Cardio-renal clinical study group

Patients with kidney failure are at a very high risk of heart disease, including heart attacks and stroke, compared to the general population. This risk starts even when kidney function is only slightly abnormal and increases dramatically in patients who need dialysis. 

Although some of this risk is explained by well-known risk factors such as high blood pressure and diabetes, this does not fully account for why patients with kidney disease are at such high risk. Further research to explain this, and develop better treatments is required.

Who we are

We are a national group dedicated to initiating and supporting clinical research in the cardio-renal field. 

The group is led by Co-Chairs, Dr Matthew Graham-Brown, Associate Professor of Renal Medicine, University of Leicester and Honorary Consultant Nephrologist at University Hospitals Leicester and Dr Krishnaraj Rathod, Clinical Senior Lecturer at the William Harvey Research Institute, NIHR Biomedical Research Centre at Queen Mary’s University of London and Consultant in International Cardiology at Barts Heart Centre, London.

They are joined by trainee co-chairs Dr Kaitlin Mayne, Clinical Lecturer in Renal Medicine, University of Glasgow and Specialty Registrar in Renal Medicine at Glasgow Renal & Transplant Unit and Dr Jemima Scott, NIHR Doctoral Research Fellow, University of Bristol and Specialty Registrar in Renal Medicine, North Bristol NHS Trust.

We are delighted to have new members and are interested in studies proposed from out with the group. 

mgb23@leicester.ac.uk

Our aims:

Developing a better understanding of and treatments for the cardiovascular complications of chronic kidney disease (CKD).

Addressing why patients with kidney disease are at such a high risk of heart problems (approximately 20 times higher than the general public of the same age).

Learning more about why patients with primarily cardiovascular disease develop kidney problems and to find better treatments to prevent this or manage this better.

Undertaking multicentre, collaborative studies and clinical trials in cardio-renal medicine to improve cardiovascular outcomes for patients with kidney disease.

Evidence gaps and challenges:

Understanding the processes that drive the high levels of cardiovascular disease in patients with CKD.

Why do dialysis patients die of sudden cardiac death?

What is optimal blood pressure for people having haemodialysis (HD)?

Tim Doulton and Prof Indy Dasgupta are leading a group looking at this important question. We are starting with preliminary work (i) to better understand patient, carer and healthcare professional perspectives on competing risks of high blood pressure and fluid removal on HD (ii) using Dialysis Outcomes and Practice Patterns Study (DOPPS) data from the US to model impacts of different BP target ranges on outcomes.

What blood pressure should we aim for in children and young people following kidney transplantation?

How should we screen asymptomatic people for coronary artery disease prior to transplantation?

Does renal revascularization for patients with high-risk clinical presentations (RCTs) and highly significant renal artery stenosis (RAS) confer benefit?

Since the publication of the ASTRAL (2009) and CORAL (2013) RCTs most centres have taken a conservative approach for the investigation and management of patients with high-grade RAS. However, a large swathe of clinical experience and published reports suggest that quite a few patients do stand to benefit from stenting, these being patients who were largely unrepresented in previous RCTs. Attention to clinical phenotype might be key, and this will be further explored by Prof Phil Kalra and colleagues. 

Ongoing studies:

The CONFIRM study

Professor James Burton and Dr Matthew Graham-Brown are leading a study assessing relationships between novel cardiac MRI scans and histology. In this study, funded by kidney research UK, patients approaching the end of their life undergo cardiac MRI scan with novel, non-contrast, measures of cardiovascular disease and donate their hearts for analysis after death for histological assessment by Professor Mary Sheppard and team at St George’s.

LIFT and ORTIZ

These two studies, both funded by AstraZeneca, are looking at whether the potassium binder sodium zirconium cyclosilicate (Lokelma®) can help maximise the use of medicines that block the renin-angiotensin system (ACE inhibitors, angiotensin receptor blockers) in CKD patients with heart failure (LIFT) and diabetic nephropathy (ORTIZ). They are led by Prof Debasish Banerjee (St. Georges) and Dr Kieran McCafferty (Barts & London). 

NIGHTLIFE-CMR

A BHF funded cardiac MRI multi-centre sub-study of the NIHR funded NIGHTLIFE study. The study Is investigating the effects of in-centre, extended hours nocturnal haemodialysis on measures of cardiovascular disease in maintenance haemodialysis patients.

The study will recruit 100 patients randomised to either extended hours dialysis nocturnal dialysis for 6 months or to continue with usual care. Participants will have a multi-parametric cardiac MRI scan and blood tests to assess circulating markers of cardiovascular disease at the start and end of the study and the study is powered to detect a difference in native T1 times, a non-contrast measure of myocardial fibrosis and inflammation. Matt Graham-Brown is the chief investigator. 

SUBCUTANEOUS FUROSEMIDE IN CARDIORENAL DISEASE

Completed studies we helped to deliver:

Publications arising are listed below.

ACHIEVEExpand

IRON-MAN

ECSERT

Is abnormal bone mineralisation associated with vascular calcification in children and young adults with chronic kidney disease?

Preventing stroke in dialysis patients with atrial fibrillation.

Iron and Muscle

Looking at the effects of giving intravenous iron supplementation to people with stages 3-4 CKD who are iron deficient (but not yet anaemic or on dialysis) combined with an exercise programme, to see if it helps improve their exercise and physical ability, as well as improve how the muscles function.

This study is funded by Kidney Research UK and is led by Dr Kate Bramham across seven UK centres (King's College Hospital, the Royal London, Guy’s and St George’s Hospitals in London and Epsom and St Helier, Leicester and Salford). 

Our impact:

The studies above are helping define the best treatment strategies to prevent cardiovascular problems in patients with chronic kidney disease by using statins or medications used for heart failure or treating high blood pressure. They have informed National and International guidelines with a direct and measurable impact on patient care. In future studies we will explore different options such as vitamin k therapy or exercise programs to see if they provide additional benefits and help reduce the risk of heart disease risk in patients with kidney failure.

A selection of publications

(past three years)

Cleland JGF, Pellicori P, Graham FJ, Lane R, Petrie MC, Ahmed F, Squire IB, Ludman A, Japp A, Al-Mohammad A, Clark AL, Szwejkowski B, Critoph C, Chong V, Schiff R, Nageh T, Glover J, McMurray JJV, Thomson EA, Robertson M, Ford I, Kalra PA, Kalra PR; IRONMAN Study Group. Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure. J Am Coll Cardiol. 2024 Oct 29;84(18):1704-1717. doi: 10.1016/j.jacc.2024.08.052. PMID: 39443013; PMCID: PMC11496827.

Kalra PR, Cleland JGF, Petrie MC, Thomson EA, Kalra PA, Squire IB, Ahmed FZ, Al-Mohammad A, Cowburn PJ, Foley PWX, Graham FJ, Japp AG, Lane RE, Lang NN, Ludman AJ, Macdougall IC, Pellicori P, Ray R, Robertson M, Seed A, Ford I; IRONMAN Study Group. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet. 2022 Dec 17;400(10369):2199-2209. doi: 10.1016/S0140-6736(22)02083-9. Epub 2022 Nov 5. PMID: 36347265.

Sinha MD et al; HOT-KID study. Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group, open-label, multicentre, randomised, controlled trial. Lancet Child Adolesc Health. 2023 Jan;7(1):26-36.

Billany RE, Vadaszy N, Bishop NC, Wilkinson TJ, Adenwalla SF, Robinson KA, Croker K, Brady EM, Wormleighton JV, Parke KS, Cooper NJ, Webster AC, Barratt J, McCann GP, Burton JO, Smith AC, Graham-Brown MP. A pilot randomised controlled trial of a structured, home-based exercise programme on cardiovascular structure and function in kidney transplant recipients: the ECSERT study design and methods. BMJ Open. 2021 Oct 5;11(10):e046945. doi: 10.1136/bmjopen-2020-046945. PMID: 34610929; PMCID: PMC8493915.

Rankin AJ et al. Myocardial changes on 3T cardiovascular magnetic resonance imaging in response to haemodialysis with fluid removal. J Cardiovasc Magn Reson. 2021 Nov 11;23(1):125 

Edy E et al. Cardiovascular magnetic resonance for the detection of descending thoracic aorta calcification in patients with end-stage renal disease. J Cardiovasc Magn Reson. 2021 Jun 24;23(1):85 

Graham-Brown MPM et al. A randomized controlled trial to investigate the effects of intra-dialytic cycling on left ventricular mass. Kidney Int. 2021 Jun;99(6):1478-1486 

Lees JS et al. The ViKTORIES trial: A randomized, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients. Am J Transplant. 2021 Oct;21(10):3356-3368 

Highton PJ et al. Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients. Eur J Appl Physiol. 2022 Mar;122(3):599-609 

March DS et al. A Cost-Effective Analysis of the CYCLE-HD Randomized Controlled Trial. Kidney Int Rep. 2021 Apr 8;6(6):1548-1557 

Lalayiannis AD et al. The burden of subclinical cardiovascular disease in children and young adults with chronic kidney disease and on dialysis Clin Kidney J (2021) 15(2): 287-294 

Lalayiannis AD et al. Studying bone mineral density in young people: The complexity of choosing a pQCT reference database Bone (2021) 143: 115713 

Bakkaloglu SA et al. Bone evaluation in paediatric chronic kidney disease: clinical practice points from the European Society for Paediatric Nephrology CKD-MBD and Dialysis working groups and CKD-MBD working group of the ERA-EDTA Nephrol Dial Transplant (2021) 36(3): 413-425 

Rankin AJ et al. Global longitudinal strain by feature-tracking cardiovascular magnetic resonance imaging predicts mortality in patients with end-stage kidney disease Clinical Kidney Journal (2021) sfab020 

Graham-Brown MPM et al. Differences in native T1 and native T2 mapping between patients on hemodialysis and control subjects. Eur J Radiol. 2021 Jul;140:109748 

Lalayiannis AD et al. Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease. Nephrol Dial Transplant (2021) 36(10): 1872-1881 

Price AM et al.; EARNEST investigators. Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation. Clin J Am Soc Nephrol (2020) 15(9): 1330-1339 

Witham MD et al. Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial. J Am Soc Nephrol (2020) 31(10): 2434-2445 

Rutherford E et al. A Randomized, Controlled Trial of the Effect of Allopurinol on Left Ventricular Mass Index in Hemodialysis Patients. Kidney Int Rep. (2020) 6(1): 146-155 

Price AM et al.; EARNEST investigators. Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation. Clin J Am Soc Nephrol. (2020) S15(9): 1330-1339 

Potpara T et al. Management of atrial fibrillation in patients with chronic kidney disease in clinical practice: a joint European Heart Rhythm Association (EHRA) and European Renal Association/European Dialysis and Transplantation Association (ERA/EDTA) physician-based survey  EP Europace (2020): 22(3): 496–505 

Lalayiannis AD et al. Assessing bone mineralisation in children with chronic kidney disease: what clinical and research tools are available? Pediatr Nephrol (2020) 35(6): 937-957 

Got a question? Get in touch.

For more information and to find out about getting involved as a patient or researcher, contact:

mgb23@leicester.ac.uk

k.s.rathod@qmul.ac.uk

Cardio-renal Clinical Study Group

Cardio-renal clinical study group

Who we are

Our aims:

Evidence gaps and challenges:

Ongoing studies:

Completed studies we helped to deliver:

Our impact:

A selection of publications

Got a question? Get in touch.

Get in touch

Quick links

Follow us

Keep up to date