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Calcineurin Inhibitor Holiday for Management of Post Transplant Acute Kidney Injury

S. Sriperumbuduri, D. Lazarus, T. Fairhead, S. Hoar, J. Karpinski, G. Knoll

Nephrology, The Ottawa hospital, Ottawa, ON, Canada

Meeting: 2019 American Transplant Congress

Abstract number: A260

Keywords: Calcineurin, Kidney transplantation, Renal dysfunction, Simulect

Session Information

Date: Saturday, June 1, 2019

Session Name: Poster Session A: Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

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*Purpose: Calcineurin inhibitors (CNI), despite dominating the armamentarium of post transplant medications, are associated with long term nephrotoxicity and also delayed recovery of renal function in the setting of acute tubular necrosis (ATN). Avoiding CNI medication in the latter setting could possibly facilitate recovery of renal function and salvage the graft. As an alternative, basiliximab could be used to suppress immunity. The seminal study by Cantarovich group from Montreal provided the initial insights into CNI holiday in solid organ transplantation.The purpose of the study is to analyse the outcomes of renal transplant patients with significant ATN and graft dysfunction where CNI was withdrawn and basiliximab was used for immunosuppression.

*Methods: We report a series of 9 renal transplant recipients, who were started on CNI holiday with basiliximab overlap. The regimen included basiliximab 20 mg iv on day 0 and day 1. Subsequent doses were given every 2 weeks. Maximum of 6 doses were used. CNI was reintroduced within 2 months if there is significant improvement in kidney function. Prior to CNI holiday, we ensured that:-

1. Within a week prior to enrolment, kidney biopsy demonstrating ATN or CNI toxicity or thrombotic microangiopathy and no rejection and doppler ultrasound of kidney demonstrating no post-renal cause for dysfunction

2. Patient is 6-12 weeks post kidney transplantation, is on a therapeutic dose of CNI and has poor renal function as defined by ongoing hemodialysis requirement or estimated GFR(Glomerular filtration rate) < 30 ml/min

*Results: Mean age was 63.7 years and male: female ratio was 5:4. Mean duration between onset of graft dysfunction and initiation of CNI holiday was 4.2 months (range 1 -9 months). Mean number of basiliximab doses received were 5 (range 4 to 6). Most common reason for withholding CNI was persistent DGF in 78 %(7) ,acute cellular rejection necessitating HD in 11%(1) and recurrent ATN due to various etiologies in 11% (1). Total of 5 patients had significant improvement in graft function with decline in creatinine. Among the 5 patients on hemodialysis, only one recovered graft function with the most recent creatinine at 200umol/L. Mean time to recovery of graft function was 2.4 months (range 2 to 3 months). Mean eGFR before and after CNI holiday among the recovered patients was 8 ml/min/1.73m2 (range 0 to 12) and 23.25 ml /min/1.73m2 (range 20 to 27). One patient developed de novo donor specific antibodies (DSA) at the end of CNI holiday. None of them had any rejections.

*Conclusions: CNI holiday may be a useful strategy to facilitate graft function recovery in case of persistent ATN. Though the use of basiliximab has a significant cost factor involved, it can potentially help in salvaging the graft and avoiding long term dialysis.

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To cite this abstract in AMA style:

Sriperumbuduri S, Lazarus D, Fairhead T, Hoar S, Karpinski J, Knoll G. Calcineurin Inhibitor Holiday for Management of Post Transplant Acute Kidney Injury [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/calcineurin-inhibitor-holiday-for-management-of-post-transplant-acute-kidney-injury/. Accessed March 8, 2021.

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