This a summary of some aspects in ICU - AKI from the clinician point of view

1. AKI – icu
Diagnosis and management
Dr. Muhamed Al Rohani, MD, FISN

2. 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

3. 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

4. • Sepsis
• Major surgery
• Low cardiac output
• Hypovolemia
• Medications (20%)
Uchino S, Kellum J, Bellomo R, et al.: Acute renal failure in
critically ill patients: A multinational, multicenter study. JAMA
2005; 294:813-818.
Common causes of AKI in ICU
• Hepatorenal syndrome
• Trauma
• Cardiopulmonary bypass
• Abdominal compartment syndrome
• Rhabdomyolysis
• Obstruction
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.

6. 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

7. Hospital survival, stratified by KDIGO stages of AKI and Long-Term Mortality
Rewa, O. & Bagshaw, S. M. (2014) Acute kidney injury—epidemiology, outcomes and economics
Nat. Rev. Nephrol. doi:10.1038/nrneph.2013.282
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)

8. Long-term survival stratified by CKD and AKI
Rewa, O. & Bagshaw, S. M. (2014) Acute kidney injury—epidemiology, outcomes and economics
Nat. Rev. Nephrol. doi:10.1038/nrneph.2013.282
Reproduced with permission from Nature Publishing Group © Wu, V. C. et al. Kidney Int. 80, 1222–1230 (2011)

9. 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

10. 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

11. (8 – 48) h

12. RIFLE Criteria
GFR criteria Urine output criteria
Risk
Injury
Failure
Loss
ESRD
High sensitivity
High specificity
Persistent ARF = complete loss of renal
function >4 weeks
End-stage renal disease
Increased creatinine x3 or
GFR decrease >75% or
creatinine 4 mg/
100 mL (acute rise of 0.5
mg/100 mL dL)
Increased creatinine x2 or
GFR decrease >50%
Increased creatinine x1.5 or
GFR decrease >25%
UO <0.5 mL kg-1
h-1 x6 hr
UO <0.5 mL kg-1
h-1 x12 hr
UO <0.3 mL kg-1
h-1 x24 hr or anuria
x12 hr

13. AKIN Definition for AKI
AKIN Conference, Vancouver 2006
Stage I
Stage II
Stage III
• Inc Scr 0.3 mg/dL or >150-
200% from baseline
• Inc Scr >200-300% from
baseline
• Inc Scr >300%
• Scr >4 with acute min rise
of 0.5 mg/dL
• Need for RRT
• <0.3 mL/kg/hr for 24 hr
• Anuria for 12 hr
<0.5 mL/kg/hr for >12 hr
<0.5 mL/kg/hr for >6 hr

14. 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.

15. 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

16. 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

17. 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

20. 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

21. ACUTE PRE-RENAL
FAILURE
AMPHOTERICIN,
ANTIHYPERTENSIVES,
DIURETICS,
DOXORUBICIN, NSAIDS,
CYCLOSPORIN-A
CHRONIC INTERSTITIAL NEPHRITIS ANALGESIC
COMBINATIONS, CHINESE HERBS, CYCLOSPORINE,
METALS (PB, Cd, Li, Ge), METHYL-CCNU
------------------------------------------------------------
-----------------------------------------------------------
OBSTRUCTION
ACYCLOVIR, ANTICHOLINERGICS,
BROMOCRIPTINE, ERGOT ALKALOIDS,
FLUOROQUINOLONE, MTX
OUTER MEDULLA
INNER MEDULLA
VASCULITIS AMPHETAMINES,
NSAIDS,
PENICILLINS,SULFONAMIDES
NEPHROTIC SYNDROME
NSAIDS, PENICILLAMINE
CAPTOPRIL
HEROIN/COCAINE
METALS (Au, Hg)
ATN(P): ACUTE TUBULAR NECROSIS
AMINOGLYCOSIDES, ANTINEOPLASTICS,
GLYCOLS, RADIOCONTRAST AGENTS
ATN(D): ACUTE TUBULAR
NECROSIS AMPHOTERICIN,
CISPLATIN, GLYCOLS
ACUTE INTERSTITIAL NEPHRITIS
ALLOPURINOL, RIFAMPIN,
VANCOMYCIN, NSAIDS
CORTEX

22. Laboratory test Prerenal
azotemia
ATN
Urine osmolality
(mOsm/kg)
> 500 <400
Urine sodium level
(mEq/L)
<20 > 40
Urine/plasma creatinine
ratio
> 40 < 20
Fractional excretion of
sodium (%)
<1 >2
Fractional excretion of
urea (%)
<35 >35
Urinary sediment Normal:
occasional
hyaline
or fine granular
casts
Renal tubular
epithelial cells:
granular and
muddy brown
casts
Diagnosis

23. The Ideal Biomarker
• Easily detectable
• Sensitive and specific
• Rapid turn around time
• Affordable
• Elevations should be significant and detectable earlier than creatinine

24. 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

25. Ultrasonography in AKI
Comprehensive Clinical Nephrology, Johnson 3rd edition
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

26. 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.

27. 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
treatment (for example, vasculitis or
glomerulonephritis)
AKI with no clear
cause
Inadequate treatment
response
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
uraemia such as pericarditis or
encephalopathy
Fluid overload +/-
pulmonary
oedema

28.  KDIGO is a global non-profit foundation
dedicated to improving the care
and outcomes of kidney disease
patients worldwide.
 Assembled working group of eighteen
thought leaders to establish global
clinical practice guidelines for AKI
 New guidelines just published.
Physicians Can Take Action
With Early Assessment of AKI
KDIGO Initiative to Set Guidelines KDIGO AKI Guidelines
28
High Risk 1 2 3
Avoid subclavian catheters
Consider ICU admission
Consider Renal Replacement Therapy
Check for changes in drug dosing
Consider Renal Replacement Therapy
Check for changes in drug dosing
Consider alternatives to radiocontrast procedures
Avoid hyperglycemia
Monitor serum creatinine and urine output
Consider functional hemodynamic monitoring
Ensure volume status and perfusion pressure
Discontinue all nephrotoxic agents when possible
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.

29. 29
KDIGO Consensus Guideline for AKI
KDIGO: Kidney Disease Improving Global Outcomes; Kidney
International Supplements (2012) 2, 1; doi:
0.1038/kisup.2012.1; MacLeod A. NCEPOD report on acute
kidney injury- must do better. Lancet 2009; 374: 1405-1406
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-
sparing management
strategies
….Why Risk Assessment Is Needed and What To Do For a Positive Test Result
KDIGO Management Options

30. Many Omissions in AKI Management
Acute Kidney Injury: Adding Insult to Injury. NCEPOD. 2009.

31. 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

32. 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.
The potential risks of fluid accumulation and overload in the setting of
AKI need to be considered
Risk factors
CHF
Cardiac dysfunction

33. 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.
SAFE Study: Status at 28 Days
*

34. Diuretics
• Olig/anuria is the common herald of impending
renal dysfunction and loop diuretics are
commonly used in this context.
• Theoretical basis is prevention of tubular
obstruction, reduction in medullary oxygen
consumption, increased renal blood flow.
1. 4 RCTs – no improvement.
2. Three meta-analyses showed diuretics do not
alter outcome but do increase the risk of side-
effects.
3. One international cohort study showed an
increased risk of death and established renal
failure.
Although nonoliguric AKI has been associated with better
outcomes than oliguric AKI,
Diuretics are ineffective:
1. in the prevention of AKI or
2. for improving outcomes once AKI occurs.
Meta-analyses have confirmed that the use of diuretics to
prevent AKI did not reduce
1. The in-hospital mortality,
2. The risk for requiring dialysis,
3. The number of dialysis sessions required, or

35. Treatment of Acute Kidney Injury Complications:
Fluid Overload
Pulmonary edema
Fluid redistribution allover the body
Anasraca
Inadequate urine output (low in comparison to intake}
All intakes should be minimized
Medical treatment
loop diuretic therapy can be initiated IV bolus
if there response change to infusion
New selective diuretics
Morphine
Nitroglycerin
Positive ventilation and intubation
Dialysis initiation.
Hyperkalemia:
Cardiac conduction,
Bradycardia, asystole
IV administration of calcium is urgently
Shifting K to intracellular:
Dextrose IV with insulin effect after 20 – 30 min
Bicarbonate solution effect < 15 min for 1 – 2 h
Avoid any source of K including drugs
Hyponatremia:
Associated with heart failure, liver failure, or diuretics.
water restriction to below the level of output is mandatory.
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.

36. Vasoactive Agents “Renal-dose” dopamine
(0.5 to 3 µg/kg per minute)
Mannitol:
could
1. prevent renal tubular cast deposition,
2. expand extracellular volume,
3. Reduce
1. intracompartmental pressure,
2. muscle edema,
3. and pain
1. However, mannitol may
2. exacerbate CHF and nephrotoxicity,
3. requires close monitoring,
4. contraindicated in
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
Nutrition:
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
a total energy intake of 20 to 30 kcal/kg/d,
In addition, in patients on RRT, 1.0 to 1.5 g of
protein/kg/d up to a maximum of 1.7 g/kg/d in patients
on CRRT and in hypercatabolic patients.

37. 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

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