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36 Nomenclature for Renal Replacement Therapy 423
(<10 ml/h/mmHg m2 ), middle flux (10–25 ml/h/mmHg m2 ), and high flux (>25 ml/
h/mmHg m
preferred for CRRT [
2
) categories. In critical care settings, high-flux membranes are typically
6, 7].
The sieving coefficient (SC) measures the ratio of a solute’s concentration in the
ultrafiltrate (Cuf) to its mean blood concentration in the filter (calculated as
+ Cpo)/2, where C
(C
pi
pi
and C
are the concentrations at the inlet and outlet of
po
the hemodiafilter, respectively). SC is a dimensionless number ranging from
0 to 1. A solute with an SC of 0 does not pass through a given membrane, while a
solute with an SC of 1 exhibits complete permeability through the membrane. SC is
specific to both the membrane and the solute. Its measurement is possible only in the
absence of a diffusion gradient and fluctuates during treatment due to various factors,
such as clotting and clogging, which reduce membrane permeability owing to
exposure to blood and plasma proteins:
SC = C
= Cpiþ C
uf
=2 = 2 × C
po
= Cpiþ C
uf
po
The membrane cutoff denotes the molecular weight of the smaller solutes retained
by the hemofilter, with their sieving coefficient (SC) approximating 0. The manufacturer typically provides a cutoff value corresponding to the molecular weight of
solutes with an SC of 0.1 and a retention onset equivalent to the molecular weight of
a solute with an SC of 0.9. During the prescription phase, the cutoff value is critically
important in selecting the appropriate membrane for removing specific target solutes.
High cutoff membranes have a cutoff value near the molecular weight of albumin,
resembling that of the native kidney. Consequently, a wide range of clinically
relevant middle molecular weight solutes can achieve an SC close to 1. This enables
effective removal of substances like myoglobin in patients with rhabdomyolysis.
Medium cutoff membranes are also available and utilized in clinical practice for
“expanded dialysis,” a technique combining convection and diffusion to achieve
significant removal of middleweight solutes without substantial albumin loss [8]. It
is important to note that the membrane cutoff and retention onset, as provided by the
manufacturer, may change after exposure to the patient’s blood due to membrane
fouling [3, 9].
Mechanisms of Fluid and Solute Transport
Physical and chemical phenomena intricately govern solute and water movements
across the filter membrane. Ultrafiltration induces a solvent shift, primarily plasma
water, through a semipermeable membrane, propelled by a pressure gradient and
contingent upon the ultrafiltration coefficient (Kuf). The transmembrane pressure
(TMP) acts as the force propelling plasma water across the hemodiafilter, and the
volume of solvent crossing the membrane per unit of time due to TMP is referred to
as Quf.
424 G. Villa and D. Degl’Innocenti
Total ultrafiltration (UF) denotes the overall volume of ultrafiltrate produced
during treatment, while net ultrafiltration (UFnet) represents the volume of plasma
water removed from the patient. When ultrafiltration alone is employed, only volume
control is achieved. To achieve volume and solute control, ultra filtration must be
coupled with fluid replacement or combined with diffusion.
TMP is determined by the hydrostatic pressure gradient across the membrane and
the average plasma oncotic pressure. CRRT machines do not directly measure
dialysate inlet pressure and oncotic pressure. Therefore, TMP is estimated as follows: [further details on TMP estimation can be provided here]
=2 –P
out
eff
is the post-filter pressure, and P
eff
is the
where P
TMP = P
is the prefilter pressure, P
pre
pre
þ P
out
effluent pressure.
During ultrafiltration, a percentage of plasma water is propelled across the
semipermeable membrane, leading to hemoconcentration within the filter fibers
throughout the treatment. The filtration fraction (FF) represents the ratio between
and plasma flow rate (Qp):
Q
uf
FF = Q
uf=Qp
where Qp equals Qb(1-HCT).
For optimal filter
performanc
e, FF should never exceed 30%. In clinical practice,
blood filtration fraction or concentration ratio (CR) is used. CR should be kept below
20–25%:
CR = Q
uf=Qb
þ Q
rPRE
= Q
rPOST
þ Q
ufNET
þ Q
rPRE=Qb
þ Q
rPRE
Behind convection, diffusion, and adsorption are the mechanisms used to remove
solutes during CRRT. Diffusion involves solute movement across a semipermeable
membrane driven by a solute concentration gradient. This process continues until an
equilibrium in solute concentrations is achieved across the membrane. The driving
force of diffusion is the concentration gradient (dc). The diffusive flux (Jd) is directly
proportional to the diffusion coefficient (D) and inversely proportional to the
distance between the blood and effluent compartments. Adsorption is a process
where blood or plasma solutes interact with the membrane structure through covalent or hydrophobic forces. Consequently, these substances are selectively or
nonselectively bonded to the membrane, either on its inner surface or within its
bulk structure. Adsorption serves as a mechanism to remove solutes, either as an
adjunctive possibility in certain hemodiafilters or as the primary mechanism in
cartridges. The device absorption capability (DAC) serves as the primary parameter
for evaluating adsorption, representin g the total amount of specific molecules
adsorbed by the device . The interaction between solute and membrane dynamics
results in adsorption and desorption processes until equilibrium is achieved [
10].
36 Nomenclature for Renal Replacement Therapy 425
Treatment Modalities
Hemodialysis relies on diffusion gradients and is primarily effective in removing
small solutes. It involves blood circulation and the use of a dialysate solution with a
countercurrent flow to maintain a concentration gradient along the length of the
hemodialyzer. Hemofiltration, on the other hand, is a convective treatment
performed without a dialysate solution. It involves the removal of water and solutes,
which can be partially replaced by the infusion of crystalloid solutions (replacement
fluids) either before the filter (pre-dilution) or after the filter (post-dilution). Postdilution is more efficient but also more prone to membrane fouling due to
hemoconcentration. Membrane fouling, characterized by the progressive deposition
of particles such as proteins or clots on the membrane surface and into pores, leads to
a deterioration in filter performance. Hemodiafiltration combines hemodialysis and
hemofiltration, utilizing both diffusive and convective solute removal mechanisms.
Isolated ultrafiltration aims to achieve fluid removal only, using ultrafiltration
without volume replacement. Hemo- or plasma-perfusion involves circulating the
patient’s blood or plasma through a sorbent. This modality can be used alone or in
combination with other modalities
Treatment Dose
Dose identifies the volume of blood cleared of waste products by the extracorporeal
treatment per unit of time. It is practically measured as the removal rate of a
representative solute (e.g., urea). In CRRT, dose is often estimated by quantifying
the effluent flow rates expressed in ml/kg/h. This method is more accessible and
reproducible at the bedside; furthermore, evidence in the literature clearly shows a
correlation between CRRT effluent dose and patient survival. Current guidelines
recommend an effective treatment dose of 20–25 ml/kg/h. In order to obtain this
dose, physicians usually prescribe a higher current dose (usually 30–35 ml/kg/h) to
compensate for the downtime that will occur during a 24-h treat ment.
The following definitions provide more information on the concept of dose:
Target dose is the clearance that the clinician wants to achieve in a specific
treatment.
Target machine dose is the clearance set in the machine to achieve a given dose.
Usually, it is obtained by setting specific (dialysate, replacement, net ultrafiltra-
tion, and thus effluent) flow rates.
Curren
estimated by treatment flow rates. During downtime (when the treatment is
stopped), its value is zero.
Average dose equals the current dose applied over the total treatment time (effective
treatment time plus the downtime).
ose is the instantaneous clearance (provided in each specific moment)
t d
426 G. Villa and D. Degl’Innocenti
Current effective delivered dose is the clearance measured (not estimated) in each
moment during the treatment by effluent and blood solute concentrations. This
dose is dynamically influenced by the performance degradation of the
hemodiafilter led by a loss of permeability due to membrane clotting and
clogging.
Average effective delivered dose is calculated as the weighted mean of the current
effective delivered dose over the total treatment time.
Efficiency also identified as clearance (K) represents the volume of blood cleared by
a specific solute over a given period of time. It is usually normalized to the ideal
patient weight (ml/kg/h). Efficiency is used to compare different treatments with
the same modality.
Intensity is the product of efficiency x time (Kt) and represents the volume of blood
cleared of a specific solute after a fixed time interval. Intensity is appropriate to
compare RRT modalities with different duration times. For example, compared to
IHD, CRRT has a low efficiency and a comparable intensity, as it is used for a
long time (24 h).
Efficacy measures the removal of a target solute achieved by a given treatment in a
given patient. It considers the total volume of blood cleared during the treatment
time and the volume of distribution of the target solute. It is obtained by dividing
the intensity by the volume of distribution of a specific solute (Kt/V).
Nomenclature of Renal Replacement Therapies
Continuous Therapies
Kidney support therapies (KST) comprise various treatments aimed at supporting or
replacing kidney function. Many clinicians view continuous therapies as the preferred KST for critically ill patients with AKI and hemodynamic instability. CRRT,
in particular, offers solute clearance and fluid removal with a more favorable and
tolerable hemodynamic impact compared to intermittent hemodialysis (IHD). However, CRRT may have limitations, including heavier nursing workload, continuous
anticoagulation requirements, the use of sterile industrially made solutions for
replacement and dialysate, higher costs, and the necessity of a large-bore duallumen central venous catheter to ensure adequate blood flow.
Different therapies can be prescribed during CRRT.
SCUF. Slow continuous ultrafiltration is based on the continuous removal of plasma
water (Ufnet); it aims to achieve volume control in patients with refractory fluid
overload. It is primarily used in patients with cardiac failure, with or without AKI,
for whom SCUF can improve cardiac filling volumes and contractility.
CVVH. Con
via the ultrafiltration of plasma water and the convective solute removal. The
ultrafiltrate is then replaced with reinfusion of crystalloid solutions as replace-
ment fluids. Such replacement fluids are administered before (pre-dilution) or
tinuous veno-venous hemofiltration achieves volume and solute control
36 Nomenclature for Renal Replacement Therapy 427
after (post-dilution) the hemofilter. This modality allows clearance of middle
molecular weight molecules, up to a weight near 60 kd (albumin), depending on
treatment parameters and SC of the membrane.
CVVHD. Continuous veno-venous hemodialysis uses diffusion as the mechanism of
transmembrane solute transport. UfNet can be added for volume control. This
modality mainly sweeps small molecules, such as electrolytes, urea, and
creatinine.
CVVHDF. Continuous veno-venous hemodiafiltration combines hemodialysis and
hemofiltration, allowing convective and diffusive clearance.
Intermittent Therapies
Intermittent treatments typically exhibit higher efficiency and last 3–5 h per session.
These treatments often feature higher blood flow rates (Qb), and a water-processing
sterilization system is utilized to produce the dialysate solution. Intermittent therapies encompass intermittent hemodialysis (IHD), intermittent hemodiafiltration
(IHDF), and intermittent high-flux dialysis (IHFD). While these treatments have
historically been less common in critical care sett ings, there has been a growing trend
in recent years to utilize them more frequently in the ICU. This shift aims to facilitate
patient movement and rehabilitation, particularly in hemodynamically stable
patients.
Hybrid Therapies
Hybrid therapies represent a category that maximizes the advantages and minimizes
the drawbacks of both continuous and intermittent therapies. Notably, these therapies reduce healthcare workload and may not necessarily require anticoagulation
during treatment. Moreover, they offer high efficacy and favorable hemodynamic
tolerance during water removal. Typically performed with equipment and disposables used for intermittent hemodialysis (IHD), hybrid therapies encompass various
techniques such as SLED (sustained low-efficiency dialysis), characterized by lower
blood and dialysate flows compared to IHD and conducted over a treatment session
of 8–12 h. Other techniques include SLEDD (slow low-efficiency extended daily
dialysis) or PIRRT (prolonged intermittent renal replacement therapy).
Conclusion
The application of renal replacement therapy (RRT) at the bedside necessitates a
profound grasp of the fundamental mechanisms governing fluid and solute transport,
membrane structure and function, and the diverse RRT modalities available. The
428 G. Villa and D. Degl’Innocenti
emergence of a multitude of extracorporeal treatment options in recent decades,
particularly for patients with multiple organ failure requiring multiple organ support
therapy, underscores the need for a multidisciplinary approach. Now more than ever,
a shared terminology is essential to optimize performance and minimize errors that
may lead to inadequate therapy delivery due to a lack of understanding of the basic
principles and operational characteristics of ex
tracorporeal therapies. Standardized
nomenclature is pivotal for facilitating comparisons between different modalities
and machine settings, both in clinical practice and research, and ultimately lays the
groundwork for enhancing patient outcomes.
References
1. Bagshaw SM, et al. Current state of the art for renal replacement therapy in critically ill patients
with acute kidney injury. Intensive Care Med. 2017;43(6):841–54.
s00134-017-4762-8.
2. Ronco C, Bellomo R, Lou Wratten M, Tetta G. Future technology for continuous renal
replacement therapies. Am J Kidney Dis. 1996;28(5 suppl 3):2–7.
S0272-6386(96)90091-8.
3. Villa G, et al. Nomenclature for renal replacement therapy and blood purification techniques in
critically ill patients: practical applications. Crit Care. 2016;20(1):1–11. https://doi.org/10.1186/
s13054-016-1456-5.
4. Neri M, et al. Nomenclature for renal replacement therapy in acute kidney injury: basic
principles. Crit Care. 2016;20(1):1–11. https://doi.org/10.1186/s13054-016-1489-9.
5. Honore PM, Spapen HD. What a clinician should know about a renal replacement membrane? J
Transl Intern Med. 2018;6(2):62–5. https://doi.org/10.2478/jtim-2018-0016.
6. Clark WR, Ronco C. CRRT efficiency and efficacy in relation to solute size. Kidney Int Suppl.
1999;56(72):3–7. https://doi.org/10.1046/j.1523-1755.56.s72.18.x.
7. Ricci Z, et al. Solute removal during continuous renal replacement therapy in critically ill
patients: convection versus diffusion. Crit Care. 2006;10(2):1–7. https://doi.org/10.1186/
cc4903.
8. Ronco C. The rise of expanded hemodialysis. Blood Purif. 2017;44(2):I–VIII. https://doi.org/
10.1159/000476012.
9. Michel T, Ksouri H, Schneider AG. Continuous renal replacement therapy: understanding
circuit hemodynamics to improve therapy adequacy. Curr Opin Crit Care. 2018;24(6):
455–62. https://doi.org/10.1097/MCC.0000000000000545.
10.
Lorenzin A,
for extracorporeal therapies. Blood Purif. 2019;48(1):18–24. https://doi.org/10.1159/
000499076.
et al. Fluid dynamics analysis by CT imaging technique of new sorbent cartridges
https://doi.org/10.1007/
https://doi.org/10.1016/
Chapter 37
Vascular Access for Renal Replacement
Therapy
Fabrizio Valente, Anna Lorenzin, and Giuliano Brunori
Introduction
Critically ill patients admitted to the intensive care unit (ICU) are at a high risk of
developing acute kidney injury (AKI). The AKI-Epidemiologic Prospective Investigation (AKI-EPI) study reported an overall AKI incidence of 57% in the ICU. Data
on patients with severe AKI requiring renal replacement therapy (RRT) indicated a
high mortality rate [1, 2].
In the ICU, beyond AKI requiring RRT, dialysis catheters (DCs) can serve as
vascular access for other blood purification techniques, such as hemoadsorption,
therapeutic apheresis, and CO
increased morbidity and mortality due to potential mechanical, thrombotic, and
infectious complications.
Radiopaque double-lumen DCs are currently the most used and are classified into
ategories:
two c
removal. However, DCs are associated with
2
• Short-term, uncuffed, and non-tunneled dialysis catheters (NTDCs)
• Long-term, cuffed, and tunneled dialysis catheters (TDCs)
NTDCs are typically placed at the bedside of the patient and, as suggested by the
Kidney Disease
Improving Global Outcomes (KDIGO) guidelines, are the first
option to start RRT in the ICU. Indeed, NTDCs are easier and faster to place than
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/978-3-031-66541-7_37.
F. Valente (
Nephrology and Dialysis Unit, Santa Chiara Hospital, Trento, Italy
e-mail: fabrizio.valente@apss.tn.it; giuliano.brunori@apss.tn.it
A. Lorenzin
Nephrology, Dialysis
Research Institute Vicenza (IRRIV), Vicenza, Italy
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A.
https://doi.org/10.1007/978-3-031-66541-7_37
✉) · G. Brunori
and Transplantation Unit, San Bortolo Hospital, International Renal
429
Cotoia et al. (eds.), Nutrition, Metabolism and Kidney Support,
430 F. Valente et al.
TDC, especially in critically ill patients. NTDCs might be more appropriate when the
recovery of renal function is unlikely or long-term RRT is required [3].
Dialysis Catheters: Technical Aspects
Catheters vary in several aspects, including material, geometry, and design, all of
which influence their performance [4]. The catheter facilitates the withdrawal of
blood from the patient and directs it into the extracorporeal circuit. The driving force
in the circuit is provi ded by the blood pump. The blood flow rate within the lumens is
influenced by pressure, resistance, blood viscosity, and geometric characteristics and
can be described by Poiseuille’s law:
4
πr
= ΔP
Q
B
where ΔP is the pressure drop, r the lumen radius, η blood viscosity coefficient, and
L the catheter length. This equation considers blood as a Newtonian fluid in a
laminar flow through a cylindrical pipe. Blood flow rate is proportional to the fourth
power of the internal lumen radius (and, by extension, the diameter) and inversely
proportional to the length; thus, blood flow rate is more significantly influenced by
the lumen radius diameter than by its length. A catheter with a lumen diameter that is
too small may not allow the achievement of the desired blood flow, and highpressure conditions could be deleterious for blood cells [5].
Even if a larger catheter seems to be more suitable, there are limitations in this
respect as well. Firstly, a catheter that is too wide could cause vessel damage and an
inflammatory reaction. Regarding flow, blood velocity inside the lumen is described
by the following equation:
8ηL
V =
Q
Q
B
B
=
π ∙ r
2
A
where A is the cross-sectional area of the lumen and depends on its radius/diameter.
With an increasing diameter, blood velocity decreases, posing a risk of thrombosis
and a higher recirculation rate [6].
Recircula
tion i
s a phenomenon in which dialyzed blood returning to the patient is
newly drawn into the extracorporeal circuit. Factors influencing recirculation include
catheter design, insertion site, blood flow, and blood volume. Under normal conditions, recirculation is approximately 10% [7].
High recirculation should be avoided due to its two main adverse effects: a
reduction in dialytic efficiency and a higher risk of extracorporeal circuit clotting.
The percentage of recirculation represents a portion of the blood flow that is already
treated and, likewise, a portion that is not withdrawn from the patient and purified.
Moreover, blood that is repeatedly circulated becomes hemoconcentrated due to
37 Vascular Access for Renal Replacement Therapy 431
Fig. 37.1 Different lumen
designs of DCs. Cycle C
(or kidney shape) is without
acute angles, feature deemed
to enable the reduction of
turbulent blood flow and
thrombosis
a
c
b
d
ultrafiltration, leading to quicker circuit clotting. In clinical practice, it is common to
reverse the bloodline position in case of catheter dysfunction; however, this procedure could significantly increase blood recirculation [8].
Non-tunneled dialysis catheters (NTDCs) and tunneled dialysis catheters (TDCs)
may differ in their lifespan of use, material, and design. Usually, NTDCs are rigid or
semirigid to ensure a rapid and easy insertion procedure. TDCs are less stiff and can
be tunneled. Their stiffness and flexibility characteristics are determined by the
material they are made of. A polyurethane catheter is stiffer but becomes more
flexible after insertion upon exposure to body temperature. A silicone one is softer
and more flexible but has a higher diameter because silicone provides less structural
support.
Another feature characterizing catheters is the design of the lumens and distal
tips. In
a cross-sectional view, different shapes of lumens based on how they are
arranged can be noticed: coaxial, double-O, double-D, and cycle-C (Fig. 37.1). Tip
design affects the way in which blood is aspirated and injected into the vessel.
Several shapes are proposed, such as step tip, split tip, and symmetric tip, but as of
now, no data have shown that one is superior to another [9].
Selection of the Site for Dialysis
The selection of the venous site for dialysis catheter (DC) insertion is crucial to
improve patient safety in the ICU. According to international guidelines, the right
internal jugular site for DCs should be regarded as the first choice, the femoral vein
432 F. Valente et al.
site as the second choice, the left internal jugular vein as the third choice, and the
subclavian vein as the last choice.
The right internal jugular vein is the
preferred site because of the absence of
anatomical angulations, a short distance to the right atrium, and a straight direction.
On the other hand, left internal jugular vein access presents multiple anatomical
bends, potential causes of flow turbulence, and, for this reason, an increased risk of
thrombosis and a higher rate of dysfunction. Subclavian vein cannulation should be
considered the last choice due to a higher risk of venous stenosis/thrombosis, which
could hamper the successful creation of an arteriovenous fistula in patients at risk for
end-stage kidney disease (ESKD) progression [3, 10].
Although femoral vein catheterization may be easier and faster to perform in
critically ill patients with respiratory distress or severe coagulopathy, previous
observational studies and guidelines suggested avoiding the femoral site due to the
higher incidence of infections and thrombosis [11–13].
The Cathedia study, including 750 critically ill patients requiring RRT in ICUs,
evaluated the risk of catheter-related infection in patients receiving a non-tunneled
dialysis catheter (NTDC). Patients were randomized into two arms, one for the
femoral site and the other for the jugular site placement. Data showed that the risk
of catheter tip colonization at removal did not differ between the femoral and jugular
sites. Additionally, there were no differences between the femoral and jugular sites
when compared for the rate of catheter-related bloodstream infection (CRBSI), with
a CRBSI incidence of 2.3 vs. 1.5 per 1000 catheter-days (P = 0.42). A subgroup
analysis of the study showed a higher incide nce of infection in obese patients
(BMI > 28 kg/m
2
) when the catheter was inserted in the femoral site [14].
A secondary data analysis from the Cathedia study revealed no differences in
terms of dialysis catheter (DC) dysfunction, defined as the inability to attain adequate blood flow during renal replacement therapy (RRT), between femoral and
jugular access. In the same study, data concerning the jugular route confirmed a
higher rate of dysfunction in the left jugular compared to the right jugular vein [15].
Careful c
onsiderati
ons should be taken when choosing the femoral vein in
potential candidates for renal transplant, as the vascular anastomosis of the renal
graft is created with the recipient’s iliac vessels. For this reason, all efforts should be
made to avoid stenosis/thrombosis of the femoral-iliac tract. Moreo ver, attention
should be paid to patients with femoral or iliac vessel pathology, prior surgery
reconstruction, and hygienic reasons (e.g., chronic diarrhea) and obese patients [16]
In pati
ents with end-stage renal disease (ESRD) on regular hemodialysis and with
a functioning arteriovenous fistula (AVF) or arteriovenous graft (AVG), if admitted
to the intensive care unit (ICU), a dialysis catheter should be placed if no expertise in
handling the AVF or AVG is provided [10].
.