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A New Perspective on Acute Kidney Injury
1. A New Perspective on Acute
Kidney Injury
by Steve Chen
Director of Nephrology,
Shin-Chu Branch of Taipei Veterans General Hospital
2. Acute kidney Injury(AKI)
Classifications
Etiology
Nutritional support
Diuretic role
Renal replacement therapy
Specific type acute kidney injury
3.
4. S-Cr based definitions of AKI
Parameter Definitions
Acute Kidney Injury Network Stage 1: ≧0.3 mg/dl increase or 50%
increase
(AKIN) over baseline
within 48Hr
Stage 2:≧100% increase over
baseline
Stage 3: ≧200% increase or 0.5mg/dl
increase
to at least 4.0 mg/dl
Acute Dialysis Quality Initiative RIFLE(R) ≧50% increase over
baseline
RIFLE(I) ≧100% increase over
baseline
RIFLE(F) ≧200% increase over
baseline or
14. BUN/Cr >15
Increased urea formation:
High protein intake
Increased intestinal absorption of urea/NH4- GI
bleeding, ureteral diversion
Catabolic state- fever, tissue necrosis, steroid
use, tetracycline use, sepsis
Decreased urea elimination:
Volume depletion
Heart failure
Obstructive nephropathy
15.
16. Nutritional profile
Hyper- Mild Moderate Severe
catabolism (>N intake (>N intake (>N intake
+5) +5 ~ 10) +10)
Prot(g/Kg/D) 0.6-1.0 0.8-1.2 1.0-1.5
Energy 25 25-30 30-35
(Kcal/Kg/D)
Mortality 20% 60% >80%
Dialysis rare prn frequent
Clinical Drug- elective sepsis or
induced surgery emergency
surgery
17. Diuretic use for ARF
Total Favorable No Equivocal
=19 studies outcome improvement outcome
Renal 7 9 2
function(18)
Need for
dialysis(14) 7 5 2
Mortality
(15) 1 14
18. Diuretic status on mortality
Urine Mortality OR for death
volume(cc/D) (%)
≦50 80 1.95
50 ~ 400 76 1.76
400 ~ 1000 43 1
1000 ~ 2000 22 0.5
≧2000 13 0.3
19. Initiation of dialysis
Kt/V <2.0/week; GFR<10.5,
Kcr<14.5,Kurea<7 ml/min per 1.73m2
Symptoms(progressive or unexplained)
Anorexia, Nausea, Vomiting
Fatigue
Sleep disturbance
Nutritional status
Decreasing edema-free BW
Hypo-albuminemia
Low SGA(≦5)
20. Dialysis for ARF
BUN>100mg/dl, Cr>10mg/dl
Hyperkalemia(>6.5meq/L,intractable)
Severe metabolic acidosis(pH<7.1)
Dysnatremia(Na>160 or <110meq/L)
Uremic symptoms
Uremic encephalopathy, pericarditis,
bleeding, gastroenteritis, neuromuscular p.
Organ edema,especially lung edema
Oliguria
Overdose with dialysable toxin
Hyperthermia
22. Hybrid RRT: EDD-f
Extended Daily Diafiltration: EDD-f
The future in critical care nephrology
Sustained Low Efficiency Daily
Diafiltration: SLEDD-f
AVVH: Accelerated VenoVenous
Hemofiltration
23. AVVH
Casey et al: AJKD 2008(Ruch University Medical Center, Chicago)
Accelerated VenoVenous Hemofiltration
Low Qb : 350 ~ 400 ml/min
Net fluid removal rate: 2.5L/Treatment
Replacement fluid in pre-dilution mode:36L
No anticoagulation
Session duration: 9 Hr/D
Advantages of both CRRT and IHD
24. SLEDD
Slow Low Efficient Daily Dialysis
Low Qb and low Qd: ≦200ml/min
Filtration rate: 25-30 ml/min
Session duration: 6 ~ 12Hr/D
Advantages of both CRRT and IHD
Kt/V targeting 1.2 ~ 1.4 per session with
a frequency of 6 times a week (Intensive);
TIW(less intensive)
25. CVVH dose in ARF
Prospective randomized trial: N= 425 in ICU ARF
CVVH with post-dilution; Qb 145 ~ 207 ml/min
Gr I: Uf=20ml/H/Kg Gr
II: Uf=35ml/H/Kg Gr
III: Uf=45ml/H/Kg
Survival at 15 days after CVVH: (adjusting)
Gr I: 41% < Gr II: 57% (p=0.0007) ∞ Gr III:
58% (p=0.0013)
Renal recovery of survivors at D15:
Gr I: 95%; Gr II: 92%; Gr III: 90%
Early start in all group survivors
Ronco et al, Lancet 355: 26-30, 2000
26. CVVHDF dose in ARF
Tolwani et al: JASN 2008( University of Alabama at Birmingham)
Prospective randomized trial: N= 200 in ICU ARF
CVVHDF with pre-filter replacement fluid; Qb
100 ~ 150 ml/min
Survival at ICU discharge or 30 days
Gr I: 56%; Gr II: 49% (p=0.32)
Renal recovery in survivors:
Gr I: 80%; Gr II: 69% (p=0.29)
Gr I: Effluent rate=20ml/H/Kg
Gr II: Effluent rate=35ml/H/Kg
A difference in survival or renal recover: not
detected
27. Dialysis dosing in critically ill patients
with AKI
Multicenter randomized trial: enrollment of 1164
to achieve a 10% difference in morality rate with
statical power of 90% with P value of 0.05
Hemo-dynamically stable: IHD
Unstable: CVVHDF(total effluent rate: 35 or 20
ml/Kg/Hr) or SLED( 6 or 3 times per week)
Primary end point: 60-day all cause mortality
Mortality: 53.6% in intensive; 51.5% in less-
intensive
Renal/Non renal organ recovery rate: similar
Palevsky PM et al NEJM 359: 7-20, 2008 (VA/NIH Acute renal failure Trial Network)
28.
29. Outcomes after acute kidney injury
Study design: Systemic review and meta-analysis
48 studies/N=47017
15 studies reported long-term data for patients without AKI
Selection criteria:
MEDLINE and EMBASE from 1985 to October 2007: hospital case
Excluded for F-U ≦ 6M
Results:
1> Incidence rate of mortality: 2.59 X (rate ratio)
8.9/100 P-Y in survivors of AKI
and 4.3/100 P-Y in survivors without
2> Mortality risk in 6 of 6 studies: 1.6~ 3.9 by adjusted RR
3> Myocardial infarct in 2R of 2 studies: 2.05 by RR
4> Incidence rate of CKD: 7.8events/100 P-Y
5> Rate of ESRD: 4.9events/100 P-Y
SG Coca et al: AJKD 53: 961-973, 2009 (Yale University)
34. AKI in acute liver failure
Incidence: 50%
Precipitants: ↓IVF , ↓ CO, Hypoxia, ↓SVR;
Sepsis, nephro-toxins; IIAP
Prevention: timely elective liver
transplantation(LT) for non-acute hepatic
failure
LT: ↓ mortality( from 80% to 40%)
35. Hepatorenal syndrome (1)
Seminar, Lancet 362: 1819-27, 2003
Incidence: 40% over 5 years in cirrhotic
ascites
Renal failure: progressive oliguria
Hyponatremia, dilutional: often
Hyperkalemia, moderate: common
Severe metabolic acidosis→ infection
Hemodynamic instability →infection
Major cause of death: severe bacterial
infection
36. Hepato-renal syndrome (2)
Chronic/ acute liver disease with advanced
hepatic failure&portal HTN
Low GFR: S-Cr > 1.5mg/dl / GFR <
40ml/min
R/O shock, infection, toxin, &fluid loss
No sustained improvement in renal
function: after diuretic withdrawal/IV NS
1500cc
Proteinuria < 500mg/D; negative sonogram
38. Hepatorenal syndrome (4)
Seminar, Lancet 362: 1819-27, 2003
Type I Type II
Definition ↑100% S-Cr in < 2 Other
W: →>2.5 mg/dl
Clinical GFR < 20mL/min GFR >20 mL/min
S-Cr, av : 3.1 mg/dl S-Cr, av : 1.6mg/dl
Severe renal failure Recurrent ascites
Survival at <0.1 <0.6
4M
39.
40. Mortality of AKI after first acute stroke
Tsagalis G et al: Clinical J Am Soc Nephrology 2009( University of Athens, Greece)
41.
42. Aminoglycoside nephrotoxicity
GM.Tobramycin>Amikacin>Netrilmycin
Risk factors:
pre-existing renal disease
advanced age
dose&duration
concurrent use of nephrotoxic agents
sepsis
hepatic failure
volume depletion; salt-restriction
metabolic
acidosis,hypokalemia,hypomagnesemia (?)
45. Dye induced nephropathy
University of Milan, NEJM 349: 1333-1340,2003
Indications:
S-Cr > 2.0 mg/dl ( C-Cr>4 mg/dl with greatest positive effect
of long-term survival)
multiple interventions
Hemo-filtration:
fluid replacement rate 1000ml/Hr
saline hydration 1ml/Kg/Hr
Time: 4-8Hr before ~18-24Hr after
In hospital mortality: 2% vs 14% p=0.02
Cumulative 1-Y mortality 10% vs 30% p=0.01
46. Dye induced nephropathy
University of Milan, NEJM 349: 1333-1340,2003
3.5
3
2.5
2
S-Cr, control
1.5 Hemofil tration
1
0.5
0
D0 D1 D2 D4 Dis
47.
48. Cardio-renal syndrome
Definition:
Baseline renal function: S-Cr > 1.3 mg/dl and
estimated C-Cr ≦60 ml/min; Worsening renal
function(≧0.3mg/dl)
Risk factors: prior CHF/older/DM/HTN/Renal
dysfunction
LVEF≧ 40%: 37 ~ 55% not characterized by
low-output state but by fluid retention
ACEI/ARB: empirical
Effective diuresis: ? Maybe in some cases
Natriuretic peptides: Nesiritide ?
49.
50. Acute phosphate nephropathy
Markowitz et al: JASN 2007 Columbia University
Definition: 1.16 ~ 6.3%
Baseline renal function: S-Cr > 1.3 mg/dl and
estimated C-Cr ≦60 ml/min; Worsening renal
function(≧0.5 ~ 1.0mg/dl) 6 ~ 12M after colonoscopy
Risk factors: Female/older/CHF/Diuretic use/ACEI use
Hydration: ≧72 ounces of clear liquids for 30 ~ 45 ml
OSP
Avoidance of anesthesia regimens: no oral intake for 4-
6 Hrs
Alternative agents in female: PEG (polyethylene glycol)
Dose reduction or avoidance in the elderly/risk factors
54. Mechanical ventilator:
independent predictor of acute kidney injury
PEEP < 6: OR=2.89 ; PEEP>6: OR=20.7
Vivino et al, Intensive Care Med 24: 808-14, 1998
Incidence:
PEEP>6: 73%
PEEP<6: 36%
Venturi mask: 17%
Vivino et al, Intensive Care Med 24: 808-14, 1998
Predictors of mortality/ dialysis in PTS with
ATN Chertow et al, JASN 9: 692-98, 1998