Clinical and Experimental Nephrology

, Volume 23, Issue 1, pp 122–134 | Cite as

Differences in peritoneal solute transport rates in peritoneal dialysis

  • Marina Asano
  • Takako Ishii
  • Akiyoshi Hirayama
  • Masashi Mizuno
  • Yasuhiro Suzuki
  • Fumiko Sakata
  • Shin-ichi Akiyama
  • Shoichi Maruyama
  • Tomoyoshi Soga
  • Hiroshi Kinashi
  • Takayuki Katsuno
  • Yasuhiko ItoEmail author
Original Article



Ultrafiltration failure associated with peritoneal membrane dysfunction is one of the main complications for patients on long-term peritoneal dialysis (PD). The dialysate-to-plasma concentration ratio (D/P) of creatinine is widely used to assess peritoneal membrane function. However, other small-sized solutes have not been studied in detail as potential indicators of peritoneal permeability.


We studied the D/Ps of small, middle-sized and large molecules in peritoneal equilibration tests in 50 PD patients. We applied metabolomic analysis of comprehensive small molecular metabolites using capillary electrophoresis time-of-flight mass spectrometry.


D/Ps of middle-sized and large molecules correlated positively with D/P creatinine. Most D/Ps of small molecules correlated positively with D/P creatinine. Among 38 small molecules contained in the dialysate, urea, citrulline and choline showed significantly lower ability to permeate than creatinine. In the relationship between D/Ps of creatinine and small molecules, regression coefficients of three molecules were less than 0.3, representing no correlation to D/P creatinine. Five molecules showed negative regression coefficients. Among these molecules, hippurate and 3-indoxyl sulfate showed relatively high teinpro binding rates, which may affect permeability. Serum concentrations of two molecules were higher in the Low Kt/V group, mainly due to high protein binding rates.


D/Ps of some molecules did not correlate with D/P creatinine. Factors other than molecular weight, such as charge and protein binding rate, are involved in peritoneal transport rates. Metabolomic analysis appears useful to analyze small molecular uremic toxins, which could accumulate in PD patients, and the status of peritoneal membrane transport for each molecule.


Peritoneal dialysis D/P creatinine Metabolite Metabolomic analysis Peritoneal membrane dysfunction 


Compliance with ethical standards

Conflict of interest

The authors have declared that no conflicts of interest exist.

Supplementary material

10157_2018_1611_MOESM1_ESM.pptx (79 kb)
Supplementary material 1 (PPTX 78 KB)
10157_2018_1611_MOESM2_ESM.pptx (84 kb)
Supplementary material 2 (PPTX 83 KB)


  1. 1.
    Churchill DN, Thorpe KE, Nolph KD, Keshaviah PR, Oreopoulos DG, Page D. Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. The Canada-USA (CANUSA) Peritoneal Dialysis Study Group. J Am Soc Nephrol. 1998;9:1285–92.PubMedGoogle Scholar
  2. 2.
    Brimble KS, Walker M, Margetts PJ, Kundhal KK, Rabbat CG. Meta-analysis: peritoneal membrane transport, mortality, and technique failure in peritoneal dialysis. J Am Soc Nephrol. 2006;17:2591–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Flessner MF. The transport barrier in intraperitoneal therapy. Am J Physiol Renal Physiol. 2005;288:F433–42.CrossRefGoogle Scholar
  4. 4.
    Rippe B, Haraldsson B. Fluid and protein fluxes across small and large pores in the microvasculature. Application of two-pore equations. Acta Physiol Scand. 1987;131:411–28.CrossRefPubMedGoogle Scholar
  5. 5.
    Rippe B, Venturoli D, Simonsen O, de Arteaga J. Fluid and electrolyte transport across the peritoneal membrane during CAPD according to the three-pore model. Perit Dial Int. 2004;24:10–27.PubMedGoogle Scholar
  6. 6.
    Venturoli D, Rippe B. Transport asymmetry in peritoneal dialysis: application of a serial heteroporous peritoneal membrane model. Am J Physiol Renal Physiol. 2001;280:F599–606.CrossRefPubMedGoogle Scholar
  7. 7.
    Mamas M, Dunn WB, Neyses L, Goodacre R. The role of metabolites and metabolomics in clinically applicable biomarkers of disease. Arch Toxicol. 2011;85:5–17.CrossRefPubMedGoogle Scholar
  8. 8.
    Hirayama A, Nakashima E, Sugimoto M, Akiyama S, Sato W, Maruyama S, et al. Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. Anal Bioanal Chem. 2012;404:3101–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Hirayama A, Tomita M, Soga T. Sheathless capillary electrophoresis-mass spectrometry with a high-sensitivity porous sprayer for cationic metabolome analysis. Analyst. 2012;137:5026–33.CrossRefPubMedGoogle Scholar
  10. 10.
    Sugimoto M, Kikuchi S, Arita M, Soga T, Nishioka T, Tomita M. Large-scale prediction of cationic metabolite identity and migration time in capillary electrophoresis mass spectrometry using artificial neural networks. Anal Chem. 2005;77:78–84.CrossRefPubMedGoogle Scholar
  11. 11.
    Banker MJ, Clark TH, Williams JA. Development and validation of a 96-well equilibrium dialysis apparatus for measuring plasma protein binding. J Pharm Sci. 2003;92:967–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Kariv I, Cao H, Oldenburg KR. Development of a high throughput equilibrium dialysis method. J Pharm Sci. 2001;90:580–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Krediet RT, Boeschoten EW, Struijk DG, Arisz L. Differences in the peritoneal transport of water, solutes and proteins between dialysis with two- and with three-litre exchanges. Nephrol Dial Transpl. 1988;3:198–204.Google Scholar
  14. 14.
    Bridges CR, Myers BD, Brenner BM, Deen WM. Glomerular charge alterations in human minimal change nephropathy. Kidney Int. 1982;22:677–84.CrossRefPubMedGoogle Scholar
  15. 15.
    Rippe B, Davies S. Permeability of peritoneal and glomerular capillaries: what are the differences according to pore theory? Perit Dial Int. 2011;31:249–58.CrossRefPubMedGoogle Scholar
  16. 16.
    Kuhlmann MK. Phosphate elimination in modalities of hemodialysis and peritoneal dialysis. Blood Purif. 2010;29:137–44.CrossRefPubMedGoogle Scholar
  17. 17.
    Zehnder C, Gutzwiller JP, Renggli K. Hemodiafiltration–a new treatment option for hyperphosphatemia in hemodialysis patients. Clin Nephrol. 1999;52:152–9.PubMedGoogle Scholar
  18. 18.
    Duranton F, Lundin U, Gayrard N, Mischak H, Aparicio M, Mourad G, et al. Plasma and urinary amino acid metabolomic profiling in patients with different levels of kidney function. Clin J Am Soc Nephrol. 2014;9:37–45.CrossRefPubMedGoogle Scholar
  19. 19.
    Chuang CK, Lin SP, Chen HH, Chen YC, Wang TJ, Shieh WH, et al. Plasma free amino acids and their metabolites in Taiwanese patients on hemodialysis and continuous ambulatory peritoneal dialysis. Clin Chim Acta. 2006; 364:209–16.CrossRefPubMedGoogle Scholar
  20. 20.
    Ilcol YO, Donmez O, Yavuz M, Dilek K, Yurtkuran M, Ulus IH. Free choline and phospholipid-bound choline concentrations in serum and dialysate during peritoneal dialysis in children and adults. Clin Biochem. 2002;35:307–13.CrossRefPubMedGoogle Scholar
  21. 21.
    Hjelle JT, Welch MH, Pavlina TM, Webb LE, Mockler DF, Miller MA, et al. Choline levels in human peritoneal dialysate. Adv Perit Dial. 1993; 9:299–302 (Conference on Peritoneal Dialysis).PubMedGoogle Scholar
  22. 22.
    Rennick B, Acara M, Hysert P, Mookerjee B. Choline loss during hemodialysis: homeostatic control of plasma choline concentrations. Kidney Int. 1976;10:329–35.CrossRefPubMedGoogle Scholar
  23. 23.
    Yung S, Chan TM. Glycosaminoglycans and proteoglycans: overlooked entities? Perit Dial Int. 2007;27(Suppl 2):104–9.Google Scholar
  24. 24.
    Sekine T, Miyazaki H, Endou H. Molecular physiology of renal organic anion transporters. Am J Physiol Renal Physiol. 2006;290:F251–61.CrossRefGoogle Scholar
  25. 25.
    Masereeuw R, Mutsaers HA, Toyohara T, Abe T, Jhawar S, Sweet DH, et al. The kidney and uremic toxin removal: glomerulus or tubule? Seminars in nephrology. 2014; 34:191–208.Google Scholar
  26. 26.
    Wilkie M. Introduction to point-counterpoint: mechanisms of glomerular filtration: pores versus an electrical field. Perit Dial Int. 2015;35:4.CrossRefPubMedGoogle Scholar
  27. 27.
    Hung SC, Kuo KL, Wu CC, Tarng DC. Indoxyl sulfate: a novel cardiovascular risk factor in chronic kidney disease. J Am Heart Assoc. 2017. Scholar
  28. 28.
    Lekawanvijit S, Kompa AR, Wang BH, Kelly DJ, Krum H. Cardiorenal syndrome: the emerging role of protein-bound uremic toxins. Circ Res. 2012;111:1470–83.CrossRefPubMedGoogle Scholar
  29. 29.
    Ito S, Yoshida M. Protein-bound uremic toxins: new culprits of cardiovascular events in chronic kidney disease patients. Toxins (Basel). 2014;6:665–78.CrossRefGoogle Scholar
  30. 30.
    Zager RA, Johannes GA, Sharma HM. Organic anion infusions exacerbate experimental acute renal failure. Am J Physiol. 1983;244:F48–55.PubMedGoogle Scholar
  31. 31.
    Satoh M, Hayashi H, Watanabe M, Ueda K, Yamato H, Yoshioka T, et al. Uremic toxins overload accelerates renal damage in a rat model of chronic renal failure. Nephron Exp Nephrol. 2003;95:e111-8.CrossRefPubMedGoogle Scholar
  32. 32.
    Maiorca R, Brunori G, Zubani R, Cancarini GC, Manili L, Camerini C, et al. Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients. A longitudinal study. Nephrol Dial Transpl. 1995;10:2295–305.CrossRefGoogle Scholar
  33. 33.
    Bargman JM, Thorpe KE, Churchill DN. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol. 2001;12:2158–62.PubMedGoogle Scholar
  34. 34.
    Canada-USA (CANUSA) Peritoneal Dialysis Study Group. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. J Am Soc Nephrol. 1996;7:198–207.Google Scholar
  35. 35.
    del Peso G, Fernandez-Reyes MJ, Hevia C, Bajo MA, Castro MJ, Cirugeda A, et al. Factors influencing peritoneal transport parameters during the first year on peritoneal dialysis: peritonitis is the main factor. Nephrol Dial Transpl. 2005;20:1201–6.CrossRefGoogle Scholar
  36. 36.
    Mizutani M, Ito Y, Mizuno M, Nishimura H, Suzuki Y, Hattori R, et al. Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate. Am J Physiol Renal Physiol. 2010;298:F721-33.CrossRefPubMedGoogle Scholar
  37. 37.
    Lambie M, Chess J, Donovan KL, Kim YL, Do JY, Lee HB, et al. Independent effects of systemic and peritoneal inflammation on peritoneal dialysis survival. J Am Soc Nephrol. 2013;24:2071–80.CrossRefPubMedGoogle Scholar
  38. 38.
    Williams JD, Craig KJ, Topley N, Von Ruhland C, Fallon M, Newman GR, et al. Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol. 2002;13:470–9.PubMedGoogle Scholar
  39. 39.
    Gotloib L, Shustak A, Jaichenko J. Loss of mesothelial electronegative fixed charges during murine septic peritonitis. Nephron. 1989;51:77–83.CrossRefPubMedGoogle Scholar
  40. 40.
    Pries AR, Secomb TW, Gaehtgens P. The endothelial surface layer. Pflugers Archiv. 2000;440:653–66.CrossRefPubMedGoogle Scholar
  41. 41.
    Tawada M, Ito Y, Hamada C, Honda K, Mizuno M, Suzuki Y, et al. Vascular endothelial cell injury is an important factor in the development of encapsulating peritoneal sclerosis in long-term peritoneal dialysis patients. PLoS One. 2016;11:e0154644.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2018

Authors and Affiliations

  • Marina Asano
    • 1
  • Takako Ishii
    • 1
  • Akiyoshi Hirayama
    • 2
  • Masashi Mizuno
    • 1
  • Yasuhiro Suzuki
    • 1
  • Fumiko Sakata
    • 1
  • Shin-ichi Akiyama
    • 1
  • Shoichi Maruyama
    • 1
  • Tomoyoshi Soga
    • 2
  • Hiroshi Kinashi
    • 3
  • Takayuki Katsuno
    • 3
  • Yasuhiko Ito
    • 3
    Email author
  1. 1.Department of Nephrology and Renal Replacement TherapyNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Institute for Advanced BiosciencesKeio UniversityTsuruokaJapan
  3. 3.Department of Nephrology and RheumatologyAichi Medical UniversityNagakuteJapan

Personalised recommendations