# Water treatment-free prolonged intermittent kidney replacement therapy: A new approach for kidney replacement therapy in the ICU setting. A retrospective study.

Noémie Zucman, Fabrice Uhel, Charles Verney, Jean-Damien Ricard, Didier Dreyfuss, Damien Roux

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Noémie Zucman, Fabrice Uhel, Charles Verney, Jean-Damien Ricard, Didier Dreyfuss, et al. Water treatment-free prolonged intermittent kidney replacement therapy: A new approach for kidney replacement therapy in the ICU setting. A retrospective study. Journal of Critical Care, 2025, 87, 10.1016/j.jcrc.2025.155014. hal-05105890

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# Water treatment-free prolonged intermittent kidney replacement therapy: A new approach for kidney replacement therapy in the ICU setting. A retrospective study.

Noémie Zucman<sup>a,b</sup>, Fabrice Uhel<sup>a,b,c</sup>, Charles Verney<sup>a,b</sup>, Jean-Damien Ricard<sup>a,b,d</sup>, Didier Dreyfuss<sup>a,b,c</sup>, Damien Roux<sup>a,b,c,*</sup>

## ARTICLE INFO

### Keywords:

Kidney replacement therapy

Renal replacement therapy

Veno-venous haemofiltration

Intermittent haemodialysis

Water treatment

Water purification

Urea reduction ratio

## ABSTRACT

The optimal modalities of kidney replacement therapy (KRT) in the ICU remain debated. Intermittent haemodialysis (IHD) and continuous veno-venous haemofiltration (CVVH) are the two main methods. Intermittent haemodialysis requires a water treatment system, which may not be available in all jurisdictions. We report the experience of an innovative strategy of intermittent KRT without water treatment system.

Based on the manufacturer's recommendations, the dialysate flow during "CVVHDF post" (post-dilution continuous veno-venous haemodiafiltration) mode was increased by connecting the substitution pump in parallel with the dialysate pump using a Y-connector. This doubled the flow rate of dialysate, allowing for 9000 mL/h during intermittent KRT sessions at a blood flow rate of 250 mL/min. We called this technique "water treatment-free prolonged intermittent kidney replacement therapy" (WTF-PIKRT).

We report our experience in 18 patients who underwent 88 WTF-PIKRT sessions (median duration 5 h (IQR [4, 6])) between August 2019 and May 2020. The median urea reduction ratio was 38 % (IQR [29,49]). Hypotension occurred during 21.6 % of sessions. Hypokalemia or hypophosphatemia occurred in less than 5 % of sessions.

WTF-PIKRT represents an attractive alternative to conventional IHD when a water treatment system is not available. Despite its lower efficacy compared with IHD, it may have significant organizational and economic impact.

## List of abbreviations

<table><tr><td>AKI</td><td>acute kidney injury</td></tr><tr><td>CVVH</td><td>continuous veno-venous haemofiltration</td></tr><tr><td>CVVHDF</td><td>continuous veno-venous haemodiafiltration</td></tr><tr><td>ICU</td><td>intensive care unit</td></tr><tr><td>IHD</td><td>intermittent haemodialysis</td></tr><tr><td>WTF-PIKRT</td><td>water treatment-free prolonged intermittent kydney replacement therapy</td></tr><tr><td>KRT</td><td>kidney replacement therapy</td></tr><tr><td>WTS</td><td>water treatment system</td></tr></table>

## 1. Introduction

The optimal modality for kidney replacement therapy (KRT) during acute kidney injury (AKI) remains debated, Continuous and intermittent techniques can be used equally in intensive care units (ICUs), based on availability and medical experience [1,2]. Organizational and medico-economic considerations come into play at the scale of an ICU when it comes to choosing a KRT strategy between intermittent haemodialysis (IHD) or continuous veno-venous haemofiltration (CVVH) [3,4]. Indeed, the use of IHD requires the installation and maintenance of a water treatment system (WTS) which is expensive. Conversely, CVVH does not require any WTS but increases nurse workload and requires

<footnote><sup>a</sup> AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, F-92700 Colombes, France</footnote>

<footnote><sup>b</sup> Université Paris Cité, Medical school, F-75018 Paris, France</footnote>

<footnote><sup>c</sup> Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Institut Necker Enfants Malades, F-75015 Paris, France</footnote>

<footnote><sup>d</sup> Université Paris Cité, UMR1137 IAME, INSERM, F-75018 Paris, France</footnote>

<footnote><sup>e</sup> Sorbonne Université, Common and Rare Kidney Diseases, INSERM, UMR-S 1155, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France</footnote>

<footnote>* Corresponding author at: Service de Médecine Intensive Réanimation, DMU ESPRIT, Louis Mourier Hospital, F-92700 Colombes, France.
E-mail address: damien.roux@aphp.fr (D. Roux).</footnote>
consumables that are more expensive. Importantly, only one patient can be treated daily with a given machine, which may pose problem during sanitary crises. This was the case during the COVID-19 pandemic where the number of patients requiring KRT raised drastically leading to impending shortage of KRT [5-7].

In our hospital, the renovation of the ICU department in 2019 required the temporary relocation of the critical care activity in a structure usually dedicated to conventional hospitalization, without access to a WTS. Together with an increased number of patients requiring KRT during the first wave of COVID-19 pandemic, this prompted us to use a novel alternative technique for intermittent KRT without WTS (see description below). We retrospectively assessed our experience with this technique.

## 2. Materials and methods

Settings of the water treatment-free prolonged intermittent kidney replacement therapy.

Representatives of the Fresenius Medical Care which manufactures the MultiFiltrate Pro® machine proposed a special setting with the HDF 1000® kit and post-dilution CVVHDF set, which allowed for delivery of IHD. To do so, the post-dilution circuit was connected to the dialysate line using a T-union system, allowing for the fluid replacement pump to double the dialysate flow up to 9600 mL/h (i.e., a third of the flow usually used for IHD). The dialysate fluid was supplied as 5-L bags (Phoxilium® 1.2 mmol/L phosphate, Baxter or Hemosol B0®, Baxter). A 5-L bag of Phoxilium® or of Hemosol B0® costs 9.57 euros or 7.34 euros, respectively. This new modality was termed Water Treatment-Free Prolonged Intermittent Kidney Replacement Therapy (WTF-PIKRT). Schematic representations of post-dilution CVVHDF and WTF-PIKRT circuits are shown in Fig. 1.

Sessions with this new modality were conducted with a dialysate flow of 9000 mL/h (4500 mL/h on each of the dialysis and fluid replacement pumps) and a blood flow of 250 mL/min. Ultrafiltration rate was set as clinically required. The patient circuit was anticoagulated with heparin in the absence of hemorrhagic risk. Duration of session was 2 to 8 h depending on KRT indication. A Two-lumen haemodialysis catheters was placed either in the right internal jugular vein (15 cm, 12Fr) or in a femoral vein (25 cm, 14Fr or 20 cm, 12Fr). Since four 5-L bags can be charged at the same time on the MultiFiltrate Pro® machine,

nurse intervention for fluid bag change was required every 90 to 120 min.

## 3. Patients and methods

In order to evaluate the tolerance and biologic performance of WTF-PIKRT, we conducted a retrospective study of all consecutive patients above 18 years old who underwent at least one session of WTF-PIKRT during their ICU stay between September 2019 and May 2020. Patient characteristics were collected from medical records. Efficacy and tolerance of KRT were assessed using parameters recorded during usual care. All Patients (and/or their relatives) entering our unit are routinely informed that clinical and laboratory data gathered during their stay may be secondarily used for research purpose. Our institutional ethics committee approved the study (CEERB Paris Nord, IRB 00006477). No funding nor honoraria were received from the manufacturer and all investigators remain free of financial relationship. Descriptive data are presented as number and/or percentage for categorical variables, and as median [25th,75th interquartile range] for continuous variables. Statistical analyses were performed in R (v3.5.1, R Foundation for Statistical Computing, Vienna, Austria).

## 4. Results

Eighteen patients underwent 88 WTF-PIKRT sessions during their ICU stay. The median age was 63 years [53;67]. Fifteen patients were male. SAPS2 score was 53 [43;61]. Among participants, four had end-stage kidney disease requiring maintenance dialysis, 14 had KDIGO 3 AKI at time of ICU-admission. Among the latter, 13 participants received WTF-PIKRT because of persistent anuria after 72 h and one because of persistent profound metabolic acidosis (pH 7.10; serum bicarbonate 7 mmol/L). The median time between ICU admission and KRT initiation was 3 days [1;5] and patients received 5 [2;10] KRT sessions. The median duration of WTF-PIKRT sessions was 5 h [4,6].

At time of KRT initiation, median plasma urea and creatinine levels were 32.0 mmol/L [23.5;38.6] and 454 µmol/L [352;619], respectively. The median serum potassium level was 5.0 mmol/L ([4.4;5.6], maximum 7.8 mmol/L) and the serum bicarbonate level was 20 mmol/L [19;22] (minimal value 7 mmol/L). Vasopressors were required before the initiation of 28 (32 %) sessions.

<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /><figcaption>**Fig. 1.** Extracorporeal circuit set-up for post-dilution CVVHDF and WTF-PIKRT.
(A) Schematic representation of the setup of continuous veno-venous haemodiafiltration (CVVHDF). (B) Schematic representation of the setup used for water treatment-free prolonged intermittent kidney replacement therapy (WTF-PIKRT). The post-dilution circuit (in grey on the panel A) is connected to the dialysate line (in green) using a T-union system, allowing the fluid replacement pump to double the dialysate flow up to 9600 mL/h (4800 mL/h maximum for each pump). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)</figcaption></figure>
After WTF-PIKRT sessions, median plasma urea (URR) and creatinine reduction ratios were 38% [29;49] and 38% [30;48], respectively. Urea reduction ratio correlated with the duration of WTF-PIKRT sessions (Spearman rho 0.39, *p* < 0.001) (Fig. 2). When present, hyperkalaemia was controlled in all patients. Hypotension requiring fluid infusion or vasopressor use or increase occurred during 19/88 (21.6 %) sessions. Mild hypokalaemia occurred after three sessions (3.4 %) but remained above 3.2 mmol/L. No hypophosphatemia was observed. Filter clotting occurred in four WTF-PIKRT sessions (4.5 %).

The median ICU length of stay was 19 [10;31] days. Sixteen patients left the ICU alive among whom 7 (including the 4 patients with end-stage kidney disease) still required KRT.

## 5. Discussion

To our knowledge, we present the first report of the use of an innovative KRT modality in ICU patients. Because it allowed for performing IHD in the absence of any WTS we called this modality water treatment-free-prolonged intermittent kidney replacement therapy. This technique only requires commercially available devices certified with European Union marking. The cost of dialysate fluid for a 5 to 6-h session is about 120 euros in our university hospital network (about twelve 5-L bags needed).

Dialysis efficacy was attested by an URR of 38% and control of serum potassium and bicarbonate levels with a median duration of sessions of 5 h and usual blood flow. Obviously the URR in our study was less than reported for conventional IHD [8,9], which amounts 50 to 60 %. This lower efficacy is explained by dialysate flow rates (around 150 mL/min) that remain much lower in than with conventional IHD (about 500 mL/min) [1]. However, this modality allowed for an acceptable metabolic control of AKI. The rate of hypokalemia observed in this study (3.4 %) was also slightly lower to the 7.1 % rate observed by Uchino et al. in 2001 during conventional intermittent haemodialysis in ICU [10].

Hemodynamic tolerance was comparable with that reported with conventional KRT methods [11,12]. Indeed, fluid expansion and/or vasopressor use/increase was required in slightly more than one fifth of sessions (19 out of 88 sessions).

Limitations of our work mainly relate to the retrospective and monocentric design of the study. This is indeed a preliminary study, in which there was no comparative IHD control arm. Dialysis efficacy was not systematically assessed at the same time for each session. Indeed, blood was sampled for determination of urea, creatinine and electrolyte levels at a time that varied from zero to four hours after the end of session. This may cause an evaluation bias. However, due to plasma urea rebound phenomena, the evaluation of URR was probably slightly underestimated [13].

## 6. Conclusion

In this preliminary evaluation of a new KRT modality, we show that WTF-PIKRT performs slightly less than conventional IHD but remains acceptable in the ICU setting. An important point to remind is that WTF-PIKRT allows units without WTS to carry out intermittent KRT sessions in several patients on the same day with a single machine. This may prove useful in case of sanitary crises and may help reduce expenditures related to KRT.

A prospective trial comparing this technique to conventional IHD to investigate non-inferiority and cost-effectiveness of this innovative KRT strategy would provide a robust evaluation of this approach.

### Ethics approval and consent to participate

All Patients (and/or their relatives) entering our unit are routinely informed that clinical and laboratory data gathered during their stay may be secondarily used for research purpose. Our institutional ethics committee approved the study (CEERB Paris Nord, IRB 00006477). No

<figure><img src="image_6.png" /><figcaption>**Fig. 2.** Urea reduction ratio in all 88 sessions and correlation with WTF-PIKRT duration.</figcaption></figure>

(A) Urea reduction ratio (URR) during “water treatment-free prolonged intermittent kidney replacement therapy” (WTF-PIKRT). Dots representing each of the 88 WTF-PIKRT sessions, and box and whiskers, as specified by Tukey. (B) Dot plot representing the relation between URR and WTF-PIKRT duration. The red line and grey area represent the linear regression line with 95 % confidence interval. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

funding nor honoraria were received from the manufacturer and all investigators remain free of financial relationship.

### Consent for publication

Not applicable.

### Availability of data and materials

The datasets used during the current study are available from the corresponding author on reasonable request.

### Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

### CRediT authorship contribution statement

**Noémie Zucman:** Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis.
**Fabrice Uhel:** Writing – review & editing, Visualization, Methodology, Data curation.
**Charles Verney:** Writing – review & editing, Validation.
**Jean-Damien Ricard:** Writing – review & editing, Validation.
**Didier Dreyfuss:** Writing – review & editing, Supervision, Project administration, Methodology.
**Damien Roux:** Writing – review & editing, Writing – original draft, Validation, Supervision, Project administration, Methodology, Investigation, Formal analysis, Conceptualization.

### Declaration of competing interest

The authors declare that they have no competing interests.

### Acknowledgements

We thank all participants of this study and all caregivers, especially nurses, who performed these WTF-IHD sessions.
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