- Department of Nephrology and Institute of Kidney Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
ZHANG Ling,
Email: zhangling_crrt@163.com
Peritoneal dialysis (PD) represents an essential renal replacement therapy for end-stage renal disease patients. However, conventional glucose-based dialysis solutions limit the clinical adoption of PD due to complications including peritoneal fibrosis and metabolic disturbances. This review systematically elaborates on advances in novel biocompatible osmotic agents: L-carnitine improves peritoneal metabolic homeostasis, while hyperbranched polyglycerol enables sustained ultrafiltration with dual peritoneal/renal protection. These innovations delineate the future direction for osmotic agent development: integrating multifunctional properties (anti-fibrotic, pro-repair, and metabolic regulation) beyond foundational osmotic efficacy.
Copyright © the editorial department of West China Medical Journal of West China Medical Publisher. All rights reserved
| 1. | Himmelfarb J, Vanholder R, Mehrotra R, et al. The current and future landscape of dialysis. Nat Rev Nephrol, 2020, 16(10): 573-585. |
| 2. | Liu FX, Gao X, Inglese G, et al. A global overview of the impact of peritoneal dialysis first or favored policies: an opinion. Perit Dial Int, 2015, 35(4): 406-420. |
| 3. | Zhou Q, Bajo MA, Del Peso G, et al. Preventing peritoneal membrane fibrosis in peritoneal dialysis patients. Kidney Int, 2016, 90(3): 515-524. |
| 4. | Fortes PC, de Moraes TP, Mendes JG, et al. Insulin resistance and glucose homeostasis in peritoneal dialysis. Perit Dial Int, 2009, 29(Suppl 2): S145-S148. |
| 5. | Lambie M, Bonomini M, Davies SJ, et al. Insulin resistance in cardiovascular disease, uremia, and peritoneal dialysis. Trends Endocrinol Metab, 2021, 32(9): 721-730. |
| 6. | Wang IK, Lin CL, Chen HC, et al. Risk of new-onset diabetes in end-stage renal disease patients undergoing dialysis: analysis from registry data of Taiwan. Nephrol Dial Transplant, 2018, 33(4): 670-675. |
| 7. | Szeto CC, Johnson DW. Low GDP solution and glucose-sparing strategies for peritoneal dialysis. Semin Nephrol, 2017, 37(1): 30-42. |
| 8. | Nataatmadja MS, Johnson DW, Pascoe EM, et al. Associations between peritoneal glucose exposure, glucose degradation product exposure, and peritoneal membrane transport characteristics in peritoneal dialysis patients: secondary analysis of the bal ANZ trial. Perit Dial Int, 2018, 38(5): 349-355. |
| 9. | Johnson DW, Brown FG, Clarke M, et al. The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial. Nephrol Dial Transplant, 2012, 27(12): 4445-4453. |
| 10. | Van Overmeire L, Goffin E, Krzesinski JM, et al. Peritoneal equilibration test with conventional ‘low pH/high glucose degradation product’ or with biocompatible ‘normal pH/low glucose degradation product’ dialysates: does it matter?. Nephrol Dial Transplant, 2013, 28(7): 1946-1951. |
| 11. | Li FK, Chan LY, Woo JC, et al. A 3-year, prospective, randomized, controlled study on amino acid dialysate in patients on CAPD. Am J Kidney Dis, 2003, 42(1): 173-183. |
| 12. | Olszowska A, Waniewski J, Stachowska-Pietka J, et al. Long peritoneal dialysis dwells with icodextrin: kinetics of transperitoneal fluid and polyglucose transport. Front Physiol, 2019, 10: 1326. |
| 13. | Dousdampanis P, Musso CG, Trigka K. Icodextrin and peritoneal dialysis: advantages and new applications. Int Urol Nephrol, 2018, 50(3): 495-500. |
| 14. | Morelle J, Sow A, Fustin CA, et al. Mechanisms of crystalloid versus colloid osmosis across the peritoneal membrane. J Am Soc Nephrol, 2018, 29(7): 1875-1886. |
| 15. | Yung S, Lui SL, Ng CK, et al. Impact of a low-glucose peritoneal dialysis regimen on fibrosis and inflammation biomarkers. Perit Dial Int, 2015, 35(2): 147-158. |
| 16. | Katsutani M, Ito T, Masaki T, et al. Glucose-based PD solution, but not icodextrin-based PD solution, induces plasminogen activator inhibitor-1 and tissue-type plasminogen activator in human peritoneal mesothelial cells via ERK1/2. Ther Apher Dial, 2007, 11(2): 94-100. |
| 17. | Dogan K, Kayalp D, Ceylan G, et al. Falsely elevated glucose concentrations in peritoneal dialysis patients using icodextrin. J Clin Lab Anal, 2016, 30(5): 506-509. |
| 18. | Breborowicz A, Połubinska A, Wu G, et al. N-acetylglucosamine reduces inflammatory response during acute peritonitis in uremic rats. Blood Purif, 2006, 24(3): 274-281. |
| 19. | Ciszewicz M, Wu G, Tam P, et al. Changes in peritoneal mesothelial cells phenotype after chronic exposure to glucose or N-acetylglucosamine. Transl Res, 2007, 150(6): 337-342. |
| 20. | Breborowicz A, Pawlaczyk-Kuzlan M, Pawlaczyk K, et al. Replacement of glucose with N-acetylglucosamine in peritoneal dialysis fluid-experimental study in rats. Perit Dial Int, 2001, 21(Suppl 3): S365-S367. |
| 21. | Virmani MA, Cirulli M. The role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int J Mol Sci, 2022, 23(5): 2717. |
| 22. | Bene J, Csiky B, Komlosi K, et al. Dynamic adaptive changes of the serum carnitine esters during and after L-carnitine supplementation in patients with maintenance haemodialysis. Scand J Clin Lab Invest, 2011, 71(4): 280-286. |
| 23. | Bene J, Csiky B, Wittmann I, et al. Dramatic decrease of carnitine esters after interruption of exogenous carnitine supply in hemodialysis patients. Ren Fail, 2012, 34(5): 555-558. |
| 24. | Virmani A, Pinto L, Bauermann O, et al. The carnitine palmitoyl transferase (CPT) system and possible relevance for neuropsychiatric and neurological conditions. Mol Neurobiol, 2015, 52(2): 826-836. |
| 25. | Indiveri C, Iacobazzi V, Tonazzi A, et al. The mitochondrial carnitine/acylcarnitine carrier: function, structure and physiopathology. Mol Aspects Med, 2011, 32(4/5/6): 223-233. |
| 26. | Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta, 2016, 1863(10): 2422-2435. |
| 27. | Pekala J, Patkowska-Sokoła B, Bodkowski R, et al. L-carnitine--metabolic functions and meaning in humans life. Curr Drug Metab, 2011, 12(7): 667-678. |
| 28. | Bajo MA, del Peso G, Castro MA, et al. Effect of bicarbonate/lactate peritoneal dialysis solutions on human mesothelial cell proliferation ex vivo. Adv Perit Dial, 2001, 17: 37-41. |
| 29. | Kuma A, Tamura M, Ishimatsu N, et al. Monocarboxylate transporter-1 mediates the protective effects of neutral-ph bicarbonate/lactate-buffered peritoneal dialysis fluid on cell viability and apoptosis. Ther Apher Dial, 2017, 21(1): 62-70. |
| 30. | Arduini A, Bonomini M, Savica V, et al. Carnitine in metabolic disease: potential for pharmacological intervention. Pharmacol Ther, 2008, 120(2): 149-156. |
| 31. | Gaggiotti E, Arduini A, Bonomini M, et al. Prevention of peritoneal sclerosis: a new proposal to substitute glucose with carnitine dialysis solution (biocompatibility testing in vitro and in rabbits). Int J Artif Organs, 2005, 28(2): 177-187. |
| 32. | Piccapane F, Bonomini M, Castellano G, et al. A novel formulation of glucose-sparing peritoneal dialysis solutions with L-carnitine improves biocompatibility on human mesothelial cells. Int J Mol Sci, 2020, 22(1): 123. |
| 33. | Bonomini M, Di Liberato L, Del Rosso G, et al. Effect of an L-carnitine-containing peritoneal dialysate on insulin sensitivity in patients treated with CAPD: a 4-month, prospective, multicenter randomized trial. Am J Kidney Dis, 2013, 62(5): 929-938. |
| 34. | Masola V, Bonomini M, Onisto M, et al. Biological effects of XyloCore, a glucose sparing PD solution, on mesothelial cells: focus on mesothelial-mesenchymal transition, inflammation and angiogenesis. Nutrients, 2021, 13(7): 2282. |
| 35. | Rago C, Lombardi T, Di Fulvio G, et al. A new peritoneal dialysis solution containing L-carnitine and xylitol for patients on continuous ambulatory peritoneal dialysis: first clinical experience. Toxins (Basel), 2021, 13(3): 174. |
| 36. | Bonomini M, Davies S, Kleophas W, et al. Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis. Perit Dial Int, 2025, 45(1): 17-25. |
| 37. | Nishimura H, Ikehara O, Naito T, et al. Evaluation of taurine as an osmotic agent for peritoneal dialysis solution. Perit Dial Int, 2009, 29(2): 204-216. |
| 38. | Tang X, Ravikumar Y, Zhang G, et al. D-allose, a typical rare sugar: properties, applications, and biosynthetic advances and challenges. Crit Rev Food Sci Nutr, 2025, 65(14): 2785-2812. |
| 39. | 张敏, 杨舒雅, 高大宽. 稀有糖 D-阿洛糖的生理功能研究进展. 生物工程学报, 2024, 40(7): 2010-2021. |
| 40. | Ozaki T, Fu HY, Onishi K, et al. Partial replacement of D-glucose with D-allose ameliorates peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid in rats. Perit Dial Int, 2024, 44(2): 125-132. |
| 41. | Mendelson AA, Guan Q, Chafeeva I, et al. Hyperbranched polyglycerol is an efficacious and biocompatible novel osmotic agent in a rodent model of peritoneal dialysis. Perit Dial Int, 2013, 33(1): 15-27. |
| 42. | Du C, Mendelson AA, Guan Q, et al. The size-dependent efficacy and biocompatibility of hyperbranched polyglycerol in peritoneal dialysis. Biomaterials, 2014, 35(5): 1378-1389. |
| 43. | Du C, Mendelson AA, Guan Q, et al. Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis. J Transl Med, 2016, 14(1): 338. |
| 44. | La Han B, Guan Q, Chafeeva I, et al. Peritoneal and systemic responses of obese type II diabetic rats to chronic exposure to a hyperbranched polyglycerol-based dialysis solution. Basic Clin Pharmacol Toxicol, 2018, 123(4): 494-503. |
| 45. | Du C, Jayo R, Mendelson AA, et al. Pharmacokinetics of small hyperbranched polyglycerols as an osmotic agent for peritoneal dialysis: plasma exposure, organ distribution and excretion in rats. Perit Dial Int, 2023, 43(4): 324-333. |
| 46. | 余学清, 吴丁财, 叶智明, 等. 一种腹膜透析液及其制备方法和应用: CN115624566B. 2023-03-10. |
| 47. | 张凌, 刘小英, 胥箐, 等. 琥珀酰明胶在制备腹膜透析液中的用途以及一种含琥珀酰明胶、枸橼酸钠的腹膜透析液: CN118976116B. 2025-01-24. |
| 48. | Rognoni C, Pohlmeier R, Tarricone R. Regional citrate anticoagulation versus systemic heparin in continuous kidney replacement therapy: examining the role of evidence in health technology assessment. Adv Ther, 2025, 42(6): 2606-2638. |
| 49. | Zhou Z, Liu C, Yang Y, et al. Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials. Crit Care, 2023, 27(1): 222. |
| 50. | Pérez-García R, Ramírez Chamond R, de Sequera Ortiz P, et al. Citrate dialysate does not induce oxidative stress or inflammation in vitro as compared to acetate dialysate. Nefrologia, 2017, 37(6): 630-637. |
| 51. | Cavallini N, Wieslander A, Braide M. Substituting citrate for lactate in peritoneal dialysis fluid improves ultrafiltration in rats. Perit Dial Int, 2009, 29(1): 36-43. |
- 1. Himmelfarb J, Vanholder R, Mehrotra R, et al. The current and future landscape of dialysis. Nat Rev Nephrol, 2020, 16(10): 573-585.
- 2. Liu FX, Gao X, Inglese G, et al. A global overview of the impact of peritoneal dialysis first or favored policies: an opinion. Perit Dial Int, 2015, 35(4): 406-420.
- 3. Zhou Q, Bajo MA, Del Peso G, et al. Preventing peritoneal membrane fibrosis in peritoneal dialysis patients. Kidney Int, 2016, 90(3): 515-524.
- 4. Fortes PC, de Moraes TP, Mendes JG, et al. Insulin resistance and glucose homeostasis in peritoneal dialysis. Perit Dial Int, 2009, 29(Suppl 2): S145-S148.
- 5. Lambie M, Bonomini M, Davies SJ, et al. Insulin resistance in cardiovascular disease, uremia, and peritoneal dialysis. Trends Endocrinol Metab, 2021, 32(9): 721-730.
- 6. Wang IK, Lin CL, Chen HC, et al. Risk of new-onset diabetes in end-stage renal disease patients undergoing dialysis: analysis from registry data of Taiwan. Nephrol Dial Transplant, 2018, 33(4): 670-675.
- 7. Szeto CC, Johnson DW. Low GDP solution and glucose-sparing strategies for peritoneal dialysis. Semin Nephrol, 2017, 37(1): 30-42.
- 8. Nataatmadja MS, Johnson DW, Pascoe EM, et al. Associations between peritoneal glucose exposure, glucose degradation product exposure, and peritoneal membrane transport characteristics in peritoneal dialysis patients: secondary analysis of the bal ANZ trial. Perit Dial Int, 2018, 38(5): 349-355.
- 9. Johnson DW, Brown FG, Clarke M, et al. The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial. Nephrol Dial Transplant, 2012, 27(12): 4445-4453.
- 10. Van Overmeire L, Goffin E, Krzesinski JM, et al. Peritoneal equilibration test with conventional ‘low pH/high glucose degradation product’ or with biocompatible ‘normal pH/low glucose degradation product’ dialysates: does it matter?. Nephrol Dial Transplant, 2013, 28(7): 1946-1951.
- 11. Li FK, Chan LY, Woo JC, et al. A 3-year, prospective, randomized, controlled study on amino acid dialysate in patients on CAPD. Am J Kidney Dis, 2003, 42(1): 173-183.
- 12. Olszowska A, Waniewski J, Stachowska-Pietka J, et al. Long peritoneal dialysis dwells with icodextrin: kinetics of transperitoneal fluid and polyglucose transport. Front Physiol, 2019, 10: 1326.
- 13. Dousdampanis P, Musso CG, Trigka K. Icodextrin and peritoneal dialysis: advantages and new applications. Int Urol Nephrol, 2018, 50(3): 495-500.
- 14. Morelle J, Sow A, Fustin CA, et al. Mechanisms of crystalloid versus colloid osmosis across the peritoneal membrane. J Am Soc Nephrol, 2018, 29(7): 1875-1886.
- 15. Yung S, Lui SL, Ng CK, et al. Impact of a low-glucose peritoneal dialysis regimen on fibrosis and inflammation biomarkers. Perit Dial Int, 2015, 35(2): 147-158.
- 16. Katsutani M, Ito T, Masaki T, et al. Glucose-based PD solution, but not icodextrin-based PD solution, induces plasminogen activator inhibitor-1 and tissue-type plasminogen activator in human peritoneal mesothelial cells via ERK1/2. Ther Apher Dial, 2007, 11(2): 94-100.
- 17. Dogan K, Kayalp D, Ceylan G, et al. Falsely elevated glucose concentrations in peritoneal dialysis patients using icodextrin. J Clin Lab Anal, 2016, 30(5): 506-509.
- 18. Breborowicz A, Połubinska A, Wu G, et al. N-acetylglucosamine reduces inflammatory response during acute peritonitis in uremic rats. Blood Purif, 2006, 24(3): 274-281.
- 19. Ciszewicz M, Wu G, Tam P, et al. Changes in peritoneal mesothelial cells phenotype after chronic exposure to glucose or N-acetylglucosamine. Transl Res, 2007, 150(6): 337-342.
- 20. Breborowicz A, Pawlaczyk-Kuzlan M, Pawlaczyk K, et al. Replacement of glucose with N-acetylglucosamine in peritoneal dialysis fluid-experimental study in rats. Perit Dial Int, 2001, 21(Suppl 3): S365-S367.
- 21. Virmani MA, Cirulli M. The role of L-carnitine in mitochondria, prevention of metabolic inflexibility and disease initiation. Int J Mol Sci, 2022, 23(5): 2717.
- 22. Bene J, Csiky B, Komlosi K, et al. Dynamic adaptive changes of the serum carnitine esters during and after L-carnitine supplementation in patients with maintenance haemodialysis. Scand J Clin Lab Invest, 2011, 71(4): 280-286.
- 23. Bene J, Csiky B, Wittmann I, et al. Dramatic decrease of carnitine esters after interruption of exogenous carnitine supply in hemodialysis patients. Ren Fail, 2012, 34(5): 555-558.
- 24. Virmani A, Pinto L, Bauermann O, et al. The carnitine palmitoyl transferase (CPT) system and possible relevance for neuropsychiatric and neurological conditions. Mol Neurobiol, 2015, 52(2): 826-836.
- 25. Indiveri C, Iacobazzi V, Tonazzi A, et al. The mitochondrial carnitine/acylcarnitine carrier: function, structure and physiopathology. Mol Aspects Med, 2011, 32(4/5/6): 223-233.
- 26. Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta, 2016, 1863(10): 2422-2435.
- 27. Pekala J, Patkowska-Sokoła B, Bodkowski R, et al. L-carnitine--metabolic functions and meaning in humans life. Curr Drug Metab, 2011, 12(7): 667-678.
- 28. Bajo MA, del Peso G, Castro MA, et al. Effect of bicarbonate/lactate peritoneal dialysis solutions on human mesothelial cell proliferation ex vivo. Adv Perit Dial, 2001, 17: 37-41.
- 29. Kuma A, Tamura M, Ishimatsu N, et al. Monocarboxylate transporter-1 mediates the protective effects of neutral-ph bicarbonate/lactate-buffered peritoneal dialysis fluid on cell viability and apoptosis. Ther Apher Dial, 2017, 21(1): 62-70.
- 30. Arduini A, Bonomini M, Savica V, et al. Carnitine in metabolic disease: potential for pharmacological intervention. Pharmacol Ther, 2008, 120(2): 149-156.
- 31. Gaggiotti E, Arduini A, Bonomini M, et al. Prevention of peritoneal sclerosis: a new proposal to substitute glucose with carnitine dialysis solution (biocompatibility testing in vitro and in rabbits). Int J Artif Organs, 2005, 28(2): 177-187.
- 32. Piccapane F, Bonomini M, Castellano G, et al. A novel formulation of glucose-sparing peritoneal dialysis solutions with L-carnitine improves biocompatibility on human mesothelial cells. Int J Mol Sci, 2020, 22(1): 123.
- 33. Bonomini M, Di Liberato L, Del Rosso G, et al. Effect of an L-carnitine-containing peritoneal dialysate on insulin sensitivity in patients treated with CAPD: a 4-month, prospective, multicenter randomized trial. Am J Kidney Dis, 2013, 62(5): 929-938.
- 34. Masola V, Bonomini M, Onisto M, et al. Biological effects of XyloCore, a glucose sparing PD solution, on mesothelial cells: focus on mesothelial-mesenchymal transition, inflammation and angiogenesis. Nutrients, 2021, 13(7): 2282.
- 35. Rago C, Lombardi T, Di Fulvio G, et al. A new peritoneal dialysis solution containing L-carnitine and xylitol for patients on continuous ambulatory peritoneal dialysis: first clinical experience. Toxins (Basel), 2021, 13(3): 174.
- 36. Bonomini M, Davies S, Kleophas W, et al. Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis. Perit Dial Int, 2025, 45(1): 17-25.
- 37. Nishimura H, Ikehara O, Naito T, et al. Evaluation of taurine as an osmotic agent for peritoneal dialysis solution. Perit Dial Int, 2009, 29(2): 204-216.
- 38. Tang X, Ravikumar Y, Zhang G, et al. D-allose, a typical rare sugar: properties, applications, and biosynthetic advances and challenges. Crit Rev Food Sci Nutr, 2025, 65(14): 2785-2812.
- 39. 张敏, 杨舒雅, 高大宽. 稀有糖 D-阿洛糖的生理功能研究进展. 生物工程学报, 2024, 40(7): 2010-2021.
- 40. Ozaki T, Fu HY, Onishi K, et al. Partial replacement of D-glucose with D-allose ameliorates peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid in rats. Perit Dial Int, 2024, 44(2): 125-132.
- 41. Mendelson AA, Guan Q, Chafeeva I, et al. Hyperbranched polyglycerol is an efficacious and biocompatible novel osmotic agent in a rodent model of peritoneal dialysis. Perit Dial Int, 2013, 33(1): 15-27.
- 42. Du C, Mendelson AA, Guan Q, et al. The size-dependent efficacy and biocompatibility of hyperbranched polyglycerol in peritoneal dialysis. Biomaterials, 2014, 35(5): 1378-1389.
- 43. Du C, Mendelson AA, Guan Q, et al. Hyperbranched polyglycerol is superior to glucose for long-term preservation of peritoneal membrane in a rat model of chronic peritoneal dialysis. J Transl Med, 2016, 14(1): 338.
- 44. La Han B, Guan Q, Chafeeva I, et al. Peritoneal and systemic responses of obese type II diabetic rats to chronic exposure to a hyperbranched polyglycerol-based dialysis solution. Basic Clin Pharmacol Toxicol, 2018, 123(4): 494-503.
- 45. Du C, Jayo R, Mendelson AA, et al. Pharmacokinetics of small hyperbranched polyglycerols as an osmotic agent for peritoneal dialysis: plasma exposure, organ distribution and excretion in rats. Perit Dial Int, 2023, 43(4): 324-333.
- 46. 余学清, 吴丁财, 叶智明, 等. 一种腹膜透析液及其制备方法和应用: CN115624566B. 2023-03-10.
- 47. 张凌, 刘小英, 胥箐, 等. 琥珀酰明胶在制备腹膜透析液中的用途以及一种含琥珀酰明胶、枸橼酸钠的腹膜透析液: CN118976116B. 2025-01-24.
- 48. Rognoni C, Pohlmeier R, Tarricone R. Regional citrate anticoagulation versus systemic heparin in continuous kidney replacement therapy: examining the role of evidence in health technology assessment. Adv Ther, 2025, 42(6): 2606-2638.
- 49. Zhou Z, Liu C, Yang Y, et al. Anticoagulation options for continuous renal replacement therapy in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials. Crit Care, 2023, 27(1): 222.
- 50. Pérez-García R, Ramírez Chamond R, de Sequera Ortiz P, et al. Citrate dialysate does not induce oxidative stress or inflammation in vitro as compared to acetate dialysate. Nefrologia, 2017, 37(6): 630-637.
- 51. Cavallini N, Wieslander A, Braide M. Substituting citrate for lactate in peritoneal dialysis fluid improves ultrafiltration in rats. Perit Dial Int, 2009, 29(1): 36-43.