Analysis of the Prevalence and Causes of Ultrafiltration Failure during Long-Term Peritoneal Dialysis: A Cross-Sectional Study

Abstract

Background Ultrafiltration failure (UFF) is a major complication of peritoneal dialysis (PD). It can occur at any stage of PD, but develops in time and is, therefore, especially important in long-term treatment. To investigate its prevalence and to identify possible causes, we performed a multicenter study in The Netherlands, where patients treated with PD for more than 4 years were studied using a peritoneal function test (standard peritoneal permeability analysis) with 3.86% glucose. UFF was defined as net UF < 400 mL after a 4-hour dwell. Results 55 patients unselected for the presence or absence of UFF were analyzed. Mean age was 48 years (range 18 – 74 years); duration of PD ranged from 48 to 144 months (median 61 months); UFF was present in 20 patients (36%). Patients with and without UFF did not differ in age or duration of PD. Median values for patients with normal UF compared to patients with UFF were, for net UF 659 mL versus 120 mL ( p < 0.01), transcapillary UF rate 3.8 versus 2.1 mL/minute ( p < 0.01), effective lymphatic absorption 1.0 versus 1.6 mL/min ( p < 0.05), mass transfer area coefficient (MTAC) for creatinine 9.0 versus 12.9 mL/min ( p < 0.01), dialysate-to-plasma ratio (D/P) for creatinine 0.71 versus 0.86 ( p < 0.01), glucose absorption 60% versus 73% ( p < 0.01), maximum dip in D/P sodium (as a measure of free water transport) 0.109 versus 0.032 ( p < 0.01), and osmotic conductance to glucose 3.0 versus 2.1 μL/min/mmHg ( p < 0.05). As causes for UFF, high MTAC creatinine, defined as > 12.5 mL/min, or a glucose absorption > 72%, both reflecting a large vascular surface, a lymphatic absorption rate (LAR) of > 2.14 mL/min, and a decreased dip in D/P sodium of < 0.046 were identified. Most patients had a combination of causes (12 patients), whereas there was only a decreased dip in D/P sodium in 3 patients, only high MTAC creatinine in 1 patient, and only high LAR in 2 patients. We could not identify a cause in 2 patients. Both groups had similar clearances of serum proteins and peritoneal restriction coefficients. However, dialysate cancer antigen 125 concentrations, reflecting mesothelial cell mass, were lower in the UFF patients (2.79 vs 5.38 U/L). Conclusion The prevalence of UFF is high in long-term PD. It is caused mainly by a large vascular surface area and by impaired channel-mediated water transport. In addition, these patients also had signs of a reduced mesothelial cell mass, indicating damage of the peritoneum on both vascular and mesothelial sites.

Mitigating peritoneal membrane characteristics in modern peritoneal dialysis therapy

“…They also exhibit reduced osmotic conductance of the peritoneal membrane -a measure of the efficiency by which glucose induces ultrafiltration. 26,27 This might occur either because the membrane is less permeable to the flow of water or because the glucose is less efficient as an osmotic agent in inducing ultrafiltration, for example, owing to impaired aquaporin function or dissipation of the glucose gradient by the fibrosed interstitium.…”

“…There can be no doubt that the efficiency of ultrafiltration achieved using low molecular weight osmolytes such as glucose is reduced and this, combined with a more rapid absorption of fluid from the peritoneal cavity, will result in worse salt and water removal. 5,27 The main thesis of this review is that this is the most important mechanism, so this will be discussed in more detail shortly. It is necessary to recognize at this stage that other explanations need to be considered.…”

Compare the effects of intravenous and intraperitoneal mesenchymal stem cell transplantation on ultrafiltration failure in a rat model of chronic peritoneal dialysis

“…2,32 The results of many studies and also our study results clearly show that PD treatment, by itself, strongly impacts peritoneal injury. 2,[32][33][34] Protection of the peritoneal membrane or healing of a damaged membrane is of crucial importance for patients with end-stage renal disease having no alternatives for renal replacement therapies, except PD. In many studies, drugs, peptides and gene therapy targeting fibrosis and/or angiogenesis could be useful for treating peritoneal fibrosis, [19][20][21][22] whereas clinically available treatment for peritoneal fibrosis in PD patients remains limited at present.…”

Opinion: What Are the Problems with Using the Peritoneal Membrane for Long‐Term Dialysis?

“…The development of ultrafiltration failure is an important problem in about one-third of PD patients treated for 4-6 years (32,33). It is associated with the development of a fast transport status (11,32,33), caused by peritoneal neoangiogenesis (12,(34)(35)(36), that can be induced by long-term exposure to glucose-containing dialysis solutions (37). In addition, this type of ultrafiltration failure is also characterized by impaired free water transport (33,(38)(39)(40).…”