RENAL REPLACEMENT THERAPY –

WHEN, HOW AND HOW MUCH ?

Sunitha Binu Varghese

DNB(Med), IDCCM, EDIC
NIRAMAYA HOSPITAL, PUNE
 INTRODUCTION
 AKI is a life threatening and disabling complication of critical
illnesses encountered in 25-50% of ICU admissions.
Hoste EA et al. AKI-EPIstudy. Intensive Care Med 2015; 41

 AKI severe enough to result in the use of RRT affects approx. 5%

of patients admitted to the ICU
The hospital mortality in patients with an AKI requiring RRT is as
high as 60%. Uchino et al. , JAMA 2005;294:813-8.

 Initial management–RX underlying cause, stopping

nephrotoxic drugs and ensure euvolaemic staus with an
adequate MAP
WHEN SHOULD RRT BE INITIATED IN AKI?
24 year old young adult with history of snake bite is
transferred from periphery after administering ASV and
admitted in ICU .

On admission,
BP – 110/70mmHg; Pulse 130/min ; RR- 28/min
sPO2 – 90% on room air .

Lab
 Hb 8gm%; WBC- 23000/cmm; Plt 52000/cmm
 BUN 120 mg/dl ;Creat4mg/dl
 Na 150meq/L, K- 7.5 meq/L
 pH- 7.1 ; PCO2 -20; PO2 -70; HCO3 - 8 meq/L
 PT 25/15 INR 1.9, APTT 45/30
ECG
 ABSOLUTE INDICATIONS FOR RRT

No RCTs exist for dialysis for life-threatening indications.

1.Hyperkalaemia
 Severe hyperkalemia refractory to standard measures .

 A specific threshold cannot be recommended

 Usually,
RRT is not commenced at values < 6.5
mmol/L where this is the sole indication.

2.Metabolic acidosis
 No specific threshold

 Anintractable acidosis (pH below 7.15)is usually

considered as an indication to commence RRT.
3.Volume overload
 Independent predictor of mortality
 Severe refractory volume overload per se (Diuretic resistant )

 RRT prevents the need for ventilatory support

 Ultrafiltration by RRT removes fluid in an iso-isomolar fashion

(vs Diuretics )

4.Uremia
 Progressive azotemia itself may be used as an indication
 Oliguria/anuria

 At present no generally accepted urea threshold

 Observational studies - a blood urea of 56–112 mg/dL is often

used as a trigger .
Other indications – severe electrolyte disorders
 Severe hypermagnesaemia
Usually observed at magnesium levels of 3–5 mmol/L.

 Severe hypercalcemia
Severe hypercalcaemia requiring RRT is a rarity

 Severe dysnatraemia
Serum sodium levels of <115 or >160 mmol/L are quoted as
indications for RRT.

The severity of the clinical condition, the rate at which the

disorder has occurred and not responding to standard medical
therapy
RELATIVE OR NON-‘RENAL’
INDICATIONS FOR RRT
 DRUG OVERDOSE OR TOXINS

 Drugs that can be effectively dialysed are characterised by

 Water solubility

 low protein binding

 low molecular weight (<500 Da)

 small volume of distribution.

 Certain alcohols (methanol, ethylene glycol), salicylate, Li,

theophylline , Mtx, barbiturates, aminoglycosides, metronidazole
,carbapenems, cephalosporins and most penicillins are removed
Rhabdomyolysis

 Afterthe failure of more established measures, including

alkaline fluid hydration, mannitol and diuretics.

Radiocontrast nephropathy

 Prominent cause of hospital-acquired AKI.

 Associated with significant mortality.

 We suggest not using prophylactic intermittent IHD or HF

for contrast-media removal in patients at increased risk for
CI-AKI. (2C) KDIGO 2012
 Adjuvant in treatment of sepsis
 Septicshock is associated with AKI in up to 50% of
patients

 Classical indicators of AKI are often not elevated initially

 Othercriteria -prolonged oliguria or severe metabolic

acidosis may be sufficient indication to commence

 Onthe basis of current evidence, RRT cannot be

recommended routinely in the absence of pronounced
AKI in sepsis
OPTIMAL TIMING

EARLY vs LATE
WHAT DOES “TIMING” CLEARLY MEAN?
NO CONSENSUS
Biochemical measures

Time relative to AKI onset

Physiologic measures Definition of

EARLY vs LATE
Time relative to Time relative to the devt
hospital or ICU of complications due to
admission AKI

More practically an “EARLY” start signifies the initiation of RRT when no

urgent indication for RRT exists.
Concept of “PRE EMPTIVE” RRT initiation
DRAWBACKS OF “EARLY” RRT
 Access and Anticoagulation

 Risk of iatrogenic episodes of hemodynamic instability

 Risk of excess clearance vital medications

 Risk of excess loss of essential substances

 Electrolyte imbalance with potential for arrhythmias,

 Unnecessary exposure to RRT in some patients .

 Increased bedside workload for providers, resource use,

and direct health costs
Meta-analysis suggesting that early initiation of RRT in
patients with AKI might be associated with improved
survival.
 Constantine J Karvellas et al.
Critical care 2011

Conclusions:
Earlier institution of RRT in critically ill patients with AKI may
have a beneficial impact on survival. However, this conclusion is
based on heterogeneous studies of variable quality and only two
RCTs
In the absence of new evidence from suitably-designed randomised
trials, a definitive treatment recommendation cannot be made.
 Artificial Kidney Initiation in Kidney Injury (AKIKI)
trial
 Multicenter trial

 620 mixed critically ill patients with AKI

 Compared two strategies for starting RRT in who were receiving

mechanical ventilation and/or vasopressors.

 Early strategy -RRT within < 6 hrs of fulfilling KDIGO stage 3

 Delayed strategy - started upon fulfilling clinical criteria

related to worsening AKI or complications

Stephane Gaudry et al . ,N Engl J Med 2016

CONCLUSIONS OF AKIKI TRIAL
 No significant difference with
regard to mortality (60 day )
between the two strategies .

 Delayed strategy - averted the

need for RRT in an appreciable
number of patients

 Delayedstrategy- RRT-free
days were greater and CRBSI
was lower
 JAMA. 2016;315(20):2190-2199

Early Versus Late Initiation of RRT In Critically Ill

Patients With Acute Kidney Injury (ELAIN) trial

 Single-center trial
 Comparing early RRT - n = 112(within 8 hours of
diagnosis of KDIGO stage 2 )with delayed RRT n =
119(within 12 hours of stage 3 AKI or no initiation or upon
an absolute indication) -
 For eligibility - NGAL > 150 ng/ml and at least one of
sepsis, fluid overload, worsening SOFA score, or receiving
vasoactive support.
CONCLUSIONS

 Among critically ill patients with

AKI - early RRT compared
with delayed initiation of RRT
reduced mortality (15.4 %
reduction) over the first 90 days

 Early strategy was also

associated with
 Greater kidney recovery ,
decreased RRT
 Duration shorter hospital stay
2 ONGOING RCT’S

 STARRT AKI
 IDEAL ICU
 Initiate RRT emergently when life-threatening
changes in fluid, electrolyte, and acid-base balance
exist. (Not Graded)

 Consider the broader clinical context, the presence

of conditions that can be modified with RRT, and
trends of laboratory tests—rather than single BUN
and creatinine thresholds alone—when making the
decision to start RRT. (Not Graded)

KDIGO GUIDELINES 2012

 TO SUMMARISE…..
 Current evidence does not support “early RRT “for all
patients with AKI

 The decision to start RRT should be individualized, taking

into account :
 severity of AKI and the
 trend in kidney function
 severity & reversibility of the underlying disease
 the risk/tolerance of fluid overload
 the potential harm associated with unnecessary RRT
RENAL REPLACEMENT THERAPY
METHODS
Which of the following statements comparing Dialysis
with Filtration are true:
A Dialysis depends on diffusion whereas filtration
depends on convection
B Filtration is more effective than dialysis at
removing small molecules
C Filtration in more effective than dialysis at
removing cytokines
D Dialysis is not as effective as Filtration at
removing water
2. Which of the following statements are true regarding
the differences between CRRT and IHD
A .CRRT is more cost effective than IHD
B. IHD is preferable to CRRT in patients who are
cardiovascularly unstable
C .IHD offers an overall survival benefit when
compared with CRRT
D .CRRT is preferable to IHD in patients with a
coexistent acute brain injury
 Continuous renal replacement therapy (CRRT)
 CVVH
 CVVHD Classification -
-based on
 CVVHDF
function and
 SCUF duration
 CAVHD

 Intermittent renal replacement therapy (IRRT)

 IHD
 PD

 ‘Hybrid’ technologies: prolonged intermittent RRT

 SLEDD
 SLEDD-f
 EDD
RRT- MODES OF ACTION
 RRT- MODES OF ACTION

1. HAEMODIALYSIS – DIFFUSION
 Blood being pumped through an extracorporeal system
that incorporates a dialyzer
 Process of solute transport across a semi-permeable membrane
 Driven by concentration gr. between blood & dialysate fluid.
 Counter current flow system .
 Effective for small sized molecules

Efficiency is affected by :
 Rate of blood flow .
 Membrane properties .
 Rate of flow of dialysate .
 Membrane surface area .
2.HAEMOFILTRATION – CONVECTION

Blood is pumped through extracorporeal system that

incorporates a semipermeable membrane .

Hydrostatic pressure gr. created across the semi -permeable

membrane removes plasma water –ULTRAFILTRATION
Solvent drag – CONVECTION

Small to medium sized molecules are removed

The filtered fluid (ultrafiltrate) is discarded and a replacement

fluid is added.
2. HAEMOFILTRATION
3. HAEMODIAFILTRATION

 Combination of filtration and dialysis.

 It has the benefits of of both techniques.

 No evidence to suggest that CVVDF has a survival

benefit when compared to CVVH

 Useful way of increasing clearance of small solutes.

CONSIDERATIONS FOR SOLUTION CHOICE

Which mode of therapy?

 CVVH: Replacement Only

 CVVHD: Dialysate Only

 CVVHDF: Both Solutions

SCUF (SLOW CONTINUOUS ULTRAFILTRATION)

 Used when the only requirement is water removal.

 CVVH with a low filtration rate.

 Itcan remove up to 6 litres of fluid a day but solute

removal is minimal.
 HYBRID RRT (HT)
 Conceptual and logistic compromise between the modern
applications of IHD and CRRT

 Most IHD machinery can be used for HT, although one

should be aware of the limitations of the machines

 Flexibility

 HT provides high small solute clearance and signifi cant

larger solute clearance
 Allows UF with minimum of cardiovascular instability

 Well tolerated by patients with severe illness

 NOMENCLATURE
 SLED or SLEDD

 SLEDD-f or SLED-f

 ED or EDD

 Prolonged (daily) intermittent RRT (PIRRT or

PDIRRT)

 Slow continuous dialysis (SCD)

 “Go slow dialysis.”

WHICH MODALITY IS MOST APPROPRIATE ?
INTERMITTENT (IHD) VS CONTINUOUS (CRRT)

Intermittent haemodialysis
 Dialysing with higher flow rates than CRRT for defined
periods of time.

 High flow rates and rapid fall in plasma osmolality

 Only suitable for patients who are cardiovascular stable

 A typical regime is 3-5 hours of dialysis 3 times a week.

 Not often useful in the critical care setting.

CRRT
 Involves filtering and/or dialysing on a continuous basis
 Done 24hrs ;daily

 Allows better fluid management

 Creates less haemodynamic disturbance

 But more expensive than IHD and requires continuous

coagulation
 Some evidence to suggest that CRRT is superior to IHD in

patients with sepsis, cardiovascular instability or with a

head injury

HEMODIAFE STUDY
 HEMODIAFE STUDY
LANCET 2006 JUL 29;368(9533):379-85

Continuous venovenous haemodiafiltration versus intermittent

haemodialysis for acute renal failure in patients with multiple-
organ dysfunction syndrome: a multicentre randomised trial
Dr Christophe Vinsonneau, MD et al.
No effect on mortality
Less dialysis dependency
with CVVHDF
Interpretation
These data suggest that, provided strict guidelines to improve
tolerance and metabolic control are used, almost all patients with
acute renal failure as part of multiple-organ dysfunction syndrome
can be treated with intermittent haemodialysis.
DIFFERENCE BETWEEN IHD & HT
Parameter IHD HT
Duration 3-5 hours 6-12 hours
Frequency Alternate day Daily
Blood flow 150-300 ml/min 70-300 ml/min
Dialysate flow Usually twice blood flow 70-300 ml/min
Fluid removal Depend on UF selected Depend on UF selected
Clearance Diffusive clearance is Clearance is deliberately low.
efficient.
It may be initially limited by
high Urea clearance.
Convective process may be
added to use of UF
Cost least Intermediate
Complications Hypotension, delayed Avoids most complications of
recovery, Dialysis IHD.
Dysequilibrium Risk of inadequate dialysis,
filter clotting
 MODIFICATIONS IN HT
Modification Rationale Name of HT

Increase in duration Allows for delivery of EDD, SLEDD

beyond 3 – 5 hours adequate dose
along with daily
dialysis

Reduction in blood and minimizes hemodynamic EDD, SLEDD

dialysate flow instability

Use of high flux Combines convective and EDDf,

dialyzer diffusive processes for SLEDDf
solute and fluid removal
 COMPARISION OF MODALITIES
 70 adults with sepsis (22) & severe falciparum malaria (48).
 34 assigned to PD and 36 to CRRT.

 Mortality was 47% with PD compared to 15% with CVVH.

(p=0.005)
 Better Uremic & Acidosis control with VVH.(p<0.005).

 CVVH more cost effective.

CONCLUSIONS
 Hemofiltration is superior to peritoneal
dialysis in the treatment of infection-associated
acute renal failure.

-Nguyen Hoan Phu (2002),NEJM;347:895

WHICH FORM OF RRT SHOULD WE USE?

 Currently the predominant modes of renal

replacement therapy are CVVH (or CVVHDF)
and HD

 No single RRT technique has been shown to offer

a survival benefit over the others in the critical
care setting.
Decision about which technique to use depends on:

1. What we want to remove from the plasma?

1. The patient`s cardiovascular status.

2. The availability of resources.

3. The clinician`s experience.

4. Other specific clinical considerations.

1. What we want to remove from the plasma?
2. The patient`s cardiovascular status -CRRT causes
less rapid fluid shifts and is the preferred option if
there is any degree of cardiovascular instability.

3. The availability of resources -- CRRT is more labour

intensive and more expensive than IHD
Availability of equipment may dictate the form of RRT.

4. The clinician`s experience --It is wise to use a form of

RRT that is familiar to all the staff involved.
5. Other specific clinical considerations

 Convective modes of RRT may be beneficial if the

patient has septic shock

 CRRT canaid feeding regimes by improving fluid

management

 CRRT may be associated with better cerebral

perfusion in patients with an acute brain injury
or fulminant hepatic failure
 Use continuous and intermittent RRT as complementary
therapies in AKI patients. (Not Graded)

 We suggest using CRRT, rather than standard intermittent

RRT, for hemodynamically unstable patients. (2B)

 We suggest using CRRT for AKI patients with acute brain

injury or other causes of increased intracranial pressure or
generalized brain edema. (2B)

KDIGO guidelines -2012

 CHOICE OF MODALITY – ISN MINIMUM
STANDARDS
 Adult patients should receive either IHD, SLED or CRRT as
the initial modality of RRT, unless all of these are
contraindicated

 PD should not be the initial modality, unless all other

modalities of RRT are not available or contraindicated.

 Hemodynamically stable patients should be managed with IHD.

 Patients with hypotension or who require vasopressor drugs

should be treated with SLED or CRRT.
 CHOICE OF MODALITY – ISN MINIMUM
STANDARDS

 The form of CRRT either CVVH, CVVHD, or a

combination (CVVHDF), should be chosen according to
clinician expertise available and the capabilities of the
machines available.

 Forpatients who do not require biochemical clearance but

only ultrafiltration, either isolated UF on a hemodialysis
machine or slow continuous ultrafiltration (SCUF) should
be used.
WHAT IS THE APPROPRIATE DOSE ?
OPTIMAL FLOW RATES / DOSE OF RRT

 The flow rate refers to the ultrafiltrate produced by the

filtration process as well as any effluent dialysis flow

 Theflow rate is a marker of solute clearance so it can

simplistically be thought of as the dose of RRT.

 Two recent randomised controlled trials have concluded

that there is no benefit to increasing the flow rate from
20 to 35ml.kg.-1hr.
ATN -Pavlevsky (2008), NEJM;359

(35ml/kg./hr-1 vs 20ml/kg./hr-1),
RENAL study
Bellomo (2009), NEJM: 361 :1627 - 38
HVHF in patients with septic shock with AKI
 DOSE AND ADEQUACY OF RRT - KDIGO
 The dose of RRT to be delivered should be prescribed before
starting each session of RRT. (Not Graded)

 We recommend frequent assessment of the actual delivered dose

in order to adjust the prescription. (1B)

 Provide RRT to achieve the goals of electrolyte, acid-base, solute,

and fluid balance that will meet the patient’s needs. (Not Graded)

 We recommend delivering an effluent volume of 20–25 ml/kg/h for

CRRT in AKI (1A).

 This will usually require a higher prescription of effluent volume.

(Not Graded)
HOW CAN THERAPY BE PROVIDED MOST
SAFELY?
1. Blood flow – High flow

2. Vascular access

When choosing a vein for insertion of a dialysis catheter in

patients with AKI, consider these preferences (Not Graded):
 First choice: right jugular vein;
 Second choice: femoral vein;
 Third choice: left jugular vein;
 Last choice: subclavian vein with preference for the dominant
side.

Length of catheter –Rt IJV- 15cm; femoral-20-24cm

Diameter - 13 or 14 F
3. Anticoagulation

4. Membrane choice –biocompatible ; POLYSULFONE

5. Replacement fluids :
We suggest using bicarbonate, rather than lactate, as a
buffer in dialysate and replacement fluid :
 for RRT in patients with AKI

 for RRT in patients with AKI and circulatory shock (1B)

 With AKI and liver failure and/or lactic acidemia. (2B)

6. Removal- DEPLETION SYNDROME

 ANTICOAGULATION
Non-pharmacological measures that can be
taken to reduce clot formation :

 Adequate central venous pressure

 Optimising vascular access

 Adding a proportion of the replacement fluid to

the patients blood before it passes through the
haemofilter (this is predilution).
Anticoagulation is NOT required when
 There is a already a degree of coagulopathy
 INR > 2-2.5
 APTT > 60 seconds
 Platelet count < 60000

 There is a high risk of bleeding.

 Anticoagulation should be considered in all other

situations .·
Strategies for Circuit Anti-Coagulation during CRRT:
 Unfractionated heparin

 Low-molecular-weight heparin- not superior to UFH

 Regional anti-coagulation (pre-filterheparin and

postfilter protamine, usually at 100 IU:1 mg ratio)

 Regional citrate anti-coagulation (pre-filter citrate and

post-filter calcium)
WHEN TO STOP RRT?
Discontinue RRT :

 When it is no longer required, either because

intrinsic kidney function has recovered to the
point that it is adequate to meet patient needs.

 Orbecause RRT is no longer consistent with the

goals of care. (Not Graded)
REPLACEMENT FLUID
 Replacement fluids vary slightly in their composition
but are all are balanced salt solutions with either a
lactate or bicarbonate buffer.

 Bicarbonate-based replacement solutions have a more

reliable buffering capacity but need to be prepared just
prior to use

 No evidence to suggest that the choice of replacement

fluid has an impact on survival or renal recovery.

 Replacement fluid can be added pre- or post-filter in

varying ratios