Int Urol Nephrol DOI 10.1007/s11255-016-1240-0
NEPHROLOGY – REVIEW
Clinical imaging of vascular disease in chronic kidney disease Alan A. Sag1 · Adrian Covic2 · Gerard London3 · Marc Vervloet4,5 · David Goldsmith6 · Jose Luis Gorriz7 · Mehmet Kanbay8
Received: 11 November 2015 / Accepted: 5 February 2016 © Springer Science+Business Media Dordrecht 2016
Abstract Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be
* Mehmet Kanbay
[email protected] 1
Division of Interventional Radiology, Department of Radiology, Koc University School of Medicine, Istanbul, Turkey
2
Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, ‘Grigore T. Popa’ University of Medicine, Iasi, Romania
3
Department of Nephrology, Manhès Hospital, Fleury Mérogis, France
4
Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands
5
Institute for Cardiovascular Research VU (ICaR‑VU), VU University Medical Center, Amsterdam, The Netherlands
6
Renal and Transplantation Department, Guy’s and St Thomas’ Hospitals, London, UK
7
Servicio de Nefrologia, Hospital Universitario Dr Peset, Valencia, Spain
8
Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques. Keywords Chronic kidney disease · Vascular calcification · Atherosclerosis · Coronary artery disease · Cardiac imaging techniques
Introduction Within every radiology report, there is actually a hidden layer of communication. This hidden communication is in the subtle prioritization of findings that ultimately create the final “impression” section of the report. Within this hierarchy of information, vascular calcifications have been largely relegated to the “findings” (but not the “impression”) section. However, a growing body of evidence seeks to define vascular calcification as an “impression-worthy” finding. And why should it be? Why should the Radiologist care deeply about bringing attention to vascular calcification in reports? Actually, the burden of proof rests on whether the visualization of vascular calcification changes clinical patient management, and as such ultimately outcome. It is no longer controversial that cardiovascular disease is the leading cause of death in patients with chronic renal insufficiency [1]. Furthermore, patients with chronic renal insufficiency have accelerated calcification of the vascular tunica intima and media, in addition to heart valves [2]. Vascular calcification is associated with increased cardiovascular mortality, [3] and chronic renal insufficiency and end-stage renal disease are pro-inflammatory states [1]. At the same time, relevant concepts include that vascular calcification is just a surrogate marker, but not in the causal path of cardiovascular complication, and as such should not be a treatment target in chronic renal insufficiency [4].
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Moreover, vascular calcification represents a late lesion of the artery, and treatment should instead be focused on athero-prevention [4]. In line with the above apparently controversial points, this report aims to address the following: 1. Does the radiologic detection of vascular calcification impact the clinical management of CKD patients beyond current biochemical laboratory analyses? 2. In patients with CKD, is arterial wall calcification a valid surrogate marker for a vulnerable plaque? 3. In patients with CKD, is there a rationale for imaging pre-calcification vascular mural events? Is it technically possible? Is it currently feasible or will it be possible to image pre-calcification vascular mural events? Is there a rationale for this? 4. Can we image decalcification? 5. Based on the above, should patients with CKD undergo routine vascular calcification screening? Of note, a point on semantics. The literature on this topic has focused on the term vascular “calcification.” Actually, the validity of using this specific term can be questioned. Whether this term was propagated from the radiology literature or basic science literature remains deeply buried in the history of the topic. Moving forward, there are two main reasons for imaging specialists to use the term “mineralization” instead of “calcification” in their reports. The first reason is that not all “bright white” objects on CT are calcium. In fact, other minerals (iodine, manganese, iron, even gadolinium) can very efficiently mimic the imaging appearance of calcium. In essence, the CT scanner cannot yet replace the microscope. Referring physicians should not be expected to know this, and therefore, the avoidance of the term “calcification” falls upon the Radiologist. Dualenergy CT (same-session double CT using two different X-ray energies) is unlikely to solve this issue if the absorptiometric spectra of these minerals overlap significantly. The second reason is that by using the term “calcification,” an open-minded approach to this topic at the bench, translational, and clinical levels is replaced by a sense of irreversibility and futility of treatment. In fact, “calcification” that proves “resistant” to anti-calcium treatments could actually be some other form of mineralization. One proposed solution would be to refer to imaging findings as “vascular mineralization” and histologically proven findings as “vascular calcification.”
Int Urol Nephrol
“hyperdense” foci and distinguished from “ossification” by the lack of an organized trabecular pattern. Ironically, at a molecular level, vessel wall calcification is caused by osteoblastic transdifferentiation of arterial mural cellular elements, as detailed later (“Basic science and molecular basis of vascular calcification”). The term “mineralization” would be a useful umbrella term including calcification, ossification, as well as deposition of other hyperdense minerals. Quantitatively, does “calcification” have a radiologic definition? Every day, “calcium score” CT scans use the value of 130 Hounsfield units to define the “whiteness” (Roentgen radiation absorption) above which a pixel on a CT image is deemed to represent calcification. Each cross-sectional slice of anatomy is divided into small pixels (“voxels”) that absorb varying amounts of radiation and appear proportionally “white.” Hounsfield units (HU) are a unit of measuring how “white” something appears on a CT image compared to pure water, which has a greyish color and measures “zero” HU. Air measures negative HU and appears black on CT images. CT dominates the evaluation of vascular calcification for several reasons: • Spatial resolution Modern multidetector CT scanners can perform imaging with a reconstructed slice thickness of
