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Concentrates BIC AF

After the introduction of dialysis concentrates acidified with citric acid with a small residual content of sodium acetate (Citrasate®) into clinical practice, acetate free concentrates BIC AF with citric acid represent another step towards the improvement in the characteristics of dialysis concentrates and the characteristics of the dialysis solution prepared from these concentrates.

The BIC AF concentrates are intended for on-line proportioning of the dialysis solution for intermittent bicarbonate haemodialysis (HD) and on-line haemodiafiltration (HDF). Dialysis therapy with these solutions is more efficient and shows, in general, higher biocompatibility than the therapy with conventional solution containing acetic acid. The BIC AF concentrates are used in the same way as the conventional ones.

In numerous studies, the concentrates with citric acid have shown a number of positive effects on the course of dialysis therapy and its outcomes with those effects being related to the replacement of acetic acid with citric acid.

 

  • HIGHER BIOCOMPATIBILITY OF DIALYSIS PROCEDURE

Reduced thrombogenicity in the extracorporeal circuit as a consequence of local drop in the concentration of ionized calcium in the dialyser due to the formation of the calcium-citrate complexes.

- Possible considerable reduction in the doses of heparin, both unfractionated (1, 2, 3, 4) as well as low-molecular weight heparin (5), or even entirely heparin-free HD or HDF fully without heparin (6, 7, 8, 9, 10).

- Well applicable, namely in patients with heparin-induced thrombocytopenia (HIT) and after surgery (8, 10).

- An advantageous option for SLED doing away with the risk of excessive alkalinization of patient associated with regional citrate anticoagulation (10, 11, 12).

Immediately following the change-over to the citric acid-containing solution, the CRP level in plasma decreases (5, 13).

Minimum concentration of acetate in dialysate or its total absence there decreases pro-inflamatory effects of dialysis and leads to decreased production of IL-1, IL-6 and other proinflamatory cytokines in monocytes and polymorphonuclear neutrophiles during dialysis with citrate-containing dialysate (6, 14, 15, 16, 17, 18, 19, 20).

Also reduction in oxidative stress characterized by lower levels of myeloperoxidase (6, 21) has been documented in citrate dialysis.

 

  • INCREASED HD/HDF EFFICIENCY UNDER OTHERWISE UNCHANGED CONDITIONS

Slight amelioration of dialysis efficiency (increase in spKt/V by 5-7%) has been found in a number of studies with citrate-containing dialysate (4,14,22), although some were not able to confirm this (23).

 

  • REDUCED FORMATION OF CALCIUM DEPOSITS IN DIALYSIS MACHINE

Formation of sediments in the hydraulic circuit of the dialysis machine is reduced due partial complexing of the calcium ions in dialysate (24).

 

  • LOWER PRODUCTION OF NITRIC OXIDE (NO)

Absence of acetate eliminates formation of nitric oxide and thus reduces possible vasodilatation (25).

 

  • LESS PRONOUNCED INCREASE IN PLASMA IONIZED CALCIUM

It is advantageous in patients prone to arrhythmias (26). On the other side, some studies found increased incidence of hypotensions due to lower calcium balance during dialysis (26, 27). However, more frequent hypotensions were not seen in other studies (23), some have even reported improved overall haemodynamic stability with use of acetate-free dialysis solutions (28).

 

  • PLASMA LEVELS OF iPTH

Lowered level of ionized calcium in plasma may lead to an increase in plasma iPTH during dialysis with citrate. Data on magnitude of this increase vary widely, ranging from a few percent (29) up to tens of percent (23). Review articles nevertheless indicate that there are no clinically significant changes in plasma iPTH and ionized and total calcium either in long-term perspective (1, 30).

 

INTENDED USE

Concentrates BIC AF are intended to carry out haemodialysis (HD) as well as on-line hemodiafiltration (HDF).

Moderate drop in plasma calcium level may appear with the conversion to these concentrates and the concentration of PTH (6) can increase. It is, therefore, advisable to use calcium concentration of 1.5 mmol/l (1, 2) together with the conversion to BIC AF concentrates in patients who were using conventional dialysis solution with calcium concentration of 1.25 mmol/l before the conversion.

BIC AF concentrates can be used on all common types of dialysis machines.

 

 

BIBLIOGRAPHY

  1. Polakovič V, Lopot F, Švára F: Dialysis concentrate Citrasate® – In vitro tests and results of the Citrasate® concentrate use in in vivo bicarbonate haemodialysis and on-line haemodiafiltration, final report, 2010, http://www.meditespharma.cz/downloads/citrasate_ref9.pdf
  2. Kossmann RJ, Callan R, Ahmad S: Fifty-five Percent Heparin Reduction is Safe with Citrate Dialysate in Chronic Dialysis Patients. ASN’s 39th Annual Renal Week Meeting November 2006
  3. Ahmad S et al: Heparin reduction with citrate dialysate. Nephrol Dial Transpl, 21, 2006, Suppl 4 (abstract)
  4. Gabutti L, Lucchini B, Marone C et al: Citrate – vs. Acetate-based Dialysate in Bicarbonate Haemodialysis: Consequences on Haemodynamics, Coagulation, Acid-base Status, and Electrolytes. BMC Nephrology, 2009, 10(1):7 doi:10.1186/1471-2369-10-7
  5. Bunia J, Wolf H, Ahrenholz P: The long-term use of citrate-enriched dialysate reduces plasma level of C-reactive protein in dialysis patients. 52nd ERA-EDTA Congress, May 28-31, 2015 London, abstract (poster)
  6. Winkler R, Ahrenholz P, Paetow W et al: Reduction of Heparin and Oxidative Potential by means of Citrasate® in High-Flux Dialysis (HDF) and Online Hemodiafiltratin (ol HDF) in Pre- and Postdilution. Chapter 24 in: Suzuki H: Hemodialysis, InTech, 2013. doi:10.5772/52037
  7. Cheng YL, Yu AW, Tsang KY et al: Anticoagulation during haemodialysis using a citrate-enriched dialysate: a feasibility study. Nephrol Dial Transplant, 2011, 26(2):641-646. doi:10.1093/ndt/gfq396
  8. Aniort J, Petitclerc T, Créput C: Safe use of Citric Acid-Based Dialysate and Heparin Removal in Postdilution Online Hemodiafiltration. Blood Purif. 2012, 34:336-343. doi:10.1159/000345342
  9. Sands JJ, Kotanko P, Segal JH et al: Effects of Citrate Acid Concentrate (Citrasate®) on Heparin N Requirements and Hemodialysis Adequacy: A Multicenter, Prospective Noninferiority Trial. Blood Purif. 2012, 33:199-204. doi:10.1159/000334157
  10. Ahmad S, Tu A: Heparin Free Slow Low Efficiency Dialysis (SLED) Using Citrate Dialysate (CD) Is Safe and Effective. CRRT Conference March 7–10, 2007, San Diego, Blood Purif. 2007, 25:191, abstract
  11. Tu A, Ahmad S: Heparin-Free Hemodialysis with Citrate-Containing Dialysate in Intensive Care Patients. Dialysis and Transplantation, October 2000, 29(10)
  12. Madison JR, Ilumin MP, Chin AI: Citrate-containing dialysate is well tolerated during slow extended daily dialysis in the ICU. J Am Soc Nephrol. 2005, 16:314A
  13. Panichi V, Fiaccadori E, Rosati A, Fanelli R, Bernabini G, Scatena A, Pizzarelli F: Post-dilution on Line Haemodiafiltration with Citrate Dialysate: First Clinical Experience in Chronic Dialysis Patients. The Scientific World J. 2013, doi:10.1155/2013/703612
  14. Lopot F, Švára F, Polakovič V: Bicarbonate haemodialysis with A-concentrate with citric acid (Citrasate®). Aktuality v nefrologii, 2009, 15(3):105-110
  15. Bryland A, Wieslander A, Carlsson O et al: Citrate treatment reduces endothelial death and inflammation under hyperglycaemic conditions. Diabetes & Vascular Disease Research, 2011, 9(1):42–51. doi:10.1177/1479164111424297
  16. Matsuyama K, Tomo T, Kadota J: Acetate-free blood purification can impact improved nutritional status in hemodialysis patients. Journal of Artificial Organs, 2011, 14(2):112-119. doi:10.1007/s10047-010-0551-7
  17. Bingel M, Lonnemann G, Koch, Dinarello CA, Shaldon S: Enhancement of in-vitro human interleukin-1 production by sodium acetate. Lancet. 1987, 329(8523):14-16. doi:10.1016/S0140-6736(87)90703-3
  18. Higuchi T, Yamamoto C, Kuno T, Okada K, Soma M, Fukuda N, Nagura Y, Takahashi S, Matsumoto K: A comparison of bicarbonate hemodialysis, hemodiafiltration, and acetate-free biofiltration on cytokine production. Ther Apher Dial. 2004, 8(6):460-467. doi:10.1111/j.1774-9979.2004.00194.x
  19. Todeschini M, Macconi D, García Fernández N, Ghilardi M, Anabaya A, Binda E, Morigi M, Cattaneo D et al: Effect of acetate-free biofiltration and bicarbonate hemodialysis on neutrophil activation. American Journal of Kidney Diseases, October 2002, 40(4):783-793
  20. Grundström G et al: Replacement of acetate with citrate in dialysis fluid: a randomized clinical trial of short term safety and fluid biocompatibility. BMC Nephrology 2013, 14(1):216. doi:10.1186/1471-2369-14-216
  21. Bunia J, Ziebig R, Wolf H, Ahrenholz P: Reduction of heparin and oxidative stress using citrate-enriched dialysate in high-flux dialysis. ERA-EDTA Congress, 2013, abstract (poster)
  22. Kossmann RJ, Gonzales A, Callan R, Ahmad S: Increased Efficiency of Hemodialysis with Citrate Dialysate: A Prospective Controlled Study. CJASN 2009, 4(9):1459-1464
  23. Calabrese G, Steckiph D, Bertucci A, Baldin C, Petraruolo M, Mancuso D, Vagelli G, Gonella M: Citrate vs. acetate dialysate-reinfusate in on-line postdilution HDF. Nephrol Dial Transplant, 2013, 28 (Suppl 1), SP416
  24. Karlsson D et al: Less calcium carbonate fouling in the pre-dialyzer ultrafilter using a new dialysis fluid containing citrate. Euromembrane Conference 2012, poster
  25. Amore A, Cirina P, Mitola S et al: Acetate intolerance is mediated by enhanced synthesis of nitric oxide by endothelial cells. J Am Soc Nephrol, 1997, 8: 1431-1436
  26. De Sequera Ortiza P, Ramóna PA, Pérez-García R, Pratsa EC, Coboa PA, Arroya RA, Diaza MO, Carreteroa MP: Accute effect of citrate bath on postdialysis alkalaemia. Nefrologia, 2015, 35:164-171. doi: 10.1016/j.nefro.2014.10.001
  27. Rocha AD, Padua VC, Oliviera E, Guimaraes MM, Lugon JR, Strogoff de Matos JP: Effects of citrate enriched bicarbonate-based dialysate on anticoagulation and dialyzer reuse in maintenance hemodialysis patients. Hemodial International, 2014, 18:467-472. doi:10.1111/hdi.12113
  28. Daimon S, Dan K, Kawano M: Comparison of Acetate-Free Citrate Hemodialysis and Bicarbonate Hemodialysis Regarding the Effect of Intra-Dialysis Hypotension and Post-Dialysis Malaise. Therap Apher and Dialysis, 2011, 15(5):460-465. doi:10.1111/j.1744-9987.2011.00976.x
  29. Šafránek R, Moučka P, Vávrová J, Palička V, Pavlíková L, Dusilová-Sulková S: Changes of Serum Calcium, Magnesium and Parathyroid Hormone Induced by Hemodialysis with Citrate-Enriched Dialysis Solution. Kidney Blood Press Research, 2015, 40:13-21. doi:10.1159/000368478
  30. Wolf H: Citrathaltige Dialysate – die Innovation für die chronische Dialyse, Teil 2. Spektrum des Dialyse & Apherese, 2015, 5:28-31

 

FURTHER READING:

Huang A, Sandholm K, Jonsson N, Nilssson A, Wieslander A, Grundström G, Hancock S, Nilsson- Ekdahl K: Low concentration of citrate reduce complement and granulocyte activation in vitro in human blood, Clin Kidney J, 2015, 8:31-37

Raimundo M, Crichton S, Lei K, Sanderson B, Smith J, Brooks J, Ng J, Lemnich Smith J: Maintaining normal levels of ionized calcium during citrate-based renal replacement therapy is associated with stable PTH, Nephron Clin Pract, 2013, 4:124-131