ROLE OF MEMBRANE TRANSPORTERS IN TRANSEPITHELIAL OXALATE SECRETION USING A SIMPLE, GENETICALLY-MODIFIABLE RENAL EPITHELIUM

Certificate Output Instructions

For best output, select "Paper Size" as "A4" and "Margin" as "0" or "None".

To save or print to PDF, please select Print Destination > Save as PDF, enable Background Graphics under "More Settings", then click "Save".

Presented the abstract " "
(Abstract co-author(s): )

Back

E-Poster Presentation

During the congress, E-Posters will be accessible to all participants on the congress website 24/7, as well as in the E-poster stations in the congress center.

Preparing your E-Poster

Please review the E-Poster format requirements carefully when preparing your E-Poster. Should your E-Poster not meet the mentioned requirements, it may not be displayed as described above.

E-Poster Submission Deadline

Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.

E-Poster Format Requirements

PDF file
Layout: Portrait (vertical orientation)
One page only (Dim A4: 210 x 297mm or PPT)
E-Poster can be prepared in PowerPoint (one (1) PowerPoint slide) but must be saved and submitted as PDF file.
File Size: Maximum file size is 2 Megabytes (2 MB)
No hyperlinks, animated images, animations, and slide transitions
Language: English
Include your abstract number
E-posters can include QR codes, tables and photos

E-Poster

Abstract Title *

ROLE OF MEMBRANE TRANSPORTERS IN TRANSEPITHELIAL OXALATE SECRETION USING A SIMPLE, GENETICALLY-MODIFIABLE RENAL EPITHELIUM

Please follow the instructions below to input your abstract title.

Abstract titles should be brief and reflect the content of the abstract.

The title will not be accepted if it exceeds 25 words.
Type in CAPITAL LETTERS.
Lowercase may be used for abbreviations only, for example, mRNA.

Co-author 1

Michael Romero romero.michael@mayo.edu Mayo Clinic Physiology & Biomed Engineering; Nephrology Rochester, MN United States *

Co-author 2

Buthainah Alsultan balsultan@alfaisal.edu Alfaisal University College of Medicine Medicine Riyadh Saudi Arabia - Mayo Clinic Physiology & Biomed Engineering Rochester, MN United States

Co-author 3

Oguz Kanca Oguz.Kanca@bcm.edu Baylor College of Medicine Molecular & Human Genetics Houston, TX United States -

Co-author 4

Adna Hassan Hassan.Adna@mayo.edu Mayo Clinic Physiology & Biomed Engineering Rochester, MN United States -

Co-author 5

Co-author 6

Co-author 7

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

70-80% of kidney stones are calcium oxalate (CaOx). Yet, our understanding of CaOx stone formation is incomplete limiting treatments (e.g., lithotripsy, percutaneous nephrolithotomy). Using mammalian kidney models, three enzymes were identified to cause hyperoxaluria, and urinary supersaturation is implicated as a CaOx stone driver. However, complexities of mammalian transepithelial oxalate (ox2‑) movements (gut, kidney) hinder determining CaOx stone cause-effect relationships.

Methods

Therefore, we use a functionally similar, simple genetic model (Drosophila Malpighian tubules, MT) to measure renal CaOx crystallization (NaOx feeding), membrane transport (intracellular pH, fluorescence, pH sensors) and ox2‑ secretion (ion chromatography). Candidate transporter-channel genes are tested for transepithelial oxalate secretion with gene-specific knockdown or knockout using CRIMIC (CRISPR-Mediated Integration Cassette) alleles in MTs due to comparable function to mammalian nephrons.

Results

MTs consist of two epithelial cell types, Stellate and Principal cells, with each transporting different solutes from the hemolymph to MT lumen. Our lab identified several membrane transporters involved: Prestin (Slc26a6, apical), Neat (Slc26a1-like, basal) and Ndae1 (Slc4a8-like, basal). Neat (2HCO3‑/ox2‑ exchange) and NDAE1 (Na+,2HCO3‑/Cl- exchange) functionally combine to takeup hemolymph ox2‑. Prestin then secretes ox2‑ via Cl-/ ox2‑exchange to create luminal MT CaOx crystals. Prestin or Neat knockdowns in principal cells decrease CaOx crystals. NDAE1 knockdown in principal cells decreases CaOx crystals and HCO3‑ transport (A), however, stellate cell knockdown of NDAE1 increases CaOx crystals like AQP (Drip, Prip)-knockdowns and enhances HCO3‑ transport (B).

Figure: Malpighian principal and stellate cells both contribute to bicarbonate and oxalate transport. (A) Principal cell HCO3‑ transport (recovery) is due to NDAE1 activity. (B) Some stellate cells have robust HCO3‑ influx. (C) Epithelial transporters moving oxalate and HCO3‑.

Conclusion

Neat and NDAE1 work together to take-up hemolymph ox2‑ then Prestin secretes ox2‑ into the MT lumen (C). Using CRIMIC alleles, we will measure CaOx crystals, ox2‑ secretion and pH regulation. These experiments will replace knocked-out Drosophila genes by a human homolog cDNA to measure functional recovery. Humanizing this simple epithelial will allow functional impact testing of variants of unknown significance (VUS) in human genes. [prior presentation: 2025 CARIBU meeting]

Kewords