Predictive properties and therapeutical use of gasotransmitters:A renal perspective

Abstract

In this thesis, we explored the predictive properties of gasotransmitters on graft survival and all-cause mortality in renal transplant recipients. To provide further evidence for the involvement of gasotransmitters in renal and cardiovascular damage we tested their therapeutical potential in experimental models of hypertension-induced disease. To validate our assumptions, clinical observational studies in renal transplant recipients were performed in which we measured the end-metabolites of gasotransmitters and their systemic biochemical reactions in order to gain better insight into the associations of H2S, NO, their metabolites and inhibitors, with renal and cardiovascular risk parameters. To substantiate the clinical findings, we performed experimental intervention studies, whereby exogenously administered H2S metabolites, sulfide containing salts, and inhibitors of H2S producing enzymes were administered in hypertensive models of renal and cardiac disease. We conclude that the gasotransmitters NO, H2S and also CO are involved in diverse (patho)physiological processes in the kidney and that therapeutical intervention with these gaseous molecules might have therapeutic potential in the protection against morbidity and mortality of patients with hypertension-induced kidney disease or after renal transplantation