Kidney Week

Abstract: TH-PO0211

Transient MOTS-c Surge Unmasks Impaired Mitochondrial Stress Signaling in Human Renovascular Disease

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Elmaraezy, Ahmed, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

Ahmed Elmaraezy, MD

• Yoon, Se-Hee, Mayo Clinic Division of Nephrology and Hypertension, Rochester, United States

Se-Hee Yoon, MD, PhD

• Yuan, Fei, Mayo Clinic Division of Nephrology and Hypertension, Rochester, United States

Fei Yuan, MD

• Zhu, Xiang yang, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

Xiang yang Zhu, MD, PhD

• Tang, Hui, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

Hui Tang

• Eirin, Alfonso, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

Alfonso Eirin, MD

• Wan, Junxiang, University of Southern California, Los Angeles, California, United States

Junxiang Wan

• Cohen, Pinchas, University of Southern California, Los Angeles, California, United States

Pinchas Cohen, MD

• Lerman, Lilach O., Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

Lilach O. Lerman, MD, PhD, FASN

Background

Renovascular disease (RVD) causes chronic renal ischemia and mitochondrial dysfunction. Percutaneous transluminal renal angioplasty (PTRA) often fails to restore kidney function, potentially partly due to ischemia-reperfusion injury (IRI), but mitochondrial involvement is unclear. Mitochondrial Open Reading Frame of the 12S rRNA-c (MOTS-c) is a mitokine with cytoprotective/antioxidant properties secreted in response to mitochondrial stress, but its role in renal ischemia is unknown.

Methods

Circulating MOTS-c was prospectively measured in 15 RVD patients before, 3h, and 3mo post-PTRA and in 10 healthy volunteers (HV). MOTS-c was compared with GDF15, FGF21, tubular injury markers (NGAL, KIM-1, TIMP-2, IGFBP-7), and renal oxygenation (BOLD MRI, R2*). ANOVA, correlations, and mixed-effects models adjusted for age, sex, BMI, eGFR, MAP, and creatinine were performed.

Results

Baseline MOTS-c was lower in RVD vs. HV (111.6 vs. 219.1 pg/ml, P<0.0001), and RVD independently predicted MOTS-c after adjustment (β=−60.4, P=0.018). At 3h post-PTRA, MOTS-c increased to HV levels (P=0.99), but returned to baseline by 3mo (P=0.006 vs. HV, Fig.1A). Serum creatinine remained unchanged, while RVD-GFR slightly increased at 3mo (P=0.026 vs. baseline). MOTS-c correlated with NGAL (r(rm)=−0.475, P=0.016) and KIM-1 (r(rm)=0.397, P=0.0496, Fig.1B-C). Cortical hypoxia (R2*) showed a similar pattern and independently associated with MOTS-c levels (β=8.79, P=0.002, Fig.1D). GDF15 remained elevated in RVD, and both GDF15 and FGF21 correlated with MOTS-c over time (r(rm)=0.41, P=0.023; r(rm)=0.43, P=0.015, Fig.1E-F). MOTS-c independently predicted GDF15 (β=2.64, P=0.028) and FGF21 (β=0.45, P=0.018).

Conclusion

Basal circulating MOTS-c level is suppressed in RVD, suggesting inadequate mitochondrial function. Transient post-PTRA MOTS-c elevation, coupled with GDF15 and FGF21, identifies a coordinated mitochondrial stress response linked to acute renal hypoxia and tubular injury. These observations warrant further investigations into mitochondrial function as a potential therapeutic target in RVD.

Funding

• Other NIH Support