Mechanisms of Cardiorenal Syndrome: From Molecular Pathways to Novel Therapeutics

  • Tomoki Ichiki
  • Yang Chen
  • John C. BurnettJrEmail author


Cardiorenal syndrome (CRS) in heart failure (HF) is the imbalance of the compensatory actions of the renoprotective natriuretic peptide (NP) system and the pathophysiologic actions of an activated renin-angiotensin-aldosterone system (RAAS), which increases the risk of progressive HF, death and rehospitalization. Kidney injury through the activation of deleterious molecular pathways involves inflammatory, pro-fibrotic, and pro-apoptotic molecular pathways, which was observed in our large animal model of HF, suggesting that a novel therapeutic for HF could target kidney injury to prevent and/or treat CRS and acute kidney injury (AKI). Further, urinary C-type NP (CNP) is activated during AKI and may be an effective urinary biomarker for CRS and AKI predicting adverse outcomes in HF. Since NP therapeutics have shown the renal protective actions, CRRL269, a designer NP was developed as a novel therapeutic for CRS and acute kidney injury (AKI). CRRL269 possesses renal enhancing properties with RAAS suppression and less hypotension than native NPs, thus representing a new and innovative drug for renoprotection in HF. The combination of using NP urinary biomarkers and designer NP therapeutics may provide the opportunity to reduce the burden of CRS in HF.


Heart failure Cardiorenal syndrome Natriuretic peptides Renin-angiotensin-aldosterone system Kidney injury Urinary C-type natriuretic peptide Designer natriuretic peptide 


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Cardiology, School of MedicineInternational University of Health and WelfareOtawaraJapan
  2. 2.Department of Cardiovascular MedicineMayo ClinicRochesterUSA

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