How the kidney maintains sulfate homeostasis in the body

Sulfate is an anion that is found in many foods. Sulfate plays a critical role in the metabolism of proteins, carbohydrates and fats. The anion has been shown to have antioxidant and anti-inflammatory properties, which may help to protect against certain illnesses. Moreover, sulfate is essential to maintain bone health. The kidney plays a central role in transporting sulfate from tubular fluid, thereby keeping it in the body. However, relatively little is know so far about disorders in sulfate metabolism. Their discovery of the researchers is based on careful work-up of a single patient, who presented with unexplained chronic chest pain and a kidney stone. By combining clinical and genetic analyses in the patient with functional expression assays, the groups of Professors Felix Knauf (Department of Nephrology and Medical Intensive Care, Charité, Berlin) and Thomas Jentsch (Leibniz-Forschungsinstitut für Molekulare Pharmakologie and Max Delbrück Center) demonstrated that a mutation in the transporter SLC26A1 found in this patient resulted in reduced function of this transporter, thereby causing sulfate deficiency due to sulfate loss in the urine. To further extend these findings to a population level, the group of Professor Anna Köttgen in Freiburg used genetic data of >5,000 individuals enrolled in the German Chronic Kidney Disease study (PI Professor Kai-Uwe Eckardt) and identified 43 variants in the gene coding the SCL26A1 transporter, whereby variants of transporter function were significantly associated with lower plasma sulfate concentrations.

In summary, by using an interdisciplinary and complementary research approach, the investigators identified a sulfate retaining transport mechanism in the kidney as a major determinant of sulfate homeostasis in humans. In view of recent evidence linking sulfate homeostasis to bone disorders, this transport mechanism may be important for musculoskeletal health.

Anja Pfau, Karen I. López-Cayuqueo, Nora Scherer, Matthias Wuttke, Annekatrin Wernstedt,Daniela González Fassrainer, Desiree E.C. Smith,
Jiddeke M. van de Kamp, Katharina Ziegeler, Kai-Uwe Eckardt, Friedrich C. Luft, Peter S. Aronson, Anna Köttgen, Thomas J. Jentsch and Felix Knauf.
SLC26A1 is a major determinant of sulfate homeostasis in humans. JCI, doi: 10.1172/JCI161849