6.2:5.6.2: We suggest using CRRT, rather

than standard intermittent RRT, for hemodynamically unstable patients. (2B)

5.6.15.6.1: Use continuous and

intermittent RRT as complementary therapies in AKI patients. (Not Graded

Dialysis Interventions for Treatment of AKI

KDIGO® AKI Guideline March 2012

StudyModality %recovering renal function

SUPPORTIHD*67%**

Morgera et al.CRRT90%

Ronco et al.CRRT90%

Mehta et al.IHD

CRRT59%

92%

BEST Kidney†IHD

CRRT65%

89%

Is their an alternative to CRRT ?Is their an alternative to CRRT ?

Typically performed over 6-12 hours

Can be performed with a conventional dialysis machine

– A little less labor intensive

– Requires less training/startup

Fliser D and Kielstei JT Nat Clin Pract Nephrol, 2006

Slow Low-Efficiency Daily Dialysis )SLEDSLED)

Slow Low-Efficiency Daily Dialysis (SLEDSLED)

Major advantages: flexibility, reduced costs, low or absent anticoagulation

Similar adequacy and hemodynamics

One small study (16 pts) showed slightly higher acidosis and lower BP (Baldwin 2007)

VA trial (Palevsky NEJM 2008) suggests similar outcomes as CRRT and IRRT.

Vanholder et al. Critical Care 2011, 15:204

Mode of therapy

Principle method of solute clearance

CVVHConvection

CVVHDDiffusion

CVVHDFConvection & Diffusion

SCUFUltrafiltration (fluids)

HowHow we can do itwe can do it ?

Processes of care, more pertinent to Nephrologists:-

Vascular Access

Membrane characteristics

Solution

Anticoagulation

Dose

5.4.15.4.1: We suggest initiating RRT in patients with AKI via an uncuffed nontunneled dialysis catheter, rather than a tunneled catheter. (2D)

5.4.25.4.2: When choosing a vein for insertion of a dialysis catheter in patients with AKI, consider these preferences (Not Graded):

First choice: right jugular vein; Second choice: femoral vein; Third choice: left jugular vein; Last choice: subclavian vein with preference for the

dominant side.

Vascular access

KDIGO® AKI Guideline March 2012

Bicarbonate versus lactate based fluid replacement in CVVH

Prospective, randomized study

Results : Serum lactate concentration was

significantly higher and the

bicarbonate was lower in patients

treated with lactate based solutions

Increased incidence of CVS events

in pts ttt with lactate solution

Hypotension

Increased dose of inotropic

support

barenborck and colleague

Barenbrock M et al; Kidney Int (2000

Solutions for CRRTSolutions for CRRT

5.7.35.7.3: We suggest using bicarbonate, rather than

lactate, as a buffer in dialysate and replacement

fluid for RRT in patients with AKI and liver

failure and/or lactic acidemia. (2B)

Dialysis Interventions for Treatment of AKI

KDIGO® AKI Guideline March 2012

TheThe MembraneMembrane

High Flux membrane , synthetic , biocompatable ,

acting by providing both methods of detoxications:

a)Diffusion : for low molecular weight toxins.

b)Convection : for large molecules.

5.5.15.5.1: We suggest to use dialyzers with a biocompatible

membrane for IHD and CRRT in patients with

AKI. (2C)

KDIGO® AKI Guideline March 2012

Modality AdvantagesDisadvantages

HeparinGood anticoagulation Thrombocytopenia bleeding

LMWHLess thrombocytopeniableeding

Citrate Lowest risk of bleedingMetabolic alkalosis,

hypocalcemia special dialysate

Regional Heparin

Reduced bleedingComplex management

Saline flushes No bleeding risk Poor efficacy

Prostacycline Reduced bleeding riskHypotension poor efficacy

Dose Dose

5.8.15.8.1: The dose of RRT to be delivered should be

prescribed before starting each session of RRT.

(Not Graded)

We recommend frequent assessment of the actual

delivered dose in order to adjust the prescription.

(1B)

5.8.25.8.2: Provide RRT to achieve the goals of

electrolyte, acid-base, solute, and fluid balance

that will meet the patient’s needs. (Not Graded)

ConclusionsConclusionsConclusionsConclusions

Early detection and treatment of AKI may improve outcomes.

Even a minor acute reduction in kidney function has an adverse prognosis.

Hunting AKI in ICU….use a RIFLE .

Continuous renal replacement therapy is a standard of care and has improved outcomes from AKI in critically ill patients.

Early start of CRRT is associated with better recovery of AKI than IHD but no difference on mortality.

There is a dialysis dose effect on out come.

Thank you Thank you

Indications for RRT in critically ill AKI patients

RenalRenal ReplacementReplacementRenal SupportRenal Support

Life-threatening indications

Hyperkalemia

Acidemia

Pulmonary edema Uremic complications Solute control Fluid removal Regulation of acid-base and electrolyte status

Nutrition Fluid removal in congestive heart failure Cytokine manipulation in sepsis Cancer chemotherapy Treatment of respiratory acidosis of ARDS Fluid management in multiorgan failure

Contrast-induced AKI4.3.1 :Use the lowest possible dose of

contrast medium in patients at risk for CI-AKI. (Not Graded)

4.3.2 :We recommend using either iso-osmolar or low-osmolar iodinated

contrast media, rather than high-osmolar iodinated contrast media in patients at

increased risk of CI-AKI. (1B)

Contrast-induced AKI4.4.1 :We recommend i.v. volume expansion

with either isotonic sodium chloride or sodium bicarbonate solutions, rather than

no i.v. volume expansion, in patients at increased risk for CI-AKI. (1A)

4.4.2 :We recommend not using oral fluids alone in patients at increased risk of CI-

AKI. (1C)4.4.3 :We suggest using oral NAC, together

with i.v. isotonic crystalloids, in patients at increased risk of CI-AKI. (2D)

Contrast-induced AKI4.4.4 :We suggest not using theophylline to

prevent CI-AKI. (2C)4.4.5 :We recommend not using fenoldopam

to prevent CI-AKI. (1B)4.5.1 :We suggest not using prophylactic

intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast-media

removal in patients at increased risk for CI-AKI. (2C)

Medications3.4.1 :We recommend not using diuretics to

prevent AKI. (1B)3.4.2 :We suggest not using diuretics to treat

AKI, except in the management of volume overload. (2C)

3.5.1 :We recommend not using low-dose dopamine to prevent or treat AKI. (1A)

3.5.2 :We suggest not using fenoldopam to prevent or treat AKI. (2C)

By AKI we actually mean “loss of small solute clearance” (urea/creatinine increase in blood)

This implies loss of GFR

So…clinically we actually mean

“acute decrease in GFR”

What do we mean by AKI?What do we mean by AKI?

How to define AKI?

Serum creatinine or other solute

If serum creatinine, do we choose

• Absolute increase ?• Percent increase ?• Over what time ?• Minimum peak ?

Change of case mix in Change of case mix in AKIAKI

1974-19791974-1979 1995-20001995-2000

Mortality: Mortality: 5454%% Mortality : Mortality : 5353%%

92%92%85%85%

Ricci, Ronco Crit Care Clin 21:357-366,2005Ricci, Ronco Crit Care Clin 21:357-366,2005

Incidence of ARF, need of RRT, and mortality in 187 patients with proven sepsis (surgical ICU Ghent –16 months)

23

50

28

53

69

0

10

20

30

40

50

60

70

Mortality ICU Mortality hosp Need of RRT

- ARF+ ARF

Hoste et al JASN 14:1022-1030,2003

%

Hospital mortality rates in RRT patients and matched control critically ill patients in Austria

0

10

20

30

40

50

60

70

Controls RRT

0

10

20

30

40

50

60

70

80

< 40 40-60 > 60

Control RRT

Ho

spita

l mo

rtal

ity

%

<40 40-60 >60Age groupsMetnitz et al Crit Care Med 30:2051-2058, 2002

ACUTE KIDNEY INJURY

The most frequent scenario is of AKI

occurring in the setting of circulatory

disturbance caused by severe illness

particularly if sepsis is involved.

Data from high quality RCTs are lackingThe current trend is to provide RRT earlierThere may be a recovery advantage to using

CRRT vs. HD for initial management of AKI but no difference on mrtalitaty

Dose: No benefit to “intensive” therapy

Dialytic Support of Dialytic Support of AKI =AKI =

ConclusionsConclusionsConclusionsConclusions

IndividualizatiIndividualizationon

Urine NGAL excretion post cardiac surgery in children

Neutrophil gelatinase associated lipocalin

Mishra J, et al, Lancent 2005; 365:1231-1238

Management priorities in AKI (I)

Detect as early as possible even minimal AKIExclude other renal causes of AKISearch for and correct prerenal and postrenal

factorsReview medications and stop nephrotoxinsOptimize cardiac output and renal blood flowRestore and/or increase urine flowMonitor fluid intake and output, daily weight

Management priorities in AKI (II)

Search for and treat acute complications (hyperkalemia, hyponatremia, acidosis hyperphosphatemia , pulmonary edema)

Provide early nutritional supportSearch for and aggressively treat infectionsInitiate dialysis before uremic complications

emergeDose drugs appropriate for their clearanceStop and repair ongoing intracellular injury

Dose Dose

RCT of 1124 critically ill pts with AKI and sepsis or at least one organ failure to intensive or less intensive renal-replacement therapy

Hemodynamically unstable pts received CRRT or SLEDD, stable pts IRRT

Intensive RRT= IRRT or SLEDD 6x/wk or CRRT at 35 ml/kg/hr

Less intensive RRT= IRRT or SLED 3x/wk or CRRT at 20 ml/kg/hr

VA/NIH Acute Renal Failure Trial Network. (NEJM 2008;359:7):

Optimal intensity of RRT is controversial

VA/NIH Acute Renal Failure Trial Network. (NEJM 2008;359:7):

No difference in mortality

1508 Critically ill patients with ARF on CVVHF were randomized to:- lowlow (25 mL/kg/hr – 747 patients) highhigh intensity (40 mL/kg/hr – 761 patients) effluent

rates.

N Engl J Med. 2009 Oct 22;361(17):1627-38

The RENAL Replacement Therapy Study

There was no difference in 90 day mortality rate (44.7%) or the need for RRT at 90 day between the two treatment groups.

5.3.2.15.3.2.1: For anticoagulation in intermittent RRT, we

recommend using either unfractionated or

low-molecular weight heparin, rather

than other anticoagulants. (1C)

5.3.2.25.3.2.2: For anticoagulation in CRRT, we suggest

using regional citrate anticoagulation

rather than heparin in patients who do not

have contraindications for citrate. (2B)

KDIGO® AKI Guideline March 2012

5.8.15.8.1: The dose of RRT to be delivered should be

prescribed before starting each session of RRT.

(Not Graded)

We recommend frequent assessment of the actual

delivered dose in order to adjust the prescription.

(1B)

5.8.25.8.2: Provide RRT to achieve the goals of electrolyte,

acid-base, solute, and fluid balance that will

meet the patient’s needs. (Not Graded)

KDIGO® AKI Guideline March 2012

Dose Dose

More than 200 different definitions of ARF +++

58 creatinine levels (1.5 to 10 mg/dl)

33 UO thresholds (0 à 950 ml/24h)

Community acquired Hospital-acquired ICU-acquiredIncidence Low Moderate (5%) High (10-20%)Cause Single Multiple MOF

pre<post<renal pre<ATN<post MOF + ATNOutcome good less good poor

70-90% survival 30-50% survival 10-30%survival

Schrier & Gottschalk, Diseases of the Kidney, 1996.