Can we treat fluid overload with fluid? Role of peritoneal dialysis in management of heart failure

This editorial refers to ‘Peritoneal dialysis relieves clinical symptoms and is well tolerated in patients with refractory heart failure and chronic kidney disease’, by M. Koch et al. published in this issue on pages 530–539 and ‘Continuous ambulatory peritoneal dialysis as a therapeutic alternative in patients with advanced congestive heart failure’, by J. Núñez et al. published in this issue on pages 540–548.

Heart failure (HF) is the most common reason for hospital admission in patients older than 65, with a total burden on healthcare of US$35–60 billion per year in the USA alone.1 In spite of a shifting paradigm in the treatment of HF over the past two decades, the currently available therapeutic modalities do not yet seem to be producing optimal results. In a study on >50 000 patients in the Acute Decompensated Heart Failure National Registry (ADHERE) database, nearly half of the patients admitted for exacerbation of HF lost <2.3 kg (33%), or even gained weight (16%) during the course of hospitalization.2 It is not then surprising that the 30-day readmission rate still remains as high as 27%, the highest among all medical conditions necessitating hospitalization.3 This lack of desired efficacy can be complicated further by potential adverse effects of the current therapies on renal function, leading to an increase in morbidity and healthcare expenditure. Consequently, there have been tremendous efforts aimed at finding newer therapeutic options (e.g. adenosine A-1 receptor antagonists) with better efficacy and safety profiles, which have not been successful in general.4 In terms of non-pharmacological approaches, extracorporeal ultrafiltration therapy has gained increasing attention due to the promising results of the recent studies and newer technological advances. However, in almost all published studies, ultrafiltration has been used as an adjuvant therapy in the setting of acute decompensation, rather than as an alternative plan of care for patients with chronic HF. Moreover, its use has been associated with suboptimal results in terms of the impact on kidney-related parameters such as glomerular filtration rate (GFR) and hyponatraemia.5 As such, it is not yet clear whether this hospital-based, invasive, and expensive therapeutic option could indeed portend any positive impact on patients' long-term outcomes.6

Peritoneal dialysis (PD) therapy for management of HF and volume overload is a home-based therapeutic option in which the removal of the excess fluid takes place in the peritoneal cavity (intracorporeal ultrafiltration). It represents another collaborative opportunity for cardiologists and nephrologists to fight against a challenging disease state. PD was first used >60 years ago in this setting, and the preliminary studies thereafter, although with a small number of patients and short follow-up periods, have reported encouraging results.

In this issue of the journal, two studies on the use of PD in the management of HF in patients without end-stage renal disease (ESRD) are published.7,8 Koch et al. studied the outcome of 118 patients with refractory HF for whom intermittent PD was initiated. These patients were elderly (mean age 73 years) and had symptomatic HF [New York Heart Association (NYHA) class III and IV] as well as severe renal dysfunction. Moreover, they presented with a high rate of significant co-morbid conditions such as diabetes and stage IV peripheral arterial disease. Interestingly, 6 months after PD therapy, this severely ill patient population showed significant improvement in their functional status and weight, with a survival rate as high as 71%. In a smaller prospective study, Núñez et al. evaluated the impact of continuous PD therapy in 25 patients with advanced HF and chronic kidney disease (chronic cardiorenal syndrome). The mean age of these patients was 75 years and they all had severe symptomatic HF (NYHA class III and IV). Similar to the first study, these patients also represented a severely ill population with a high prevalence of co-morbidities. The authors mainly focused on the impact of PD on various markers of symptom relief and quality of life, and found significant improvement in 6 min walk test, Minnesota Living With Heart Failure Questionnaire, and NYHA functional class. Of note, the number of days of HF-related hospitalization during the first 6 months after initiation of PD therapy dramatically decreased compared with the 6 months prior to this therapy (median 16 vs. 0 days, P < 0.001).

It is noteworthy that although PD was initiated for cardiac indications and volume overload, in both studies the patient population presented with significant renal dysfunction; the clearance of creatinine and urea were 19.2 and 7.6 mL/min, respectively, in the study by Koch et al., while the median estimated GFR was 33 mL/min/1.73 m2 in the second study. Nevertheless, the results are in agreement with the findings of several previous investigators reporting on the positive impact of PD on symptoms of volume overload, functional status, number of days of HF-related hospitalizations, and quality of life.

The benefits of peritoneal dialysis

Table 1 summarizes a number of benefits that have been proposed for the use of PD in the context of refractory HF and volume overload. Two points merit special attention in this regard: first, the beneficial effects of PD might not be the same for all patients with HF, and could indeed depend on patient-related factors such as co-morbid conditions. For example, while in HF patients with more severe renal dysfunction PD can help manage perturbation in sodium and water excretion which is frequently observed at this stage, removal of the pro-inflammatory cytokines might portend the major beneficial effect for those with milder renal dysfunction. Similarly, the optimal PD modality and regimen (e.g. intermittent vs. continuous) is likely to be different in these two populations. This might explain the results of some of the previous studies that reported unexpected and even contradictory findings in certain patient populations such as those with ESRD (see below).

Secondly, through highly modifiable regimens, PD provides the opportunity to customize the rate of water and sodium removal according to the specific needs of the patients (e.g. absence or presence of hypertension and renal dysfunction) and their lifestyle. Use of icodextrin PD solution is especially advantageous in the setting of HF where removal of sodium, the major determinant of extracellular volume, is at least as important as water extraction. This glucose polymer generates colloid osmotic forces, hence leading to enhanced sodium transport across interendothelial clefts of the capillaries in the peritoneal membrane. In fact, previous experience in patients with HF has shown that removal of free water without sodium, although helpful with reduction of oedema and weight, is not likely to affect mortality or HF-related morbidity significantly.9 PD therapy can efficiently remove sodium, which not only can be enhanced through the use of icodextrin, but can also be tailored to the clinical status of the patients and their needs.10

Finally, recent studies point to intra-abdominal hypertension and venous congestion as important factors in the development of renal dysfunction in a subset of patients with HF.11 Moreover, mechanical removal of fluid (e.g. via paracentesis) has been shown to improve renal function in these patients through reduction in intra-abdominal pressure.12 PD has the advantage of providing a permanent outlet (i.e. catheter) in the abdominal cavity, providing the opportunity of keeping the intra-abdominal pressure and renal venous congestion at their lowest, hence having the potential for better preservation of renal function in the long term, especially in those patients with right-sided heart failure.

Considerations and concerns

Based on the currently available data, a discrepancy might exist between the beneficial impact of PD in ESRD and non-ESRD patients with HF. Despite several proposed benefits of PD in the setting of HF for the non-ESRD population, it is noteworthy that two large registry-based studies on ESRD populations (one from the USA and one from Europe) have found that PD is associated with an increased risk of death compared with haemodialysis in HF patients, while these two modalities are associated with similar outcomes in patients without HF.13,14 It is not clear whether this finding is related to unexplored underlying mechanism(s), the interplay of a number of well-known phenomena (e.g. difficulty in management of volume status in ESRD patients with significantly reduced urine volume), or a simple reflection of the inherent limitations of the registry-based data (e.g. treatment-by-indication bias). Nevertheless, the results of these studies should at least question the common assumption that ESRD patients with HF always benefit more from PD than haemodialysis due to generation of gentle continuous ultrafiltration with minimal impact on haemodynamic status.

Concerning the studies on non-ESRD patients with HF, two major limitations exist which could hamper more widespread acceptance of this therapeutic approach: lack of a reasonably matched control group and relatively short follow-up periods. Based on the results of the studies that have consistently reported a significant improvement in the quality of life of these patients, measured through various markers and methods, it is safe to claim that HF morbidity is not replaced by morbidity related to PD therapy. As such, if future studies with longer follow-ups demonstrate that PD therapy for refractory HF is not associated with an adverse impact on survival compared with conventional therapy, a major barrier for its more widespread use is likely to be removed, especially for those patients with frequent HF-related hospitalizations.

Conclusion

Based on the existing data on the role of PD therapy for refractory HF, the biological and clinical ‘plausibility’ of this strategy is now established, and the fact that it is a safe and efficacious method for improving patients' cardiac function, symptoms, and quality of life is ascertained. As such, PD therapy should be considered for patients in whom other less invasive management strategies have not been successful. Future focus should be on designing large-scale randomized controlled studies in which PD is compared with conventional therapies. Such studies need also to address several thus far unanswered questions and uncertainties. Which subset(s) of HF patients would benefit most from PD therapy? Do patients with milder renal dysfunction benefit more from PD compared with those having more severe renal disease? What is the optimal PD regimen in this setting, and should the choice of modality and regimen be affected by a patient's co-morbid conditions? Are the observed beneficial effects of PD sustainable? Do the above-mentioned intermediate-term favourable results translate into an impact on natural history of the disease and survival benefit? Is long-term PD therapy cost-effective compared with conventional therapy?

Conflict of interest: none declared.