BACKGROUND: Blockade of the renin-angiotensin system (RAS) exerts beneficial effects in patients with mild-to-moderate chronic kidney disease, yet evidence suggesting a similar benefit in haemodialysis (HD) patients is not available. Furthermore, knowledge of the effects of RAS blockade on systemic RAS components in HD patients is limited. Analysis of the quantity and dynamics of all known peripheral constituents of the RAS may yield important pathomechanistic information of a widespread therapeutic measure in HD patients. METHODS: Fifty-two HD patients from the following groups were analysed cross-sectionally: patients without RAS blockade (n = 16), angiotensin-converting enzyme inhibitor (ACEi) users (n = 8), angiotensin receptor blocker (ARB) users (n = 11), patients on ACEi plus ARB (dual blockade, n = 8) and anephric patients (n = 9). Ten healthy volunteers served as controls. Angiotensin metabolites were quantified by mass spectrometry. RESULTS: In general, HD patients showed a broad variability of RAS activity. Patients without RAS blockade displayed angiotensin metabolite patterns similar to healthy controls. ACEi therapy increased plasma Ang 1-10 and Ang 1-7 concentrations, whereas ARB treatment increased both Ang 1-8 and Ang 1-5, while suppressing Ang 1-7 to minimal levels. Dual RAS blockade resulted in high levels of Ang 1-10 and suppressed levels of other angiotensins. Anephric patients were completely devoid of detectable levels of circulating angiotensins. CONCLUSION: In HD patients, the activity status of the systemic RAS is highly distorted with the emergence of crucial angiotensin metabolites upon distinct RAS blockade. The characterization of molecular RAS patterns associated with specific RAS interfering therapies may help to individualize future clinical studies and therapies.
BACKGROUND: Blockade of the renin-angiotensin system (RAS) exerts beneficial effects in patients with mild-to-moderate chronic kidney disease, yet evidence suggesting a similar benefit in haemodialysis (HD) patients is not available. Furthermore, knowledge of the effects of RAS blockade on systemic RAS components in HDpatients is limited. Analysis of the quantity and dynamics of all known peripheral constituents of the RAS may yield important pathomechanistic information of a widespread therapeutic measure in HDpatients. METHODS: Fifty-two HDpatients from the following groups were analysed cross-sectionally: patients without RAS blockade (n = 16), angiotensin-converting enzyme inhibitor (ACEi) users (n = 8), angiotensin receptor blocker (ARB) users (n = 11), patients on ACEi plus ARB (dual blockade, n = 8) and anephric patients (n = 9). Ten healthy volunteers served as controls. Angiotensin metabolites were quantified by mass spectrometry. RESULTS: In general, HDpatients showed a broad variability of RAS activity. Patients without RAS blockade displayed angiotensin metabolite patterns similar to healthy controls. ACEi therapy increased plasma Ang 1-10 and Ang 1-7 concentrations, whereas ARB treatment increased both Ang 1-8 and Ang 1-5, while suppressing Ang 1-7 to minimal levels. Dual RAS blockade resulted in high levels of Ang 1-10 and suppressed levels of other angiotensins. Anephric patients were completely devoid of detectable levels of circulating angiotensins. CONCLUSION: In HDpatients, the activity status of the systemic RAS is highly distorted with the emergence of crucial angiotensin metabolites upon distinct RAS blockade. The characterization of molecular RAS patterns associated with specific RAS interfering therapies may help to individualize future clinical studies and therapies.
Authors: Lodi C W Roksnoer; Richard van Veghel; René de Vries; Ingrid M Garrelds; Usha M Bhaggoe; Edith C H Friesema; Frank P J Leijten; Marko Poglitsch; Oliver Domenig; Marian C Clahsen-van Groningen; Ewout J Hoorn; A H Jan Danser; Wendy W Batenburg Journal: Kidney Int Date: 2015-04-01 Impact factor: 10.612
Authors: Marlies Antlanger; Oliver Domenig; Johannes J Kovarik; Christopher C Kaltenecker; Chantal Kopecky; Marko Poglitsch; Marcus D Säemann Journal: J Renin Angiotensin Aldosterone Syst Date: 2017 Apr-Jun Impact factor: 1.636
Authors: Markus M Rinschen; Oleg Palygin; Gary Siuzdak; Alexander Staruschenko; Ashraf El-Meanawy; Xavier Domingo-Almenara; Amelia Palermo; Lashodya V Dissanayake; Daria Golosova; Michael A Schafroth; Carlos Guijas; Fatih Demir; Johannes Jaegers; Megan L Gliozzi; Jingchuan Xue; Martin Hoehne; Thomas Benzing; Bernard P Kok; Enrique Saez; Markus Bleich; Nina Himmerkus; Ora A Weisz; Benjamin F Cravatt; Marcus Krüger; H Paul Benton Journal: Nat Commun Date: 2022-07-14 Impact factor: 17.694
Authors: Oliver Domenig; Arndt Manzel; Nadja Grobe; Eva Königshausen; Christopher C Kaltenecker; Johannes J Kovarik; Johannes Stegbauer; Susan B Gurley; Dunja van Oyen; Marlies Antlanger; Michael Bader; Daisy Motta-Santos; Robson A Santos; Khalid M Elased; Marcus D Säemann; Ralf A Linker; Marko Poglitsch Journal: Sci Rep Date: 2016-09-21 Impact factor: 4.379
Authors: Éva Larouche-Lebel; Kerry A Loughran; Mark A Oyama; Phil F Solter; Danielle S Laughlin; Melissa D Sánchez; Charles-Antoine Assenmacher; Philip R Fox; Ryan C Fries Journal: J Vet Intern Med Date: 2019-06-28 Impact factor: 3.333
Authors: Corinna Göppner; Ian J Orozco; Maja B Hoegg-Beiler; Audrey H Soria; Christian A Hübner; Fabio L Fernandes-Rosa; Sheerazed Boulkroun; Maria-Christina Zennaro; Thomas J Jentsch Journal: Nat Commun Date: 2019-10-15 Impact factor: 14.919