Download Renal replacement therapy in acute kidney injury

Clinical Practice Guideline for
Acute Kidney Injury
신장내과 정경환
Definition of AKI
AKI is defined as any of the following (Not Graded):
Increase in SCr by X0.3 mg/dl) within 48hours; or
Increase in SCr to X1.5 times baseline, which is known or
presumed to have occurred within the prior 7 days;
or
Urine volume <0.5 ml/kg/h for 6 hours
Potentially reversible
ACUTE KIDNEY INJURY (AKI)
ENCOMPASSES A WIDE SPECTRUM OF INJURY TO THE KIDNEYS, NOT JUST KIDNEY FAILURE
Background
• Detection is now based on monitoring level of serum creatinine
with or without urine output
• AKI is seen in 13–18% of all hospitalised people
–
older people are at higher risk
• NCEPOD in 2009 reported systemic deficiencies in the care of
patients
• Cost of inpatient NHS Kidney Care is high (estimated between
£620 million/yr)
Equivalent to cost of breast cancer or combined cost of lung
£434 -
Staging of AKI for adults
Assessing risk of acute kidney injury
•
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•
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chronic kidney disease
heart failure
liver disease
diabetes
history of acute kidney injury
oliguria (urine output less than 0.5 ml/kg/hour)
neurological or cognitive impairment or disability, which may mean
limited access to
hypovolaemia
use of drugs with nephrotoxic potential
sepsis
deteriorating early warning scores
age 65 years or over
Hemodynamic monitoring and support
for prevention and management of AKI
Kidney International Supplements (2012) 2, 19–36
Albumin vs. Saline
•
•
•
4% human albumin vs 0.9% saline with isotonic saline in ICU patients
3497 receive albumin and 3500 to receive saline
Albumin is safe
– No more effective than isotonic saline for fluid resuscitation
– No difference in renal outcomes (ex. need & duration of RRT)
– 27% less study fluid compared to the saline arm (2247 vs. 3096 ml)
N Engl J Med 2004; 350: 2247–2256.
Hydroxyethylstarch vs. Saline
•
•
•
mean MW of HES between 70000 and 670000 Da
6% HES is iso-oncotic, whereas 10% HES is hyperoncotic
Hypertonic HES may induce osmotic nephrosis, higher rate of AKI
Hydroxyethylstarch vs. Saline
• Colloids : aid in reaching resuscitation goals, avoid excessive
fluid administration in patients requiring large volume
resuscitation, or in specific patient subsets (e.g., a cirrhotic
patient with spontaneous peritonitis, or in burns )
• Volulyte : 6% HES iso-oncotic, renal injury ??
The use of Vasopressor in AKI
• No difference in primary outcome with dopamine as the
first-line vasopressor agent and with norepinephrine
– dopamine was associated with a greater adverse events
• Vasopressin increases blood pressure and enhances
dieresis, but has not as yet been proven to enhance
survival nor to reduce the need for RRT
– Reduce progression to renal failure and mortality in
patients at risk of kidney injury who have septic shock
The use of diuretics in AKI
The use of diuretics in AKI
The use of diuretics in AKI
• No evidence that the use of loop diuretics reduces the severity of AKI, or
improves outcomes
• Management of fluid balance, hyperkalemia, and hypercalcemia
• Resistance to diuretics:
• High-dose furosemide (>1 g/d) may cause ototoxicity
• Continuous infusion a dose of 0.5 mg/kg/hour was not ototoxicity
Prevention of aminoglycoside
related AKI
• risk of AKI up to 25%
• should be restricted to treat severe infections where
aminoglycosides are the best, or only, therapeutic option
• Older patients (>65 years), pre-existing renal dysfunction, septic
patients with intravascular volume depletion and rapid alterations in
fluid dynamics diabetes mellitus, concomitant use of other
nephrotoxic drugs, prolonged use, excessive blood levels, or
repeated exposure to separate courses of aminoglycoside therapy
over a short time interval
Prevention of aminoglycoside
related AKI
• Single-dose daily or extended-interval dosing of
aminoglycosides advantages to maintain antimicrobial
activity while limiting possible nephrotoxicity
Contrast-induced AKI
Epidemiology of CI-AKI
• SCr increase >0.5 mg/dl, or a SCr increase >25%, or a
decrease >25% of eGFR, or the composite of all three
definitions
• Incidence: Risk factor에 따라 3.3 ~ 24%
• Requiring dialysis : 4% of renal impairment, 3% of
patients undergoing primary percutaneous coronary
interventions for acute coronary syndrome
Nonpharmacological prevention
strategies of CI-AKI
Pharmacological prevention
strategies of CI-AKI
• Extracellular volume expansion counteract both the
intrarenal hemodynamic alterations and the direct
tubulotoxic effects
• urine flow rate >150 ml/h, >1.0–1.5 ml/kg/h of
i.v. fluid has to be administered for 3–12 hours before
and 6–12 hours after contrast-media exposure
Pharmacological prevention
strategies of CI-AKI
Severity of AKI is dependent on level of rise in Serum
Creatinine compared to base line
• Stage 1
– >/= 26 µmol/L or 1.5 x baseline
• Stage 2
– > 2– 3 x baseline
• Stage 3
–
> 3 x from baseline
or serum creatinine >/= 350 umol/L (after a rise of 50µmol/L)
Prevention of AKI
Offer intravenous volume expansion to adults having iodinated contrast
agents if:
• at increased risk of contrast-induced acute kidney injury because of risk
factors
• they have an acute illness
– Offer either isotonic sodium bicarbonate or 0.9% sodium chloride.
– consider temporarily stopping ACE inhibitors and ARBs in adults having
iodinated contrast agents if they have CKD with eGFR <40
• Discuss care with a nephrology team before offering iodinated contrast
agent to adults with contraindications to intravenous fluids.
Identifying the cause/s of AKI
• Urinalysis
– urine dipstick testing
• Document the results
– and ensure that appropriate action is taken
• Think of acute nephritis and referral to the nephrology team
– when no obvious cause of AKI is identified
– Urine dipstick showing haematuria and proteinuria without UTI or
trauma due to catheterisation.
Identifying the cause/s of AKI
• Ultrasound of Kidney/Urinary tract
– Do not routinely offer ultrasound
• if the cause of the AKI has been identified.
– If pyelonephrosis is suspected
• perform within 6hours of assessment
– When cause of AKI is not identified or at risk of urinary tract obstruction
• perform within 24hours of assessment
Managing AKI key priorities
• Follow AKI management bundle
• Relieve urological obstruction
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pyelonephrosis
an obstructed solitary kidney
bilateral upper urinary tract obstruction
complications of AKI caused by urological obstruction.
7 Steps of AKI Management Bundle
•
Confirm
•
Assess fluid status
•
Undertake full physiological observations (early warning score)
•
Urine dip
•
Stop nephrotoxic drugs
•
Daily U&Es
•
(Consider renal ultrasound and urinary catheter)
Dialysis Interventions for Treatment of AKI
• Life-threatening indications
–
–
–
–
Hyperkalemia (약물 조절 및 medical manage 먼저)
Acidemia (underlying dis 경과에 따라 결정)
Pulmonary edema
Uremic complications (pericarditis, bleeding 등)
• Nonemergent indications
– Solute control (BUN: catabolic rate, volume status 고려
SCr: age, race, muscle mass, catabolic rate 고려)
– Fluid removal (Fluid overload)
Timing of initiation of RRT
• The traditional thresholds used in stable CKD may be
inappropriately high in AKI.
– The increased catabolism associated with critical illness and the
need to administer adequate nutritional protein will lead to
increased urea generation.
• Septic shock, major trauma, burn injury
– It is often difficult to limit fluid intake in these patients, in part
due to the administration of intravenous medications.
• GI bleeding, rhabdomyolysis
– 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.
• Acute lung injury/acute respiratory distress syndrome (ARDS)
– Longer duration of mechanical ventilation, weaning failure,
delayed tissue healing, and cardiopulmonary complication have
been associated with fluid overload.
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 RRT: Meta-analysis
112 mg/dL
76 mg/dL
68 mg/dL
60 mg/dL
4.52 mg/dL
2.83 mg/dL
RIFLE criteria: Risk
SCr increased x 1.5
UO < 0.5mL/kg/h x 6hrs
: Injury
SCr increased x 2
UO < 0.5mL/kg/h x 12hrs
100 mg/dL
Early initiation of RRT in critically ill patients with AKI may have
beneficial impact on survival.
Early
Late
Renal Failure 2012
Cumulative patient survival between early and late RRT
Early
Late
Critical Care 2013
Renal Replacement Therapy for AKI
Peritoneal
Dialysis
(PD)
Itermittent
Hemodialysis
(iHD)
Sustained Low
Efficiency
Daily Dialysis
(SLEDD)
Continuous
Renal Replacement
Therapies
(CRRT)
IHD vs. CRRT in AKI: Meta-analysis
Mortality
JAMA 2008
IHD vs. CRRT in AKI: Meta-analysis
Dialysis Dependency
JAMA 2008
IHD vs. CRRT in AKI: volume control and MAP
24hr fluid balance
Baseline and Intradialytic MAP
AJKD 2004
RRT modality in AKI
•
CRRT preferred
– Continuous removal of toxins
– Severe hemodynamic instability
– Persistent ongoing metabolic acidosis
– Large fluid removal requirements
– No treatment-induced increase of intracranial pressure
•
IHD preferred
– Recovery phase of critical illness
– Lower costs than CRRT
•
SLED
– Slower volume and solute removal
Modality of renal replacement therapy
for patients with AKI
5.6.1: Use continuous and intermittent RRT as
complementary therapies in AKI patients.
(Not Graded)
5.6.2: We suggest using CRRT, rather than
standard intermittent RRT, for hemodynamically
unstable patients. (2B)
5.6.3: We suggest using CRRT, rather than
intermittent RRT, for AKI patients with acute
brain injury or other causes of increased
intracranial pressure or generalized brain
edema(2B)
Design of acute hemofilter
Diffusion
Solutes moves from side of higher concentration to side of lower concentration across semipermeable membrane
- Depended on size, shape, and charge of molecule
Efficient in removal of small-molecular-weight species such as electrolytes (< 500 daltons)
Time
Start:
End:
Difference in Concentrations
Blood
Dialysate
Concentrations in Equilibrium
Blood
Dialysate
Blood
Dialysate
Filtration / Ultrafiltration
Movement of solvent across a semi-permeable membrane from a region of high
to low pressure (usually hydrostatic)
Responsible for the removal of excess total body water
Higher ultrafiltration yield higher clearance
+
Pressure
Pressure
Pressure
-
+
-
+
-
Convection
As solvent moves down a pressure gradient, dissolved solutes are dragged
across the membrane.
Removal is depended on the sieving coefficient (cut-off) of the membrane
Responsible for the removal of both small-and middle-molecular-weight species
(up to 40,000 daltons)
Pressure
Pressure
Low flow =
Low CONVECTION
Pressure
High flow =
High CONVECTION
Adsorption
es
Molecular adherence to the surface or interior of the membrane
High levels of adsorption can cause filters to clog and become ineffective
No specific membrane recommendations as no studies to definitively prove
superior performance under specific modality
Size of molecules cleared by CRRT
Type of Molecules
Size
Small
<500 Da
Middle
500–5000 Da
Low molecular
weight proteins
Large Proteins
5000–50,000 Da
>50,000 Da
Example
Mode of Removal
Urea, creatinine, amino acids
Convection, Diffusion
Vit. B12, inulin, myoglobin,
Convection better than
vancomycin
Diffusion
B2m, inflammatory mediator
Convection or
e.g. cytokines, complement
Adsorption (on to filter)
Albumin
Only minimal removal by
standard CRRT
Therapy Mode of CRRT with multiFiltrate
SCUF (Slow Continuous Ultrafiltration)
CVVH (Continuous VenoVenous Hemofiltration)
CVVHD (Continuous VenoVenous Hemodialysis)
CVVHDF (Continuous VenoVenous Hemodiafiltration)
Continuous Veno-Venous HDF
CVVHDF aims to provide diffusive & convective clearance of excess waste products;
removal of small/middle/large (elimination of mediators) molecules; balance of
electrolytes, acid/base and excess fluid.
Post-dilution CVVHDF, representing the most efficient CRRT procedure
Offers maximum clearances for both small and larger solutes from undiluted
blood, especially with large exchange volumes
CVVHDF with exchange volumes higher than >35mL/h/kg is considered as high-volume
therapy
The typical total filtration rates in HDF and HF is <20% of the effective blood
flow rate
To prescribed high exchange rate: high blood flow rates and adequate vascular
access are required
CVVHDF Treatment
Filtrate
(Dialysate+
Replacemen)
2000mL/hour.
Blood
UF-Pump
100mL/hour.
Excess fluid
+
=
Total
Ultrafiltrate
2100mL/hour
2000mL/min.
Hemodiafilter
Balance
Heater
Dialysate
solution
1000mL/hour.
Infusion
Replacement fluids
1000mL/hour.
Slow Continuous Ultrafiltration (SCUF)
Treatment for patients with volume overload and without uremia or significant electrolyte
disturbances
Gentle dehydration of the patient by slow fluid removal for 24 hr/day or
for only some hours a day
The treatment is carried out with high-flux membranes and the objective is to achieve
volume control in fluid overloaded patients.
Since low filtration rates are required, filters with small surface are
generally employed.
UF is formed at a rate of less than 300 ml/hour and replacement is not
infused
The treatment is not suitable for solute control, but only volume control such as:
congestive cardiac/heart failure / Pulmonary edema
Slow Continuous Ultrafiltration (SCUF)
SCUF
 UF

Arterial

Venous
10L
Filtrate
Drainage
Bag
Hemoperfusion (Adsorption)
HP
Charcoal Filter

Arterial

Venous
Hemoperfusion (Adsorption)
HP - toxins substance are being removed by
adsorption
Water and lipid soluble substances with
molecular weights ranging from 100 to
40,000 daltons
Charcoal Filter
It is employed to removed toxin substances
from the patient’s blood which cannot be
removed by dialysis or hemofiltration.
A therapy choice for curing the patients who
have taken heavy misused drugs such as
sleeping pills.
protein bound drugs
lipid soluble drugs

Arterial

Venous
Dose of RRT
Landmark trial by Ronco, patients receiving <35ml/h/kg filtration rate suffered the
highest mortality rate.
70
*: p<0,002 vs. 20 ml/h/kg
56.8*
survival, %
60
50
57.9*
41.1
40
•
prospective, randomised study of critically ill
patients with ARF
•
postdilution-CVVH,
ca. 140 patients per group
•
Primary end point: survival 15 days after end of
CVVH
•
significantly improved survival at high
replacement volumes
30
Flow rate of the total effluent =
the
the
the
20
10
the sum of
dialysate rate and
replacement fluid rate and
fluid removal rate
0
20 ml/h/kg
35 ml/h/kg**
filtration rate
45 ml/h/kg
** 70kg patient = 2.5L/hr
Ronco C et al, Lancet, 356:26-30 (2000)
Dose of RRT
In CVVHDF post dilution, the mortality between 25ml/kg/h and 40ml/kg/h of effluent
flow has no significant differences.
• 1508 enrolled patients and 747 were
randomly assigned to high-intensity
therapy, 743 in the lower-intensity
group.
•
Primary outcome measure: death
within 90 days after randomization.
•
At 90 days, 6.8% of survivors in the
higher intensity group and 4.4% of
survivors in the low group.
N Engl J Med 2009;361:1627-1638
KDIGO Guideline for RRT dose
5.8.3. Delivering a Kt/V of 3.9/week when using in intermittent or
extended RRT in AKI.
5.8.4. Delivering an effluent volume of 20-25ml/kg/h for CRRT in AKI.
This will usually require a higher prescription of effluent volume.
Flow setting
• Blood flow rate
─ maximum 180ml/min, usually 100-150 ml/min
• Replacement fluid rate
– non- catabolic patient 인 경우 1,000 ml/hr로 시작
hypercatabolic state인 경우 1,000- 1,500 ml/hr로 시작
– sepsis, ARDS with MOF patient경우 1,000- 1,500 ml/hr로 시작하
여 maximum 2,000 ml/hr 까지 증가시킴
• Dialysate flow rate
– 1,000 ml/hr로 시작하여 hypercatabolic patient인 경우에는 2,500
ml/hr까지 올릴 수 있다. (BFR의 1/5 – 1/10유지)
• Ultrafiltration rate
Criteria for stopping
renal replacement therapy in AKI
• Urine output seems to be a very important predictor of successful
discontinuation of RRT
• Urine CrCl (measured over 24 hours) > 15 ml/min