Definition Acute renal failure first proposed by Homer
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Transcript Definition Acute renal failure first proposed by Homer
Advances in Acute renal failure
Acute renal failure first proposed by
Homer Smith
Text book: ‘The Kidney Structure and
Function in Health and Disease1951
35 definitions in literature
(Kellum et al. Curr Opin Crit Care 2002;8:509-514)
35 definitions in literature
(Kellum et al. Curr Opin Crit Care 2002;8:509-514)
Prevalence: 1 to 25% in ICU
Mortality: 15 to 60%
Why ‘RIFLE’ Criteria
ARDS & Sepsis: Definitions not perfect;
but found to be useful
Need to classify the severity of syndrome;
rather than only severest form
ARF= Dialysis dependence
Lack of single definition Held ARF
research 20 years back
(Bellomo R et al. Intensive Care Med. 2001 Nov;27(11):1685-
Citated till now in 546 articles
Severity
classes
Oliguria/
ARF
Outcome
classes
Decline in GFR Abrupt; 1 to 7 days
At all levels Both UOP & S. Cr Change sustained for >24
hours.
Relationship between S. Cr & GFR Depends on the phase
of recovering renal failure
Certainly steady state often not reached
Both S. Cr & GFR changes Always be considered in terms of
the baseline
When baseline is unknown or confronted with a patient who
has elevated S.Cr ??? Suggestion MDRD formula
Oliguria insensitive marker: many patients remain nonoliguric
Conventional definition
Rapid decline hours to weeks
Decline in GFR
Retention of nitrogenous waste products
1. Fails to describe dynamic process initiation,
maintenance & recovery
2. Emphasis on overt failure of kidneys; belies that mild
decrement of renal function A/w cardiac events
Hoste et al. : Only 14% of patients of ‘F’ Received dialysis;
but 5 times hospital mortality (Crit Care 2006; 10: R73)
AKI Incidence by RIFLE : 2-10 times higher
than conventional definition
No AKI
5.5%
Risk
8.8%
Injury
11.4%
Failure
26.3%
Relationship: RIFLE class V/s Outcome
Six studies
M
or
ta
lit
y
Hoste EA Curr Opin Crit Care 2006; 12; 531-537
Limitations of RIFLE
Urine output
Diuretic use: sensitivity & specificty
For accurate measurement: requires catheter
Hoste
(Crit Care 2006:10:R73)
S. Cr + UOP
Mortality: 8.8%, 11.4%; 26.3%
Uchino (Crit Care Med 2006:34:1913-1917)
S.Cr
15.1%; 29.2%; 41.1%
Need to know baseline S.Cr
Not always known
RIFLE advises to use MDRD;
MDRD for CKD
RIFLE Version 1.2 or AKIN Stages
Stages 1,2 and 3 instead of R. I and F Bagshaw et al. **
Increase in S. Cr at least 0.3 mg/dL
even if it does not reach 50%
threshold
A 48 hour window on first
documentation of any criteria
Increase in sensitivity
by 1%
Use of RRT, classifies patient to ‘F’
regardless of S.Cr or UOP
-
Caution: May exclude
patients that should
be included in AKI
diagnosis
**
NDT 2008; 23 (5);1564-1579
JAMA
2005;294:813-818
29,269 patients in ICUs
Largest prospective study
Period prevalence
5.7% (1.4 to 25.9%)
Median age
67 years
Contributing factors
Septic shock (47.5%)
Major surgery, Cardiogenic shock
Mortality
60.3%
Septic patients
70.2%
618 patients in ICUs
Mean age
59.5 years
Co-morbidities
CKD 30%
CAD 37%
DM 29%
In-hospital mortality
37%
AKI superimposed on CKD lower mortality than AKI
Nature Reviews Nephrology
2006, 2 (7) 364
Nature Reviews Nephrology
2006, 2 (7) 364
Hospital incidence
Nature Reviews Nephrology
2006, 2 (7) 364
Disease categories of AKI
Disease
Pre-renal azotemia caused by
Percentage
55-60
acute renal hypoperfusion
Intrinsic renal azotemia
35-40
Diseases of large vessels, small
vessela, glomeruli, interstititum &
Tubules**ATN
Post renal azotemia due to
<5
obstruction
** Accounts for 90% of intrinsic renal category
Diagnosis of ARF
Often diagnosed Increase in S. Cr & Urea
BUN to S. Cr ratio = 15 : 1
Hypercatabolic
Hypercatabolic ARF ARF
Schrier Kid Int 1979 ; 15: 205-216
LR: Likelihood ratio
Renal biopsy in ARF
Indications
Oliguria > 2 weeks Schrier
> 6 weeksOTCN
Anuria Flawed Patchy
necrosis Angiogram
to know perfusion of
cortices
Systemic disease
Heavy proteinuria &
haematuria
Marked hypertension
No circulatory disturbance
to account for ATN
Gomez. CJASN 3; 674: 2008
Largest registry 2281 ARF biopsies
AKI as an indication
16%
Most commonly
Elderly; 32%>60y
ATN
Only 5%; Intense
selection bias:
Only those not
presumed to be
ATN clinically
biopsied
What is not
clarified
Initially thought to
be ATN finally
biopsied
Gomez. CJASN 3; 674: 2008
Past = Contraindications
Sheath
Needle
Protective cover
Needle + Specimen
Modified Colapinto aspiration needle
Interventional radiologist
25 high risk patients
21 (84%) tissue adequate
17Perforation of renal
capsule
6 of them coil embolization
1 RVT after one week
Feasibility of
transjugular
biopsy well
documented
Clinical benefit
to be established
Previous criteria: Early v/s Late; Qualitative
CJASN 3; 876-880; 2008
Proposed: Quantitative; Based on RIFLE criteria
Timing
RRT: Early versus Late
Mortality
V. Seabra et al, AJKD, 52: 272-284; 2008
Renal recovery
V. Seabra et al, AJKD, 52: 272-284; 2008
V. Seabra et al, AJKD, 52: 272-284; 2008
Dosing
160 patients Randomized to daily HD v/s Alternate day HD
Alt day HD
Daily HD
Duration of HD (hr)
3.4 ± 0.5
3.3 ± 0.4
Kt/v (delivered)
0.94 ± 0.11
0.91 ± 0.12
Mortality
Resolution of ARF (days)
46%
16 ± 6
28%
9±2
??? A case of inadequate dialysis
Mean time averaged BUN
104 ± 18
60 ± 20
9.5 ± 1.2
5.3 ±1.2
(mg/dL)
Mean time averaged S.Cr
(mg/dL)
Dosing
Survival rate
41%
57%**
58%**
Optimal dose is 35 ml/kg/hr = 50.4 L/d
Dosing
Palevsky et al.
Intensive treatment
IHD &/ or SLED: Six times a
week
CVVH: 35 ml/kg/hr
Less Intensive treatment
Thrice a week
20 ml/kg/hr
Allowed patient transition from one mode to another as
long as they stayed within the intensive or less intensive
groups
Dosing
Dosing
CORRESPONDENCE
1. 6 days delay in initiation of treatment
2. 219 protocol deviations Isolated UF in less
intensive group
3. SLED more in intensive group
4. Treatment for 28 d only. Mortality At 60 d; 10%
of patients received extra dialysis
Dosing
Bellomo et al.
1508 patients randomized
CVVHDF
40 ml/kg/hour 25 ml/kg/hour
Deaths at 90 d
44.7%
44.7%
RRT dependence
6.8%
4.4%
at 90 d
Hypophosph65%**
54%
otemia
Dosing
Bellomo et al.
Mortality: No difference
2010 Vol. 38, No.5;
1360
Eight RCTs in last decade
At present Four discussed
Recommendations
Dialysis dose: Kt/V: 1.4 & effluent volume
25 to 30 ml/kg/hour
Daily monitoring of delivered dose
Nutrition & drug dosing monitored
Plateau: no
further benefit
Steep
correlation bet
the dose &
survival
What is
unknown even
after VA/NIH ATN?
1. Breaking point
2. BP for diff
modes of
dialysis
What is
gainedVA/
NIH ATN
1. Not to risk
under dialysis
2. Dialysis dose
monitoring
CRRT v/s IHD: Six
RCTs Last 10 years; In Europe & US
CRRT
IHD
John S et al.
NDT 16; 320-327, 2001
No difference in mortality 70% in both
Mehta et al. KI 60; 1154-1163;
Mortality
2001
ICU: 59%
Hospital:
65%
41%
47%
After covariate adjustment:
No difference
Augustine JJ AJKD 2004; 44: 1000-1007
No difference in mortality
Greater haemodynamic stability in CRRT
Uhelinger DE et al.
NDT 2005; 20:1630-1637
Mortality: 34%
Gasporvic et al.
Renal fail 25; 855-866;2003
No difference in mortality
Hemodiafe study
Vinsonneau et al, Lancet, 368, 379-385,
2006
No difference in mortality
38%
p= NS
CRRT v/s IHD
Crit Care Med, 36: 610-617; 2008
Continuous versus intermittent renal replacement therapy
for critically ill patients with acute kidney injury: A metaanalysis
Bagshaw, Sean M. MD, MSc; Berthiaume, Luc R. MD; Delaney, Anthony
MBBS, MSc; Bellomo, Rinaldo MD
CRRT v/s IHD
Crit Care Med, 36: 610-617; 2008
Continuous versus intermittent renal replacement therapy
for critically ill patients with acute kidney injury: A metaanalysis
Bagshaw,
Seanwas
M. MD,
MSc; Berthiaume,
R. MD; Delaney,
Anthony
There
suggestion
thatLuccontinuous
RRT
had
MBBS, MSc; Bellomo, Rinaldo MD
fewer episodes of hemodynamic instability and
better control of fluid balance.
In the context of these limitations, the initial RRT
modality did not seem to affect mortality or
recovery to RRT independence
Death
Renal recovery
Intermittent, continuous and hybrid
techniques offer specific advantages
All are part of a medley race in dialysis of
critically ill
Prospective RCT
Hypercatabolic patients
87 patients
CEPD & TPD cross over trail 12 hour wash out after initial
dialysis
Baxter dialysate bags & Cycler machines
CEPD
Weekly Kt/V 1.80 ± 0.32
“Just fell short of
dialysis adequacy”
TPD
2.43 ± 0.87
Higher clearances
Less expensive (Rs.7165)
Both Reasonable options for the treatment of ARF
NEJM 347; 12: 895; 2004
Hemofiltration versus Acute PD
78 patients
48 Malaria; 22 Sepsis
Mortality
Acute PD : 47%
Haemofiltration: 15%
John T Daugirdas
1.Predominance of malaria
2.Comparison of state of art CVVH with
rustic PD
3.CVVH was low intensity; still
patients recovered fast
Kid Int 2008; 73: 587- 593
120 patients randomized
HVPD Tenckhoff catheter placed by a nephrologist
7 days a week
Dianeal solution
Home choice (Baxter)
Weekly Kt/V= 3.6 ± 0.6
DHD 3 hour session
6 days a week
Weekly Kt/V= 4.7 ± 0.6
Kid Int 2008; 73: 587- 593
Summary
RIFLE Criteria
AKIN criteria
Epidemiology
Single standard definition
Severity of class Mortality
Impact not yet known
Incidence of ARF
Mortality relatively static
LR of ATN high
>6 RTEC & GC
Transjugular biopsy Possible to do; Utility unknown
Early dialysis
Effective
Intense dialysis
No effective;
Not to risk under dialysis
Dose
Kt/V=1.4; CRRT 25-30 ml/kg/hr
Daily monitoring
CRRT v/s HD
No difference
PD
Reasonable option
Biomarkers
Qualities
Accurate, reliable
Relatively non-invasive/acceptable to patients
Rapidly measurable, standardized assay
Sensitive/specific with reproducible cutoff values
Neutrophil gelatinase
assosciated lipocalin (NGAL)
25 kDa, protein
Expressed in neutrophils
Kidney, lungs, trachea,
stomach, colon
Increased in PT—after injury
KIM-1
First novel renal biomarker
discovered
IL-18
Role in inflammation, Activating
macrophages
Mediates ischemic renal injury
Cystatin C
Non-glycosylated LMW(13.4 kDa)
cystine protease
Synthesized at constant rate by all
nucleated cells
(Grubb AO Adv. Clin. Chem. 2000; 35: 63–99.)
Freely filtered glomerulus
Completely reabsorbed PT
(Han WK et al. Kid Int. 2002; 62: 237–44)
Readily assayed Automated
A transmembrane protein in PT immunonephelometric
(Herget-Rosenthal S Clin. Nephrol. 2005; 64:
41–6)
As a GFR measurementrobust
than S Cr
Urine
Urine
Current status of AKI biomarkers
Biomarker Sample Cardiac
Source surgery
CIN
Sepsis
RT
NGAL
Plasma
Early
Early
Early
Early
NGAL
Urine
Early
Early
Early
Early
Cystatin C
Plasma
Intermediate
Intermediate Intermediate Intermediate
IL-18*
Urine
Intermediate
Absent
Intermediate Intermediate
KIM-1*
Urine
Intermediate
Not tested
Not tested
Not tested
* Commercial test not yet available
Devarajan P Contrib Nephrol 2007, 156, 203-212
Acute versus Chronic
History
Suggests chronicity
Vague ill health
Nocturia
Pruritus
Skin pigmentation
‘Bit of protein’ in urine
‘Bit of problem in kidneys’
Kidney sizes
USG standard
Size: 3.7 ± 0.4 cm times of L2 VB
Broad waxy casts
Chronic renal failure or rapidly
progressive; never ARF
Carbamylated Hb (expressed as µg
carbamyl valine per gram (CV/g) Hb)
CRF: 129.0 ±8.1
ARF: 55.6±6.2
Normal: 31.6±1.3 **
Present in both
Anemia, Hypocal, Hyperphos,
Hyperuricemia
** Alian Wynckel Nephrol Dial Transplant (2000) 15: 1183-1188
Fractional Excretion of Sodium (Fe Na)
Ratio of Na+ clearance to the Cr. Clearance
UNa+ / PNa+ X PCr / UCr X 100
Pre-renal azotemia
ATN
Na+Reabsorbed avidly
D/t Suppression of ANP
Activation of R-AT-Aldo
Na+ Reabsorption is
inhibited as tubule is
damaged
Creatinine reabsorption smaller extent than Cr in both
conditions
<1%
>1%
FeNA > 1.0 in pre-renal
azotemia
FeNa < 1.0 in ATN
Diuretics
Milder form of ATNs intermediate syndrome
Underlying salt losing
nephropathy
Damage only to cortico medullary junction;
preservation of LOH
Adrenal insuffficiency
Ischemia, Rhabdomyolysis, AGs, RCA, HRS
Espinel JAMA 236; 579-581, 1976
Pre-renal azotemia with
FeNA >1 d/t diuretic
use
Fractional excretion of
Lithium & UA remains
low
Prognosis
Oliguric patients with
ARF with Fe Na
<1%High
likelihood of
response to diuretics
Renal failure indices
FeNa (%)
Renal failure index UNa/Ucr/Pcr
Urinary Na+ concentration (mEq/L)
Plasma BUN/creatinine ratio
Fe UA (%)
Fe Lithium (%)
Pre renal azotemia ATN
<1
>1
<1
>1
<10
>20
>20
<10–15
<7
>15
<7
>20
Urinary creatinine/plasma creatinine ratio
>40
<20
Urinary urea nitrogen/plasma urea nitrogen
ratio
>8
<3
>1.018
>500
Hyaline casts
<1.012
<250
RTECs & casts,
Muddy brown
granular casts
Urine specific gravity
Urine osmolality (mOsm/kg H2O)
Urine sediment
Treatment Usually started on same lines whether it is prerenal azotemia or ATN
DOSING
MEHTA R., McDONALD KI 2001
166 patients randomized
84 to CRRT, 82 to IHD
Patients with Mean Arterial Pressure (MAP) < 70 mm Hg
excluded
Mortality
ICUpatients
CRRT
59%
Hospital patients 65%
IHD
41%
P
Significant
47%
Significant
The mortality was worse in CRRT group, but on subgroup
analysis the renal recovery was better on CRRT
Criticism: Patients with MAP < 70 mm Hg have been excluded
Changing Trends in Acute Renal Failure in Thirdworld Countries — Chandigarh Study
K. S. Chugh et al. Q J M 1989; 73:1117-1123
Percentage
1965 to 1974
Diarrhoeal
23
diseases
Sepsis & drugs
37
Obstretic
22
Surgical causes
11
1981 to 1986
10
50
9
31 d/t ↑
obstructive
uropathy
Epidemiologic Trend Changes in Acute Renal Failure
—A Tertiary Center Experience from South India
M. Jayakumar, Renal failure, (5 ) 2006 , 405 - 410
Number of patients
Mean age
1112 between 1994 to 2004
37.08 ± 3.4 yrs
Males
Medical
Obstetric
Surgical
669 (60.1%)
87.6 %
8.9%
3.4 %
Most common medical
cause
Other causes
Diarrhoeal disease
RRT
69%
Mortality
Dialysis depedence
19.6%
8.18%
Lepto, Malaria, Drugs
RIFLE
3 Severity classes
2 Outcome classes
Risk
Injury
Failure
Loss
End stage kidney
Based on changes
in S.Cr or UOP
Worst of each
criteria to be used
Duration of loss of
kidney function
disease
Hoste et al. : Only 14% of patients of ‘F’
Received dialysis; but 5 times hospital
mortality (Crit Care 2006; 10: R73)
Survival rate
41%
57%**
58%**
Optimal dose is 35 ml/kg/hr = 50.4 L/d