The fate of sulfate in chronic heart failure

Abstract

37New leads to advance our understanding of heart failure (HF) pathophysiology are urgently 38 needed. Previous studies have linked urinary sulfate excretion to a favourable cardiovascular 39 risk profile. Sulfate is not only the end-product of hydrogen sulfide metabolism, but is also 40 directly involved in various (patho)physiological processes, provoking scientific interest in its 41 renal handling. This study investigates sulfate clearance in chronic HF (CHF) patients and 42 healthy individuals and considers its relationship with disease outcome. 43Parameters related to renal sulfate handling were determined in and compared between 96 44 previously characterized CHF patients and sex-matched healthy individuals. Among patients, 45 sulfate clearance was analysed for associations with clinical and outcome parameters. 46

SGLT2 inhibition versus sulfonylurea treatment effects on electrolyte and acid–base balance: secondary analysis of a clinical trial reaching glycemic equipoise: Tubular effects of SGLT2 inhibition in Type 2 diabetes

“…Because SGLT2 inhibition increases the luminal sodium gradient, this may explain the increase in plasma sulfate concentrations. In patients with heart failure sulfate clearance is related to diuretic use, creatinine clearance, and sodium excretion [22]. Thus, dapagliflozin may increase plasma sulfate, because of its diuretic properties and its effects on GFR and sodium excretion.…”

Pushing arterial-venous plasma biomarkers to new heights: A model for personalised redox metabolomics?

“…Unexpectedly, even the concentration of serum total free thiols was found to predict outcome in clinical conditions ranging from renal to cardiac disease [10], [22]; this may be due to the enhanced formation of cysteine and glutathione adducts with albumin under conditions of oxidative stress [5]. Even circulating sulfate, the final oxidation product of H 2 S and also a dietary constituent, may be of prognostic value in disease settings associated with oxidative stress [21]. In parallel with the renewed interest in the biological effects of these aminothiols and other sulfur-based mediators and biomarkers in biology, our group recently developed a novel mass spectrometry-based method that allows rapid and specific quantification of the plasma thiol metabolome with simultaneous measurement of aminothiols and sulfide [42].…”

Urinary Excretion of Sulfur Metabolites and Risk of Cardiovascular Events and All-Cause Mortality in the General Population

“…Although the interaction was only borderline significant, the observed trend substantiates the notion that urinary sulfate excretion is not a reflection of renal function. Interestingly, in CHF patients both urinary excretion and clearance, but not the plasma concentration of sulfate have been found to be associated with favorable disease outcome (18). Collectively, these findings suggest that the renal handling of sulfate is of importance.…”

“…This may create the impression that sulfate excretion is not directly connected to CVD and related mortality. However, studies on renal transplant recipients(45) and CHF patients (18) have shown urinary sulfate excretion to be associated with a beneficial CV risk profile and patient survival. It should also be noted that the definition of a CV event is limited to acute incidents, whereas CV causes of death also include chronic forms of CVD, such as CHF.…”

“…The final published version may differ from this proof. group has shown both urinary excretion and clearance of sulfate to be associated with a decreased rehospitalization rate and increased patient survival in chronic heart failure (CHF) (18). The apparent link to CV (patho)physiology led us to hypothesize that urinary excretion of sulfur metabolites is inversely associated with CV events and mortality in the general population.…”