Ultrafiltration Failure (UFF)

UF failure may be defined as a net UF < 400 mL at 4 hours of dwell (i.e., drain volume < 2400 mL/4 hrs) using a hypertonic glucose solution such as a 4.25% PD solution, or when patients are unable to achieve a daily UF volume > 750 mL once anuric, in the absence of catheter malfunction, fluid leaks or extensive intraperitoneal adhesions(1–5). It is based on the net UF obtained after a standard dialysis dwell and the glucose concentration of the PD solution used. UFF results in the inability to achieve adequate fluid balance and subsequent fluid overload.  In most patients on continuous ambulatory PD (CAPD), UF capacity and membrane characteristics appear stable for up to 3 years. However, the risk of UF failure tends to increase with time on treatment and is not just as a result of the loss of residual kidney function (RKF) but progressive membrane injury. Progressive membrane injury leads to inadequate solute transfer, high solute transfer, decreased UF and decreased convective clearance. Cumulative risk of permanent UF loss has been shown to be 9% at 4 years and 35 – 50% over 5 years(6). UF failure has also been shown to cause technique failure in 1.7 – 13.7% of PD patients(7). Diagnostic tests usually involve assessing peritoneal membrane function (with the PET for example), measuring drain volume and determining the type of UF failure(8).

Types of UFF

UFF characterized by high small solute transport, also known as type I UFF, is characterized by high solute transport. This type of failure is thought to be due to an increase in effective peritoneal surface area and/or permeability, resulting from the presence of vasculopathy and endothelial dysfunction, increased glucose absorption from dialysate, increased protein loss into dialysate and decreased UF. Type I UFF is the most common cause of permanent UF capacity loss and is associated with increased mortality and morbidity, and patients have a poor prognosis(9,10). Type I UFF is also associated with increased inflammation, as can occur during peritonitis(11,12).

Aquaporins are essential for water transport and UF(13,14).  UF failure due to aquaporin deficiency in PD may be yet another type of UFF, albeit rare. Although the etiology is still unclear, it may involve reduction of aquaporins in the peritoneal membrane or may be the result of increased reactive carbonyl compounds (RCOs) and glycation end products related to the use of conventional PD solutions(13–16). Its diagnosis is usually based on the presence of altered sodium sieving.

UF failure characterized by low solute transport, or type II membrane failure, is relatively rare and mostly seen in patients with peritoneal sclerosis(8). It is characterized by decreased solute and water transport with decreased UF capacity and reflects major disruption of peritoneal membrane and/or intraperitoneal fluid distribution. It is usually due to adhesions, trapped fluid or sclerosing peritonitis.

UFF due to high lymphatic absorption or type III membrane failure is characterized by increased resorption of dialysate from the peritoneal cavity due to increased lymphatic flow(8). The etiology is not known and exclusion of mechanical problems (leaks and catheter dysfunction) and other types of membrane failure can lead to its differential diagnosis of low UF despite normal membrane function.

Treatment

Treatment of UFF mostly depends on the type of membrane failure.  In the case of UFF with increased solute transport (Type I) the mainstay of therapy is shortening the dwell time, providing more frequent exchanges and preventing peritonitis(8,17,18).  Eliminating long dwell exchanges is highly recommended.  Temporary discontinuation of PD to allow a rest period for about 4 – 12 weeks has been reported to restore membrane function(8,17–20). In cases of UFF due to or aquaporin failure, shorter dwells with higher glucose solutions or the use of polyglucose for long dwells are recommended. For cases of UFF with low solute transfer (Type II), transfer to HD may be required for adequate patient management. However, if some degree of RRF is present, maintenance on this dialytic modality may be feasible. If UFF due with high lymphatic absorption (Type III) is suspected, all interventions that maximize UF (short dwell time, high tonicity of dialysate) need to be combined. This would serve to maintain the balance between continuous tissue reabsorption and declining UF. Pharmacologic interventions not recommended at this time due to the lack of supporting evidence.

References

  1. Twardowski ZJ, Nolph KO, Khanna R, Prowant BF, Ryan LP, Moore HL, Nielsen MP. Peritoneal Equilibration Test. Perit Dial Int. 1987;7(3):138-148. Available from: http://www.pdiconnect.com/cgi/content/abstract/7/3/138.
  2. Davies SJ, Brown B, Bryan J, Russell GI. Clinical evaluation of the peritoneal equilibration test: a population-based study. Nephrol Dial Transplant. 1993;8(1):64-70. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8381939.
  3. Ho-dac-Pannekeet MM, Atasever B, Struijk DG, Krediet RT. Analysis of ultrafiltration failure in peritoneal dialysis patients by means of standard peritoneal permeability analysis. Perit Dial Int. 1997;17(2):144-150. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9159834.
  4. Krediet RT, Imholz AL, Struijk DG, Koomen GC, Arisz L. Ultrafiltration failure in continuous ambulatory peritoneal dialysis. Perit Dial Int. 1993;13 Suppl 2:S59-S66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8399673.
  5. Davies SJ, Mushahar L, Yu Z, Lambie M. Determinants of peritoneal membrane function over time. Semin Nephrol. 2011;31(2):172-182. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21439431.
  6. Heimbürger O, Wang T, Lindholm B. Alterations in water and solute transport with time on peritoneal dialysis. Perit Dial Int. 1999;19 Suppl 2:S83-S90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10406499.
  7. Chaudhary K. Peritoneal Dialysis Drop-out: Causes and Prevention Strategies. Int J Nephrol. 2011;2011:434608. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3205769&tool=p….
  8. Mujais S, Nolph K, Gokal R, Blake P, Burkart J, Coles G, Kawaguchi Y, Kawanishi H, Korbet S, Krediet R, et al. Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis. Perit Dial Int. 2000;20 Suppl 4:S5-S21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11098926.
  9. Davies SJ. Mitigating peritoneal membrane characteristics in modern peritoneal dialysis therapy. Kidney Int Suppl. 2006;(103):S76-S83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17080116.
  10. Chung SH, Heimbürger O, Lindholm B. Poor outcomes for fast transporters on PD: the rise and fall of a clinical concern. Semin Dial. 2008;21(1):7-10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18251948.
  11. Buemi M, Aloisi C, Cutroneo G, Nostro L, Favaloro A, Favaloro A. Flowing time on the peritoneal membrane. Nephrol Dial Transplant. 2004;19(1):26-29. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14671034.
  12. Krediet RT, Zuyderhoudt FM, Boeschoten EW, Arisz L. Alterations in the peritoneal transport of water and solutes during peritonitis in continuous ambulatory peritoneal dialysis patients. Eur J Clin Invest. 1987;17(1):43-52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3106050.
  13. Kim Y-L. Update on mechanisms of ultrafiltration failure. Perit Dial Int. 2009;29 Suppl 2:S123-S127. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19270200.
  14. Lai KN, Lam MF, Leung JC. Peritoneal function: the role of aquaporins. Perit Dial Int. 2003;23 Suppl 2:S20-S25. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17986548.
  15. Monquil MC, Imholz AL, Struijk DG, Krediet RT. Does impaired transcellular water transport contribute to net ultrafiltration failure during CAPD? Perit Dial Int. 1995;15(1):42-48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7734560.
  16. Panasiuk E, Pietrzak B, Klos M. Characteristics of peritoneum after peritonitis. Adv Perit Dial. 1988;4:42-45. Available from: http://www.advancesinpd.com/adv88/pt1peritoneum88.html.
  17. Aguirre AR, Abensur H. Protective measures against ultrafiltration failure in peritoneal dialysis patients. Clinics (Sao Paulo). 2011;66(12):2151-2157. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3226613&tool=p….
  18. Selgas R, Bajo MA, Castro MJ, Sánchez-Tomero JA, Cirugeda A. Managing ultrafiltration failure by peritoneal resting. Perit Dial Int. 2000;20(6):595-597. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11216544.
  19. Rodrigues A, Cabrita A, Maia P, Guimarães S. Peritoneal rest may successfully recover ultrafiltration in patients who develop peritoneal hyperpermeability with time on continuous ambulatory peritoneal dialysis. Adv Perit Dial. 2002;18:78-80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12402593.
  20. Zareie M, Keuning ED, ter Wee PM, Beelen RHJ, van den Born J. Peritoneal dialysis fluid-induced changes of the peritoneal membrane are reversible after peritoneal rest in rats. Nephrol Dial Transplant. 2005;20(1):189-193. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15572385.

The information and reference materials contained in this document are intended solely for the general education of the reader. It is intended to provide pertinent data to assist you in forming your own conclusions and making decisions. This document should not be considered an endorsement of the information provided nor is it intended for treatment purposes and is not a substitute for professional evaluation and diagnosis. Additionally, this information is not intended to advocate any indication, dosage or other claim that is not covered, if applicable, in the FDA-approved label.

P/N 102496-01 Rev. A 06/2016