Analysis of ultrafiltration volume during long dwell with icodextrin in automated peritoneal dialysis

Abstract

Icodextrin's unique osmotic properties enable effective fluid volume management in the peritoneal cavity by limiting reabsorption. However, its efficacy fluctuates during prolonged dwell periods in automated peritoneal dialysis (APD), posing challenges and increasing the risk of treatment failure. This study examines negative ultrafiltration (UF) during daytime dwell in APD patients using icodextrin and aims to identify associated factors. A retrospective observational monocentric study on UF during prolonged icodextrin dwell periods in APD was conducted among 27 incident patients at the University Hospital of Caen in Normandy, France. The primary focus was the presence of negative daytime UF, with intraperitoneal pressure (IPP) as the main exposure variable. Statistical analyses, including group comparisons and univariate and multivariate logistic regressions, explored associations between negative daytime UF, IPP, and other relevant variables. While no variable showed a significant correlation, IPP (OR=1.06), Volume of the last injection (OR=0.97), and Body Mass Index (OR=0.97) exhibited interesting trends. The multivariate analysis showed no significant association between the variables and negative daytime UF. Nevertheless, IPP was the only variable that improved the model's quality, suggesting a potential link for further exploration. This study raises important questions for future research and clinical practice regarding the systematic measure of the IPP during peritoneal dialysis treatments, despite its limitations, including a small sample size and the retrospective observational nature of the methodology, affecting the statistical power and the ability to establish causal links.

Introduction

In 2022, only 6% of patients in stage 5 chronic kidney disease (CKD) in France were treated with peritoneal dialysis (PD), which highlights its relatively low adoption rate[1]. Automated peritoneal dialysis (APD), however, remains a cornerstone therapy for managing end-stage kidney disease (ESKD), offering flexibility and effectiveness in achieving fluid and solute clearance[2][3][4][5][6]. APD provides several benefits, particularly for patients requiring urgent initiation of dialysis, as it has been associated with a lower incidence of PD-related complications compared to urgent start of hemodialysis[7].

However, challenges persist in the effective use of APD, particularly in addressing negative daytime ultrafiltration (UF) when icodextrin is used[8][9][10][11]. Icodextrin, a complex polysaccharide solution, is widely used in PD for its ability to sustain UF during long daytime dwell periods and reduce glucose-related complications[11][12][13][14][15][16]. Nonetheless, negative UF or UF failure during the long dwell remains a significant clinical challenge, potentially leading to fluid overload and associated morbidities[8][10][11].

According to the International Society for Peritoneal Dialysis (ISPD), UF failure is defined as a net UF of less than 400 mL after a 4-hour dwell with glucose/dextrose 3.86%/4.25%, or less than 100 mL with glucose/dextrose 2.27%/2.5%[17]. Several factors contribute to UF variation under icodextrin, including patient membrane characteristics, hydrostatic and osmotic pressures, dialysate composition, and metabolic factors [8–10,18,19]. Lambie et al[8]closely examined these influences, emphasizing the importance of individualized management.

Another critical factor can be the intraperitoneal pressure (IPP), the pressure exerted within the abdominal cavity[20]. IPP is influenced by factors such as the volume of fluid in the peritoneal cavity, patient morphology, posture, and abdominal muscle tone [21,22][21][22]. IPP measurement, first described by Durand et al.[22][23][24]in the 1990s, is a simple and non-invasive procedure. It involves placing the patient in a supine position and estimating the pressure by measuring the height of the dialysate column in tubing connected to the catheter, using the mid-axillary line as the reference point[22][23][24]. For a patient in a supine position, IPP typically ranges between 8 and 18 cmH2O for an infused peritoneal volume of 2 L[23][24].

Our study aimed to analyze the occurrence of negative daytime UF during icodextrin long dwell in patients undergoing APD, focusing specifically on this occurrence and identifying potential associated factors.

Materials and methods

Study population

This retrospective, observational, monocentric study was conducted in the Nephrology Department at the University Hospital of Caen in Normandy, France. It included all adult incident patients undergoing PD at our center from August 31, 2018, when systematic IPP measurement was initiated, until September 12, 2022. The study focused on patients who received APD treatment for at least six months after starting PD. Exclusion criteria comprised patients with an APD duration of less than 30 days or those who initiated APD more than six months after starting PD.

Definition of variables

Patient characteristics included in the study were obtained from the French Language Peritoneal Dialysis Registry, RDPLF. The following variables were extracted: age, gender, initial nephropathy, modified Charlson index (mCCI), diabetic status, weight, and height.

Dialysis prescriptions were sourced from medical records and included the following variables: total dialysis volume, volume per cycle, volume of the last injection, total dialysis duration, dwell time per cycle, daytime dwell duration, number of nighttime cycles, use of hypertonic solution, use of icodextrin, and the percentage of icodextrin used, when applicable. Additionally, data on residual diuresis volume, IPP measurements, and the dates and results of the first peritoneal equilibration test (PET) and first clearance were collected.

Peritoneal dialysis outcomes were retrieved from the monitoring sheets for the first week of the second month of PD for patients included in the study, using Renalsoft® and Sharesource® software. The extracted variables included daytime, nighttime, and 24-hour UF, dwell time per cycle, daytime dwell duration, total per-cycle volume, and daytime dwell volumes. These variables were collected over the seven days leading up to the extraction and averaged, based on the assumption that this averaging would correct for variability within patients.

Events of interest

The primary outcome of interest was the occurrence of negative daytime UF, defined as an average daytime UF of less than 0 during the data extraction week. Patients included in the study were categorized based on the presence or absence of negative daytime UF (yes/no).

Explanatory variables

The primary exposure variable was IPP, measured in cm of H2O with a 2 liter intraperitoneal dwell. At our center, IPP is routinely measured on the fourth day of patient training, prior to the initiation of PD. This measurement has been systematically performed since August 31, 2018, marking the start of patient inclusions in this study. The IPP measurement protocol adheres to the guidelines set forth by the ISPD[17].

Statistical Analysis

Linear variables were summarized using medians and interquartile ranges (IQR), while categorical variables were reported as frequencies and percentages. Patients were categorized based on the primary outcome, namely daytime UF, a binary qualitative variable with negative or positive classifications.

For further exploration of the association between negative daytime UF (the primary event of interest), IPP (the primary exposure variable), and other relevant exposure variables, graphical representations and univariate logistic regression analyses were performed. Each variable was analyzed separately in

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