Kidney Week

Abstract: TH-PO0035

Vasopressin Increases Apical ROMK Expression in the Inner Stripe of the Outer Medullary Thick Ascending Limb

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

• Bellingkrodt, Antonia Lucrezia, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Antonia Lucrezia Bellingkrodt

• Curry, Joshua N., Oregon Health & Science University, Portland, Oregon, United States

Joshua N. Curry, MD, PhD

• Ellison, David H., Oregon Health & Science University, Portland, Oregon, United States

David H. Ellison, MD, FASN

• Bahena-López, Jessica Paola, Oregon Health & Science University, Portland, Oregon, United States

Jessica Paola Bahena-López, MD, PhD

• Bachmann, Sebastian, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Sebastian Bachmann, PhD

Background

Using quantitative immunofluorescence imaging and enriched thick ascending limb (TAL) transcriptomics, we recently identified cellular heterogeneity within the TAL including distinct ROMK-positive and ROMK-negative cell populations associated with claudin mosaicism (PMID: 40471686). Transcriptional profiling demonstrated higher expression of the vasopressin receptor Avpr2 within medullary TAL subpopulations, including both ROMK-positive (TAL- α) and ROMK-negative (TAL-γ) populations of the inner stripe of the outer medulla (ISOM). We hypothesized that activation of AVPR2 signaling with the selective agonist desmopressin (ddAVP) would lead to increased apical ROMK expression within medullary TAL subpopulations.

Methods

Brattleboro rats, which lack endogenous vasopressin, were treated with either vehicle or ddAVP. Animals were euthanized at multiple time points following treatment (30 minutes, 7 hours, and 72 hours). Kidneys were perfusion-fixed and processed for quantitative immunofluorescence microscopy. Apical ROMK localization and the fraction of ROMK-negative TAL cells were quantified across distinct nephron regions, including cortex, outer stripe, and ISOM, with assessment of the fraction of ROMK-negative TAL cells. In situ hybridization was performed for qualitative imaging of ROMK mRNA transcripts.

Results

Treatment with ddAVP significantly reduced the fraction of ROMK-negative TAL cells within the ISOM at both 7 hours and 72 hours compared with vehicle-treated controls (both p<0.05). In contrast, no significant change in the proportion of ROMK-negative cells was observed within the cortex or outer strip of the outer medulla following ddAVP treatment. Using in situ hybridization, we found that ROMK mRNA signal was increased in TAL cells within the ISOM.

Conclusion

Desmopressin promotes increased apical ROMK expression within ISOM TAL cell populations. Given medullary TAL subpopulations are characterized by apical ROMK expression (TAL-α) or basolateral Kir4.1 expression (TAL-γ), these findings raise the possibility that vasopressin signaling induces TAL-γ cells to adopt a more TAL-α–like phenotype. Whether this represents transient regulation of ROMK localization/expression or a broader cell-state transition within medullary TAL remains unknown. Future studies will aim to determine whether these changes reflect reversible physiologic adaptation or stable phenotypic remodeling.

Acknowledgment

Supported by NIH grants 1R01DK142027 (DHE), K08DK147727 (JNC), 26CDA1614573 (JNC).

Funding

• NIDDK Support