The dangerous liaison: Coronary and kidney disease

Reason does not work instinctively, but requires trial, practice, and instruction in order to gradually progress from one level of insight to another. (Immanuel Kant) It is well known that patients affected by CKD are exposed to a high risk of cardiovascular (CV) events, aside from the presence of the traditional CV risk factors, and that CKD is considered an important risk-modifier in coronary artery disease (CAD).2 The risk of CV events in patients affected by CKD appears to be greater than in the general population and is present from the very initial phase of the disease, running parallel to the decrease of renal function. CV events represent the main mechanism leading to mortality in patients with CKD,3,4 a phenomenon observed not only in patients with the end-stage form but also in subjects at the beginning stages of the disease, who represent the target population for the implementation of CV prevention measures. The strict association between CKD and CV risk is related not only to a higher prevalence of the classic CV risk factors in patients with renal impairment compared with the general population, but also to the occurrence of new CV risk determinants connected to the uraemic state.5 In particular, CKD is characterized by a chronic inflammatory state, disorders of calcium and phosphorus metabolism, volume and pressure overload, and anaemia, which represent the main pathophysiological determinants related to the excessive CV risk. The interaction among these factors leads to the phenomenon of ‘accelerated atherosclerosis’, responsible for a high incidence of coronary events and mortality related to CAD in CKD patients, even before the occurrence of end-stage renal disease.6 The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guidelines, published in 2002,1 estimated that the risk excess of CV events and CV mortality observed in CKD is sufficient to start considering patients with renal impairment in the group of subjects at high CV risk, independently of the baseline presence of traditional CV risk factors.7 Thus, the current approach of nephrologists, despite common beliefs, is to focus high attention on the initial stages of CKD in order to identify early an increased risk of future CV events. For instance, the Prevention of Renal and Vascular End-stage Disease (PREVEND) study8 reported that subjects with CKD stage 1 or 2 already exhibit a clearly increased risk for adverse CV and renal outcomes and should receive equal attention as subjects with stage 3 CKD. Furthermore, the authors reported that the presence of urinary albumin excretion (UAE) >30 mg/24h, even in the absence of an overt CKD, is an efficient predictor of future occurrence of CV disease. Additionally, it can be expected that UAE can also be used to improve risk stratification for these outcomes in subjects with stage 3 CKD. Only recently have cardiologists clearly understood that renal impairment should not only be considered as a marker of risk, but that a complex interplay between the two conditions exists, and a multidimensional approach to the patient is crucial for an optimal therapeutic management. The paper of Wagner et al. (2017), published in this issue of the European Journal of Preventive Cardiology, which reports insights from the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) IV trial of the European Society of Cardiology, describes the interplay between CKD and CAD. In particular, the study describes the problem from a different point of view, from the perspective of the cardiologist, which is complementary to the nephrologist’s approach to the problem. Specifically, the paper analyses this complex interaction starting from patients who have experienced a coronary event, thus representing an important debate opportunity among cardiologists and nephrologists. The survey is well illustrated and efficiently argues the phenotypic complexity of patients with multiple major comorbidities. However, aside from the data reported, it seems important to emphasize some relevant aspects that emerge from the analysis of this study. The concept that impaired kidney function during hospital stay does not imply CKD is actually novel and crucial, and has to be emphasized to clinicians. Moreover, the reported observation that the overall prevalence of CKD, at least the more severe stages, in ambulatory CAD patients presents a wide variation across a broad variety of European countries is unexpected and intriguing. In this analysis of EUROASPIRE IV, the risk factors responsible for a decline of renal function in patients with cardiac events are well described, such as older age, female gender, presence of classic CV risk factors, history of CAD and congestive heart failure. These determinants also represent the well-known negative prognostic markers in CAD patients. Indeed, great attention is focused on the dynamic variability of renal function in these patients. The authors identify cardiac output and concomitant pharmacological therapy as the major determinants of the decline of renal function, even if the specific role of treatments cannot be completely elucidated from available and reported data. However, probably the pathophysiological mechanisms are more complex and go beyond the classic haemodynamic events, as cardiologists do not always perceive the importance of non-haemodynamic components, autocrine or paracrine, that might influence intraglomerular haemodynamics. Thus, in different phases of the natural history of a patient with a coronary event, these pathophysiological mechanisms may have a different and specific role. Beyond contrast-induced nephropathy, a further factor accountable for a deterioration of renal function, often forgotten by cardiologists, is the phenomenon of atheroembolism secondary to radiologic invasive vascular procedures. The real incidence of this condition is difficult to assess, and few studies are available on the ante-mortem incidence of the disease; however, it seems to be a non-infrequent and continuously increasing event in daily clinical practice. Given the premises and the aspects highlighted as especially novel and stimulating, the insights from EUROASPIRE IV are crucial for the cardiologic community and deserve careful consideration; thus, prospective and specific in-depth analysis is warranted. The objective is an integration of the different approaches of the nephrologist and the cardiologist, the former looking at CAD as a prognostic determinant and as the first cause of death in CKD, the latter considering CKD as a risk factor for adverse cardiac events. Specifically, the aim of a multidimensional approach is the development of a model of care that might interrupt the complex interplay between cardiac and renal impairment to reduce mortality in both CAD and CKD patients. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The author(s) received no financial support for the research, authorship, and/or publication of this article.