News | 2014
Interdependent relationship of heart and kidneys: Scientists develop diagnostic tools for cardiovascular complications of renal dysfunction
Cardiovascular diseases (CVDs) are the number one cause of death globally: more people die annually from CVDs than from any other single cause. CVD risk factors that can be treated or changed include tobacco exposure, high blood pressure (hypertension), high cholesterol, obesity, physical inactivity, diabetes, unhealthy diets, and harmful use of alcohol. What people often don’t keep in mind is that almost all these factors also increase the risk for impairments of renal function potentially resulting in chronic kidney diseases (CKDs). Moreover, as observational studies have shown, CVDs, once present, can directly contribute to worsening kidney function and vice versa potentially resulting in the serious and feared cardio-renal syndrome (CRS). CRS, the coexistence of cardiovascular and kidney disease in the same patient, considerably complicates therapy for each of the two conditions and may drastically reduce life expectancy. The incidence of de novo CVD events is thereby already increasing in early stages of CKD characterized by only minimally decreased renal function. As a result, cardiovascular complications like heart failure, myocardial infarction, arrhythmias, and sudden cardiac death account for most of deaths in patients with renal failure.
Left-sided heart failure may be considered a single continuous spectrum of conditions that may manifest in two phenotypic extremes:
- Systolic heart failure (heart failure with reduced ejection fraction; HFrEF) is characterized by decreased left ventricular contractile function and therefore pumping force to push blood into circulation.
- Diastolic heart failure (heart failure with preserved ejection fraction, HFpEF) is characterized by pathological heterogeneity mainly comprising impaired relaxation (increased stiffness) as well as elevated filling pressure resulting in impaired filling with blood during the resting period in between pumping actions. Symptomatic clinically overt HFpEF is preceded by asymptomatic pre-clinical left ventricular diastolic dysfunction (LVDD) with hypertension as important risk factor for the progression to the overt syndrome.
Both phenotypes of left-sided heart failure along with LVDD can now be detected by the use of innovative clinical proteomics, developed by Germany's Mosaiques Diagnostics GmbH. While the detection of diastolic heart failure and LVDD has already been possible for some time, a diagnostic test for systolic heart failure has just recently been developed. Greek, Australian, Danish and German scientists teamed-up to identify a HFrEF-specific pattern of urine peptide biomarkers utilizing advanced state-of-the-art proteomic technology. They performed the urinary proteome analysis (UPA) in the urine samples of almost 700 individuals with and without HFrEF. As a result of the study UPA is able to discriminate HFrEF patients from healthy individuals and patients with LVDD.
Heart failure is often detected too late since adverse alterations of the structure of the heart can already be present despite the absence of signs and symptoms. Thus, the sooner the heart failure is detected the better. While this is important for at risk individuals in the general population, it is, as already indicated, even more important for at risk individuals with renal dysfunctions no matter how minor these dysfunctions are.
„Urinary proteome analysis is an interesting and promising tool that can be used to detect a range of diseases at an early development stage. Diagnosis from patient samples is obtained in a risk-free, non-invasive and painless procedure. Considering cardiovascular diseases the early detecting and treatment of the systolic and underestimated diastolic failure is desirable. Proteomics can be useful at that point. Also protein fragments seem to distinguish people who have coronary artery disease from those who don't“ says Prof. Dr. Constantin von zur Mühlen, University and Heart Research Center Freiburg/Bad Krozingen, Germany.
Jan A. Staessen, MD, PhD, Head of Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences points out: „Research over the past two years identified unique urinary proteomic signatures that are diagnostic for diastolic left ventricular dysfunction, the presence and progression of renal dysfunction, and the 5 year prediction of cardiovascular and cardiac complications. Further refinement of these biomarkers in longitudinal population studies will facilitate the early detection of diastolic left ventricular dysfunction, a condition that affects 25% of Europeans and carries a high risk to progress to overt heart failure. Similarly, the unique urinary proteomic biomarker signature raises hope that physicians will soon be able to estimate the risk of deteriorating renal function, for instance in patients with subclinical left ventricular dysfunction, or to predict the risk of imminent cardiovascular complications over and beyond classical risk factors. Using the urinary proteome as a screening or diagnostic tool therefore enables the institution of preventive and therapeutic measures earlier than is currently the case that is prior to the development of overt cardiovascular, cardiac or renal disease.“
Prof. Dr. Raymond Vanholder, University of Gent, Department of Nephrology, elaborates the cardiorenal syndrome: “This study finds a number of urinary peptidic biomarkers which allow discriminating patients with heart failure from controls. The fact that these markers are found in urine to my opinion points to the intense links between kidney and heart disease. Not only are patients with kidney failure more prone to develop cardio-vascular damage of which heart failure is one of the principal components, but also is heart failure prone to cause kidney failure due to renal hypoperfusion and ischemia. Heart failure is a common complication of renal failure, first of all because of the link with cardio-vascular disease but also because kidney failure patients more easily retain salt and water leading to fluid overload. In addition both kidney and heart failure may share common patho-physiologic mechanisms, because collagen fragments I and III were not only found in this study, but also in studies seeking early biomarkers of chronic kidney disease. These findings point to the still often neglected need to check cardiac failure patients for kidney failure and vice versa, but also to treat kidney failure by active dietary salt restriction, since the kidneys alone are not functioning well enough to handle salt and fluid overload, even if treatment with diuretics is installed.“
The studies in regard of HFrEF have partially been funded by the European heart research projects EU-MASCARA and HOMAGE.
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