Seeing the holistic perspective – Cardiorenal

The cardiorenal syndrome defines disorders involving both the heart and kidneys where an acute or chronic dysfunction in one of the organs may induce an acute or chronic dysfunction in the other organ. Both the heart and the kidney are involved in stabilizing the hemodynamic variations and tissue perfusion via a highly integrated signalling system. This has a large impact on developing drugs targeting both the acute and chronic dysfunction in either of these organs, shown previously for several therapeutic targets including ACE/ARBs and SGLT2s.

 

The importance of considering cardiorenal aspects

 

Current tools to assess the cardiorenal interplay, such as circulating biomarkers, are often not organ-specific and lack the ability to give mechanistic insights valuable in clinical research. Magnetic resonance imaging (MRI) and its integration with positron emission tomography (PET) are imaging technologies that are key to study the intricate interplay between the heart and the kidney. The non-invasive, non-radiating characteristics of MRI and low-radiation characteristics of PET/MRI allow for repeated examinations following drug effects both in the acute and chronic settings over a long period of time. This type of advanced imaging can provide key insights on e.g. hemodynamic cross-talk between the heart and the kidneys.

 

Antaros Medical has a long background in performing cardiac MRI and PET studies including recent work (Nuutila et al, EASD 2020, Lubberink et al, J Nucl Cardiol. 2019). We also have in-house expertise in kidney MRI (ASN 2018 & 2020, ERA-EDTA 2019). This, combined with over 250 years of experience from the pharma industry, gives us unique capabilities to tailor and perform trials in the cardiorenal space. With previous and ongoing experience from multiple clinical imaging trials we have generated insights to support clinical questions related to both mode of action as well as drug efficacy and safety of novel treatments for both kidney and cardiovascular disease. As proud partners of both the IMI consortia BEAT-DKD and the COST action PARENCHIMA, we drive the imaging science for kidney disease forward.

 

In the HEROIC study (Yaqoob et al. BMJ Open, 2020), we are assessing both the heart and the kidney with MRI over 5 years in 500 subjects performing kidney biopsy, aiming to further increase the understanding of relationships of MRI and kidney fibrosis, longitudinal changes and the cardiorenal interplay from a holistic perspective. The results from this study will further guide the design of both renal and cardiorenal trials to generate insights to support decision-making in this field.

“Imaging can provide key insights on cardiorenal effects, important for both mode of action as well as drug efficacy and safety in drug development”

 

Paul Hockings

Senior Imaging Director

Drug classes with cardiorenal effects

Several drug classes exhibit cardiorenal effects, highlighting the importance of looking at the holistic perspective. The mechanisms behind these effects are in some cases well-established while for others still an area of intense research aiming at elucidating the unlaying favourable mechanisms.

 

  • Drugs inhibiting the angiotensin converting enzyme (ACE) and angiotensin II receptor agonists (ARBs) have positive effects on both reducing risk of cardiovascular disease (CVD) events and delaying end-stage renal disease (ESRD) in patients with chronic kidney disease (Wang et al. Am J Kidney Dis. 2016)
  • The sodium-glucose cotransporter-2 (SGLT2) inhibitors were first developed to lower blood glucose in diabetes patients. In studies designed to investigate the safety of SGLT2 inhibition on CVD, positive effects were seen on both kidney function and a reduction of CVD events (Perkovic et al. Diabetes Obes Metab.  2019)
  • Other drug classes such as mineralocorticoid receptor agonists (MRAs) and glucagon like peptide 1 (GLP-1) receptor agonists also have positive effects across the cardiorenal axis (Buse et al. Diabetes Obes Metab. 2020)