Dr. Osama El-Shahat

Consultant Nephrologist Head of Nephrology Department

New Mansoura General Hospital (international) ISN Educational Ambassador

Objectives

Treatment Non- dialytic support

Dialytic support

Diagnosis Incidence

Mortality

Biomarkers

Definatinon ARF 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?

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

Can we do staging for AKI?

AKIN Classification

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: 1979 to 2002

Rates 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

Kidney International advance online publication , 1

May 2013

Mortality in AKI

Causes of AKI

Pre renal Intrinsic renal Post renal

Decrease in

effective

blood volume.

Arterial

occlusion

Or

stenosis.

Homodynamic

Form.

Vascular

Vasculitis.

Malignant

hypertension

Acute

Glomerulo

nephritis

Acute

Interstitial

nephritis

Acute

Tubular

necrosis

Ischemic. Nephrotoxic.

Obstruction

Of

Collecting

System

Or

Extra renal

drainage

Exogenous

Antibiotic

Radio contrast

cisplatin

Endogenous

Intra tubular pigment

Intra tubular protein.

Intra tubular crystal.

Causes of AKI

Post-OP, sepsis,

shock,multi-organ

failure 70%

Obstructive

uropathy 15%

Glomerulonephritis 5%

Nephrotoxic agents 10% reduced blood flow

ischemia

acute tubular necrosis

Timing nephrology consultation (Mehta, Am J Med 2002)

In-hospital mortality

Early

consult

Delayed

consult P

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

Kidney International (2013) 83, 901–908

Early Referral

Biomarkers are foot prints of actual

organ damage

Creatinine Not A Biomarker

The creatinine level is influenced by multiple non-

renal factors, such as age, gender, muscle mass, muscle

metabolism, diet, medications, and hydration status

In AKI, the serum creatinine level can take several

hours or days to reach a new steady state and thus does

not reflect the actual decrease in GFR in the acute

setting

Because of renal reserve, the serum creatinine level

may not rise until more than half of the kidney

function has been lost

Creatinine is late, or is it too late?

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 AF Area under the ROC

Day - 2 Day - 1 Day 0

≥ 50 % increase 0.82 0.97 0.99

≥ 100 % increase 0.92 0.98 0.98

≥ 200 % increase 0.97 0.99 0.99

•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 earlier

2. RIFLE- I ( ≥ 100 % increase): 1.2 ± 0.9 days earlier

3. RIFLE- F ( ≥ 200 % increase): 1.0 ± 0.6 days earlier

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

Indications of Renal Biopsy

1

Urine

No cast

FENa<1% Muddy

brown cast

FENa>1%

Red cell

cast

White cell

cast

eosinophil

Pre-renal ATN Glomerular Interstitial

Biopsy

2. Unknown cause

3. Prolonged ATN

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.

3.4.1: 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 )

There is insufficient evidence that the low-dose dopamine

improves survival or obviates the need for dialysis in persons with

acute renal failure. The routine use of low-dose dopamine should be

discouraged until a prospective, randomized, placebo-controlled trial

establishes its safety and 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 AKI

3.5.1: We recommend not using low-dose dopamine to prevent or

treat AKI. (1A)

IV Fluids in AKI

3.1.1: 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.

(2B)

Contrast Induced AKI

isotonic sodium with either expansion volume. i.v: We recommend 4.4.1. volume expansion, i.v, rather than no chloride or sodium bicarbonate solutions

)A1AKI. (-in patients at increased risk for CI

or )IHD( hemodialysisnot using prophylactic intermittent : We suggest 4.5.1hemofiltration (HF) for contrast-media removal in patients at increased risk for

)C2AKI. (-CI

, in crystalloids isotonic. i.v with together, NAC oral: We suggest using 4.4.3

)D2AKI. (-patients at increased risk of CI

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)

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 (Risk)

Risk for more severe AKI

Monitor (prevent

progression)

Stage 2 (Injury)

Risk of AKI-related

mortality/morbidity high

Conservative therapy)

Stage 3 (Failure)

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

Indications for RRT in critically ill AKI patients

Renal Indications

Life-threatening indications

Hyperkalemia

Metabolic Acidosis

Pulmonary edema

Uremic omplications

Dialysis Interventions for Treatment of AKI

5.1.1: Initiate RRT emergently when life-threatening

changes in fluid, electrolyte, and acid-base balance

exist.(Not Graded)

5.1.2: Consider the broader clinical context, the presence

of conditions that can be modified with RRT, and trends

of laboratory tests—rather than single BUN and

creatinine thresholds alone—when making the decision

to start RRT. (Not Graded)

Conclusions

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 .

Early referral will improve outcome

When to start RRT ?

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

Early RRT seems better

What Modality ?

Renal Replacement Therapy in AKI

1. Peritoneal dialysis (PD)

2. Intermittent Hemodialysis (IHD)

3. Slow Low-Efficiency Dialysis (SLED)

4. Continuous Renal Replacement Therapy (CRRT)

• Slow Continuous Ultrafiltration (SCUF)

• Continuous Venovenous Hemofiltration (CVVH)

• Continuous Venovenous Hemodialysis (CVVHD)

• Continuous Venovenous Diafiltration (CVVHDF)

Peritoneal Dialysis (PD) In AkI

Advantages

Hemodynamic stability

Slow correction

Easy access placement

No Anticoagulation

Tolerated in children

Disadvantages Risk of infections

Difficulty to use with abdominals

surgery

Logestics

PD … the modality first used for the treatment of KI

Blood Purif 2013;36:226–230 DOI: 10.1159/000356627

What are the modalities of CRRT ?

Mode of

therapy

Principle method of

solute clearance

CVVH Convection

CVVHD Diffusion

CVVHDF Convection & Diffusion

SCUF Ultrafiltration (fluids)

Potential Advantages of CRRT

Homodynamic stability

Recovery of renal function

Brain edema

Biocompatibility

Removal of cytokines

Nutritional support

Correction of metabolic acidosis

CVVH Avoids Hypertensive Episodes

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

Dialysis Interventions for Treatment of AKI

5.6.2: We suggest using CRRT, rather than standard

intermittent RRT, for hemodynamically unstable

patients. (2B)

5.6.1: Use continuous and intermittent RRT as

complementary therapies in AKI patients. (Not Graded

Recovery from ARF in IHD vs CRRT

Study Modality % recovering renal

function

SUPPORT IHD* 67%**

Morgera et al. CRRT 90%

Ronco et al. CRRT 90%

Mehta et al. IHD

CRRT

59%

92%

BEST Kidney† IHD

CRRT

65%

89%

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 (SLED)

Slow Low-Efficiency Daily Dialysis (SLED)

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

How we can do it ?

Processes of care, more pertinent to

Nephrologists:-

Vascular Access

Membrane characteristics

Solution

Anticoagulation

Dose

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

5.4.2: 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

The Membrane

5.5.1: We suggest to use dialyzers with a biocompatible

membrane for IHD and CRRT in patients with AKI. (2C)

High Flux membrane , synthetic , biocompatable ,

acting by providing both methods of detoxications:

a) Diffusion : for low molecular weight toxins.

b) Convection : for large molecules.

KDIGO® AKI Guideline March 2012

5.3.2.1: For anticoagulation in intermittent RRT, we

recommend using either unfractionated or

low-molecular weight heparin, rather than

other anticoagulants. (1C)

5.3.2.2: 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

Conclusions

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 .

Early referral will improve outcome

Conclusions

Data from high quality RCTs are lacking

The current trend is to provide RRT earlier

There may be a recovery advantage to using CRRT vs.

HD for initial management of AKI but no difference on

mortality

Dose: No benefit to “intensive” therapy

Dialytic Support of AKI = Individualization