Urine biomarker flags kidney transplant rejection before it strikes

The study, published in Molecular Biology Reports, enrolled 52 participants: 15 kidney transplant recipients who went on to develop biopsy-proven rejection, 17 recipients whose grafts remained clinically stable, and 20 healthy controls. The team, led by Samar Bizhani with colleagues including Afsoon Afshari, Ramin Yaghobi and Jamshid Roozbeh, collected paired urine and blood samples in the early postoperative period and measured a panel of non-coding RNA molecules using SYBR Green-based quantitative real-time PCR.

The standout finding concerned hsa_circ_0001334, a circular RNA derived from the MCM2 host gene. Urinary levels of this molecule were markedly upregulated in recipients who subsequently developed rejection, with a p-value below 0.0001. Crucially, the linear host gene MCM2 itself showed no such change, suggesting the circular form carries specific information rather than simply reflecting general transcriptional activity.

They are thought to act as sponges for microRNAs within competitive endogenous RNA networks, indirectly regulating protein-coding genes.

The researchers also examined a putative regulatory axis involving hsa_circ_0001334, the microRNA hsa-miR-665, and the CNR2 messenger RNA. In recipients who later developed biopsy-proven rejection, urinary hsa-miR-665 expression was lower while CNR2 expression was higher, a pattern consistent with the proposed sponge mechanism in which the circular RNA sequesters the microRNA and lifts its repression of the target gene. The authors suggest this axis may participate in immune-mediated injury during allograft rejection.

A second circular RNA, hsa_circ_0071475, showed only a modest elevation compared with healthy controls and no change in blood, underscoring that the signal was specific to one molecule and one compartment. The panel also included related microRNAs hsa-miR-1208 and hsa-miR-1183 and the target mRNA ADORA2B, analysed alongside non-parametric statistical tests, Spearman correlation and receiver-operating-characteristic analysis.

Receiver-operating-characteristic analysis yielded an area under the curve of 1.00 for urinary hsa_circ_0001334, with a p-value of 0.0006, indicating perfect preliminary discrimination between recipients who later rejected and those who did not. The authors are careful to characterise this as preliminary predictive discrimination from a small cohort rather than validated diagnostic performance, and they call for confirmation in larger independent cohorts.

The authors position urinary hsa_circ_0001334 as a candidate for early risk stratification of subsequent rejection rather than a replacement for histological diagnosis.

Several caveats temper the excitement. Functional studies demonstrating that the circRNA-microRNA-mRNA axis causally contributes to rejection have not yet been performed, and the authors explicitly state that further validation and mechanistic work are required to confirm clinical utility.

Subject of Research: A circular RNA biomarker in urine associated with subsequent kidney allograft rejection

Article Title: Urinary circRNA hsa_circ_0001334: a potential non-invasive early indicator of subsequent renal allograft rejection

Article References: Bizhani, S., Afshari, A., Yaghobi, R., & Roozbeh, J. (2026). Urinary circRNA hsa_circ_0001334: a potential non-invasive early indicator of subsequent renal allograft rejection. Molecular Biology Reports, 53(1), Article 1825. https://doi.org/10.1007/s11033-026-13047-4

Image Credits: AI Generated

DOI: 10.1007/s11033-026-13047-4

Keywords: circular RNA, kidney transplant, allograft rejection, biomarker, urine test, hsa_circ_0001334, ceRNA, hsa-miR-665, CNR2, ROC analysis, non-invasive diagnostics, Molecular Biology Reports