AKI – icu

Diagnosis and management

Dr. Muhamed Al Rohani, MD, FISN
How can we identify AKI?
Definition
Biomarkers
Outcomes
Risk factors
What can we do to protect against the development of AKI during routine
ICU care?
Fluid and their types
Vasopressors
Nephrotoxicity (medications, contrast dye)
How should we manage a patient who is critically ill with AKI?
General management
Nutrition
Anticoagulation
Dialysate composition
What is the impact of renal replacement therapy on mortality and recovery?
Dialyzer
Timing
Mode and dose of renal replacement therapy
 Natural history of AKI. Patients who develop AKI may experience (1) complete recovery of renal
function, (2) development of progressive chronic kidney disease (CKD), (3) exacerbation of the
rate of progression of preexisting CKD; or (4) irreversible loss of...

Cerdá J et al. CJASN 2008;3:881-886

©2008 by American Society of Nephrology

 Common causes of AKI in ICU
• Sepsis • Hepatorenal syndrome
• Major surgery • Trauma
• Low cardiac output • Cardiopulmonary bypass
• Abdominal compartment syndrome
• Hypovolemia
• Rhabdomyolysis
• Medications (20%)
• Obstruction

Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in

Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An
critically ill patients: A multinational, multicenter study. JAMA update and primer for the Intensivist. Critical Care Medicine 2010; 38:261-275.
2005; 294:813-818.
 Conceptual model of AKI

Murugan, R. & Kellum, J. A. (2011) Acute kidney injury: what’s the prognosis?
Nat. Rev. Nephrol. doi:10.1038/nrneph.2011.13
Hospital survival, stratified by KDIGO stages of AKI and Long-Term Mortality

Reproduced with permission from Oxford University Press © Wang, H. E. et al. Comparison of absolute serum creatinine changes versus
Kidney Disease: Improving Global Outcomes consensus definitions for characterizing stages of acute kidney injury. 28, 1447–1454 (2013)
Rewa, O. & Bagshaw, S. M. (2014) Acute kidney injury—epidemiology, outcomes and economics
Nat. Rev. Nephrol. doi:10.1038/nrneph.2013.282
 Long-term survival stratified by CKD and AKI

Reproduced with permission from Nature Publishing Group © Wu, V. C. et al. Kidney Int. 80, 1222–1230 (2011)

Rewa, O. & Bagshaw, S. M. (2014) Acute kidney injury—epidemiology, outcomes and economics
Nat. Rev. Nephrol. doi:10.1038/nrneph.2013.282
Definitions - KDIGO
• AKI is defined when
• serum creatinine rises by ≥ 26µmol/L within 48 hours or

• serum creatinine rises ≥ 1.5X the reference value which is

known or presumed to have occurred within one week or

• urine output is < 0.5ml/kg/hr for >6 consecutive hours

Risk of AKI varies by definition used and timing of assessment

Murugan, R. & Kellum, J. A. (2011) Acute kidney injury: what’s the prognosis?
Nat. Rev. Nephrol. doi:10.1038/nrneph.2011.13
(8 – 48) h
RIFLE Criteria
GFR criteria Urine output criteria

Increased creatinine x1.5 or UO <0.5 mL kg-1

Risk GFR decrease >25% h-1 x6 hr High sensitivity

Increased creatinine x2 or UO <0.5 mL kg-1

Injury GFR decrease >50% h-1 x12 hr

Increased creatinine x3 or
GFR decrease >75% or UO <0.3 mL kg-1

a
Oliguri
Failure creatinine 4 mg/ h x24 hr or anuria
-1
High specificity
100 mL (acute rise of 0.5 x12 hr
mg/100 mL dL)

Persistent ARF = complete loss of renal

Loss function >4 weeks

ESRD End-stage renal disease

AKIN Definition for AKI
AKIN Conference, Vancouver 2006

• Inc Scr 0.3 mg/dL or >150-

Stage I 200% from baseline
<0.5 mL/kg/hr for >6 hr

• Inc Scr >200-300% from

Stage II baseline
<0.5 mL/kg/hr for >12 hr

• Inc Scr >300%

• Scr >4 with acute min rise • <0.3 mL/kg/hr for 24 hr
Stage III of 0.5 mg/dL • Anuria for 12 hr
• Need for RRT
Limitations of SCr

Dennen P, Douglas I, Anderson R,: Acute Kidney Injury in the Intensive Care Unit: An update and primer for the Intensivist. Critical
Care Medicine 2010; 38:261-275.
 Figure 1 Association between the incidence and mortality for acute kidney injury when
assessed by a | absolute changes in serum creatinine levels and
b | changes in serum creatinine levels relative to baseline

Rewa, O. & Bagshaw, S. M. (2014) Acute kidney injury—epidemiology, outcomes and economics
Nat. Rev. Nephrol. doi:10.1038/nrneph.2013.282
Risk factors in people with acute illness :
1. Age ≥65 years.
2. Heart failure.
3. Liver disease.
4. Chronic kidney disease (particularly if eGFR <60).
5. Past history of AKI.
6. Diabetes.
7. Anemia
8. Dehyration
9. Hypovolaemia.
10.Haematological malignancy.
11.Symptoms or history of urological obstruction, or a risk factor
for it.
12.Sepsis.
13.Use of iodinated contrast agents within the previous week.
14.Current or recent medication with nephrotoxic potential
Figure 3 Incidence of various organ failure among critically ill patients

Murugan, R. & Kellum, J. A. (2011) Acute kidney injury: what’s the prognosis?
Nat. Rev. Nephrol. doi:10.1038/nrneph.2011.13
 Key pathogenic pathways involved in the clinical course of sepsis that also have implications in
the pathophysiology of sepsis-induced acute kidney injury.

Zarjou A , and Agarwal A JASN 2011;22:999-1006

©2011 by American Society of Nephrology

 ATN(P): ACUTE TUBULAR NECROSIS ATN(D): ACUTE TUBULAR
AMINOGLYCOSIDES, ANTINEOPLASTICS, NECROSIS AMPHOTERICIN,
GLYCOLS, RADIOCONTRAST AGENTS CISPLATIN, GLYCOLS

NEPHROTIC SYNDROME
NSAIDS, PENICILLAMINE
CAPTOPRIL
HEROIN/COCAINE
METALS (Au, Hg)

CORTEX
VASCULITIS AMPHETAMINES,
NSAIDS,
-----------------------------------------------------------
PENICILLINS,SULFONAMIDES

ACUTE PRE-RENAL INNER MEDULLA

FAILURE
AMPHOTERICIN, OBSTRUCTION
ANTIHYPERTENSIVES, ------------------------------------------------------------
ACYCLOVIR, ANTICHOLINERGICS,
DIURETICS, OUTER MEDULLA
DOXORUBICIN, NSAIDS, BROMOCRIPTINE, ERGOT ALKALOIDS,
CYCLOSPORIN-A FLUOROQUINOLONE, MTX

ACUTE INTERSTITIAL NEPHRITIS CHRONIC INTERSTITIAL NEPHRITIS ANALGESIC

COMBINATIONS, CHINESE HERBS, CYCLOSPORINE,
ALLOPURINOL, RIFAMPIN, METALS (PB, Cd, Li, Ge), METHYL-CCNU
VANCOMYCIN, NSAIDS
 Diagnosis

Laboratory test Prerenal ATN

azotemia
Urine osmolality > 500 <400
(mOsm/kg)
Urine sodium level <20 > 40
(mEq/L)
Urine/plasma creatinine > 40 < 20
ratio
Fractional excretion of <1 >2
sodium (%)
Fractional excretion of <35 >35
urea (%)
Urinary sediment Normal: Renal tubular
occasional epithelial cells:
hyaline granular and
or fine granular muddy brown
casts casts
The Ideal Biomarker
• Easily detectable
• Sensitive and specific
• Rapid turn around time
• Affordable
• Elevations should be significant and detectable earlier than creatinine
 Biomarkers
1. Kidney injury molecule 1 (KIM-1),
a) Detectable in urine
b) Elevated within 12 hours of ischemic insult
c) Predictor of mortality

2. Neutrophil gelatinase–associated lipo- calin (NGAL),

a) Urine levels used for detection
b) Very early detector of ischemic injury
c) Increased with nephrotoxicity
3. Cystatin C,
a) Filtered by glomerulus, resorbed by tubules
b) Urinary and serum levels
4. Interleukin (IL)–18,
a) In urine and serum
Ultrasonography in AKI
Observation Clue to diagnosis of
Shrunken kidneys Chronic kidney disease
Normal size kidneys Echogenic Acute GN
Normal Echo Prerenal
Acute renal artery
occlusion
Enlarged kidneys Malignancy, renal vein thrombosis, diabetic
nephropathy, HIV
Hydronephrosis Obstructive nephropathy

Comprehensive Clinical Nephrology, Johnson 3rd edition

 FDA OKs NephroCheck to Assess Risk for Acute Kidney Injury
Robert Lowes September 05, 2014

The new test, called NephroCheck (Astute Medical), spots telltale proteins associated with AKI, once known as acute
renal injury.

NephroCheck detects the presence of insulin-like growth-factor binding protein 7 (IGFBP7) and tissue inhibitor of
metalloproteinases (TIMP-2) in the urine, which are associated with acute kidney injury. Within 20 minutes, the test
provides a score based on the amount of the proteins present that correlates to the patient’s risk of developing AKI
within 12 hours of the test being performed.
 Referral
Discuss AKI management with a nephrologist/paediatric nephrologist as soon as possible
(and within 24 hours) if one of the following is present:

Potential diagnosis requiring specialist AKI with no clear Inadequate treatment

treatment (for example, vasculitis or cause response
glomerulonephritis)

Complications associated with AKI Stage 3 AKI eGFR is less than < 30
ml/min/1.73 m2 after AKI
episode

Patients with renal transplant and AKI CKD stage 4 or 5

Renal replacement therapy:

Refer adults, children and young people immediately for RRT if any of the following are not
responding to medical management:

Hyperkalaemia Metabolic acidosis Symptoms or complications of Fluid overload +/-

uraemia such as pericarditis or pulmonary
encephalopathy oedema
Physicians Can Take Action
With Early Assessment of AKI

KDIGO Initiative to Set Guidelines KDIGO AKI Guidelines

 KDIGO is a global non-profit foundation High Risk 1 2 3

dedicated to improving the care Discontinue all nephrotoxic agents when possible

and outcomes of kidney disease patients Ensure volume status and perfusion pressure

worldwide. Consider functional hemodynamic monitoring

Monitor serum creatinine and urine output

Avoid hyperglycemia

 Assembled working group of eighteen Consider alternatives to radiocontrast procedures

thought leaders to establish global Check for changes in drug dosing

clinical practice guidelines for AKI Consider Renal Replacement Therapy

Check for changes in drug dosing

Consider Renal Replacement Therapy

 New guidelines just published. Consider ICU admission

Avoid subclavian catheters

Kidney Disease: Improving Global Outcomes (KDIGO)

Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline
for Acute Kidney Injury. Kidney Int Suppl 2012; Volume 2, Issue 1:1–126.
28
 KDIGO Management Options
….Why Risk Assessment Is Needed and What To Do For a Positive Test Result
KDIGO Consensus Guideline for AKI

Actions
recommended
to start when
patients are at
high risk…

…But NO available
method to reliably
identify high risk to
aid clinical
judgment …often resulting in
failure to initiate kidney- KDIGO: Kidney Disease Improving Global Outcomes; Kidney
sparing management International Supplements (2012) 2, 1; doi:
0.1038/kisup.2012.1; MacLeod A. NCEPOD report on acute 29
strategies kidney injury- must do better. Lancet 2009; 374: 1405-1406
Many Omissions in AKI Management

Acute Kidney Injury: Adding Insult to Injury. NCEPOD. 2009.

 Advanced algorithm for the management of patients receiving iodinated contrast media
(taken from reference 86 after permission).

Lameire N et al. NDT Plus 2009;2:1-10

© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights
reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Initial fluid resuscitation:
crystalloids for a minimum of 30 ml/kg
Albumin in patients who continue to
require substantial amounts of
crystalloid
 to maintain adequate mean arterial
pressure (MAP).

Vasopressors should be initiated to

maintain MAP above 65 mm Hg,
norepinephrine
dobutamine (myocardial dysfunction or
ongoing signs of hypoperfusion)

Liberal fluid approach appears beneficial during the first hours of

shock,
Conservative approach should be followed after resolution of shock.
Risk factors
The potential risks of fluid accumulation and overload in the setting of CHF
AKI need to be considered Cardiac dysfunction
 *
SAFE Study: Status at 28 Days
Albumin Saline

Mortality (%) 20.9 21.1

ICU Stay (Days) 6.5 ± 6.6 6.2 ± 6.2

Hospital Stay (Days) 15.3 ± 9.6 15.6 ± 9.6

Ventilation Days 4.5 ± 6.1 4.3 ± 6.7

NB: A 2004 Cochrane review (by Alderson P et al) and a 2009 Annals systematic review
(by McIntyre L & Green RS) also concluded that albumin did not show any remarkable
benefits in improving mortality but the authors noted that the trials were largely
dominated by the SAFE study sample size.

Finfer S, et al. SAFE Study Investigators. N Engl J Med. 2004;350(22):2247-2256.

Alderson P, et al. Cochrane Database Syst Rev. 2004;4:CD001208.
McIntyre L, et al. Am Emerg Med. 2009;54(1):114-116.
 Diuretics
Diuretics
1. 4 RCTs – no improvement.
1. 4 RCTs – no improvement.
2. Three meta-analyses showed diuretics do not
2. Three meta-analyses showed diuretics do not
alter outcome but do increase the risk of side-
alter outcome but do increase the risk of side-
effects.
effects.
3. One international cohort study showed an
3. One international cohort study showed an
increased risk of death and established renal
increased risk of death and established renal
failure.
failure.
• Olig/anuria is the common herald of impending
• Olig/anuria is the common
renal dysfunction and loop herald of impending
diuretics are
renal dysfunction and loop diuretics
commonly used in this context. are
commonly used in this context.
• Theoretical basis is prevention of tubular
• Theoretical basis
obstruction, is prevention
reduction of tubular
in medullary oxygen
obstruction, reduction in medullary oxygen
consumption, increased renal blood flow.
consumption, increased renal blood flow.
Although nonoliguric AKI has been associated with better
Although nonoliguric AKI has been associated with better
outcomes than oliguric AKI,
outcomes than oliguric AKI,
Diuretics are ineffective:
Diuretics are ineffective:
1. in the prevention of AKI or
1. in the prevention of AKI or
2. for improving outcomes once AKI occurs.
2. for improving outcomes once AKI occurs.
Meta-analyses have confirmed that the use of diuretics to
Meta-analyses have confirmed that the use of diuretics to
prevent AKI did not reduce
prevent AKI did not reduce
3. The in-hospital mortality,
3. The in-hospital mortality,
4. The risk for requiring dialysis,
4. The risk for requiring dialysis,
5. The number of dialysis sessions required, or
5. The number of dialysis sessions required, or
Treatment of Acute Kidney Injury Complications:

Fluid Overload Hyperkalemia:

Pulmonary edema
Cardiac conduction,
Fluid redistribution allover the body
Bradycardia, asystole
Anasraca
IV administration of calcium is urgently
Inadequate urine output (low in comparison to intake}
Shifting K to intracellular:
Dextrose IV with insulin effect after 20 – 30 min
All intakes should be minimized
Bicarbonate solution effect < 15 min for 1 – 2 h
Medical treatment
loop diuretic therapy can be initiated IV bolus
Avoid any source of K including drugs
if there response change to infusion
New selective diuretics
Morphine Hyponatremia:
Nitroglycerin Associated with heart failure, liver failure, or diuretics.
Positive ventilation and intubation water restriction to below the level of output is mandatory.
Dialysis initiation. In patients with true volume depletion with associated pre-renal AKI,
isotonic saline will need to be administered to correct both disorders.
Hypernatremia:
Water should be administered orally or intravenously as dextrose in
water to correct serum sodium concentration at a maximum rate of 8
to 10 mmol/l/day.
Dialysis and CRRT.
Mannitol:
could
1. prevent renal tubular cast deposition,
2. expand extracellular volume, Vasoactive Agents “Renal-dose” dopamine
3. Reduce (0.5 to 3 µg/kg per minute)
1. intracompartmental pressure,
2. muscle edema, Nutrition:
3. and pain Patients with AKI should receive a basic intake of 0.8 to
1.0 g of protein per kilogram per day if not catabolic and
1. However, mannitol may a total energy intake of 20 to 30 kcal/kg/d,
2. exacerbate CHF and nephrotoxicity, In addition, in patients on RRT, 1.0 to 1.5 g of
3. requires close monitoring, protein/kg/d up to a maximum of 1.7 g/kg/d in patients
4. contraindicated in on CRRT and in hypercatabolic patients.
1. oliguria,
2. hypervolemia,
3. hypertension, and
4. heart failure.

Mannitol administration is considered, if urinary flow

is sustained above 20 ml/h, given at a rate of 5 g/h
added to each liter of infusate and not exceeding 1 to 2
Acute Kidney Injury
Management/Interventions
• 11a Emergency Dialysis
• Intermittent hemodialysis (HD)
• Used when rapid changes are required
• Continuous Renal Replacement Therapy (CRRT)
• Much slower blood flow rates than HD
• CVVHD
• Continuous venovenous hemodialysis
• Solute loss via convection/diffusion
• CVVH
• Continuous venovenous hemofiltration
• Solute loss via convection (more like mammalian filtration)
• Replacement fluid via hemodilution

• Both use double lumen catheter

Dose of RRT and Mortality in AKI

TOTAL CRRT
< 35 ml/kg/hour ≥ 35 ml/kg/hour P
Length of ICU stay (days) 13 (6.5 to 26) 15 (9 to 28) 8 (4 to 18) < 0.001
 Patients who survived 19 (11 to 32) 19.5 (12 to 33.5) 15 (8 to 26) 0.063
 Patients who died 10 (4 to 19) 12 (6 to 20) 4.5 (3 to 9.5) < 0.001
Duration of MV (days) 10 (4 to 19) 12 (5 to 21) 5 (2.5 to 13) < 0.001
 Patients who survived 14 (4.5 to 22) 14 (5 to 24) 7 (4 to 17) 0.031
 Patients who died 8.5 (3 to 17) 10 (5 to 18) 4 (2 to 9.5) < 0.001
TOTAL IRRT
< 6 sessions/week ≥ 6 sessions/week P
Length of ICU stay (days) 14 (6.5 to 23) 18 (15 to 31) 9.5 (6 to 18) 0.023
 Patients who survived 11 (6 to 20) 18 (13 to 35) 8 (5.5 to 14) 0.008
 Patients who died 17 (12 to 23) 18 (17 to 23) 15 (12 to 22) 0.597
Duration of MV (days) 8 (1 to 17) 14 (5 to 21) 6 (0 to 14) 0.030
 Patients who survived 5 (0 to 13) 12 (3 to 24) 2.5 (0 to 10) 0.026
 Patients who died 17 (11 to 21) 18 (17 to 21) 14 (8 to 18) 0.252

Vesconi S, Cruz DN, Fumagalli R et al. Crit Care. 2009;13(2):R57.