Kidney Transplant Recipients Not Reaching the Expected Post-Transplant Creatinine Range Most Likely Show Calcineurin-Inhibitor Nephrotoxicity Upon Histology
1University Hospital Zürich, Zürich, Switzerland, 2University Hospital Zurich, Zürich, Switzerland
Meeting: 2022 American Transplant Congress
Abstract number: 1550
Keywords: Calcineurin, Glomerular filtration rate (GFR), Kidney transplantation, Vascular disease
Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes
Session Information
Session Name: Biomarkers: Clinical Outcomes
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Very recently, our own data suggested that approximately 25% of deceased-donor kidney transplant recipients (KTRs) and 10% of living-donor KTRs don’t reach the expected creatinine range (ExpCrea) according to the formula from Mueller et al. The ExpCrea formula integrates both the metabolic demand of the recipient and the nephron supply of the donor, and considers the single kidney’s adaptive increase. To determine its value as a biomarker to identify KTRs with an underlying pathology accounting for this discrepancy between observed creatinine and ExpCrea, indication biopsies performed only by reason of not reaching the ExpCreat are required.
*Methods: A total of 16 KTRs underwent kidney allograft biopsies at a median of 5 months (range 2-12 months) post-transplant for indication of not reaching the ExpCreat. To ensure diagnostic accuracy, we combined histology, and Molecular Microscope Diagnostic System (MMDx) with clinical follow-up data of kidney allograft function.
*Results: Upon histology, 5/16 KTRs (31%) showed rejection (1 ABMR, 1 TCMR, 3 borderline changes), whereas only 1/16 KTRs (6%) showed rejection by MMDx. Among 4/16 KTRs (25%) with discrepant findings between histology and MMDx, a higher diagnostic accuracy was suggested in 3/4 KTRs for the MMDx diagnosis according to the clinical course. However, thorough histologic analysis revealed results of therapeutic relevance indicating vasculopathy/calcineurin-inhibitor (CNI)- nephrotoxicity in 9/16 KTRs (56%). Stably increased creatinine at 6 months post-transplant in KTRs with previous delayed graft function (DGF) and low-level proteinuria was highly predictive of a diagnosis of vasculopathy/CNI nephrotoxicity. Change of immunosuppression to a CNI-free regimen with belatacept was associated with a fall in creatinine within the expected range in 3/4 KTRs (75%).
*Conclusions: The ExpCreat formula has the potential to become an easily applicable biomarker to early identify KTRs at risk of suffering from CNI-nephrotoxicity who may benefit from a switch to a CNI-free immunosuppression regimen.
To cite this abstract in AMA style:
Moos Svon, Valkova K, Matter L, Müller TF, Schachtner T. Kidney Transplant Recipients Not Reaching the Expected Post-Transplant Creatinine Range Most Likely Show Calcineurin-Inhibitor Nephrotoxicity Upon Histology [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/kidney-transplant-recipients-not-reaching-the-expected-post-transplant-creatinine-range-most-likely-show-calcineurin-inhibitor-nephrotoxicity-upon-histology/. Accessed May 18, 2025.« Back to 2022 American Transplant Congress