Discordance between creatinine and cystatin C-based estimation of glomerular filtration rate (eGFR) in solid organ transplant recipients

Mary Kathryn Bohn; Meshach Asare-Werehene; Felix Leung; Davor Brinc; Rajeevan Selvaratnam

doi:10.1016/j.clinbiochem.2024.110853

Discordance between creatinine and cystatin C-based estimation of glomerular filtration rate (eGFR) in solid organ transplant recipients

Clin Biochem. 2024 Nov 20:135:110853. doi: 10.1016/j.clinbiochem.2024.110853. Online ahead of print.

Authors

Mary Kathryn Bohn¹, Meshach Asare-Werehene¹, Felix Leung², Davor Brinc³, Rajeevan Selvaratnam⁴

Affiliations

¹ Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
² Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada; Division of Clinical Biochemistry, Pathology & Laboratory Medicine, Sinai Health System, Toronto, ON, Canada.
³ Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Clinical Biochemistry, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
⁴ Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Clinical Biochemistry, Laboratory Medicine Program, University Health Network, Toronto, ON, Canada. Electronic address: [email protected].

PMID: 39577715
DOI: 10.1016/j.clinbiochem.2024.110853

Abstract

Background: Estimation of glomerular filtration rate is a critical component of assessing kidney function post-solid organ transplantation and in monitoring risk of acute injury. Our objective was to evaluate estimated glomerular filtration rate (eGFR) as derived from creatinine (eGFR_cr), cystatin C (eGFR_cys), and both (eGFR_cr-cys) in a cohort of transplant recipients.

Methods: A total of 47 unique post-solid organ transplant patients receiving tacrolimus were included. Residual specimens were assayed for creatinine (Jaffe and enzymatic), cystatin C, and tacrolimus. eGFR was estimated using the 2021 CKD-EPI formulae. Results were compared by Deming regression and bias was assessed using non-parametric cumulative distribution plots. Percent agreement in chronic kidney disease (CKD) by stage was evaluated across equations.

Results: eGFR_c_ys relative to eGFR_c_r estimates demonstrated a median bias of -22 mL/min/1.73 m² and an overall 21.3 % [95 % CI: 12.1, 35.0] agreement in CKD staging. eGFR_cr-cys demonstrated a median bias of -14 mL/min/1.73 m² and overall agreement of 34.0 % [95 % CI: 22.3, 48.4] relative to eGFR_cr (enzymatic). Discordance increased proportionally with eGFR and did not differ by creatinine assay (Jaffe or enzymatic).

Conclusion: Cystatin C incorporation leads to markedly negative biases between eGFR estimates in patients with solid organ transplant, implying lack of applicability of eGFR_cys or GFR_cr-cys in the transplant setting. This highlights the dependency of patient characteristics on equation performance and the need to consider confounding factors in interpretation and utilization of cystatin C based equations.

Keywords: 2021 CKD-EPI; Jaffe; chronic kidney disease; corticosteroids; creatinine; cystatin C; eGFR; enzymatic creatinine; estimated glomerular filtration rate; immunosuppression; kidney transplant recipients; lung transplant recipients; picrate; picric acid; prednisolone; tacrolimus; transplant; trimethoprim.