Renal Replacement Therapy
Classic mnemonic "AEIOU": Acidosis, Electrolyte disturbances (ie hyperkalemia), Ingestions, Overload (fluid), Uremia
No clear cutoff values for acidosis, hyperkalemia, degree of fluid overload, uremia, etc.
Some suggestion that initiation of continuous renal replacement therapy (CRRT) in patients with less fluid overload (ie <20%) is associated with improved mortality in the PICU though this remains an association and not causal. Randomizing patients to CRRT at different degrees of fluid overload would help answer this question. See the below table for studies that have demonstrated this association between fluid overload at CRRT initiation and outcome. Alobaidi et al also showed this association between fluid overload and mortality in a 2018 metaanalysis.
Importantly, even if fluid overload causes increased mortality (an assertion not yet definitively shown), it is unclear whether intervening to prevent fluid overload would necessarily mean a decrease in mortality. Nonetheless, there is a general trend towards initiating CRRT earlier rather than later in critically ill pediatric patients
However, in contrast, some adult studies have suggested improved outcomes with later initiation of CRRT (Schneider et al, Nephrol Dial Transplant 2012, Elseviers et al, Crit Care 2010).
AKIKI, NEJM 2016, a French multicenter RCT of 620 adult ICU patients (on vasoactives and/or mechanical ventilation) with KDIGO stage 3 AKI randomized to early or delayed initiation of renal replacement therapy showed no differences in mortality with early vs. delayed initiation (48.5 vs 49.7%, respectively). Furthermore, 49% of the patients in the delayed group did not require renal replacement therapies.It should be noted that a large proportion of patients receiving iHD (>50%) vs CRRT (~30%).
Similarly, the IDEAL ICU Trial was stopped early for futility after 488 patients. The RCT compared adult patients with septic shock with renal failure (as defined by RIFLE criteria) and whether early (upon diagnosis of renal failure) or delayed (waiting 48 hours) affected outcomes (90 day mortality as primary outcome). There was no difference in overall mortality (58% in early group and 54% in delayed group, p=0.38) and 38% of those in the delayed group did not require renal replacement therapy.
ELAIN (Zabrock, JAMA 2016) did demonstrate lower 90 day mortality (39 vs 55%) in adult critical care patients randomized to earlier RRT (within 8 hours of KDIGO stage 2) vs later (within 12 hours of stage 3 AKI).
STARRT-AKI trial also did not show benefit to an accelerated use of CRRT vs standard care
A meta analysis (Gaudry et al, Lancet 2020) using individual data also did not show benefit for early RRT in critically ill adults with AKI.
Catheter site selection: At least in adults, the CATHEDIA study did not demonstrate an increased rate of infection in femoral vs. IJ non tunneled HD catheters, except in those with BMI >28. Conversely, in those with BMI <24.2, IJ catheters were associated with a higher rate of catheter colonization and hematoma.
Fundamentals of Dialysis and Ultrafiltration
Diffusion: Transport of solutes across a semi-permeable membrane, generated by a concentration gradient. In dialysis, this is generated using a dialysate solution running countercurrent to the blood and separated from the blood via a semi-permeable membrane. The composition of the dialysate (generally physiologic electrolyte levels) determines the concentration gradient, and this, along with the dialysate flow rate, determines the amount of diffusion or removal of electrolytes that occurs
Figure 1: Diffusion across a semi-permeable membrane
Convection: Solutes are transported across a semi-permeable membrane with solvents (fluid) as a result of solute drag due to a transmembrane pressure.
Figure 2: Convection
Ultrafiltration: Movement of fluid (plasma water) through a semi-permeable membrane due to a pressure gradient
Adsorption: Molecules adhere to the surface of semi-permeable membrane, removing it from the circulation (can occur with TNF and other cytokines, beta-2 microglobulin, etc)
Figure 3: Adsorption to the Membrane
Figure 4: Membrane Selectivity Based On Molecular Size
Figure 5: Clearance Based On Molecular Size
Peritoneal Dialysis (PD)
peritoneal membrane used as a dialyzing membrane
Dialysis fluid instilled into the peritoneal space permits diffusion of particles out of the blood (ie with a hypertonic solution, water moves out of the blood)'
As plasma water moves out of the blood, it also drags solute and so convection occurs
Fluid removal slower and more gentle
Adjustments in fluid osmolality and dwell time can be made to adjust volume removed
Also provides metabolic control and can correct uremia
Need access to intraabdominal space
Risk for infection/peritonitis
High dextrose solutions can lead to hyperglycemia
Reduction of diaphargmatic excursion due to filling of the abdomen
Potential issues in critically ill patients who may have ascites and already be at risk for intraabdominal hypertension/abdominal compartment syndrome
Intermittent Hemodialysis (iHD)
Rapid and high efficiency fluid removal and metabolic control
Optimal modality for particle removal (ie toxins) such as ammonia
The rapidity of fluid removal may be a drawback in critically ill patients who may be hemodynamically unstable
Vascular access critical with need for large caliber catheters to facilitate sufficient blood flow for dialysis to occur and for clotting to be prevented
Continuous Renal Replacement Therapy (CRRT)
Extracorporeal device that essentially functions as a kidney, providing continuous fluid removal and blood purification
Utilizes a semi-permeable membrane (filter) with counter-current dialysate fluid to remove fluid and particles via diffusion, convection, as well as adsorption
1) SCUF: Slow Continuous Ultrafiltration: Basically, take blood out from the patient, pass it through a semipermeable membrane at pressure, leading to fluid removal (ultrafiltration) with some solute loss as a result of convection. No dialysate solution or replacement fluid is used.
Figure 6: SCUF
2) CVVH: Continuous Veno-venous hemofiltration: Utilizes convection but no dialysate fluid so no diffusion
3) CVVHDF: Continuous veno-venous hemodiafiltration: Utilizes convection as well as a dialysate fluid to produce diffusion
Figure 7: CVVHDF
Anticoagulation for CRRT
Need to anticoagulate as the blood that comes into contact with the artificial tubing/filter of the CRRT machine is prone to clot
Generally achieved with regional anticoagulation, meaning only the blood that is entering the CRRT circuit is anticoagulated via the entire patient (systemic anticogaulation)
Done using citrate, which chelates calcium. Calcium is a critical cofactor in nearly every step of the coagulation cascade.
Hence, blood is drawn out of the patient, Citrate is infused into it, reducing the ionized calcium from a normal value of ~ 1.0-1.2 mmol/L to a value of 0.25-0.4 mmol/L, thus effectively anticoagulating it as it traverses the CRRT circuit
The patient requires a Calcium Chloride infusion to restore their ionized calcium or else they would be effectively systemically anticoagulated (and likely have cardiovascular collapse from hypocalcemia)
Citrate lock can occur. Citrate is normally cleared by the liver. Hence, in the setting of liver injury or failure, citrate can accumulate, still bound to calcium. Hence, the patient's total calcium may be very high, yet their ionized calcium remains normal
Treatment: Increase the dialysate infusion rate which increases the amount of citrate removed from the blood, thus returning less citrate to the patient
Decrease blood flow rate and citrate rate (decreases the rate of citrate delivery to the liver, thus allowing proportionally more clearance- but also decreases the effectiveness of your renal replacement therapy)
Reset the citrate and calcium infusion to the starting rate, which decreases the amount of citrate being delivered to the patient, allowing the current citrate levels to be metabolized by the patient
Hold citrate and calcium infusions for a short time period (requires frequent monitoring of circuit and patient ionized calcium)
Titrate calcium chloride infusion to achieve patient ionized calcium level goals of 1.1-1.3 mmol/L.
Titrate citrate infusion to achieve circuit ionized calcium levels of 0.25-0.4 mmol/L
General Dosing Guidelines
Blood Flow Rate – 5ml-10ml/kg/min
Dialysate Rate – 2000ml/m2/1.73
Replacement Rate – 2000ml/m2/1.73
Post: 50 – 100 ml/hour (Prevent clotting in venous chamber)
Dialysate and Replacement Combined Rate 2000ml/m2/1.73 (Any combination)
Patient Fluid Removal Rate – Net Loss 1-2ml/kg/hr
Standard Solution – PrismaSol
Na 140 mEq/L
Cl 106.2 mEq/L
HCO3 32 mEq/L
Mg 1.2 mg/dL
Additives: Potassium 0 – 4 mEq/L (Standard 3 mEq/L), Phosphate 0.75 – 1.5 mg/dL (Standard 1.5mg/dL)
M 60 Filter Set
< 25 Kg Patients
Priming Volume – 93 ml
Membrane Characteristics – AN69
Membrane Size – 0.6 m2
Maximum BFR – 180 ml/min
Maximum Ultrafiltration – 38-55 ml/min (2280 – 3300 ml/hour)
BFR 100-180 respective
HF 1000 Filter Set
> 25 Kg Patients
Priming Volume – 165 ml
Membrane Characteristics - PAES (Polyarylethersulfone)
Membrane Size – 1.15 m2
Maximum BFR – 400 ml/min
Maximum Ultrafiltration – 74 ml/min (4440 ml/hour)
BFR – 200 ml/min
Extracorporeal circulating volume is less the 10% of the patients total calculated blood volume.
Standard Initiation with a saline primed circuit, if the circuit volume is < 10% of the patients calculated blood volume
Bypass Maneuver Initiation with PRBC, if the circuit volume is >10% of the patients calculated blood volume
Prior to initiation, obtain a patient ABG with ICa ++.
Protocol includes infusion of 30mEq NaHCO3- pre-filter at initiation
Have calcium chloride, volume, Sodium Bicarbonate, and vasoactives available for initiation (i.e. epinphrine spritzer)
Figure 8: Citrate and Calcium Titration Guidelines
Special Considerations for CRRT
The AN-69 membrane (M60 filter) used for smaller patients (<25 kg) is known to be associated with profound hypotensive events upon blood contact with the membrane. This is thought to be related to bradykinin release and is thought to be more profound with low blood pH. Hence, pretreating with bicarbonate to ensure a less acidic pH is often done. The AN-69 membrane also appears to provide relatively high IL-6 clearance
Fever can be masked as the extracorporeal circuit effectively acts like a large radiator, hence vigilance for infection is critical
Protein (essential amino acids) can be lost with CRRT, hence, protein supplementation (generally ~ 3 g/kg/day) is recommended
1) Tobe SW, Aujla P, Walele AA, Oliver MJ, Naimark DM, Perkins NS, Beardsall M: A novel regional citrate anticoagulation protocol for CRRT using only commercially available solutions. J Crit Care 18: 121–129, 2003
2) S. Walters, C. Porter, P.D. Brophy: Dialysis and pediatric acute kidney injury: choice of renal support modality.Pediatr Nephrol. 24:37-48 2009
3) J.A. Foland, J.D. Fortenberry, B.L. Warshaw, et al.: Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med. 32:1771-1776 2004
4) S.L. Goldstein, H. Currier, C. Graf, et al.: Outcome in children receiving continuous venovenous hemofiltration. Pediatrics. 107:1309-1312 2001
5) Dr. Kera Lucritz's CRRT Fellow Presentation
6) NEJM Review Article on CRRT