Associations of Serum Uromodulin and Urinary Epidermal Growth Factor with Measured Glomerular Filtration Rate and Interstitial Fibrosis in Kidney Transplantation

Joe Chan, My Svensson, Tone M Tannæs, Bard Waldum-Grevbo, Trond Jenssen, Ivar A Eide, Joe Chan, My Svensson, Tone M Tannæs, Bard Waldum-Grevbo, Trond Jenssen, Ivar A Eide

Abstract

Introduction: Noninvasive biomarkers that reflect tubular health and allow early recognition of accelerated graft fibrosis development are warranted. Serum uromodulin (sUmod) and urinary epidermal growth factor (uEGF) originate from kidney tubules and may reflect functional nephron mass. The aim of this study was to investigate the associations between sUmod and uEGF with measured glomerular filtration rate (mGFR) and kidney allograft interstitial fibrosis percentage (IF%) score.

Methods: sUmod and uEGF measurements, mGFR by iohexol-clearance and kidney allograft biopsies were obtained from kidney transplant recipients (KTRs) included in the Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial at 8 weeks (baseline) and at 1 year after transplantation (end of study). Associations were analyzed with univariable and multivariable linear regression.

Results: Ninety patients at baseline and 48 patients at end of study had complete study variable assessments. uEGF normalized to urinary creatinine (uEGF/Cr) was associated with mGFR both at baseline (standardized β-coefficient [Std. β-coeff] = 0.457 [p = <0.001]) and at end of study (Std. β-coeff = 0.637 [p = <0.001]). sUmod was only associated with mGFR at end of study (Std. β-coeff = 0.443 [p = 0.002]). uEGF/Cr, sUmod, and mGFR were associated with graft IF% score both at baseline (Std. β-coeff = -0.349 [p = 0.001], -0.274 [p = 0.009] and -0.289 [p = 0.006], respectively) and at end of study (Std. β-coeff = -0.365 [p = 0.011], -0.347 [p = 0.016] and -0.405 [p = 0.004], respectively). The results remained largely unchanged in multivariable analysis.

Conclusion: uEGF/Cr and sUmod were associated with mGFR and graft IF% score. Our results indicate a possible role of uEGF/Cr and sUmod in the follow-up of KTRs.

Keywords: Epidermal growth factor; Interstitial fibrosis; Kidney transplantation; Measured glomerular filtration rate; Uromodulin.

Conflict of interest statement

The other authors have no disclosures. The results presented in this article have not been published previously in whole or part.

© 2022 The Author(s). Published by S. Karger AG, Basel.

Figures

Fig. 1
Fig. 1
Scatter plot with linear regression line showing association between change in sUmod and change in uEGF during follow-up.
Fig. 2
Fig. 2
Scatter plots with linear regression lines showing associations of uEGF and sUmod with measured glomerular filtration rate at baseline and at end of study.
Fig. 3
Fig. 3
Scatter plots with linear regression lines showing associations of measured glomerular filtration rate, uEGF, and sUmod with graft interstitial fibrosis percentage score at baseline and at end of study.

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