- Renal replacement therapies are important in critical care for managing complications of renal failure such as fluid, electrolyte and acid-base imbalances. There are many questions around optimal therapy including timing, dose and modality. - Acute kidney injury is common in the ICU and associated with worse outcomes. Continuous renal replacement therapies may provide more stable volume and chemistry control compared to intermittent therapies. - High volume hemofiltration shows promise for removing inflammatory mediators in sepsis but optimal dose is still unclear. Renal replacement therapies have an important role beyond renal support as blood purification techniques.

1. RENAL REPLACEMENT
THERAPIES IN CRITICAL CARE
DR YOGESH RATHOD
CHRISTIAN MEDICAL COLLEGE, VELLORE.

2. TOO MANY QUESTIONS?
• What therapy should we use?
• When should we start it?
• What are we trying to achieve?
• How much therapy is enough?
• When do we stop/switch?
• Can we improve outcomes?
Does the literature help us?

3. RENAL FAILURE OF ANY CAUSE
Many physiologic derangements:
• Homeostasis of water and electrolytes as the excretion of the daily
metabolic load of fixed hydrogen ions is no longer possible.
• Toxic end-products of nitrogen metabolism (urea, creatinine, uric acid,
among others) accumulate in blood and tissue.
• Endocrine organ dysfunction and failing production of erythropoietin and
1,25 dihydroxycholecalciferol (calcitriol).

4. EVALUATING ARF
• Severity of ARF/AKI should not be estimated from measurements of blood urea
or creatinine alone .
• Cockcroft & Gault equation or MDRD eGFR or reciprocal creatinine plots should
not be used when the GFR is <30 mL/min or to determine the need for acute
RRT.

5. AKI CLASSIFICATION SYSTEMS 1: RIFLE
Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information
technology needs: the second International Consensus Conference of the Acute Dialysis Initiative (ADQI) group. Crit Care 2004; 8: R204–R212.

6. AKI CLASSIFICATION SYSTEMS 2: AKIN
Stage Creatinine criteria Urine output criteria
1
1.5 - 2 x baseline (or rise > 26.4
mmol/L)
< 0.5 ml/kg/hour for > 6 hours
2 >2 - 3 x baseline < 0.5 ml/kg/hour for > 12 hours
3
> 3 x baseline (or > 354 mmol/L
with acute rise > 44 mmol/L)
< 0.3 ml/kg/hour for 24 hours or
anuria for 12 hours
Patients receiving RRT are Stage 3 regardless of creatinine or urine output
Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an
initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.

7. PROPOSED INDICATIONS FOR RRT
• Oliguria < 200ml/12 hours
• Anuria < 50 ml/12 hours
• Hyperkalaemia > 6.5 mmol/L
• Severe acidaemia pH < 7.0
• Uraemia > 30 mmol/L
• Uraemic complications (pericarditis, nausea, vomiting, poor appetite,
hemorrhage, lethargy, malaise, somnolence, stupor, coma, delirium, asterixis,
tremor, seizures)
• Dysnatraemias > 155 or < 120 mmol/L
• Hyper/(hypo)thermia
• Drug overdose with dialysable drug
• Refractory hypertension
Lameire, N et al. Lancet 2005; 365: 417-430

8. “NON-RENAL” INDICATIONS
• TO GET RID OF Substances with higher degrees of protein binding
and sometimes for substances with very long plasma half-lives.
• In general, the size of the molecule and the degree of protein
binding determines the degree to which the substance can be
removed (i.e. smaller, nonprotein bound substances are easiest to
remove).
• RRT can be used as sorbent hemoperfusion for substances that
include drugs, poisons, contrast agents, and cytokines.

9. ACUTE KIDNEY INJURY IN THE ICU
• AKI is common: 3-35%* of admissions
• AKI is associated with increased mortality
• “Minor” rises in Cr associated with worse outcome
• AKI developing after ICU admission (late) is associated
with worse outcome than AKI at admission
• AKI requiring RRT occurs in about 4-5% of ICU
admissions and is associated with worst mortality risk
**
* Brivet, FG et al. Crit Care Med 1996; 24: 192-198
** Metnitz, PG et al. Crit Care Med 2002; 30: 2051-2058

10. MORTALITY BY AKI SEVERITY
Clermont, G et al. Kidney International 2002; 62: 986-996

11. THE IDEAL RENAL REPLACEMENT
THERAPY
• Allows control of intra/extravascular volume
• Corrects acid-base disturbances
• Corrects uraemia & effectively clears “toxins”
• Promotes renal recovery
• Improves survival
• Is free of complications
• Clears drugs effectively (?)

12. INTERMITTENT THERAPIES - PROS
(Relatively) Inexpensive
Flexible timing allows for mobility/transport
Rapid correction of fluid overload
Rapid removal of dialyzable drugs
Rapid correction of acidosis & electrolyte
abnormality
Minimises anticoagulant exposure

13. Intermittent Therapies - CONS
Hypotension 30-
60%
Cerebral oedema
Limited therapy duration
Renal injury & ischaemia
Gut/coronary ischaemia

14. INTRADIALYTIC HYPOTENSION:
RISK FACTORS
• LVH with diastolic dysfunction or LV systolic dysfunction / CHF
• Valvular heart disease
• Pericardial disease
• Poor nutritional status / hypoalbuminaemia
• Uraemic neuropathy or autonomic dysfunction
• Severe anaemia
• High volume ultrafiltration requirements
• Predialysis SBP of <100 mm Hg
• Age 65 years +
• Pressor requirement

15. MANAGING INTRA-DIALYTIC
HYPOTENSION
• Dialysate temperature modelling
• Low temperature dialysate
• Dialysate sodium profiling
• Hypertonic Na at start decreasing to 135 by end
• Prevents plasma volume decrease
• Midodrine if not on pressors
• Colloid/crystalloid boluses
• Sertraline (longer term HD)
2005 National Kidney Foundation K/DOQI GUIDELINES

16. CONTINUOUS THERAPIES - PROS
Haemodynamic stability => ?? better renal
recovery
Stable and predictable volume control
Stable and predictable control of chemistry
Stable intracranial pressure
Disease modification by cytokine removal
(CVVH)?

17. Continuous Therapies - CONS
Anticoagulation requirements
Higher potential for filter clotting
Expense – fluids etc.
Immobility & Transport issues
Increased bleeding risk
High heparin exposure

18. RRT MOLECULAR
TRANSPORT MECHANISMS
• Ultrafiltration
• Diffusion
• Convection
• Adsorption
Fluid Transport
Solute Transport
}

19. SEMI-PERMEABLE MEMBRANES
• Semi-permeable membranes are the basis of all
blood purification therapies.
• They allow water and some solutes to pass
through the membrane, while cellular
components and other solutes remain behind.
• The water and solutes that pass through the
membrane are called ultrafiltrate.
• The membrane and its housing are referred to as

20. ULTRAFILTRATION
• Ultrafiltration is the passage of fluid through a membrane under
a pressure gradient.
• Pressures that drive ultrafiltration can be positive, that is the
pressure pushes fluid through the filter.
• They can also be negative, there may be suction applied that
pulls the fluid to the other side of the filter.
• Also osmotic pressure from non-permeable solutes.
• The rate of UF will depend upon the pressures applied to the
filter and on the rate at which the blood passes through the filter.
• Higher pressures and faster flows increase the rate of
ultrafiltration.
• Lower pressures and slower flows decrease the rate of
ultrafiltration.

21. Blood Out
Blood Into waste
(to patient)
(From patient)
HIGH PRESSLOW PRESS
Fluid Volume
Reduction
ULTRAFILTRATION

22. DIFFUSION
• Diffusion is the movement of a solute across a
membrane via a concentration gradient.
• For diffusion to occur, another fluid must flow on the
opposite side of the semi-permeable membrane. In
blood purification this fluid is called dialysate.
• Solutes always diffuse across a membrane from an
area of higher concentration to an area of lower
concentration until equilibration.

23. HAEMODIALYSIS: DIFFUSION
Dialysate In
Dialysate Out
(to waste)
Blood Out
Blood In
(to patient)
(from patient)
HIGH CONCLOW CONC

24. CONVECTION
• Convection is the movement of solutes through a
membrane by the force of water (“solvent drag”).
• Convection is able to move very large molecules if the
flow of fluid through the membrane is fast enough.
• In CRRT this property is maximized by using
replacement fluids.
• Replacement fluids are crystalloid fluids administered
at a fast rate just before or just after the blood enters
the filter.

25. to waste
HIGH PRESSLOW PRESS
Repl.
Solution
HAEMOFILTRATION:
CONVECTION
Blood Out
Blood In
(to patient)
(from patient)

26. ADSORPTION
• Adsorption is the removal of solutes from the blood
because they cling to the membrane.
• In blood purification. High levels of solute/molecule
adsorption can cause filters to clog and become ineffective.

27. ADSORPTION
• Molecular adherence to the surface or interior of the
membrane.

28. MOLECULAR WEIGHTS
Daltons
 Inflammatory Mediators (1,200-40,000)
“small”
“middle”
“large”

29. MAJOR RENAL REPLACEMENT TECHNIQUES
Intermittent ContinuousHybrid
IHD
Intermittent
haemodialysis
IUF
Isolated
Ultrafiltration
SLEDD
Sustained (or slow)
low efficiency daily
dialysis
SLEDD-F
Sustained (or slow)
low efficiency daily
dialysis with filtration
CVVH
Continuous veno-
venous haemofiltration
CVVHD
Continuous veno-
venous haemodialysis
CVVHDF
Continuous veno-
venous
haemodiafiltration
SCUF
Slow continuous
ultrafiltration

30. CRRT TREATMENT GOALS
• The concept behind CRRT is to dialyse patients in a
more physiologic way, slowly, over 24 hours, just like
the kidney
• Tolerated well by hemodynamically unstable patients
• Maintain fluid, electrolyte, acid/base balance
• Prevent further damage to kidney tissue
• Promote healing and total renal recovery
• Allow other supportive measures; nutritional support

31. RRT FOR ACUTE RENAL FAILURE
• Newer evidence from RENAL and ATN trials
suggest no difference between higher
therapy CRRT dose and better outcome
• There is no definitive evidence for
superiority of one therapy over another,
and wide practice variation exists
• Accepted indications for RTT vary
• No definitive evidence on timing of RRT

32. CRRT MODES OF THERAPY
• SCUF - Slow Continuous Ultrafiltration
• CVVH - Continuous Veno-Venous Hemofiltration
• CVVHD - Continuous Veno-Venous HemoDialysis
• CVVHDF - Continuous Veno-Venous HemoDiaFiltration

33. VASCULAR ACCESS AND THE
EXTRACORPOREAL CIRCUIT
• There are two options for vascular access for CRRT, venovenous and
arteriovenous.
• Venovenous access is by far the most commonly used in the modern ICU.

34. ELECTROLYTES & PH BALANCE
• Another primary goal for CRRT, specifically:
• Sodium
• Potassium
• Calcium
• Glucose
• Phosphate
• Bicarbonate or lactate buffer
• Dialysate and replacement solutions are used
in CRRT to attain this goal.

35. ANTICOAGULATION & CRRT
• Anticoagulation is needed as the clotting cascades are activated
when the blood touches the non-endothelial surfaces of the
tubing and filter.
• CRRT can be run without anticoagulation

36. SCUF
Primary therapeutic goal:
– Safe and effective management of fluid removal from the
patient
• No dialysate or replacement fluid is used
• Primary indication is fluid overload without uremia or
significant electrolyte imbalance.
• Removes water from the bloodstream through ultrafiltration.
• The amount of fluid in the effluent bag is the same as the
amount removed from the patient.
• Fluid removal rates are typically closer to 100-300 mL/hour.

37. SCUF
• High flux membranes
• Up to 24 hrs per day
• Objective VOLUME control
• Not suitable for solute
clearance
• Blood flow 50-200 ml/min
• UF rate 2-8 ml/min

38. SLED(D) & SLED(D)-F : HYBRID THERAPY
• Conventional dialysis equipment
• Online dialysis fluid preparation
• Excellent small molecule detoxification
• Cardiovascular stability as good as CRRT
• Reduced anticoagulation requirement
• 11 hrs SLED comparable to 23 hrs CVVH
• Decreased costs compared to CRRT
• Phosphate supplementation required
Fliser, T & Kielstein JT. Nature Clin Practice Neph 2006; 2: 32-39
Berbece, AN & Richardson, RMA. Kidney International 2006; 70: 963-968

39. COMPLICATIONS OF CRRT
• Bleeding
• Hypothermia
• Electrolyte Imbalances
• Acid-Base Imbalances
• Infection
• Appropriate Dosing of Medications

40. BEYOND RENAL
REPLACEMENT…
RRT AS BLOOD PURIFICATION
THERAPY

41. EXTRACORPOREAL BLOOD
PURIFICATION THERAPY (EBT)
Intermittent Continuous
TPE
Therapeutic
plasma exchange
HVHF
High volume
haemofiltration
UHVHF
Ultra-high volume
haemofiltration
PHVHF
Pulsed high volume
haemofiltration
CPFA
Coupled plasma
filtration and
adsorption

42. PEAK CONCENTRATION HYPOTHESIS
• Removes cytokines from blood compartment
during pro-inflammatory phase of sepsis
• Assumes blood cytokine level needs to fall
• Assumes reduced “free” cytokine levels leads
to decreased tissue effects and organ failure
• Favours therapy such as HVHF, UHVHF, CPFA
• But tissue/interstitial cytokine levels
unknown
Ronco, C & Bellomo, R. Artificial Organs 2003; 27: 792-801

43. THRESHOLD IMMUNOMODULATION
HYPOTHESIS
• More dynamic view of cytokine system
• Mediators and pro-mediators removed from blood to alter tissue
cytokine levels but blood level does not need to fall
• ? pro-inflammatory processes halted when cytokines fall to
“threshold” level
• We don’t know when such a point is reached
Honore, PM & Matson, JR. Critical Care Medicine 2004; 32: 896-897

44. MEDIATOR DELIVERY HYPOTHESIS
• HVHF with high incoming fluid volumes (3-6 L/hour)
increases lymph flow 20-40 times
• “Drag” of mediators and cytokines with lymph
• Pulls cytokines from tissues to blood for removal and
tissue levels fall
• High fluid exchange is key
Di Carlo, JV & Alexander, SR. Int J Artif Organs 2005; 28: 777-786

45. HIGH VOLUME HAEMOFILTRATION
• May reduce unbound fraction of cytokines
• Removes
– endothelin-I (causes early pulm hypertension in sepsis)
– endogenous cannabinoids (vasoplegic in sepsis)
– myodepressant factor
– PAI-I so may eventually reduce DIC
• Reduces post-sepsis immunoparalysis (CARS)
• Reduces inflammatory cell apoptosis
• Human trials probably using too low a dose (40 ml/kg/hour vs
100+ ml/kg/hour in animals)

46. SUMMARY
ARF is not an innocent bystander in ICU
We must ensure adequate dosing of RRT
Choice of RRT mode may not be critical
Septic ARF may be a different beast
We must strive to avert acute renal failure