Volume Overload and Survival in Patients on Peritoneal Dialysis

Patients on peritoneal dialysis receive individualized dialysis prescription by combining various techniques (automated versus manual), dialysis solutions (tonicity, biocompatibility, type of osmotic agent), and number and duration of dwells. The goal is to optimize maintenance of residual kidney function, preserve the peritoneal membrane, and control uremic symptoms, volume, and nutritional status, all designed to prolong technique and patient survival.

In patients receiving renal replacement therapy, elevated systolic blood pressure and volume overload are associated with a higher risk of mortality. Both factors occur equally in patients in hemodialysis and peritoneal dialysis. In a large cohort of patients on hemodialysis, baseline and cumulative volume overload over 1 year, assessed by bioimpedance spectroscopy, was associated with mortality, independent of baseline blood pressure.

Among prevalent peritoneal dialysis patients, volume overload is frequent and associated with mortality. Until the start of the international multicenter study Initiative for Patient Outcomes in Dialysis-Peritoneal Dialysis (IPOD-PD), there were few data on incident patients on peritoneal dialysis. It is thought that the risk of technique failure (defined as a switch to hemodialysis) may be reduced and that patient survival may be improved with active management of volume overload. However, most current strategies used to reduce volume overload include the risk of adverse side effects, such as faster degradation of the peritoneal membrane by the use of hypertonic exchanges or faster decline of residual kidney function when volume depletion follows.

The IPOD-PD study investigated volume status in a population of incident patients on peritoneal dialysis to relate patient characteristics and practice patterns over a long-term follow-up to volume status and patient-relevant outcomes. Results of the study were reported by Wim Van Biesen, MD, PhD, and colleagues in the Clinical Journal of the American Society of Nephrology [2019;14(June):882-893].

The study recruited consecutive incident participants on peritoneal dialysis from included centers between January 2011 and December 2012; participant follow-up continued until December 2015, and lasted a minimum of 3 and a maximum of 5 years.

A total of 1092 participants were recruited in 135 centers from 28 countries Of the participants recruited from Asia Pacific, all but two were recruited in South Korea. Following application of exclusion criteria, the final analysis consisted of 1054 participants from Western Europe (n=715), Eastern Europe and Middle East (n=80), Asia Pacific (n=129), and Latin America (n=130). Thirty-six percent of participants were euvolemic at the start of peritoneal dialysis; however, the majority showed either moderate (33%) or severe (24%) volume overload, with some differences between regions.

At the start of the study, 77% of the participants were treated with continuous ambulatory peritoneal dialysis; in all regions, during the first 3 years on dialysis, the proportion of automated peritoneal dialysis increased to 38%. The majority of participants (73%) were prescribed biocompatible solutions (defined as peritoneal dialysis solutions prepared in two-chamber bags); different regions differed somewhat in proportion of patients prescribed biocompatible solutions.

At baseline, 31% of the entire cohort were prescribed hypertonic peritoneal dialysis solutions, defined as at least one exchange with a dextrose concentration >1.5%. At month 36, the percentage had increased to 51%. At baseline, hypertonic solutions were prescribed to 34% and 28% of volume-overloaded and non-volume-overloaded participants, respectively. At month 36, the percentages were 50% and 53%. There were substantial differences between regions in use of hypertonic solutions.

At three years, the cumulative study dropout rate was 74%. The primary causes of dropout were transfer to hemodialysis (23%) and transplantation (22%). Dropout for any reason was lowest in the Asia Pacific region: at 3 years, 60% of participants were still on peritoneal dialysis, compared with 26%, 23%, and 16% in Western Europe, Eastern Europe and Middle East, and Latin America, respectively.

Prior to the start of peritoneal dialysis treatment, mean volume overload was 1.9 L, with a reduction to 1.2 L during the first year. At years 2 and 3, volume overload remained relatively stable at 1.4 L both years. At all time points, volume overload was higher in men than in women and higher in participants with versus without diabetes. In all groups, the course of relative volume overload showed a slight and similar decrease. After 3 years of follow-up up, the mean relative volume overload in the remaining cohort was lower than at baseline in participants from all regions with the exception of those from Latin America, where the mean volume overload increased.

Prior to the start of peritoneal dialysis, 57% of participants had a relative volume overload of >7%. After 1, 2, and 3 years of follow-up, the proportion decreased to 48%, 49%, and 53%, respectively. At all time points, relative fluid retention (<–7%) was found in 3% to 8% of participants. On average, mean relative volume increased in the first year in participants with volume depletion at baseline; among participants with volume overload at baseline a decreasing trend in mean relative volume was seen in the first year. Follow-up observations indicated that both groups (with and without volume depletion) tended toward euvolemia.

After controlling for change to hemodialysis and transplantation, in a competing risk model on time to death, the variables volume overload (defined as >17.3%; the 75^th percentile of relative volume overload at month 1 in the study), age, cardiovascular disease, liver disease, and diabetes were used. The subdistributional hazard ratio for participants with volume overload was 1.59 compared with participants without volume overload (95% confidence interval, 1.08-2.33; P=.02).

The observational design of the study was cited by the researchers as a limitation to the findings, as was the possible limiting of the generalizability of the observations.

The researchers said, “In conclusion, our study found that substantial volume overload was present in this incident cohort of participants on peritoneal dialysis, with men and patients with diabetes being more affected. Volume overload was associated with mortality. The study revealed different treatment practices across centers and regions. Despite not using hypertonic exchanges, automated peritoneal dialysis, or polyglucose, the best technique survival was noted in Asia Pacific.”

Takeaway Points

1. In patients receiving renal replacement therapy, via either hemodialysis or peritoneal dialysis, elevated systolic blood pressure and volume overload are associated with increased risk for mortality.
2. Researchers conducted a prospective cohort study to follow-up volume status in patients on peritoneal dialysis and relate those data to patient outcomes.
3. In the large cohort with varying treatment practices across centers and regions, a large proportion of patients had volume overload at initiation of dialysis. Over time, there was improvement in volume overload; there was an association between the improvement and survival.