Kidney Week

Abstract: TH-PO0101

Rare Variants in the Sulfate Transporter SLC26A1 Strongly Affect Plasma Sulfate Levels

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Clinical 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

• 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Pitzken, Felix, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Felix Pitzken

• Vaughan, Lisa E., Mayo Clinic Department of Quantitative Health Sciences, Rochester, Minnesota, United States

Lisa E. Vaughan, MS

• Song, Esther Gawon, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Esther Gawon Song

• Penter, Tiberius Carl Friedrich, Charite - Universitatsmedizin Berlin, Berlin, BE, Germany

Tiberius Carl Friedrich Penter

• Bizer, Benjamin, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

Benjamin Bizer, MD

• Olson, Janet Elaine, Mayo Clinic Department of Quantitative Health Sciences, Rochester, Minnesota, United States

Janet Elaine Olson, PhD, MPH

• Aronson, Peter S., Yale School of Medicine, New Haven, Connecticut, United States

Peter S. Aronson, MD, FASN

• Knauf, Felix, Mayo Clinic Division of Nephrology and Hypertension, Rochester, Minnesota, United States

Felix Knauf, MD

Background

Fracture risk and disordered bone mineralization are well-recognized consequences of impaired renal mineral handling, but current frameworks largely overlook sulfate homeostasis. SLC26A1 mediates proximal tubular sulfate reabsorption, and recent studies have linked damaging SLC26A1 variants to hyposulfatemia and musculoskeletal phenotypes. However, these analyses were limited by semiquantitative sulfate measurements and small numbers of variant carriers.

Methods

We analyzed absolute plasma sulfate concentrations in 3,751 individuals from the Mayo Clinic Biobank (N = 52,863) (mean age 59 years; 61% female), including 1,250 qualifying SLC26A1-variant carriers and 2,501 randomly selected age- and sex-matched controls. Absolute plasma sulfate concentrations were quantified by IC-MS/MS using isotopically labeled internal standards and compared between cases and controls using Welch's unequal variance t-test. Variant-specific plasma sulfate effects among variants with more than 10 carriers were evaluated using one-way ANOVA.

Results

SLC26A1 variant carriers exhibited significantly lower absolute plasma sulfate concentrations compared with controls (mean ± SD: 295 ± 94 vs. 319 ± 90 µM, absolute change of−25 µM, (95% CI −30 to −18 ; -7.5 percent change, p < 0.001). Among SLC26A1 variants with more than 10 carriers, Ser358Leu, Leu483Gln, Arg372Leu, and Arg515Cys were associated with the largest observed plasma sulfate reductions relative to controls, ranging from −21.3% to −25.5% (all p < 0.01).

Conclusion

These findings support an association between rare SLC26A1 variants and reduced plasma sulfate concentrations in humans. Additional analyses are ongoing to evaluate musculoskeletal traits and the broader clinical implications of genetically reduced sulfate homeostasis by SLC26A1.

Acknowledgment

We thank the Mayo Clinic Biobank participants and study team for their support and contribution to this work.

Violin plot of plasma sulfate concentration in controls and SLC26A1 variant carriers.

Funding

• Private Foundation Support