Long Non-Coding RNA NNT-AS1 Links Inflammation, Tubular Injury, and Prognosis in Septic AKI.
Journal
Nephrology (Carlton, Vic.)
Journal Volume
30
Journal Issue
11
Start Page
Article number e70142
ISSN
1440-1797
Date Issued
2025-11
Author(s)
Chou, Yu-Ting
Abstract
The recent study by Zhang et al. explored the prognostic value of the long non-coding RNA (lncRNA) NNT-AS1 in patients with sepsis-induced acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). The identification of NNT-AS1 as an independent predictor of 28-day mortality, and the exploration of its possible role in tubular injury via miR-582-5p regulation mark an important advance in the study of AKI and deserve recognition (Figure 1). Sepsis-induced AKI represents one of the most devastating complications in critical care, with mortality rates exceeding 50% in patients requiring CRRT [1]. Beyond hemodynamic instability and systemic inflammation, molecular mechanisms driving tubular injury and impaired renal recovery are increasingly recognized as pivotal determinants of outcomes and prognosis [2]. lncRNAs have emerged as important regulators of gene expression in kidney injury, modulating processes such as oxidative stress, inflammation, and apoptosis [3]. Among them, NNT-AS1—a natural antisense transcript of nicotinamide nucleotide transhydrogenase—has been linked to diabetic nephropathy [4], and renal cell carcinoma [5]. NNT-AS1 appears to function primarily through a competitive endogenous RNA (ceRNA) mechanism, sponging microRNAs (miRNAs) such as miR-582-5p [6], thereby influencing downstream inflammatory and oxidative pathways. In their recent study, Zhang et al. extend these findings to clinical practice by demonstrating that elevated serum NNT-AS1 levels in patients with sepsis-induced AKI undergoing CRRT are independently associated with increased 28-day mortality. Their remarkable clinical results are supported by in vitro experiments. LPS-stimulated HK-2 cells provided a mechanistic model in which NNT-AS1 promotes oxidative stress, inflammatory cytokine release, and tubular injury via miR-582-5p suppression. Knockdown of NNT-AS1 attenuated these effects, improving cell viability and reducing apoptosis. This work is noteworthy in two respects. First, it identifies a novel RNA biomarker with a potential prognostic role in septic AKI. Combined with the well-established clinical scoring systems such as SOFA and APACHE II, early and more precise risk stratification is achievable. Second, it provides mechanistic insight into how NNT-AS1 may mediate renal injury in sepsis, opening promising opportunities for RNA-targeted therapies. Future studies validating NNT-AS1 across diverse AKI etiologies and assessing its dynamic changes during CRRT, will be essential to define its translational potential. The authors declare no conflicts of interest.
Subjects
acute renal failure (ARF)
continuous renal replacement therapy (CRRT)
inflammation
sepsis
SDGs
Type
editorial