Authors' recommendations: Positive crossmatch kidney transplantation using plasmapheresis or IVIG based protocols offer the potential of kidney transplantation to sensitised patients who would otherwise remain on dialysis indefinitely.The studies included in this report, presented an overview of the evidence for the two most commonly used desensitising protocols, high-dose IVIG and plasmapheresis plus low-dose IVIG. Unfortunately, due to various factors, namely the differences among the studies with respect to the definition of positive crossmatch status and what constitutes successful desensitisation, the drug protocols used and patient characteristics, it was not possible to conduct a meaningful comparison between the studies. Despite these shortcomings, the data from the included studies demonstrated that kidney transplantation in crossmatch positive and highly sensitised patients is potentially feasible. The data available from one level II and one level IV study on the high-dose IVIG protocol suggested that high dose IVIG-based desensitisation produces a transient reduction in anti-HLA antibodies. While rejection rates were approximately 30% in both studies, and were significantly higher than for the placebo group in the comparative study, the overall graft failure rate did not differ from patients treated with placebo after 3 years. Two level III studies compared the results of patients receiving plasmapheresis plus low-dose IVIG-based protocols with crossmatch negative controls. In terms of rejection rates, there appears to be significantly more acute rejection episodes in patients who have undergone desensitisation using plasmapheresis-based protocols as opposed to negative crossmatch patients who did not require desensitisation. The results for long-term (> 1 year) graft survival were equivocal. Only one study (level III evidence) compared the plasmapheresis low-dose IVIGbased protocol with the high-dose IVIG-based protocol. The results suggested that the plasmapheresis-based protocols result in better outcomes. Namely, successful desensitisation rates and humoral rejection rates were better with the use of plasmapheresis low-dose IVIG protocols, although the patient and graft survival rates were not reported for the individual treatment groups. Furthermore, the study suggests that in patients who are non responders to the IVIG only protocol,desensitisation may be an option using a plasmapheresis based protocol. In terms of safety and kidney function, the use of either desensitisation protocol did not appear to have any significant adverse events associated.The inclusion of studies with mixed or other protocols added to the evidence available by confirming that the use of desensitisation is not associated with any major adverse events. Furthermore, these studies added support to data from the previous studies suggesting that desensitisation success and the clinical outcomes following transplantation are associated with pre-operative sensitisation levels.While positive crossmatch kidney transplantation may be a potentially useful strategy for expanding the availability of donor organs for sensitised patients, the desensitisation protocols used to facilitate this are still in a developmental stage. It is still not clear exactly how the protocols work and which blood factors are preeminent in the rejection of foreign tissue in transplant recipients. Thus, it is not completely clear which factors need to be targeted, and which factors affect the success of the protocols.

Project Status: Completed

URL for project: http://www.horizonscanning.gov.au/internet/horizon/publishing.nsf/Content/211ABF81A69CA39DCA2575AD0080F3DC/$File/Desensitisation%20protocols%20for%20human%20leukocyte%20antigen%20antibodies%20in%20renal%20transplantation%20June%202009.pdf

Year Published: 2009

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Australia

Organisation Name: Australian Safety and Efficacy Register of New Interventional Procedures-Surgical

Contact Address: ASERNIP-S 24 King William Street, Kent Town SA 5067 Australia Tel: +61 8 8219 0900

Contact Name: racs.asernip@surgeons.org

Contact Email: racs.asernip@surgeons.org

Copyright: Australian Safety and Efficacy Register of New Interventional Procedures - Surgical (ASERNIP-S)