Sulfate handling in proximal renal tubular defects: an exploratory study

Renal tubular disease causes loss of electrolytes and other molecules. One of these electrolytes is inorganic sulfate, which is reabsorbed by dedicated transporters, including NaS1, encoded by the SLC13A1 gene. Still, inorganic sulfate is rarely measured in clinical practice, although it is essential for the development and functioning of several organ systems. The importance of adequate sulfate stores is emphasized by genetic disorders impairing sulfate metabolism in the brain, bone, and the endocrine system, causing severe neurodevelopmental disorders, skeletal dysplasia, and hormonal imbalance. Low availability due to renal loss of inorganic sulfate has also been linked to these disorders. We aimed to assess the prevalence of renal inorganic sulfate wasting in renal tubular diseases in a small cohort as an exploratory study.

Inorganic sulfate was measured in serum and urine of patients with proximal renal tubular disorders using remnant material obtained during routine check-ups. Fractional excretion of inorganic sulfate was calculated alongside plasma inorganic sulfate concentrations and cystatin C-based eGFR.

Fourteen patients were included, in whom 1 to 4 paired measurements of urine and plasma inorganic sulfate were available. Five patients had decreased plasma sulfate on at least one occasion; 13 patients had increased fractional excretion in at least one measurement. In patients with cystinosis, during cysteamine treatment plasma inorganic sulfate levels were often normal despite increased fractional excretion.

Increased inorganic sulfate loss is prevalent in children with proximal tubular defects and sulfate stores can be repleted by oral drugs like cysteamine.