Hydrogen sulfide increases after a single hemodialysis session

Abstract

To the Editor: Hydrogen sulfide, H2S, the third endogenous gas with cardiovascular properties after nitric oxide and carbon monoxide, is a newly recognized vasorelaxant, and H2S deficiency is involved in the pathogenesis of hypertension and atherosclerosis.1.Wang R. Hydrogen sulfide: a new EDRF.Kidney Int. 2009; 76: 700-704Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar We demonstrated that in hemodialysis patients, H2S levels are decreased through transcriptional deregulation of genes encoding H2S-producing enzymes.2.Perna A.F. Luciano M.G. Ingrosso D. et al.Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes.Nephrol Dial Transplant. 2009; 24: 3756-3763Crossref PubMed Scopus (70) Google Scholar In fact, gene expression of cystathionine γ-lyase (CSE), an enzyme implicated in H2S formation, is downregulated in these patients.2.Perna A.F. Luciano M.G. Ingrosso D. et al.Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes.Nephrol Dial Transplant. 2009; 24: 3756-3763Crossref PubMed Scopus (70) Google Scholar We measured H2S levels before and after a single standard 4-h hemodialysis session in 131 patients, in two dialysis sessions separated by 1 month. Measurement was performed by a slight modification of our previously published method.2.Perna A.F. Luciano M.G. Ingrosso D. et al.Hydrogen sulphide-generating pathways in haemodialysis patients: a study on relevant metabolites and transcriptional regulation of genes encoding for key enzymes.Nephrol Dial Transplant. 2009; 24: 3756-3763Crossref PubMed Scopus (70) Google Scholar Basically, a 20-min incubation period was added before deproteinization. Homocysteine is a main direct H2S precursor in vivo, which functions through the catalytic activity of either cystathionine β-synthase or CSE (see Perna et al.3.Perna A.F. Sepe I. Lanza D. et al.The gasotransmitter hydrogen sulfide in hemodialysis patients.J Nephrol. 2010; 23: S92-S96PubMed Google Scholar for a review). Plasma total homocysteine was also measured by using high-performance liquid chromatography separation and fluorescence detection.4.Perna A.F. Satta E. Acanfora F. et al.Increased plasma protein homocysteinylation in hemodialysis patients.Kidney Int. 2006; 69: 869-876Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar Both H2S and homocysteine data are expressed as μmol/l concentrations. Results were analyzed with a paired two-tailed t-test. Plasma H2S was significantly increased after dialysis (Figure 1 shows mean and s.e.). Homocysteine levels were 40.90±2.087μmol/l (s.e.) before dialysis and 21.83±1.142μmol/l (s.e.) after dialysis, a highly significant decrease. No correlation was found between these two parameters. However, the stoichiometry of homocysteine metabolic conversion, yielding H2S, is encompassed in the range 1:1–2:1, depending on the enzyme and/or the specific reaction involved. After hemodialysis, the average reduction in circulating homocysteine concentrations is -20μmol/l, whereas H2S increase approaches +10μmol/l; this is in the order of magnitude of what is expected for the reaction stoichiometry and is highly consistent with the interpretation of an improved homocysteine metabolism toward H2S formation during dialysis. Homocysteine is lowered by hemodialysis; however, this can only in part be due to increased clearance through the hemofilter, as, with respect to other aminothiols, most homocysteine is transported in circulation covalently bound to serum albumin.5.Sengupta S. Chen H. Togawa T. et al.Albumin thiolate anion is an intermediate in the formation of albumin-S-S-homocysteine.J Biol Chem. 2001; 276: 30111-30117Crossref PubMed Scopus (151) Google Scholar Another mechanism (e.g., facilitated metabolism as the result of removal of enzyme inhibition due to a uremic toxin) is therefore likely to occur. We conclude that hemodialysis is effective in acutely reestablishing the altered H2S homeostasis in these patients. We propose that plasma H2S elevation could be due to an increase in its production secondary to removal of a uremic toxin, inhibiting CSE, consistent with our previous findings, and contributing to low blood pressure levels frequently seen after dialysis.