Peter O'Keeffe

Renal Replacement Therapy: Summary

Summary: Renal Replacement in Acute Kidney Injury: Controversy and Consensus
Ronco et al. Critical Care (2015) 19:146
DOI 10.1186/s13054-015-0850-8
This review is an up-to-date overview of RRT in AKI.

Principles of RRT
Extra-corporeal Circuit-Circuit pressures are constantly monitored to assess for pressure drop and and transmembrane
pressures are calculated to monitor the filter clotting process.
-Key variable in filter patency is concentration polarisation : accumulation of particles in the inner
part of the hollow fibre that leads to decrease in membrane permeability and performance.
-Possible solutions: maximising blood flow rate (Qb) and optimising ultra-filtration to blood flow
ratio.
-Changes in fibre structure and filter geometry are manufacturer dependent.
Vascular Access-Jugular sites: equivalent to femoral in terms of infections, possibly preferable in obesity. Left
Jugular catheters : greater rates of complication. Deeper insertion into the right atrium has the
advantage in terms of filter life and possibly performance.
-Subclavian Sites: to be avoided due to risk of thrombosis- jeopardising future AV fistula formation
in the event long-term haemodialysis is needed.
Pre Or Post-Dilution
-Pre-dilution HF :less efficient because the filtrate contains fewer solutes as dilute blood enters the
filter but lower haemo-concentration reduces risk of clotting.
-Post-dilution: the best mode to measure creatinine-urea clearance because clearance equals
effluent rate.
Ultra-filtration
-Fluid overload after acute resuscitation worsens outcomes.
-Setting the rate of fluid removal needs consideration of the severity of complications of fluid
overload, anticipated fluid intake, expected rate of vascular refilling, and cardiovascular
tolerance to transient reduction in intra-vascular volume due to ultra-filtration.
-There are no good predictors of tolerance to fluid removal: fluid removal trial is the only option in
assessing cardiovascular tolerance with available haemodynamic tools.

Timing, Mode and Dose

When to Start
-There is no clear data on when to begin. In sepsis early initiation did not limit end-organ damage
and actually prolonged need for support. However delaying initiation of RRT is associated with
higher mortality and increased hospital/ICU stay. Therefore no clear guidance on when to start
RRT.
-Fluid overload may be a major outcome determinant for critically ill patients with AKI at CRRT
start: starting ultra-filtration when a lower degree of fluid accumulation has been reached and

targeting negative fluid balance in the first hours of treatment may improve outcome but data is
insufficient as yet.
When to Stop
-Data is even poorer on when to cease RRT.
-Current practice: measure urine output and serum creatinine while on a constant dose of CRRT and
calculate endogenous creatinine clearance using urine and serum concentration of creatinine. The
current assumption is that endogenous creatinine clearance of 15-20ml/min can allow cessation of
renal support.
- Observational data suggests urine output is the best predictor of successful termination of CRRT
(urine output more than 400ml per day).
-Recommends using the Acute Renal Failure Trial Network protocol: (Crcl is assessed when urine
output is 30ml/hr or a decreased creatinine level is noted on CRRT; renal support discontinued
when CrCl exceeded 20ml/min and was left to local discretion when in the range of 1220ml/minute).
Continuous Versus Intermittent Techniques
-Both show satisfactory metabolic control and research has not shown a difference in mortality or
survival rate. However data is not conclusive as sickest patients often excluded.
-A systematic analysis of observational studies found CRRT was superior in rate of renal renal
recovery versus IHD.
-Current consensus: CRRT is the optimal treatment in haemodynamically unstable patients with
IHD more suitable in patients leaving ICU.
Hybrid Therapies
-These are intermediate forms of therapy between IHD and CRRT. SLED is one more studied mode.
-SLED (sustained low efficiency dialysis) possible advantages: shorter stays and ventilations, more
rapid mobilisation. Possible problems include difficulty optimising antibiotics.
Dose of Renal Replacement Therapy
-New multi-centre RCTs suggest 20-30ml/Kg per hour is optimal as increased intensity of RRT was
not associated with improved outcomes.
(previously since Vincenza trial of 2000 recommendation was 35ml/kg/hr)

Potential Complications
Metabolic Complications
-Severe hypophosphataemia occurs in half of ICU patients and CRRT can contribute to this. It
requires treatment with supplementation. Hypomagnesaemia can also occur.
Anticoagulation
-Generally this is required to maintain filter patency and circuit patency during RRT.
-Greater use of point of care testing is recommended.

Heparin, Heparins and Thrombin Inhibitors

-Unfractionated Heparin: the most widely used. Advantages include: low cost, ease of
monitoring, simple administration and crucially ease of reversibility with protamine. Side-effects
include: bleeding, HITT, effects on serum lipids.
-Low-Molecular Weight Heparin: Advantages: a lower rate of HIT, less affinity for antithrombin,

less platelet activation, less inactivation by platelet factor 4, greater and more consistent
bioavailability and no metabolic side effects. However LMWH is eliminated by CRRT.

Regional Citrate Anticoagulation

-Sodium citrate has been increasingly studied due to complications associated with heparin and
LMWH. Advantages: less bleeding, increased filter lifespan and reduced transfusion rates and need
for anti-thrombin III/platelet supplementation and potential anti-inflammatory effects.
Disadvantages: metabolic consequences like accumulation in liver failure.

Antibiotic Dosing In RRT

-Current recommendations of antibiotic dosing in CRRT are based on deficient studies. When
possible, antibiotic concentrations should be measured in patients undergoing CRRT and dosing
schedules adapted to the individual patient.

RRT as an Adjunct in Sepsis

-CRRT removes cytokines and inflammatory mediators but outcomes don't seem to be affected by
this. This is likely a problem with the studies ie. timing of implementation and patient selection.
Standard filtration membranes have demonstrated poor efficacy at removing cytokines likely due to
the limited pore size of the standard blood purification membranes. High Cut-off membranes with
larger pores have been developed and have been found to have greater cytokine removal capability.
Research is ongoing.
-Adsorption Coupled plasma filtration and adsorption involves separating the plasma from the
blood by means of a plasma filter and passing the plasma through a synthetic resin cartridge for
adsorption and returning it to the blood where a second filter for small molecules and fluid is used
for the reconstituted blood. Pilot study is promising and an RCT is underway.
-Polymyxin B Haemoperfusion decreases macrophage activity and inactivates circulating proapoptotic factors possibly involved in pathogenic mechanisms of sepsis. A systematic review
showed benefits in arterial pressure, gas exchange and mortality. However there are methodological
problems with this data. EUPHAS trial has shown improved blood pressure, reduced organ failure
and possibly improved survival and we await the results of two other important RCTs.

Renal Replacement Therapy In Other Conditions

Cardiac Failure and Cardiorenal Syndromes
-Mechanical ultra-filtration may be useful in resolving fluid overload by achieving greater sodium
removal per unit volume than diuretic therapy. Evidence is inconclusive but RCTs point to greater
utility in diuretic resistant fluid overloaded heart failure patients.
Respiratory Failure
-Combining RRT with extra-corporeal CO2 removal techniques may help re-establish acid-base
homeostasis and reduce vasopressor demands as well as ventilator pressures. Extracorporeal CO2
removal in series with CRRT might contribute to further reduce tidal volumes and even help avoid
intubation.
Acute Brain Injury

-AKI is an independent predictor of poor outcome in acute brain injury patients.

-Starting RRT can worsen Intracranial Pressure and arterial hypotension resulting in brain
hypoperfusion. Use of bicarbonate buffers can also increase CO2 production which causes raised
CO2 partial pressure and cerebral vasodilation with increased risk of high ICP.
-CRRT is first option in acute brain injury as it is associated with a lesser ICP increase. Because of
the risk of cerebral haemorrhage, Citrate may be the preferred anti-coagulant.