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Acute Kidney Injury for Core Trainees
1. A C U T E K I D N E Y I N J U R Y
J I M R I T C H I E
2. O B J E C T I V E S
• Define, stage and manage AKI events
• Appreciate the clinical relevance / pathology of AKI
• Understand local and national referral criteria /
pathways
• Highlight less common, intrinsic renal pathology
• Understand the long term implications of AKI
3. O U T L I N E
• Perspectives - historical and current
• Identification and definition of AKI
• Pathogenesis
• NICE guidelines, care bundles and CQUINs
• The other 20%
• Dialysis, long term outcomes and final thoughts
4. P E R C E P T I O N S
Acute physician / nephrologist
Acute physician / ICU
Nephrologist / arse
5. R E A L I T Y
J U N E 2 0 1 3
A U G / S E P T
2 0 0 9
M A Y / J U N E
2 0 0 9
P A T I E N T S W I T H
A K I 1 8 1 5 1 1
P E R C E N T A G E
R E C O G N I S E D 8 9 % 7 3 % 6 3 %
R E P E A T
B L O O D S 1 0 0 % 8 0 % 5 9 %
D I P S T I C K 3 3 % 2 7 % 2 2 %
I V I P R E S C R I B E D 8 8 % 7 3 % 6 8 %
F L U I D B A L A N C E 4 4 % 2 0 % 1 8 %
D R U G S R E V I E W 8 3 % 4 0 % 2 7 %
Courtesy of Dr R Nipah - EAU. Salford Royal NHS Foundation Trust
J U N E 2 0 1 3
A U G / S E P T
2 0 0 9
M A Y / J U N E
2 0 0 9
P A T I E N T S W I T H
A K I 1 8 1 5 1 1
P E R C E N T A G E
R E C O G N I S E D 8 9 % 7 3 % 6 3 %
R E P E A T
B L O O D S 1 0 0 % 8 0 % 5 9 %
D I P S T I C K 3 3 % 2 7 % 2 2 %
I V I P R E S C R I B E D 8 8 % 7 3 % 6 8 %
F L U I D B A L A N C E 4 4 % 2 0 % 1 8 %
D R U G S R E V I E W 8 3 % 4 0 % 2 7 %
11. C O N C E P T U A L P A T H W A Y F O R
A K I
N O R M
A L
R I S K
D A M A
G E
G F R
F A L L
K I D N E
Y
F A I L U
R E
D E A T
H
What we see
Where we define AKI
12. W H A T I S A K I ?
AKI is potentially all of these things
M E A S U R E M E N T C H A N G E
A B S O L U T E C R E A T I N I N E > 1 3 0 - > 6 0 0
R E L A T I V E C R E A T I N I N E 1 0 % - 1 0 0 %
U R I N E O U T P U T 0 - 3 0 M L / H O U R
N E E D T O D I A L Y S I S ! ! !
13. W H A T I S A K I ?
“A clinical syndrome
characterised by a rapid
reduction in renal
excretory function due to
several different causes.”
14. H O W I S A K I D E F I N E D
S T A G E C R E A T I N I N E U R I N E O U T P U T
1
1 . 5 - 1 . 9 X B A S L I N E
> 2 6 U M O L / L I N C R E A S E
< 0 . 5 M L / K G / H R F O R 6 - 1 2
H O U R S
2 2 . 0 - 2 . 9 X B A S E L I N E
< 0 . 5 M L / K G / H R F O R > 1 2
H O U R S
3
3 . 0 X B A S E L I N E
S C R > 3 5 3 U M O L / L
R R T
< 0 . 3 M L / K G / H O U R F O R > 2 4
H O U R S
A N U R I A > 1 2 H O U R S
15. I N C I D E N C E O F A K I
5 - 15% of all
non-elective
admissions
16. N U M B E R S P E R 1 0 0 0 / B E D S
• AKI 1 - 2727 / year [227 / month]
• AKI 2 - 782 / year [65 / month]
• AKI 3 - 636 / year [53 / month]
17. N U M B E R S I N C R I T I C A L C A R E
Murugan et al - Nat Rev Nephrol 2012;7(4):209-217
18. N I C E G U I D E L I N E S
• CG196 - Issued August 2013
• Areas covered
- assessing risk
- prevention
- detection
- management
19. N I C E G U I D E L I N E S -
P R E V E N T I O N
• Use of EWS triggers
• Systems in place to monitor urine output
• Caution around iodinated contrast
- medication review
- adequate hydration
20. R I S K F A C T O R A S S E S S M E N T
• CKD
• Age >65
• Heart failure
• Liver disease
• Diabetes
• Previous AKI
• Acute illness / sepsis
• ‘Nephrotoxic’ drugs
• Neuological / cognitive
impairment
• History of urological
obstruction
NICE- 2013; CG169
21. R I S K F A C T O R A S S E S S M E N T
Kane-Gill et al - Am J Kidney Dis. 2015;65(6):860-869
22. I N V E S T I G A T I O N
• Urine dipstick - consider renal referral if
‣ haematuria and proteinuria
- without UTI
- without catheter related trauma
• Renal tract ultrasound
- suspicion of obstruction / pyonephrosis (6 hours)
- no identified cause for AKI (24 hours)
NICE- 2013; CG169
24. C A U S E S O F A K I
Pre - renal
-25 - 60%
Renal
-35 - 70%
-80 - 90%
ischaemic
Post - renal
-5% (hospital)
-20%
(community)
25. A C U T E T U B U L A R N E C R O S I S
Hypoperfusion /
ischaemia
Direct
effect
Haemodynamic
changes
Fall in GFR Fall in U/O
Tubular damage
Cells shed
Casts form
Backleak
27. F L U I D S
Catecholamines -> PCT
effect
Pain / sepsis -> ADH
stimulation
Hypotension -> RAAS
activation
Can lead to salt / water
retention
Sepsis -> capillary leak
Reduced hepatic synthetic activity
Can lead to hypoalbuminaemia
Hypo-oncotic ECF
28. E V I D E N C E F O R F L U I D S ?
• Early Goal Directed Therapy -
Surviving Sepsis
• 30ml/kg crystalloid
• No data have considered renal
outcomes
• Adverse effects of fluid
overload?
29. E V I D E N C E F O R F L U I D S ?
• There are no data to suggest that aggressive hydration
improves outcomes in AKI
- Obvious dehydration
- Contrast mediated injury / crush injury
E D G T
E D G T ( F L U I D
N E U T R A L )
V A S O A C T I V E
N O
V A S O A C T I V E S
O D D S R A T I O 0 . 5 9 0 . 4 7 0 . 5 2 0 . 7 5
9 5 % C I 0 . 3 9 - 0 . 8 9 0 . 2 9 - 0 . 7 6 0 . 3 4 - 0 . 8 0 0 . 3 7 - 1 . 5 3
E D G T
E D G T ( F L U I D
N E U T R A L )
V A S O A C T I V E
N O
V A S O A C T I V E S
O D D S R A T I O 0 . 5 9 0 . 4 7 0 . 5 2 0 . 7 5
9 5 % C I 0 . 3 9 - 0 . 8 9 0 . 2 9 - 0 . 7 6 0 . 3 4 - 0 . 8 0 0 . 3 7 - 1 . 5 3
Prowie et al - Crit Care 2012;16(4):230-245
30. E V I D E N C E F O R F L U I D S ?
Prowie et al - Crit Care 2012;16(4):230-245
31. E V I D E N C E A G A I N S T F L U I D S …
• 170 RRT requiring AKI secondary to ATN - primary
end point of freedom from dialysis at 12 months
- 61 (36%) recovered function (51 prior to discharge)
- 1% increase in fluid overload associated with 3%
reduction in chance of recovery
Heung et al - Nephrol Dial Transplant 2012;27(3):956-61
32. E V I D E N C E A G A I N S T F L U I D S …
• All AKI episodes in 618 patients over a 2-year period
- fluid overload associated with mortality
- dose dependent relationship
- present in dialysed and non-dialysed patients
Bouchard et al - Kid Int 2009;76:422-427
Dialysis
AKI
33. W H I C H F L U I D - S T A R C H E S ?
• Can deposit in the kidneys
• No mortality benefit in acutely unwell patient
- n = 804, HR death 1.17 [95% CI 1.01 - 1.36], p=0.03
- n = 7000, RR death 1.06 [95% CI 0.96 - 1.18],
p=0.26
• 20% increased risk for RRT
Perner et al - NEJM 20012;367:124-134
Myburgh et al - NEJM 2012;367:1901-11
34. W H I C H F L U I D - A L B U M I N ?
SAFE Investigators - NEJM 2004;350:2247-56
35. W H I C H F L U I D - C R Y S T A L L O I D S ?
Chowdhury et al - Ann Surg 2012;256:18-24
Yunos et al - JAMA. 2012;308(15):1566-1572
36. R E N A L R E P L A C E M E N T T H E R A P Y
• Refractory hyperkalaemia
• Profound acidaemia
• Uraemic symptoms
- pericarditis
- encephalopathy
• Fluid overload and pulmonary oedema
37. E V I D E N C E F O R R R T T I M I N G
“Beliefs about when to initiate dialysis in patients with
AKI are passionately held, and are - on the whole -
unsupported by reliable evidence”
Wilson et al - cJASN 2014;9:1510-1512
When is early
Who will progress
Recovery between
early / late timings
38. E V I D E N C E F O R R R T T I M I N G
• 102 patients - prospective study
• Single center in India
• Early start; sCr >620
• 80% volume depletion
Jamale et al - Am J Kidney Dis 2013;62(6):1030-1033
Vaara et al - cJASN 2014;5(9):1577-1585
• 986 patients - retrospective study
• Multi-centre study
• 4 patient groups (propensity matched)
• Possible benefit from early RRT 27% vs.
49%
39. R E F E R R A L C R I T E R I A
• AKI with no clear cause
• AKI 3
• Possible diagnosis of vasculitis / GN…
• AKI in CKD 4 / 5
• AKI in renal transplant
• Inadequate response to treatment / complications of AKI
NICE- 2013; CG169
41. L O N G T E R M O U T C O M E S
CKD
ESKD
Coca et al - Kidney Int 2012;81(5):442-448
42. L O N G T E R M O U T C O M E S
“Dose dependent” effect
Interaction with pre-existing CKD
43. G F R D E C L I N E P O S T - A K I
Ritchie, Asar, Kalra et al - Unpublished data. Under review Stat Med
No AKI
AKI 1
AKI 2/3
Recovery period ~1 month.
78% / year increase
8%
4%
44. B I O M A R K E R S F O R A K I
N O R M
A L
R I S K
D A M A
G E
G F R
F A L L
K I D N E
Y
F A I L U
R E
D E A T
H
What we see
Where we define AKI
M A R K
E R
A C T I O
N
• NGAL
• IL-18
• KIM-1
• L-FABP
• Cystatin-C
45. B I O M A R K E R S
• All can predict AKI
• None have led to an intervention to prevent AKI
developing
• None have a clear role above established markers
46. B I O M A R K E R S - E V E N T S
Perianayagam et al - Am J Kidney Dis 2009;54(6):1025-1033
47. B I O M A R K E R S - O U T C O M E
M O R T A L I T Y R O C A U C
L - F A B P 0 . 8 9
N G A L 0 . 8 3
I L - 1 8 0 . 8 3
C R 0 . 7 3
A P A C H E I I 0 . 9 0
Doi et al - Crit Care Med 2011;39(11)
48. C Q U I N
• Commissioning for Quality and Innovation Payment
Framework
• Links income to achieving quality improvement plans
49. A K I C Q U I N
• Discharge summary information for patients coded as
having an AKI
‣ stage
‣ evidence of medication review
‣ follow up blood tests
- type
- frequency
2009 NCEPOD report
Only 50% of AKI care considered good
Poor assessment of risk factors
Unacceptable delay in recognition of post-admission in AKI in 43%
22 patients died with a primary diagnosis of post-admission AKI which was predictable and avoidable
Complications missed (13%), avoidable (17%) or badly managed (22%)
NCEPOD recommendation - initial clerking for all emergency admission should include AKI risk factor. All emergency patients should have electrolytes checked on admission and appropriately thereafter.
Unacceptable delay in recognition of post admission AKI in 43%
Complication missed (13%), avoidable (17%), badly managed (22%)
33% inadequate investigations
29% inadequacies in management
Poor recognition of acute illness, hypovolaemia, sepsis
AKI does not discriminate by age
All trusts must comply
AKI is a consequence of disease
The pattern and burden of AKI appears to be particularly significant in developing countries [3] and therefore the recently published Kidney Disease Improving Global Guidelines (KDIGO) Clinical Practice Guidelines for Acute AKI Definition
A key recommendation is that clinicians effectively adopt the previously published AKI Network definition of AKI [5] as one of the following:
• An increase in serum creatinine by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 h
• An increase in serum creatinine to ≥1.5 times baseline within the previous 7 days
• Urine volume ≤0.5 ml/kg/h for 6 h
Furthermore, KDIGO suggests that AKI should be staged according to severity as outlined in table
Kidney Injury provides a welcome and timely synthesis of the evidence base to support the management of AKI . AKI Definition
A key recommendation is that clinicians effectively adopt the previously published AKI Network definition of AKI [5] as one of the following:
• An increase in serum creatinine by ≥0.3 mg/dl (≥26.5 µmol/l) within 48 h
• An increase in serum creatinine to ≥1.5 times baseline within the previous 7 days
• Urine volume ≤0.5 ml/kg/h for 6 h
Furthermore, KDIGO suggests that AKI should be staged according to severity as outlined in table
SRFT audit data
62% of AKI 1 occurred in our hospital
177 AKI 1
51% did not progress
27% -> AKI2
21% -> AKI 3
3198 adults, 198 European ICU
Chart shows rates of organ dysfunction in admitted patients
Irrespective of reasons for critical care admission, ~50% of patients with develop AKI
As age increases, models using other factors function less well
Age is a dominant factor
Limitation of this study is that is represents a US ICU population
Discussion slide
Causes of aki depend on where acquired
ATN often seen as the number 1 cause. Debabteable….
Direct glomerular effects - mesangial contraction reducing effective surface area
Vasocontriction - RAAS activation, increased AII, reduced prostocyclin levels
Tubular damage - neuohormonal effeects (eNOS) alterirng heamdynamics
Dead tubular cells shed into lumen forming casts - local obstruction, opposed filration pressure, decreased gfr
This also causes backleak - ie filtrate back into the cirulcation - reduces effective GFR and urine vol
2/3 body weight is water
1/3 of this is extracellular - mainly interstitial; some plasma; some transcellular
Changes in fluid balance when acutely unwell lead to a tendency to retain fluids but also to re-distribute to the ‘wrong’ compartments
Explains often poor response to fluids etc in terms of a diuresis
CIN / rhabdomyolysis are exceptions
Meta-analysis of EGDT in prevention of post-operative AKI
For all EDGT ~555 ml extra fluid in non-aki group
Better result in EDGT with equal fluids (ie. vasoactives)
Similar result if just stratified by ionotropes
No between group difference if no ionotropes in study
Patients at a tertiary renal center over a 12 month period
Percent fluid overload was calculated based on the following formula: [(Weight at dialysis initiation – Baseline weight)/Baseline weight] × 100%. Recognizing that weight changes (gain or loss) may begin to occur pre-hospitalization, we defined baseline weight as the average outpatient weight recorded within 3 months preceding hospitalization.
KM plot suggests that this is an early modifiable factor (i.e. separation does not continue)
Not just RRT dependent AKI
30 day mortality 37% vs. 25%; 60 day 46% vs. 32%; discharge 48% vs. 35%
Dialysis needing patient OR death 2.07 if overloaded
Non-dialysis patients OR death 3.14 if overloaded
KM shows survival
Bar chart shows dose dependent relationship - hypovolaemia and hypervolaemia bad
Also - volume overload at time of peak sCr - less likely to recover renal function
Low molecular weight hydroxyethyl starches
Hence not recommended in acutely ill patients of any real nature
6997 patient
Albumin vs. crystalloid
Death - RR 0.99
ICU stay 6.5 vs 6.2 days
Same for LOS, LO ventilation, RRT, days RRT
Hyperchloridaemia can cause afferent arteriolar constriction and therefore theoretically reduce GFR
Randomised trial of 12 healthy volunteers - 2L saline or plasmalye: reduced renal perfusion seen in saline group
ICU trial (pre/post intervention by year) 760 vs 773 patients. 694 mol vs 496 chloride
RIFLE-defined AKI (odds ratio, 0.52 [95% CI, 0.37-0.75]; P.001) and use of RRT (odds ratio, 0.52 [95% CI, 0.33-0.81]; P = .004)
Even in CKD there is no absolute definition for when RRT should start
Several RCT have shown no survival benefit from early start in CKD There is no “optimal” form of RRT in AKI - not going to cover this
INDIA - signal to increased death in early start group
FINNAKI - RRT within 12 hours (conventional indications) >12 hours (conventional indication; before convention indicatoin; no rat
Ongoing -
Staart-AKI (Standard vs accelerated initiation of RRT in AKI). 90 day mortality in 100 patients being randomised to RRT within 12 hours or study criteria / based on clinical need. Excellent overall survival!
IDEAL-ICU - 864 septic AKI in France. Early vs/late RRT
Questions are also about selection / AKI cause etc
These are criteria for discussion. They do not equate to transfer
Meta-analysis of 36 studies
AKI associated with excess risk for development of CKD (HR 8) and ESRD (HR 3)
In addition, long term increased risk for death (HR 2) - ie risk increased after AKI recovery
Dose effect shows biological plausibility - worse AKI associated with increased risk for both CKD and ESRD
CKD is such a potent risk factor for ESRD. However, AKI episodes still increase risk (though not as much as in the non-CKD population). Raises questions of monitoring…
Comparable data for proteinuria / non-proteinuria
