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Re: ‘Shoot the renals’ - The evidence is actually round the corner!

Dear Editor,

It was with great interest that we read the recent articles by Dear et al[1] and Luft et al[2] in the December edition of Heart. The issue of when to investigate and treat a patient with suspected ARVD is one of considerable controversy at present. The AHA provide guidelines[3] that recommend performing simultaneous renal arteriography with coronary arteriography in order to facilitate pro-active treatment of renal arterial lesions with ‘drive-by’ angioplasty and stenting. However, the paucity of randomised controlled trials (RCTs) and large studies in ARVD is well known, thus leaving the guidelines open to criticism. In particular, ideal management in ARVD, and prediction of renal and blood pressure outcome following revascularization remains elusive. The complex relationship between the degree of renal artery stenosis (RAS), hypertension, intra-parenchymal damage[4 5], early atherosclerotic induced damage[6] and cardiovascular co-morbidity[7 8] make this a much more challenging condition. The articles by Dear et al[1] and Luft et al[2] acknowledge the lack of firm evidence to support the guidelines, and thus the frustration of screening ‘for an entity that has no sound basis for management’[2] can be understood.

In order to best answer the perplexing questions surrounding revascularization as a management option, large scale prospective RCTs are required in order to determine the overall effects of intervention in RAS, and more specifically, help identify which sub-groups of patients might benefit from revascularization. Whilst the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial is underway, it should be noted that the main ASTRAL (Angioplasty and STent for Renal Artery Lesions) trial[9] completed recruitment in April 2007. ASTRAL is the largest trial in ARVD to date with nearly 8 times as many patients recruited than in the previous largest RCT[10]. 806 patients from 58 centres have been entered into ASTRAL, half allocated to receiving optimal medical treatment and half revascularization and medical therapy. The primary aim of ASTRAL is to determine whether renal endovascular revascularization procedures (angioplasty and/or stenting) impact upon renal functional outcome. Secondary outcome measures include mortality, clinic blood pressure and major vascular events. Preliminary results, which involve a minimum 6 months follow up for all enrolled patients, are due to be reported in March 2008.

Due to the increasing awareness of the strong relationship between ARVD and cardiac dysfunction and structure, two cardiac substudies have also been undertaken. A previous pilot study at our centre showed a trend towards improvement of cardiac measurements post renal-revascularisation (left ventricular mass index, left ventricular fractional fibre shortening, left ventricular end systolic dimameter and left ventricular end diastolic diameter[11]. The ASTRAL cardiac substudies have been conducted in a randomized, prospective manner, with subjects being randomized to have either revascularizaion with medical therapy or medical therapy alone, as for the main trial. The first sub-study, based upon echocardiography, enrolled around 110 patients from 15 centres, and the cardiac magnetic resonance imaging (CMR) sub-study, 65 patients from 6 centres. The aim of these studies is to show whether beneficial changes in cardiac structure and function follow renal revascularization procedures. Positive results from these studies would provide a new dimension of opportunity to improve ARVD patient welfare which would engage the cardiological community further. Results of the sub-studies will be available in October 2008.

We eagerly await the results of the ASTRAL trial and its cardiac sub- studies, as they provide an imminent chance to increase our understanding of the complex inter-relationship between cardiac and renal disease in ARVD.

Constantina Chrysochou 1, Janet Hegarty 1, Paul R Kalra 2, Keith Wheatley 3, John Moss 4, Philip A Kalra 1

1 Department of Renal Medicine, Salford Royal Hospitals NHS Foundation Trust, Stott Lane, Salford, Manchester
2 Department of Cardiology, Portsmouth Hospitals NHS trust, Portsmouth
3 Birmingham Clinical Trials Unit, University of Birmingham, Edgbaston, Birmingham
4 Department of Vascular Radiology, Gartnavel Hospital, Glasgow

References

1 Dear JW, Padfield PL, Webb DJ.
New guidelines for drive-by renal arteriography may lead to an unjustifiable increase in percutaneous intervention.
Heart 2007 Dec;93(12):1528-32.

2 Luft FC, Gross CM.
Commentary: Shoot the renals!
Heart 2007 Dec;93(12):1530-2.

3 White CJ, Jaff MR, Haskal ZJ, et al.
Indications for renal arteriography at the time of coronary arteriography: a science advisory from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Councils on Cardiovascular Radiology and Intervention and on Kidney in Cardiovascular Disease.
Circulation 2006 Oct 24;114(17):1892-5.

4 Makanjuola AD, Suresh M, Laboi P, et al.
Proteinuria in atherosclerotic renovascular disease.
QJM 1999 Sep;92(9):515-8.

5 Wright JR, Shurrab AE, Cheung C, et al.
A prospective study of the determinants of renal functional outcome and mortality in atherosclerotic renovascular disease.
Am J Kidney Dis 2002 Jun;39(6):1153-61.

6 Chade AR, Rodriguez-Porcel M, Grande JP, et al.
Distinct renal injury in early atherosclerosis and renovascular disease.
Circulation 2002 Aug 27;106(9):1165-71.

7 Conlon PJ, Little MA, Pieper K, et al.
Severity of renal vascular disease predicts mortality in patients undergoing coronary angiography.
Kidney Int 2001 Oct;60(4):1490-7.

8 Shurrab AE, MacDowall P, Wright J, et al.
The importance of associated extra-renal vascular disease on the outcome of patients with atherosclerotic renovascular disease.
Nephron Clin Pract 2003;93(2):C51-C57.

9 Mistry S, Ives N, Harding J, et al.
Angioplasty and STent for Renal Artery Lesions (ASTRAL trial): rationale, methods and results so far.
J Hum Hypertens 2007 Jul;21(7):511-5.

10 van Jaarsveld BC, Krijnen P, Pieterman H, et al.
The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery stenosis. Dutch Renal Artery Stenosis Intervention Cooperative Study Group.
N Engl J Med 2000 Apr 6;342(14):1007-14.