Clinical Kidney Journal, 2023, vol. 16, no.

1, 5–18

https:/doi.org/10.1093/ckj/sfac171
Advance Access Publication Date: 27 July 2022
CKJ Review

CKJ REVIEW

Intradialytic parenteral nutrition for patients on

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hemodialysis: when, how and to whom?
Juan J. Carrero 1 , David Severs2 , Didier Aguilera3 , Enrico Fiaccadori4 ,
Martin G. Gonzalez5 , Christoph C. Haufe6 , Daniel Teta7 , Pablo Molina 8

and Wesley Visser9

1
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden,
2
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus Medical Center,
Rotterdam, The Netherlands, 3 Centre Hospitalier de Vichy, Vichy, France, 4 Parma University Medical School
Hospital, Parma, Italy, 5 Hospital Universitario de La Princesa, Madrid, Spain, 6 KfH Kidney Center, Erfurt,
Germany, 7 Hôpital du Valais, Sion, Switzerland, 8 Department of Nephrology, FISABIO, Hospital Universitari
Doctor Peset, Universitat de València, Valencia, Spain and 9 Department of Internal Medicine, Division of
Dietetics, Erasmus Medical Center, Rotterdam, The Netherlands
Correspondence to: Juan J. Carrero; E-mail: [email protected]

ABSTRACT
Hemodialysis is associated with high morbidity and mortality rates as well as low quality of life. Altered nutritional
status and protein-energy wasting are important indicators of these risks. Maintaining optimal nutritional status in
patients with hemodialysis is a critical but sometimes overlooked aspect of care. Nutritional support strategies usually
begin with dietary counseling and oral nutritional supplements. Patients may not comply with this advice or oral
nutritional supplements, however , or compliance may be affected by other complications of progressive chronic kidney
disease. Intradialytic parenteral nutrition (IDPN) may be a possibility in these cases, but lack of knowledge on practical
aspects of IDPN delivery are seldom discussed and may represent a barrier. In this review, we, as a consensus panel of
clinicians experienced with IDPN, survey existing literature and summarize our views on when to use IDPN, which
patients may be best suited for IDPN, and how to effectively deliver and monitor this strategy for nutritional support.

LAY SUMMARY
Hemodialysis for patients with chronic kidney disease is associated with high morbidity and mortality rates as well
as low quality of life. Poor nutritional status is an important predictor of these risks, so maintaining optimal nutrition
in patients on hemodialysis is a critical but sometimes overlooked aspect of care. Because many patients undergoing
hemodialysis cannot maintain good nutrition through daily diet or oral nutritional supplements, intravenous delivery
of nutrition during hemodialysis sessions has been proposed as another way to support nutrition over time. In this
review, a consensus panel of experienced clinicians reviews the available literature and provides experience-based
guidance on when to use this nutritional strategy, which patients may be best suited for this approach, practical
strategies for delivery, and how to monitor patients receiving this nutrition during hemodialysis.

Received: 24.3.2022; Editorial decision: 29.6.2022

© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative
Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution,
and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]

5
 6 J.J. Carrero et al.

GRAPHICAL ABSTRACT

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Keywords: chronic kidney disease, hemodialysis, parenteral nutrition, protein-energy malnutrition

INTRODUCTION To complement and add to the current guidance on the use

of IDPN, we reviewed indications, clinical goals, indicators of
Chronic kidney disease (CKD) is associated with high morbidity clinical response, practical aspects, potential complications, and
and mortality rates as well as low quality of life (QOL), with nu- challenges of IDPN therapy.
tritional status being an important indicator of these risks [1–3].
Markers of nutritional status inevitably decline in CKD over time,
resulting in progressive depletion of protein and energy stores
Scope of the problem: protein energy wasting in
(i.e. fat and muscle). This condition, termed ‘protein-energy
patients on dialysis
wasting’ (PEW), is highly prevalent in patients on hemodialysis
(HD) and is often associated with reduced functional capacity As opportunities for kidney transplantation expand worldwide,
[4]. PEW is attributed to a variety of complex causes that can remaining patients on chronic HD are more likely to have
collectively be grouped into factors leading to undernutrition multiple comorbidities that may adversely affect nutritional
(poor appetite and low spontaneous nutrient intake) [5–8] and status and loss of muscle mass and strength. Muscle mass loss
factors leading to catabolism of muscle protein (inflammation, and accelerated muscle protein breakdown have been reported
resistance to anabolic drive, metabolic acidosis, and others) [9]. in multiple studies of patients receiving HD, enhanced by pre-
A variety of strategies are available to provide nutritional sup- cipitating factors such as inflammation [5], metabolic acidosis,
port to patients receiving HD who experience or are at risk of resistance to anabolic drive, poor physical activity, and older
developing PEW. These include regular counseling by a dieti- age [6–9]. Diabetes, especially when suboptimally controlled,
tian, oral nutritional supplements (ONSs), and intradialytic par- may be another condition leading to muscle protein breakdown
enteral nutrition (IDPN). Although narrative reviews [10–14] and in these patients [6–8]. These factors are exacerbated by fatigue,
clinical guidelines [15–17] discuss the role of IDPN in patients on poor appetite, and inadequate protein and energy intake [9, 19].
HD, practical aspects of IDPN delivery are seldom discussed. As As a result, PEW is common in patients on dialysis. In a meta-
identified in a recent Australian survey, uneven and sometimes analysis of 90 studies including 16 434 patients on maintenance
insufficient clinical guidance on the use of IDPN as a nutritional dialysis, most studies reported a prevalence of PEW between 28%
support strategy has resulted in uneven uptake [18], along with and 54% [20]. Considering that those studies included clinically
concerns regarding costs and insurance coverage [12]. stable patients, the real prevalence may be even higher.
 Intradialytic parenteral nutrition consensus 7

15%-20%

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Acute-phase protein synthesis

FIGURE 1: The effects of hemodialysis coupled with inadequate nutrient intake on muscle loss. Dialysis contributes to underlying factors that result in protein energy
wasting. The dialysis process induces the activation of defense mechanisms, and the body reacts by increasing acute phase protein synthesis and initiating the
inflammation cascade. In this setting, chronic undernutrition and amino acid (AA) losses into dialysate lead to low availability of circulating AA for protein synthesis.
The body, in turn, increases muscle protein catabolism to promote AA release as a substrate for acute-phase proteins; this muscle catabolism activates cytokine
production in the muscle, which tends to perpetuate this process in a vicious cycle.

The HD procedure itself can result in infectious, inflamma- clinical experience, however, it is not uncommon that patients
tory, or volume-related complications that contribute to PEW with sustained PEW require additional nutritional support be-
[9]. It also affects protein and energy homeostasis: Amino acid yond ONS. Meanwhile, in clinical practice, nonadherence is the
and protein loss during the HD session coupled with low nutri- main limitation to daily nutritional intake, including ONS [31].
ent intake result in low nutrient availability for muscle synthe- We are not aware of any reports that quantify real-life compli-
sis [9, 21–24]. HD has a profound catabolic effect, especially on ance to ONS, but long-term use of ONS may create challenges in
protein homeostasis, that affects whole-body and skeletal pro- this regard because of loss of appetite; early satiety; and issues
tein homeostasis (Fig. 1) [9]. Nutritional support strategies during related to taste, flavor (less appealing or always the same taste),
the dialysis session can counteract this negative protein balance palatability, and food acceptability issues (habituation, social sit-
and help maintain adequate nutritional status over time. This uation, culture, etc) [31].
maintenance can be achieved through oral nutritional support, Considering these potential hindrances to ONS, we believe
such as protein- and energy-enriched meals [25, 26] or oral ONSs that IDPN can be considered as a strategy to complement spon-
[27] but also through IDPN [27, 28]. taneous oral intake that does not depend on patient compli-
ance. Both IDPN and ONS have been proven to prevent derange-
ments in protein uptake during HD [25], and, like ONS, IDPN
Defining intradialytic parenteral nutrition helps maintain adequate nutrition status over time.

The use of HD access for the delivery of PN eliminates the need

for an additional permanent catheter placement or port system
Indications and clinical goals for intradialytic
placement and is instead allows delivery through the venous
parenteral nutrition
drip chamber in the extracorporeal circuit. IDPN is administered
throughout the HD session, which typically lasts about 4 hours Reflecting our own evaluation of available evidence and guide-
and is usually done three times per week [15]. The IDPN admix- lines, IDPN is indicated in malnourished, non-critically ill hos-
ture typically contains dextrose, amino acids, and lipids and may pitalized patients with acute kidney injury or CKD on HD and
contain electrolytes, trace elements, and vitamins [29]. Because in patients on chronic HD at risk for undernutrition who can
IDPN is time and volume restricted, it is considered a form of safely feed orally but cannot meet nutritional guidelines with
supplemental nutrition support adjuvant to any oral intake. Be- diet alone (Fig. 2) [15, 17, 32].
cause it is intermittently delivered, IDPN can only provide up to We feel that IDPN should be considered an intervention re-
25% of a patient’s targeted nutrient intake. served for situations when efforts to improve oral intake or
Although comprehensive data and guidance are still lacking, effectively deliver regular ONS have been inadequate, but we
the current consensus is that until additional data on IDPN are stress that IDPN can also be a valuable tool in patients with CKD
available that demonstrate superiority to other strategies (i.e. di- at risk for malnutrition [9, 28, 33].
etary counselling or ONS), IDPN ought to be reserved for situa- Defining ‘inadequate intake’ or ‘at risk of malnutrition’ is,
tions when other strategies fail to maintain nutritional status however, not straightforward, given the many factors that may
[30]. We feel, however, that it is important to consider the rela- underlie it. Because of this, the US National Kidney Foundation
tive benefits and limitations of ONS and IDPN. ONS is a simple, Kidney Disease Outcomes Quality Initiative (KDOQI) 2020 guide-
low-cost strategy to maintain nutritional status over time. In our lines do not provide specific thresholds to define malnutrition
 8 J.J. Carrero et al.

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functionality, and QOL
functionality, and QOL

monthly, or quarterly

FIGURE 2: A streamlined decision tree for nutritional support based on clinical guidelines and panel consensus.

[15], together with the potential confounding effect of inflam- course of 1 year. Adding IDPN to ONS resulted in similar nu-
mation and volume overload in most standard routine markers. tritional parameters compared with ONS alone. Regardless of
KDOQI guidelines recommend evaluating complementary mal- the strategy, an improvement in nutritional status, defined by
nutrition markers and interpreting them together when mak- increases in prealbumin after the intervention, was associated
ing diagnosis. On the basis of this recommendation, we remain with a higher 2-year survival and lower hospitalization rates [37].
vague in our definition of ‘malnutrition’ as we feel that defining It is not feasible to conduct a trial that randomized malnour-
numerical thresholds may give a false impression of accuracy; ished patients to treatment or placebo, but these findings con-
specific thresholds are not supported by clinical evidence and firm that restoring nutritional status, regardless of strategy, im-
should be decided on an individual patient basis. proves long-term patient outcomes.
IDPN should, in any case, be seen as a complement to es-
tablished ONS so that dietary intake requirements are met, es-
pecially with respect to protein. We suggest that patients suit- Composition of intradialytic parenteral nutrition
able for IDPN should demonstrate an oral intake of greater than solutions
20 kcal/kg and 0.8 g of protein/kg/day. IDPN may also offer an op-
portunity to provide more balanced nutrition and reach individ- Available guideline recommendations are nonspecific in terms
ual patient nutritional goals when regular oral intake is imbal- of the choice of IDPN solution and other practical aspects of IDPN
anced. Ultimately, the overarching goal of IDPN should be to im- administration, with suggested nutrition targets summarized in
prove nutritional status in patients receiving HD or, at the least, Table 2 [15–17, 42]. Available options for IDPN solutions include
to avoid declines in nutritional status over time. customized, compounded bags or commercially prepared ready-
to-use (RTU) bags. IDPN requires a consideration of individual
patient needs in terms of amino acids and energy. We agree that
amino acid provision, rather than total calories, is the most im-
Clinical outcomes seen with intradialytic parenteral
portant consideration of any IDPN solution. We therefore sug-
nutrition
gest that it would be reasonable to target an amino acid con-
Available evidence has reported multiple effects on clinical out- tent that, at the least, overcomes anabolic resistance as well as
comes resulting from IDPN, as shown in Table 1 [34–41]. In the intradialytic amino acid losses. The work done by Pupim and
largest available randomized study of IDPN, 186 patients on HD colleagues [28] evaluated IDPN containing 0.6 g amino acids/kg
were randomized to receive ONS with or without IDPN over the body weight administered in patients on HD without evidence
Table 1. Clinical outcomes reported with the use of IDPNa

RCTs with control groups Secondary outcomes

IDPN Serum Serum
% Patients content per Primary Triceps pre-albumin, Serum nPNA, creatinine,
Authors n Design Daysb completed session outcome Body weight skinfold mg/L albumin, g/L g/kg/day μmol/L
Guarnieri 18 eAA vs 60 100 14 g/d (eAA); ↑ BW with eAA: No NR No change NR No change
1980 [34] eAA + non- 10 g/d eAA 66 ± 6.5 to change
eAA vs no (eAA + non- (P < .05); 68 ± 6.1 kg
treatment eAA) decrease in eAA + non-
other groups eAA:
73 ± 5.3 to
71 ± 5.7 kg
Control:
61 ± 4.5 to
59 ± 5.3 kg
Cano 1990 26 IDPN vs no 90 100 Fat ↑ BW, IDPN: No IDPN: IDPN: NR IDPN:
[35] IDPN 16 kcal/kg + AA s-albumin +2 ± 0.47% change +20 ± 11.6 +0.95 ± 0.63 +998 ± 444
0.08 g/kg and Control: Control: Control: Control:
s-creatinine −1.5 ± 0.94% −18 ± 13.9 −0.43 ± 0.63 −725 ± 379
with IDPN (P < .01) (P < .05) (P < .05) (P < .01)
Navarro 17 IDPN vs no 90 100 25.7 g AA Prevention NR No NR IDPN: IDPN; No change
2000 [36] IDPN of change 36.2 ± 0.5 to 1.07 ± 0.02 to
reductions 42.2 ± 0.5 1.18 ± 0.02
in plasma P < .05) P < .05)
AA concen- Control: no Control: no
tration with change change
IDPN
Cano 2007 186 IDPN + ONS 365 67 Not specified Mortality Increase NR IDPN: 32 ± 0.5 to Increase NR
[37] vs ONS (NS) with both 240 ± 5.1 to 33.5 ± 0.5 with with both
alone treatments 265 ± 10 (NS both treatments
(NS between treatments (NS between
between groups) (NS between groups)
groups) groups)
Liu 2016 32 ONS vs 270 100 250 mL of ↑ S-albumin NR NR AA: 330 AA: 39 No change No change
[38] ONS + glu- 50% glucose and (235–367) to (37–41) to 39
cose vs solution; prealbumin 341 (38–41), no
ONS + glu- 21 g AA with AA; no (288–348), no change in
cose + AA difference in change in glucose and
SGA glucose and control
between control groups,
groups groups, P < .05 for
P < .05 for AA
AA vs
control
Intradialytic parenteral nutrition consensus
9

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 10

Table 1. Continued

RCTs with control groups Secondary outcomes

IDPN Serum Serum
% Patients content per Primary Body Triceps pre-albumin, Serum nPNA, creatinine,
Authors n Design Daysb completed session outcome weight skinfold mg/L albumin, g/L g/kg/day μmol/L
J.J. Carrero et al.

Marsen IDPN + stan- 196 60.4 Glucose: ↑ NR NR IDPN: No change No change No change
2017 [39] 107 dard 1.35 ± 0.36 g/kg Prealbumin 209 ± 9.9 to
nutritional AA: with IDPN 236 ± 11.5
counseling 0.68 ± 0.13 g/kg) Control:
vs standard 226 ± 9.2 to
nutritional 224 ± 10.1
counseling (P = .02)
only
Thabet 40 IDPN vs 180 100 16 mL/kg ↓ MIS with No change No NR IDPN: NR NR
2017 [40] control (not to IDPN vs change 30 ± 0.9 to
exceed control 33 ± 0.7
1000 mL per (P = .001). Control:
session; IDPN: 30.±0.9 to
composition 12 ± 0.5 to 29 ± 0.9
not reported) 3 ± 0.3 (P = .003)
Control:
10 ± 0.5 to
10 ± 0.5
RCTs without control groups Body Triceps Serum pre- Serum nPNA, Serum
weight skinfold albumin, albumin, g/L g/kg/day creatinine,
mg/L μmol/L
Cano 2006 35 Olive 35 100 16 ml/kg In both No change NR Olive oil: Olive oil: Olive oil: Olive oil:
[41] oil–based vs (AA, 50 g/L; groups: ↑ 254 ± 3.3 to 34 ± 0.2 to 1.0 ± 0.02 to 631 ± 10.7 to
soybean glucose, nPNA, 259 ± 3.7 35 ± 0.2 1.2 ± 0.02 630 ± 10.3
oil–based 125 g/L; fat, s-albumin, (NS) (P < .01) (P < .01) (NS)
IDPN 50 g/L) prealbumin, Soybean: Soybean: Soybean: Soybean:
s-creatinine 231 ± 3.1 to 34 ± 0.2 to 0.9 ± 0.02 to 590 ± 8.5 to
254 ± 3.6 36 ± 0.2 1.2 ± 0.02 627 ± 9.8
(P < .05); NS (P < .01); NS (P < .01); NS (P < .01);
between between between NS
groups groups groups between
groups

a
Data are provided as mean ± SEM or median (IQR) unless otherwise noted. AA: amino acid; BW: body weight; eAA: essential amino acid; IDPN: intradialytic parenteral nutrition; IQR: interquartile range; MIS: malnutrition
inflammation score; nPCR: normalized protein catabolic rate; NR: not reported; NS: not significant; ONS: oral nutritional supplement RCT: randomized controlled trial; SGA: subjective global assessment.
b
Refers to the duration of the intervention.

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 Intradialytic parenteral nutrition consensus 11

Table 2. Current recommendations for IDPN composition

AAs Energy Glucose Fat

(per session) (kcal/session) (g/session) (g/session)

KDOQI Clinical Practice guideline for Nutrition in CKD: Not specified

2020 Update [15]
ESPEN: Guideline on clinical nutrition in hospitalized NS
patients with acute or chronic kidney disease (2021) [33]
DGEMa : Guidelines on enteral and parenteral nutrition in At least 500–800 Max. 50–80 Max. 20–30
patients with kidney disease (2015) [16] 0.5 g/kg
ESPEN: Guidelines on parenteral nutrition: adult renal 30–60 g 800–1200 NS NS
failure (2009) [17]

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a
Recommends limiting the applicable nutrient supply to avoid metabolic disorders. AA: amino acid; CKD: chronic kidney disease; DGEM: Deutsche Gesellschaft für
Ernährungsmedizin (German Association for Nutritional Medicine); ESPEN: European Society for Parenteral and Enteral Nutrition; KDOQI: Kidney Disease Outcomes
Quality Initiative; NS: not specified.

of inflammation, which reversed the net protein degradation in- prepared products, and the limited time window between prepa-
herent with the HD session, and this protein content may be ration and administration.
suitable for some patients. Meanwhile, we stress that the pres-
ence of significant inflammation or other factors that lead to an- Commercial ready-to-use solutions
abolic resistance may necessitate a higher amino acid content. Unlike compounded solutions, commercial RTU bags can be
Ready-to-use (RTU) or all-in-one commercially produced IDPN safely stored at room temperature for long periods before use,
products meet the nutritional needs of most patients in the set- in some cases up to 2 years. In general, solutions considered for
ting of IDPN. IDPN usually do not contain electrolytes. Moreover, because of
The amount of nutrients that can be provided depends on the the limited time for delivery during a standard HD session, the
length of the HD session because of the limitation of metabolic total infused volume is constrained. RTU products can also be
tolerance. Therefore, a 2-hour HD session allows for less nutrient used to tailor macronutrient delivery, by selecting products with
supply than a 4-hour session. For the provision of an appropri- a comparably high amino acid–to energy ratio to compensate for
ate amount of amino acid and calories, considering a maximum poor spontaneous oral protein intake or to select products for a
infusion rate, we suggest that IDPN be delivered during a ses- strategy to control carbohydrate delivery. Depending on specific
sion lasting at least 3.5 hours. Although some clinicians calcu- patient needs, clinicians may also decide to provide or withhold
late nutrient delivery of 0.8 g amino acids and 15 kcal/kg ideal components such as lipids.
body weight per session, others adapt the volume of the solu- All-in-one commercially produced RTU bags differ not only
tion available at their institution, taking into consideration the with regard to their nutrient content and available bag formats
patient’s body weight. but also as to whether an IDPN application has been specifically
Clinicians should consider strategies for balancing energy applied for and included in the licensed dosing guidance for the
and protein delivery when using commercially available prod- respective product.
ucts. These strategies may also be used to tailor macronutrient
delivery. For instance, IDPN can provide a higher-than-normal
amino acid–to-energy product to compensate for regular poor Aspects of administration decision-making with
oral intake [43]. Commercially available IDPN can also be used intradialytic parenteral nutrition
in a strategy to control carbohydrate delivery [13]. As for total Depending on a given patient’s needs, specific IDPN components
nutrients provided during a dialysis session, the rational view is may be withheld, including lipids, vitamins, and trace elements.
to consider individual amino acids, energy, and lipids needs and In our experience, vitamins or trace elements are rarely needed
to supplement nutrients that are not met in IDPN with sponta- as an addition to IDPN, except for patients with specific known
neous oral intake or ONS. deficiencies. Although many patients with CKD may exhibit
Electrolytes are usually not part of the IDPN composition, these deficiencies, IDPN should always be considered only an in-
which reflects our experience in this setting. Most manufactur- termittent, supplemental nutrition strategy, and many patients
ers offer an electrolyte-free option, which may be preferred in possibly already receive routine oral supplements regularly [44].
these patients. Vitamins and trace elements are added when Other clinically important factors for consideration include
needed. total volume to be delivered and infusion rate during the IDPN
session. These will be dictated by the anticipated duration of
the HD session and individual patient body weight, among other
Compounded intradialytic parenteral nutrition solutions factors. In addition, amino acid delivery is an important consid-
eration to maintain a positive protein balance and depends on
Although compounding allows for tailoring of admixtures to individual patient dietary intake outside of HD.
specific patient needs, there are limitations related to process
complexity when ordering and delivering IDPN during HD. These
Criteria for reconsidering or delaying intradialytic parenteral
limitations include increased costs related to employee time for
nutrition
preparation, the need for a sterile compounding facility and all
the related process regulations that apply to this preparation There are no absolute contraindications for IDPN, but we have
setting, complex logistical challenges related to the safe trans- formulated several criteria for reconsidering or delaying IDPN
portation and the requirement for refrigeration during storage of (Box 1). Most of these were exclusion criteria in randomized
 12 J.J. Carrero et al.

controlled trials (RCTs). Uncontrolled diabetes, hypertension, initiating IDPN at 125 mL/hour in the first week, with the full
or evidence of volume overload may also require a delay in a dose of 250 mL/hour during a 4-hour session (max. 300 mL/hour
plan for regular IDPN administration, and the presence of se- during a session lasting at least 3.5 hours) achieved in the
vere malnutrition should prompt a more aggressive nutritional second week. If during a dialysis session IDPN is temporarily
approach (Box 1). Some of these RCTs excluded patients with interrupted for any reason, then resumed, the infusion rate
diabetes [34, 35, 38, 40] or patients with uncontrolled diabetes should not be increased to try to compensate for the loss of
[39]. Although significant increases in serum triglycerides have time. It is preferable to increase the length of the HD session or
not been demonstrated during IDPN, IDPN should not be started discard the excess IDPN volume after the HD session ends.
in cases where the baseline triglyceride level is already signifi- If transfusion of blood products or the use of intravenous
cantly elevated. Cano et al. excluded patients with triglyceride iron is required during the HD session in addition to IDPN, these
levels above 200 mg/dL [41], but we recommend a somewhat products should be administered through the arterial chamber,
more liberal cutoff of 500 mg/dL based on our clinical experience. maintaining the IDPN through the venous chamber. The con-

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Although uncontrolled hypertension and fluid overload have not comitant administration of antibiotics that require an extended
been used as exclusion criteria in published RCTs, we recom- infusion time (e.g. vancomycin) is discouraged. If these drugs are
mend exercising caution in these patients because of concerns necessary, however, and a second venous port is not available,
regarding excessive ultrafiltration volume. Some trials excluded IDPN should be delivered through the arterial port while the ve-
patients with recent enteral or parenteral tube feeding [37–39]. nous chamber is used for antibiotics. Use of the arterial port for
Similarly, although the lower boundaries of spontaneous intake IDPN delivery may result in greater losses of its ingredients in
we formulated have not been defined as exclusion criteria in ex- the dialysate.
isting studies, we expect IDPN to fail to reach the suggested tar-
gets mentioned in Table 4 in these patients, in whom enteral Important considerations and potential limitations to IDPN
nutrition may lead to better outcomes.
The infusion rate depends on the composition of the IDPN solu-
tion. For instance, to avoid exceeding triglyceride clearance, in-
fusion of a typical 1-L lipid-containing admixture should occur
Box 1. Suggested clinical criteria for over at least 3.5 hours. Likewise, hyperglycemia can occur if a
intradialytic parenteral nutrition high amount of carbohydrates is delivered in the IDPN solution.
Considerations for IDPN: This could be followed by hyperinsulinemia and hypoglycemia
by the end of the HD session, especially if the IDPN infusion is
• Established risk of malnutrition
terminated before the dialysis session is complete. Note that this
• Failed attempt at intensive oral nutrition or poor com-
clinical outcome is often the result of excessive exogenous in-
pliance with ONS
sulin administration during dialysis, which should be avoided.
Possible contraindications or factors requiring a delay in
IDPN:
Patient monitoring during intradialytic parenteral
• Severe malnutrition requiring more intensive interven- nutrition treatment
tion, including temporary parenteral nutrition
General guidance has been published on patient monitoring dur-
• Baseline triglyceride level >500 mg/dl
ing IDPN, both during the session and over the course of a long-
• Spontaneous intake of <20 kcal/kg and/or <0.8 g of pro-
term IDPN plan [14, 15, 45, 46]. We propose a variety of moni-
tein/kg/day (consider enteral nutrition)
toring practices to detect complications during the first weeks
• Uncontrolled diabetes or hypertension
of IDPN support, especially related to the potential risk for hy-
• Evidence of volume overload
perglycemia. We also agree with available guidance on track-
ing the effectiveness of IDPN over time and strategies to detect
any complications with prolonged treatment. These suggestions
are summarized in Table 3. Blood pressure and volume status
Clinical aspects of intradialytic parenteral nutrition
should also be monitored to detect possible volume overload
setup
during the infusion, and the ultrafiltration rate should be ad-
The addition of IDPN to an HD session requires careful planning justed accordingly to remove the extra fluid provided by IDPN
and equipment setup by professionals specifically trained in HD [15]. In general, patients should also be monitored for possible
administration [45]; we stress that the proper timing and process hemodynamic intolerance, such as nausea, vomiting, discom-
for bag preparation should also be considered. For reference, a fort, hypotension, respiratory distress, and cardiac arrhythmias
general schematic of the HD circuit, including IDPN, is shown in during the IDPN infusion [45]. It is imperative that the target dry
Figure 3. The IDPN bag should be agitated before the adminis- weight is regularly reevaluated to accommodate changes in body
tration set is inserted, and the infusion line should then be con- composition.
nected from the external infusion pump to the venous chamber Patients with diabetes do not require any specific considera-
of the machine. Pump flow rate should be set according to the tions during IDPN, although monitoring for both hyperglycemia
IDPN formulation and at a rate that ensures individual patient and hypoglycemia during IDPN is an important aspect of
safety, with the infusion rate determined according to a patient’s the support of all patients during the HD session [14]. The
ideal body weight. A typical pragmatic solution is to reduce the addition or adjustment of insulin may be needed to address
total amount infused (typically 1 L) only when the patient’s body hyperglycemia. In the case of a new or additional insulin re-
weight is less than 60 kg or when a shorter dialysis duration lim- quirement, the use of insulin analogues should be individually
its the infused volume. tailored through consultation with an endocrinologist to avoid
IDPN requires a stepwise approach to administration, with postdialytic hypoglycemia [15]. A carbohydrate-rich snack con-
incremental increases occurring over the course of at least 1 sumed around 30 minutes before the discontinuation of IDPN
week of HD sessions. For a typical RTU solution, we suggest infusion can aid in preventing postinfusion hypoglycemia.
 Intradialytic parenteral nutrition consensus 13

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FIGURE 3: Schematic review of a hemodialysis circuit. Adapted from: National Institute of Diabetes and Digestive and Kidney Diseases, https://www.niddk.nih.gov/
health-information/kidney-disease/kidney-failure/hemodialysis (December 3, 2021, date last accessed).

Laboratory monitoring between IDPN infusions may be war- experience and on the markers and tools usually available at the
ranted to track long-term nutritional parameters [41]. The com- clinic. These are general markers of nutritional status, not spe-
position of the IDPN solution should be considered to guide cific to IDPN, and we believe that any improvement in them is
a schedule for routine monitoring of blood glucose, triglyc- likely to indicate a gain in nutritional status. In agreement with
erides, and liver tests [46]. In cases of severe hypertriglyc- the 2020 KDOQI guidelines [15], we recommend assessing two
eridemia, IDPN is withheld or a solution is infused that excludes or more biomarkers at a time and interpreting them together, as
lipids. all of them are imperfect measures that may be influenced by
processes such as inflammation or fluid overload. Some but not
all of these parameters have been used as outcome measures
Optimal duration of intradialytic parenteral nutrition
in IDPN-related RCTs, including body weight [34, 35, 37, 40, 41],
Although the optimal duration of IDPN may depend on individ- albumin [34–41], and prealbumin [35, 37, 39, 41] (Table 1), show-
ual patient factors, it is reasonable to suggest that a course of ing in general good response to the intervention. We suggest
IDPN during HD should continue for a minimum of at least 3 that other indicators of nutritional status that are commonly
months to allow for meaningful evaluation [47]. After this period, used to evaluate effectiveness of ONS, particularly subjective
nutritional status should be reassessed to guide the continued global assessment, protein intake, and body composition (e.g. by
need for IDPN. bioelectrical impedance) [15], may also offer important insights
into the effectiveness of IDPN, despite not having been formally
assessed in clinical trials. We also suggest that repeated as-
Determining clinical success with intradialytic sessments of muscle strength by handgrip strength as well as
parenteral nutrition measurements of gait speed could help assess IDPN efficacy over
Monitoring response to therapy is a critical aspect of patient time.
care, and a variety of measures may be proposed to assess To summarize our suggestions based on current evidence,
the effectiveness of IDPN over time, as summarized in Table 4 experience, and best practices, we have developed the suggested
[47]. The choice of markers in this table is based on our clinical protocol shown in Box 2.
 14 J.J. Carrero et al.

Table 3. Suggested parameters to assess the safety and tolerance of IDPN

Comments and suggested Frequency of

Parameter Frequency of measurements management occurrence

Symptoms related to reaction to In each HD session and especially • If reaction suspected, stop IDPN. Very rare
IDPN: Nausea, vomiting, during the first week of IDPN
discomfort, hypotension,
respiratory distress, and
cardiac arrhythmias (rare)
Hemodynamic monitoring (BP, During and after each HD session. • Assess dry weight and adequate Common (changes
heart rate) and volume length of dialysis session for an in dry weight)
status should be closely adequate ultrafiltration rate

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monitored during and after (< 10 mL/kg/hour).
hemodynamic monitoring • Ultrafiltration rate should be
adjusted accordingly to remove
the extra fluid IDPN provides.
Blood glucose levelsa • In patients with diabetes, In case of hyperglycemia: Common in patients
measure glucose before the start • Subcutaneous short-acting with diabetes and
dialysis, after 2 hours, and before insulin when glucose prediabetes
finishing dialysis treatment. >12 mmol/L (>220 mg/dL) in
• In patients who do not have increasing doses depending on
diabetes, measure as in patients blood glucose levels.
with diabetes during the first 3 In case of hypoglycemia: Very rare if insulin is
dialysis sessions, and then • Teach patients about the signs not used
discontinue monitoring unless and symptoms of hypoglycemia.
results were outside of safe • Encourage all patients receiving
blood glucose ranges.b IDPN to bring 15- to 30-g
carbohydrate snack to the
dialysis session and consume it
20–30 minutes before the end of
the dialysis session.
Liver tests (alkaline Before dialysis session during the In case of significant disturbances, Very rare
phosphatase, ALT, total first 2 weeks, and then every 4–6 stop IDPN and resume it once
bilirubin) and blood weeks to coincide with regular solved.
triglycerides dialysis blood work.

a
Blood may be drawn by finger poke or from the HD line. If drawn from the HD line and the result is high, repeat the test using the finger poke method to verify results
(recirculation may result in falsely elevated blood glucose levels). ALT: alanine aminotransferase; BP: blood pressure; HD: hemodialysis; IDPN: intradialytic parenteral
nutrition.
b
After three dialysis sessions, a pattern of persistently raised blood glucose levels is apparent in patients without diabetes, and then monitoring may be interrupted
if results are inside of safe blood glucose ranges {e.g. <12 mmol/L [<220 mg/dL]} and the patient does not require additional subcutaneous insulin. Otherwise, glucose
monitoring before the start of dialysis, after 2 hours, and before finishing dialysis treatment should be maintained.

• Addition of vitamins or trace elements is rarely needed

Box 2. A suggested summary protocol for
intradialytic parenteral nutrition IDPN setup:
support
Consider progression of support to IDPN: • Pump flow 250–300 mL/hour for patients with body
weight ≥60 kg, proportionally decreased rate for pa-
• Patients unable to maintain adequate oral intake or fol- tients with lower body weight; start with pump flow
low dietary counseling* 125 mL/hour in first week
• Patients unable to tolerate adequate oral intake because
of comorbid gastrointestinal issues Patient monitoring during IDPN:
• Gastrointestinal issues related to poor tolerability of
• Symptoms related to IDPN tolerance:
ONS (bloating, early satiety, diarrhea, nausea and
◦ In each HD session and especially during the first
regurgitation)
week of IDPN
Choice of IDPN composition: • Hemodynamic monitoring:
◦ Blood pressure, heart rate, and volume status should
• Consider an amino acid target >0.5 g/kg body weight (or
be closely monitored during and after the HD session
ideal body weight)
• Blood glucose:
• Max 50–80 g glucose per session
◦ In patients with diabetes, measure glucose before the
• Max 30–50 g lipids per session
start dialysis, after 2 hours, and before the end
• No evidence for enrichment with n-3 PUFA
of the HD session
 Intradialytic parenteral nutrition consensus 15

Table 4. Suggested parameters to assess the effectiveness of IDPN

Parameter Frequency of measurements Suggested criteria for IDPN effectiveness.

Dry weight • During and after each HD session • A tendency to increase edema-free body weight during the
past 3 months
Predialysis albumin and • Initial treatment • A tendency to increase mean albumin levels during the past
prealbumin levels • Weekly for 2 weeks 3 months
• Then, every 4–6 weeks to coincide • A tendency to increase mean prealbumin levels during the
with regular dialysis blood work past 3 months
SGA • Initial treatment • SGA improvement (SGA Score A, B) during the past 3 months
• Then, every 3 months
Body stores assessment by • Initial treatment • A tendency to increase/preserve lean tissue mass and fat

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bioelectrical impedance • Then, every 4–6 weeks to coincide during the past 3 months
with regular dialysis blood work
Dietary interview or diarya • Initial treatment • Caloric intake ≥25–30 kcal/kg/day
• Then, every 3 months • Protein intake ≥1.0 g/kg/day
Handgrip strength • Initial treatment • A tendency to improve/preserve muscle strength, as
• Then, every 3 months assessed by handgrip strength during the past 3 months,
with a minimum cutoff of 16 kg and 27 kg for women and
men, respectively
Gait speed • Initial treatment • A tendency to improve/preserve physical performance, as
• Then, every 3 months assessed by gait speed, during the past 3 months, with a
minimum cutoff of 0.8 m/second.
• Low physical performance gait speed >0.8 m/second

a
Three-day dietary records followed by interviews and calculating nutrient intake by an experienced registered renal dietitian; should include intake derived from
IDPN. HD: hemodynamic; IDPN: intradialytic parenteral nutrition; SGA: subjective global assessment.
Adapted from: García de Lorenzo A, Arrieta J, Ayúcar A et al. Nutrición parenteral intradiálisis en el enfermo renal crónico: consenso SEN-SENPE [Intra-dialysis parenteral
nutrition in chronic renal patients: consensus SEN-SENPE]. Nutr Hosp 2010; 25 :375–377

◦ In patients who do not have diabetes, measure Practical considerations and potential barriers to
glucose before the start dialysis, after 2 hours, and intradialytic parenteral nutrition
before the end of the HD session during the first
three HD sessions, and then discontinue monitoring The use of IDPN is challenged not only by the outstanding clini-
unless results are outside safe blood glucose ranges cal questions we have discussed but by operational and admin-
• Liver tests, triglyceride levels: istrative challenges unique to this setting. For instance, in a re-
◦ Before the HD session during the first 2 weeks, and cent survey of kidney dietitians in Australia, bureaucratic obsta-
then every 4–6 weeks to coincide with regular cles and misconceptions about the value of IDPN as a method
dialysis blood work for routine nutritional support have both been cited as hurdles
to IDPN. Nevertheless, IDPN use was not reported as uncommon,
Length of IDPN intervention: and respondents cited the presence of a consistent care protocol,
• Minimum of 3 months, up to 6 months, barring the need support from medical and administrative staff, and dietitian ex-
to discontinue perience as factors facilitating the regular use of IDPN [18]. Staff
availability and training are also critical factors in a facility’s abil-
Assessments of IDPN efficacy: ity to consistently provide IDPN. This finding likely indicates a
• During and after every HD session: need for all stakeholders involved in IDPN, including clinicians,
◦ Changes in patient dry weight dietitians, nurses, patients, caregivers, and care coordinators, to
• With initial session, then weekly for 2 weeks, then every ensure the success of this or any other nutritional intervention
4–6 weeks to coincide with regular dialysis blood work: in patients with CKD.
◦ Predialysis albumin and prealbumin levels
◦ Body stores assessment by bioelectrical impedance Costs and regulatory concerns
• With initial session, then every 3 months:
◦ Subjective global assessment Regulatory concerns and costs are other major factors that
◦ Dietary interview or diary affect IDPN use in clinical practice, especially in the United
◦ Handgrip strength States, because of variable insurance eligibility and resulting
◦ Gait speed coverage of costs [30, 48, 49]. The costs of IDPN are often con-
• Monthly: siderably greater than those associated with ONS or nutritional
◦ Normalized protein nitrogen appearance counseling, and comparative efficacy studies suggest similar
• Reassess IDPN plan at 6 months benefits from both therapies [48]. Such conclusions often re-
fer to a 1998 study that examined IDPN-related costs and did
*Consider enteral nutrition when spontaneous intake not demonstrate lasting overall cost savings with IDPN after 6
<20 kcal/kg/day or <0.8 g protein/kg/day. months of therapy [30, 48, 49]. The authors concluded that for
IDPN to be considered a clinically superior and cost-effective
 16 J.J. Carrero et al.

treatment, data would be needed to demonstrate that IDPN con- nel for setup and patient monitoring and the costs associated
sistently reduced the risk of mortality; improved patient func- with IDPN compared with ONS or counseling remain important
tion and QOL; and provided benefits that were specific to IDPN challenges to its consistent use in practice.
therapy and not the result of potential confounders in terms of Because adequate nutrition has such an important impact on
patient population, baseline nutritional status, or other clinical patient mobility and function, future research is warranted to in-
factors [48]. We argue that such evidence is not available for any vestigate whether improved nutritional support with a strategy
form of nutritional support in the context of CKD. Also, costs like IDPN in patients with CKD may preserve nutritional status
in 1998 may not reflect current costs, and reimbursement prac- and muscle mass, which affects physical function and QOL over
tices across countries may provide a different scenario to the US time. As current evidence is limited, we further suggest that fu-
system. There is strong evidence, however, that treating malnu- ture studies should better evaluate parameters such as the op-
trition is cost-effective: In one 2007 regression modeling analy- timal patient population, duration of treatment, and composi-
sis of US dialysis patient data, researchers projected that 1400 tion of IDPN. In the meantime, our own clinical experience and

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lives could be saved and $36 million in Medicare costs could be current guidance suggests that IDPN is a valuable tool to help
avoided with increases in albumin levels of 0.2 g/dL as a result maintain nutritional status in many patients with CKD who hare
of nutritional support [50]. undergoing HD.

ACKNOWLEDGEMENTS
Guidance for future research
We would like to dedicate this work to the memory of Gabrielle
Future trials in IDPN should aim for a level of robustness that Luft, Ph.D.
allows for the evaluation of important aspects of therapy, in-
cluding the speed of restoration of nutritional status compared
with other interventions, the capacity of IDPN to sustain this im-
FUNDING
provement over time, and the impact of IDPN on the preven- The authors received no financial support for the research, au-
tion of muscle loss as well as muscle gain (Box 3). We recog- thorship, and/or publication of this article. The organization of
nize that the sample size and the duration of these trials may be the Virtual Meeting that motivated this publication was funded
challenging. by Baxter Healthcare SA.

DATA AVAILABILITY STATEMENT

Box 3. Suggestions for future intervention Data sharing is not applicable to this article as no datasets were
studies generated or analyzed.
Topic: Effectiveness of IDPN in treating PEW

• Comparator: CONFLICT OF INTEREST STATEMENT

◦ Other type of nutritional support (e.g. ONS)
J.J. Carrero has received speaker fees from Baxter Healthcare SA.
• Short-term outcomes of interest:
M.G. Gonzalez has engaged in expert testimony for Baxter
◦ Speed of restoration of nutritional status
Biopharma and has received speaker fees from AstraZeneca.
◦ Muscle mass
C.C. Haufe has received speaker fees from Baxter Healthcare SA,
◦ Functional capacity
AstraZeneca, and Astellas Pharma Inc, and consulting fees from
• Possible trial duration:
CSL Vifor. P. Molina has received consulting and/or speaker fees
◦ 3–4 months
from Fresnius-Kabi, CSL Vifor, Baxter, Abbott, Amgen, Palex Med-
Topic: Effectiveness of IDPN in preventing deterioration of ical, and Sanofi. D. Severs has received consulting fees, speaker
nutritional status fees, and research grant funds from Baxter. W.J. Visser has re-
ceived speaker fees and research grant funds from Baxter.
• Study design:
◦ Phase 1: effectiveness study as above (malnourished
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