Download Renal replacement therapy in acute kidney injury

Renal replacement therapy
in acute kidney injury
경희대학교 의과대학 문 주 영
The artificial kidney: a dialyser with a great area
Willem J. Kolff
Acta Med Scand, 1944, 117, 121-134
Contents
• Prescription and delivery of RRT
– Timing of initiation of RRT
– Modality of RRT
– Dose of RRT
• Special settings
– Hepatorenal syndrome
– Congestive heart failure
– Light chain disease
Timing of initiation of RRT
• The traditional thresholds used in stable CKD may be
inappropriately high in AKI
– AKI in the ICU often occurs in the setting of multiple organ
dysfunction, and the impact of renal failure on other failing
organs should be considered in the timing of RRT.
– the increased catabolism associated with critical illness and
the need to administer adequate nutritional protein will lead to
increased urea generation.
– it is often difficult to limit fluid intake in these patients, in
part due to the administration of intravenous medications.
– patients who are critically ill may be more sensitive to
metabolic derangements, and swings in their acid-base and
electrolyte status may be poorly tolerated.
The counterargument of early
initiation of RRT
• There are potential safety concerns regarding earlier
initiation of dialysis
– Insertion and prolonged placement of an indwelling dialysis
catheter
– The need for anticoagulation
– Hypotension associated with therapy
• and its consequences (including the potential for delayed renal
recovery)
– Leukocyte activation from contact with dialysis membranes,
among others.
Timing of initiation of dialysis and its
associated with mortality : IHD
Early RRT
Late RRT
No. of
patients
Study
Study method
Effect of early initiation
Parsons et al.
1961
Prospective/
observational
BUN 120150mg/dL
BUN>200mg/dL,
clinical
detoriation
33
↓Mortality, ↓Infection
Fisher
1966
Prospective/
observational
BUN<150mg/dL,
clinical
detoriation
BUN>200mg/dL
235
↓Mortality
Kleinknecht et al.
1972
Prospective/
observational
Maintenance of
BUN <200mg/dL
BUN>350mg/dL,
electrolyte
disturbance
500
↓Mortality,↓GI
hemorrhage
Conger
1975
Prospective/
randomized
Maintenance of
pre-HD
BUN<70mg/dL,
Scr <5mg/dL
BUN ~150mg/dL,
Scr ~10mg/dL
clinical indication
18
↓Mortality, ↓Infection
and GI complications
Gillum et al.
1986
Prospective/
randomized
Maintenance of
pre-HD
BUN<60mg/dL,
Scr <5mg/dL
Maintenance of
pre-HD BUN
<100mg/dL, Scr
<9mg/dL
34
↓Mortality,
↑hemorrhage and
septic complications
Timing of initiation of dialysis and its
associated with mortality : CRRT
Early RRT
Late RRT
No. of
patients
Study
Study method
Effect of early initiation
Gettings et al.
1999
Retrospective
BUN <60mg/dL
BUN>60mg/dL
100
↓Mortality
Bouman et al.
2002
Prospective/
randomized
12h after
meeting
Inclusion criteria
BUN>112mg/dL,
K > 6.5 mEq/L,
severe pulmonary
edema
106
No effect on
mortality
Elahi et al.
2004
Retrospective
0.78 ± 0.2 days
between surgery
and RRT
2.55 ± 2.2 days
between surgery
and RRT
64
↓Mortality
Demirkilic et al.
2004
Prospective/
Observational
Urine output
<100ml
Within 8h after
surgery
Scr >5mg/dL or
serum
K >5.5mEq/L
61
↓Mortality
Multiple modality
studies
Liu et al. 2006
Retrospective
BUN≤76mg/dL
BUN>76mg/dL
243
↓Mortality
Survival according to RRT modality
Clin J Am Soc Nephrol 2010; 5: 1-8
Intermittent vs Continuous
Prospective observational study
RR higher for CRRT
0.56 0.60
RR lower for CRRT
Clinical Nephrology 2005; 63: 335-345
Intermittent vs Continuous
Prospective randomized multicenter study
44
41 mg/dL
Lancet 2006; 368: 379-385
SLED (Slow Low Efficiency daily Dialysis)
1.54 ± 0.55 1.36 ± 0.62 mg/dL
1.54 ± 0.55 1.07 ± 0.55 mg/dL
Kidney Int 2006; 70: 963-968
RRT modality in AKI
• CRRT preferred
–
–
–
–
Brain edema
Severe hemodynamic instability
Persistent ongoing metabolic acidosis
Large fluid removal requirements
• IHD preferred
– Recovery phase of critical illness
• SLED
– The promising alternative modality
Dose of RRT : IHD
NEJM 2002, 346, 305-310
Dose of RRT : CVVHDF
HD 9 + HF 11 = 20 ml/kg/hr
HD 15 + HF 20 = 35 ml/kg/hr
J Am Soc Nephrol 2008; 19, 1233-1238
The VA/NIH Acute Renal Failure Trail
Network (ATN Study)
Large, multicenter, randomized, controlled trial
Intensive therapy
: six times/week or,
: 35ml/kg/hr
Less intensive therapy
: three times/week or,
: 20ml/kg/hr
NEJM, 2008, 359, 7-20
The dialyzer membrane selection in AKI
• Safety
– To minimize blood membrane reactions and hypotension
episodes
• Removal of systemic inflammatory cytokines, chemokines
– High-flux vs Superflux membrane
– Adsorption of protein bound solutes
• Removal of systemic anticoagulation during dialysis
– Adsorb heparin onto the dialyzer surface
Sieving coefficients of substance with target
molecular weight ranges
11800 Da
66800 Da
TNF-α
IL-6
Polymethylmethacrylate (PMMA) in
septic shock as a cytokine modulator
Mol Med 2008; 14:257-263
Hepatorenal syndrome (HRS)
• Type 1
– Rapidly progressive kidney failure that affects individuals
with liver cirrhosis, with a doubling of serum creatinine to
a level greater than 2.5 mg/dL or a halving of the
creatinine clearance to less than 20 mL/min over a period
of less than two weeks
– Median survival rate : 2-4 weeks
• Type 2
– Steady and slowly progressive rise in serum creatinine
– Median survival rate : 5-6 months
Molecular Adsorbents Recirculating System
(MARS) ; Albumin dialysis
250 cc
Not permeable to albumin
Albumin dialysis (Diffusion)
50000 Da
Prometheus
; Fractionated plasma separation and absorption
753 cc
Permeable to albumin
Fractionated plasma separation
250000 Da
Prometheus
; Fractionated plasma separation and absorption (FPSA)
MARS vs Prometheus
J Hepatol, 2005, 43, 451-457
MARS vs Prometheus
J Hepatol, 2005, 43, 451-457
RELIEF trial : MARS
• 189 patients with acute-on-chronic liver failure
– MARS vs Standard therapy
– Treatment with MARS was scheduled at low dose (up to ten
sessions of 6-8 hours during 21 days) and the main endpoint was
survival at 28 days.
• Overall survival was not statistically different overall
–
–
–
–
40.8% vs. 40.0% at day 28 (OR: 0.77, 95% CI: 0.37-1.59)
serum creatinine (20.0 ± 33.1% vs. 6.4 ± 33.5 %; p= 0.02)
bilirubin (26.4 ± 26.1% vs. 8.9 ±22.3%; p=0.001)
higher improvement in HE (as estimated by the percentage of
evaluations in which HE decreased from II- IV at inclusion to 0-I during
therapy, 56 % vs. 39 % p=0.06) was observed in MARS
European Association for the Study of the Liver (EASL) 2010
HELIOS study : Prometheus
• 145 patients with cirrhosis and rapid deterioration of their liver
function
– Prometheus vs Standard therapy
– the first large prospective randomized controlled trial on the
survival of patients with the condition
• Overall survival was not statistically different overall
– 66% vs. 63% p=0.7 at day 28 and 47% vs. 38% p=0.35 at day 90
• Only sub-groups with hepatorenal syndrome type I and MELD
score > 30 was a significant survival benefit with treatment with
FPSA observed
European Association for the Study of the Liver (EASL) 2010
MARS vs Prometheus
• Indications for Extracorporeal liver support
–
–
–
–
–
Acute on chronic liver failure
Graft dysfunction after liver TPL
Liver failure after liver surgery
Refractory cholestatic pruritus
Intoxications with highly albumin-bound substances
Nat Clin Pract Nephrol, 2007, 3, 451-457
Congestive heart failure (CHF)
• Diuretics dilemma
– Diminished renal function and concurrent sodium and
water retention in acute decompensations of heart
failure (ADHF) presents a therapeutic dilemma with
regard to submaximal diuretic therapy
Peripheral Ultrafiltration ?
How Much? How Fast?
Extravascular fluid
• The rate of fluid removed per hour from
the intravascular space (IVS) must
not exceed the rate of fluid entering the
intravascular space from
extravascular spaces (interstitial,
intracellular)
PRR
• The rate of fluid entering the
intravascular space = Plasma Refill
Rate (PRR)
Therefore, UFR ≤ PRR
• Hematocrit sensor
• Bioimpedance vector analysis (BIVA)
Intravascular fluid
• The rate of fluid removed from the
intravascular space = UF rate (UFR)
IVS
UFR
What is the peripheral ultrafiltration?
Aquapheresis by Aquadex
(CHF solutions, USA)
DEDYCA
(Bellco, Italy)
Low blood flow
10–40 vs 0-100 mL/min
Low blood volume
33 vs <100 mL
Precise fluid
removal rates
Quick and easy
setup
10–500 vs 0-1000 mL/h
Access
Less than 10 min
Peripheral or
central venovenous
UNLOAD trial
• Ultrafiltration versus Inravenous Diuretics for Patients
Hospitalization for Acute Decompensated Congestive
Heart Failure
Hypotension episode
Renal failure rate
J Am Coll Cardiol, 2007, 49, 675-683
UNLOAD trial
: Vasoactive Drugs Requirement
J Am Coll Cardiol, 2007, 49, 675-683
Peripheral Ultrafiltration Therapy
(1) More effective sodium and water clearance,
(2) Improved pulmonary vascular resistance due to reduction
of extracellular pulmonary edema,
(3) Enhanced norepinephrine clearance from the circulation,
(4) ‘Resetting’ of neurohormonal activation via baroreceptormediated reflexes and
(5) Direct removal of myocardial depressant factors.
2009 focused update incorporated in the
ACC/AHA 2005 Guidelines
4.5.2. Treatment in the Hospital
4.5.2.1. Diuretics: The Patient With Volume Overload
• Ultrafiltration is reasonable for patients with refractory
congestion not responding to medical therapy.
(Level of Evidence: B)
-… If all diuretic strategies are unsuccessful,
ultrafiltration or another renal replacement strategy may be
reasonable. Ultrafiltration moves water and small- to mediumweight solutes across a semipermeable membrane to reduce
volume overload. Because the electrolyte concentration is
similar to plasma, relatively more sodium can be removed than
by diuretics.
Consultation with a kidney specialist may be appropriate
before opting for any mechanical strategy to affect diuresis.
Wearable continuous ambulatory
ultrafiltration
Kidney Int 2008; 73: 497-502
Dialysis treatment in multiple myeloma
• Free light chain
– Kappa FLCs : 22.5 kDa
– Lambda FLCs : 45 kDa
– Not possible with routine dialyzer d/t small pore
• High Cutoff membrane (HCO)
Removal of immunoglobun free light chains
by hemodialysis for multiple myeloma
Chemotherapy + High cut-off membrane dialysis
Treatment Success
Treatment Failure
Artif Organs. 2008, 32, 910-7, J Am Soc Nephrol. 2007, 18, 886-895
Ongoing study
• European trial of free light chain removal by
extended haemodialysis in cast nephropathy
(EuLITE): A randomised control trial
– Control group
• Chemotherapy (modified PAD regimen)
• Hemodialysis (High-flux)
– Intervention group
• Chemotherapy (modified PAD regimen)
• Hemodialysis (extended FLC removal protocol using Gambro
HCO 1100)
Removal of immunoglobun free light chains
by hemodialysis for multiple myeloma
12
QB = 250 ml/min
QD = 500 ml/min
kappa clearance
lambda clearance
albumin clearance
albumin loss
50
10
40
8
30
6
20
4
10
2
0
2 x HCO1100
in vivo1
Theralite
2 x HCO1100
in vitro2
Albumin clearance [ml/min]
* Albumin loss [g/h]
FLC clearance [ml/min]
60
0
1
Artificial Organs 2008,;32: 910–917
2
Gambro Test Report, EBA080820A, E. Bart (2008)
Survival of AKI
• Mortality of AKI with RRT
– With a hospital mortality rate : 50.7%
– the first and second year after hospital discharge
: 11.3% and 3.4%
The term ‘RRT’ is therefore not quite accurate….
– The kideny not merely a filtration organ
– Current dialysis replace only the filtration function of
the failed kidney.
Less recognized role of kidney
: Immunoregulation
• Metabolic activity
• Synthesizing glutahione(GSH),
and Free-radical scavenging enzymes
• Gluconeogenesis
• Ammoniogenesis
• GSH reclamation
• Activation of vitmain D3
Mortality
Seminars in Dialysis 2009; 22: 603-609
Renal tubule assist device (RAD)
J Am Soc Nephrol 2008; 19: 1034-1040
RAD vs CRRT
J Am Soc Nephrol 2008; 19: 1034-1040
Advantages of renal bio-replacemet therapy
compared with the current treatment
Seminars in Dialysis 2009; 22: 603-609
Summary
• Prescription and delivery of RRT
– Clinical scoring systems and biomarkers are needed that
identify patients who are likely to benefit from early RRT.
– Current data do not suggest superiority of any specific
modality of renal support.
– IHD : delivered single-pool Kt/Vurea > 1.2
CRRT : effluent flow rates > 20 mL/kg/hr
Sepsis > 35 mL/kg/hr
Summary
• Hepatorenal syndrome
– MARS vs Prometheus
• Congestive heart failure
– Out-patient based aquapheresis
• Multiple myeloma
– Chemotherapy + High cut-off membrane dialysis
• Renal tubule assist device