New leads to advance our understanding of
heart failure (HF) pathophysiology are urgently needed. Previous studies have linked urinary
sulfate excretion to a favorable cardiovascular risk profile.
Sulfate is not only the end product of
hydrogen sulfide metabolism but is also directly involved in various (patho)physiological processes, provoking scientific interest in its renal handling. This study investigates
sulfate clearance in chronic HF (CHF) patients and healthy individuals and considers its relationship with disease outcome. Parameters related to renal
sulfate handling were determined in and compared between 96 previously characterized CHF patients and sex-matched healthy individuals. Among patients,
sulfate clearance was analyzed for associations with clinical and outcome parameters. In CHF patients, plasma
sulfate concentrations are significantly higher, whereas 24-h urinary excretion, fractional excretion, and clearance of
sulfate are significantly lower, compared with healthy individuals. Among patients,
sulfate clearance is independently associated with
diuretics use,
creatinine clearance and 24-h urinary
sodium excretion.
Sulfate clearance is associated with favorable disease outcome [hazard ratio per SD increase 0.38 (95% confidence interval 0.23-0.63), P < 0.001]. Although significance was lost after adjustment for
creatinine clearance, the decrease of
sulfate clearance in patients is independent of this parameter, indicating that
sulfate clearance is not merely a reflection of renal function. This exploratory study reveals aberrant
sulfate clearance as a potential contributor to CHF pathophysiology, with reduced levels in patients and a positive association with favorable disease outcome. Further research is needed to unravel the nature of its involvement and to determine its potential as a
biomarker and target for
therapy.NEW & NOTEWORTHY
Sulfate clearance is decreased in chronic
heart failure patients compared with healthy individuals. Among patients,
sulfate clearance is positively associated with favorable disease outcome, i.e., a decreased
rehospitalization rate and increased patient survival. Hence, decreased
sulfate clearance may be involved in the pathophysiology of
heart failure.