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. 2024 Mar 27;17(5):sfae091.
doi: 10.1093/ckj/sfae091. eCollection 2024 May.

Performances of acute kidney injury biomarkers vary according to sex

Stanislas Faguer  1   2   3 , Alexis Piedrafita  1   2   3 , Ana Belen Sanz  4 , Justyna Siwy  5 , Ioanna K Mina  5   6 , Melinda Alves  2   3 , Paul Bousquet  7 , Bertrand Marcheix  3   8 , Audrey Casemayou  1   2   3 , Julie Klein  2   3 , Vincent Minville  3   7 , Benjamin Breuil  2   3 , Alberto Ortiz  4 , Joost P Schanstra  2   3
Affiliations

Performances of acute kidney injury biomarkers vary according to sex

Stanislas Faguer et al. Clin Kidney J. .

Abstract

Background: Before implementing individualized strategies to treat acute kidney injury (AKI), identifying clusters of patients with divergent pathophysiological mechanisms, diagnosis criteria or outcomes is of the utmost importance. Here we studied sex-related molecular mechanisms in cardiac bypass (CBP) surgery patients developing AKI.

Methods: We compared the characteristics of 1170 patients referred for CBP surgery using multivariate logistic regression and propensity score-based analysis. Performances of the candidate urinary biomarkers at <4 h post-surgery, urinary neutrophil gelatinase-associated lipocalin (uNGAL), [IGFBP7]·[TIMP-2] product (NephroCheck) and a recently developed AKI signature of 204 urinary peptides (AKI204) to predict AKI were compared in both sexes.

Results: Incidence (∼25%) and severity of AKI were similar in men and women, even after adjustment for the usual risk factors of AKI, including baseline estimated glomerular filtration rate, age, diabetes mellitus, length of CBP and red blood cell transfusion. However, at the molecular level, performances of uNGAL, NephroCheck and AKI204 to predict AKI strongly diverged between men and women. In the full cohort, as well as in subgroups of men and women, the multimarker AKI204 signature outperformed uNGAL and NephroCheck and predicted the development of AKI significantly better in women than in men. Analysis of AKI204 at the single-peptide level suggested divergences of AKI mechanisms between sexes due to increased kidney inflammation in women (increased abundance of urinary fragments of osteopontin and uromodulin).

Conclusions: In patients referred for CBP surgery, significant clinical and biological differences between men and women as well as sexual dimorphism of AKI biomarker performances were identified. The urinary peptide signature points to sex-related molecular mechanisms underlying AKI.

Keywords: NGAL; NephroCheck; acute kidney injury; biomarkers; peptidomics; sexual dimorphism.

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Conflict of interest statement

J.S. and I.A. are employees of Mosaiques Diagnostics

Figures

Figure 1:
Figure 1:
Performances of urinary biomarkers to predict AKI in a cohort of CBP surgery patients (receiver operating characteristics curves analysis). (A) Overall cohort, all biomarkers (AKI204 versus uNGAL, P < .001; AKI204 versus NephroCheck, P < .001; uNGAL versus NephroCheck, P = .38. Men and women assessed separately for (B) AKI204 (P < .001), (C) NephroCheck (P = .002) and (D) uNGAL (P < .001). (E) Men, all biomarkers (AKI204 versus uNGAL, P < .001; AKI204 versus NephroCheck, P = .15; uNGAL versus NephroCheck, P = .08). (F) Women, all biomarkers (AKI204 versus uNGAL, P = .002; AKI204 versus NephroCheck, P < .001; uNGAL versus NephroCheck, P = .04).
Figure 2:
Figure 2:
Urinary peptides 3–4 h after CBP surgery that are significantly divergent in women or men developing AKI among the 204 peptides of AKI204. Peptides with P-values <.05 (after Benjamin–Hochberg correction for multiple testing) are reported (mixed effects analysis of AKI and gender).
See this image and copyright information in PMC

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