# Urinary apolipoprotein A4 as a biomarker for renal allograft injury in kidney transplant recipients

**Authors:** Youn Kyung Kee, Dong Ho Shin, Jieun Oh, Ji Young Park, Dong Hyun Kim, Kyungjai Ko, Samuel Lee, Hee Jung Jeon

PMC · DOI: 10.1371/journal.pone.0324529 · PLOS One · 2025-05-21

## TL;DR

This study shows that higher levels of urinary apolipoprotein A4 may indicate kidney transplant rejection and could help predict rapid loss of kidney function.

## Contribution

The study identifies urinary apolipoprotein A4 as a novel potential biomarker for monitoring kidney transplant recipients.

## Key findings

- Urinary ApoA-IV levels inversely correlate with estimated glomerular filtration rate (GFR) in kidney transplant recipients.
- Higher ApoA-IV levels are significantly associated with rapid renal function decline.
- ApoA-IV shows strong predictive power with an area under the ROC curve of 0.834 for rapid function decline.

## Abstract

Chronic renal allograft injury (CRAI) is a major cause of allograft loss in kidney transplant recipients (KTRs). The aim of this study was to evaluate the associations of urinary apolipoprotein A4 (ApoA-IV) levels with renal function and rapid renal function decline in KTRs. This study included 50 KTRs. Proteomic analysis via liquid chromatography‒mass spectrometry and tandem mass spectrometry (LC-MS/MS) was performed to identify potential urinary biomarkers. The SWATH (sequential window acquisition of all theoretical mass spectra) method was used for protein quantification. Urinary ApoA-IV levels were validated by enzyme-linked immunosorbent assay (ELISA). Rapid renal function decline was defined as an estimated glomerular filtration rate (GFR) decrease of >3 mL/min/1.73 m2 per year or initiation of dialysis. The log-transformed urinary ApoA-IV levels measured by ELISA had a significantly inverse correlation with the estimated GFR (r = -0.72, P < 0.001). Moreover, urinary ApoA-IV levels were higher in patients with rapid renal function decline than in those with stable renal function (215.4 ± 181.8 μg/mL vs. 42.5 ± 72.4 μg/mL, P = 0.001). Univariate logistic regression analysis revealed that log-transformed urinary ApoA-IV levels were significantly associated with rapid renal function decline (odds ratio [OR] 6.70, 95% confidence interval [CI] 2.56–22.83; P < 0.001). Multiple logistic regression showed urinary ApoA-IV levels remained a significant risk factor for rapid renal function decline (OR 4.10, 95% CI 1.10–19.55; P = 0.047). ROC curve analysis revealed the area under the curve (AUC) of 0.834 (95% CI 0.722–0.945, P < 0.001) for urinary ApoA-IV levels in predicting rapid renal function decline. Our results suggest that urinary ApoA-IV levels might be a potential biomarker for renal allograft function and could be used as a predictor for rapid renal function decline in KTRs.

## Full-text entities

- **Genes:** APOA4 (apolipoprotein A4) [NCBI Gene 337] {aka ADTKD6}
- **Diseases:** renal function (MESH:D058186), renal allograft injury (MESH:D007674), CRAI (MESH:D051436), Rapid renal function decline (MESH:C538001)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12094748/full.md

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Source: https://tomesphere.com/paper/PMC12094748