Change in Estimated Glomerular Filtration Rate and Risk of Allograft Failure in Patients Diagnosed with Active Antibody-Mediated Rejection Following Kidney Transplantation
1East Carolina University, Greenville, NC, 2University of Manitoba, Winnipeg, MB, Canada, 3University of Wisconsin, Madison, WI, 4Vitaeris, Inc, Vancouver, BC, Canada, 5University Hospital Vall d'Hebron, Barcelona, Spain, 6CTI Clinical Trial & Consulting, Covington, KY
Meeting: 2019 American Transplant Congress
Abstract number: A197
Keywords: Graft survival, Multivariate analysis, Prediction models, Renal function
Session Information
Date: Saturday, June 1, 2019
Session Name: Poster Session A: Kidney Chronic Antibody Mediated Rejection
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: There are challenges in designing an adequate and well-controlled study of patients with active antibody-mediated rejection (ABMR), especially in the absence of a valid surrogate marker. The objective of this study was to evaluate the functional relationship between change in estimated GFR (eGFR) following diagnosis of active ABMR and risk of death-censored graft failure (DCGF), defined as graft loss or eGFR < 15 mL/min/1.73 m2 occurring at any time over the course of patient follow up.
*Methods: Recipients of solitary KTx between January 1995 and August 2013 who were diagnosed with biopsy-proven ABMR at least one-year post-KTx and had a minimum of 3 years follow-up. Serial measures of eGFR were calculated using the MDRD 4-variable equation. The relationship between change in eGFR and risk of DCGF was assessed using the joint modelling (JM) framework. Within the JM framework, two models are fit to the data simultaneously: one for the longitudinal process (change in eGFR) and one for the event process (time to DCGF). Joint estimation of the two models is achieved by assuming they are correlated via individual random effects.
*Results: A total of 91 patients across three participating centers were included in the analysis: 9 (10%) from Barcelona, 27 (30%) from Manitoba, and 55 (60%) from Wisconsin. The mean (SD) age of the recipient at time of KTx was 39.4 (15.1) years, 27.5% were female and 86.8% were white. Median length of time from KTx to diagnosis of active ABMR was 63 months. Median follow-up post-diagnosis of active ABMR was 62 months. Spaghetti plots suggest a linear trend in the change in eGFR; especially in the first 12 months post-diagnosis of active ABMR. Results of the joint model are presented in Table 1. Baseline eGFR and slope (per month change in eGFR up to 12 months post-diagnosis of active ABMR) are associated with risk of DCGF: for each mL increase in baseline eGFR or improvement in mL/month of eGFR slope, risk of DCGF is significantly reduced.
*Conclusions: This study provides important insight into the utility of pivotal trial endpoints and can be used for sample size estimation given a set of assumptions based on the anticipated eGFR profile.
| A. Linear Mixed Effects (random intercept-slope) Model for the Longitudinal eGFR Process | ||||
| Comparison | Estimate | Standard Error | P-value | |
| Intercept | 50.884 | 7.869 | <0.0001 | |
| Time (slope) | Per month | -0.757 | 0.104 | <0.0001 |
| B. Cox’s Hazards Model for Time to Death-censored Graft Failure | ||||
| Comparison | Estimate (Log hazard ratio) | Standard Error | P-value | |
| Estimated GFR at time of diagnosis | Per unit increase | -0.128 | 0.030 | <0.0001 |
| Slope | Per month increase in eGFR | -2.233 | 0.580 | <0.0001 |
To cite this abstract in AMA style:
Irish W, Nickerson P, Astor B, Chong E, Wiebe C, Moreso F, Seron D, Crespo M, Gache L, Djamali A. Change in Estimated Glomerular Filtration Rate and Risk of Allograft Failure in Patients Diagnosed with Active Antibody-Mediated Rejection Following Kidney Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/change-in-estimated-glomerular-filtration-rate-and-risk-of-allograft-failure-in-patients-diagnosed-with-active-antibody-mediated-rejection-following-kidney-transplantation/. Accessed March 8, 2021.« Back to 2019 American Transplant Congress