Towards clinical translation of urinary vitronectin for non-invasive detection and monitoring of renal fibrosis in kidney transplant patients

Background: Interstitial fibrosis and tubular atrophy (IFTA) is a critical factor in the prognosis of kidney health. Currently, IFTA quantitation in kidney biopsy samples is crucial for diagnosis and assessing disease severity, but the available non-invasive biomarkers are not satisfactory. Proteomic studies identified urinary vitronectin (VTN) as a potential biomarker for kidney fibrosis. As mass spectrometry techniques are not practical for use in clinical settings, we tested whether evaluation of urinary VTN levels through enzyme-linked immunosorbent assay (ELISA) can help monitor fibrotic changes in kidney transplant recipients and prove the clinical viability of the assay.

Methods: A total of 58 kidney transplant (KTx) patients who underwent renal biopsy were included in the study. Patients were categorized into two groups referred as no fibrosis (0%) or with fibrosis (≥ 5%) based on their histological findings. In a subsequent/follow-up analysis, the time elapsed from transplantation was also considered. The urinary levels of VTN were measured using ELISA.

Results: VTN (p = 0.0180) and VTN normalized by urinary creatinine levels (p = 0.0037), were significantly increased in patients with fibrotic grafts. When focusing on patients with long-term grafts (> 3 years from transplantation, n = 36), VTN exhibited superior potential in identifying fibrotic grafts compared to albuminuria (VTN p = 0.0040 vs. albuminuria p = 0.0132). Importantly, in this group, while albuminuria correctly identified 71% of fibrotic patients, the combination of VTN plus albuminuria correctly classified 89% of fibrotic grafts detected by renal biopsy.

Conclusions: VTN has emerged as a valid indicator of renal fibrosis. Of interest, urinary levels of VTN in combination with conventional clinical parameters (such as albuminuria) significantly improved the non-invasive detection of renal fibrosis in kidney transplant patients.