Evaluation of Endothelial (dys)Function, Left Ventricular Structure and Function in Patients with Chronic Kidney Disease.

BACKGROUND: Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and cardiovascular complications in chronic kidney disease (CKD). Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), is considered as a marker of endothelial dysfunction. The aim of this study was to evaluate serum ADMA, eNOS concentration and left ventricular structure and function in CKD patients and to assess the impact of the type of dialyzer on serum ADMA and eNOS concentrations after a haemodialysis (HD) session. MATERIAL AND METHODS: Peripheral blood was collected from 35 predialysis CKD patients, 40 CKD patients on HD and 15 healthy subjects. Patients on HD were divided into two groups according to the dialyzer used based on polynephron or cellulose membranes. Plasma ADMA and eNOS concentrations were assessed. All subjects underwent echocardiography and were evaluated for selected biochemical parameters. RESULTS: We found significantly higher serum ADMA (p<0.05) and significantly lower eNOS (p<0.05) concentration in CKD patients compared with healthy subjects. Both dialyzers significantly reduced serum ADMA concentration (p<0.05) but none of the analysed dialyzers showed superiority when comparing the results. We showed that stage V CKD patients, who had the highest serum ADMA concentration had the lowest left ventricle ejection fraction (LVEF) and the highest left ventricle mass (LVM) and left ventricular end diastolic diameter (LVEDd). CONCLUSIONS: Our results supports the presence of endothelial dysfunction in CKD patients. Correlation between elevated serum AMDA concentration and disadvantageous changes in left ventricular structure and function may indicate an important role of endothelial dysfunction in cardiovascular complications in CKD patients.

Sudden cardiac death in CKD patients.

The risk of sudden cardiac death (SCD) is high in chronic kidney disease patients, and it increases with the progression of kidney function deterioration. The most common causes of SDC are the following: ventricular tachycardia, ventricular tachyarrhythmia, tachycardia torsade de pointes, sustained ventricular fibrillation and bradyarrhythmia. Dialysis influences cardiovascular system and results in hemodynamic disturbances as well as electrolyte shifts altering myocardial electrophysiology. Studies suggest that this procedure exerts both detrimental (poor volume control can exacerbate hypertension and left ventricle hypertrophy) and beneficial effects (associated with fluid removal and subsequent decrease in left ventricle stretch). Dialysis-related vulnerability to serious arrhythmias is the result of sudden shifts in fluid status and electrolytes, particularly potassium, which alter the physiological milieu. Also Ca(2+) ions, in which concentration alters during dialysis, are of key importance in the contraction of vascular smooth muscle cells and cardiac myocytes, thus exerting significant effects on hemodynamics. Due to the fact that SCD occurs with similar frequency in peritoneal dialysis and in hemodialysis patients, it seems that end-stage renal disease factors are more important than the specific ones associated with dialysis type. The results of randomized trials suggested that hemodialysis patients may not derive the same benefit of cardiovascular disease therapy including beta-blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors as the general population with normal kidney function. Noninvasive tests used to stratify SCD risk in HD patients have poor positive value, and thus, combining tests including HRV, baroreceptor sensitivity and effectiveness index as well as its function indices and heart rate turbulence should be implemented. There are only few large randomized placebo-controlled trials assessing the influence of cardioprotective medications or implantable cardioverter defibrillator (ICD) implantation in dialysis patients on life quality and survival, and their results are sometimes contradictory. The decision concerning treatment and/or ICD implantation in this group of patients should be made on the basis of careful assessment of individual risk factors. Moreover, due to the high hazard of cardiovascular mortality including SCD in dialysis patients, physicians should concentrate on the early selection of high-risk patients, monitoring them and introduction of preventive measures.

Markers of increased cardiovascular risk in patients with chronic kidney disease.

BACKGROUND: Epidemiological studies have shown that chronic kidney disease (CKD) is an important risk factor for atherosclerosis and cardiovascular disease (CAD). The aim of the study was to determine markers of increased risk of CAD and to achieve a better understanding of agents implicated in the process of atherosclerosis in CKD patients. METHODS: The study group consisted of a total of 139 patients with CKD while the control group comprised 45 healthy volunteers. Concentrations of osteoprotegerin, osteopontin, osteocalcin, matrix γ-carboxyglutamic acid (Gla) protein (MGP), fetuin A, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1) and renalase were measured by the ELISA method. RESULTS: We observed decreased levels of fetuin A (control vs. CKD group: 37.5 vs. 33.2 ng/ml, p = 0.018), and increased concentrations of osteocalcin (control vs. CKD group: 9.1 ± 6.0 vs. 13.6 ± 10.3 ng/ml, p = 0.05), MMP-2 (113.1 ± 75.0 vs. 166.0 ± 129.9 ng/ml, p = 0.045), TIMP-2 (22.1 ± 5.1 vs. 25.4 ± 7,0 ng/ml, p = 0.005) and renalase (251.0 ± 157 vs. 316.1 ± 155.3 ng/ml, p = 0.026). In patients with CKD (in comparison to control group), left ventricle ejection fraction: 53.0 ± 3,5% vs. 48.5%, p = 0.012) and calcification of the aortic valve (9.5% vs. 39.8%, p = 0.008) were observed more frequently. CONCLUSIONS: Decreased levels of fetuin A and increased concentration of osteocalcin, renalase, MMP-2 and TIMP-2 suggest that these factors may be involved in the pathogenesis of CAD in patients with CKD. Significantly increased indices of cardiac hypertrophy and its dysfunction in patients with CKD are indicators of pathological mechanisms occurring in cardiovascular system in this group of patients.

Heart function disturbances in chronic kidney disease - echocardiographic indices.

INTRODUCTION: In chronic kidney disease (CKD) patients left ventricular (LV) diastolic dysfunction occurs frequently and is associated with heart failure (HF) and higher mortality. Left ventricular systolic dysfunction is associated with coronary artery disease (CAD) and is a major determinant of prognosis. The aim of this study was to assess indices of LV diastolic dysfunction in CKD patients. MATERIAL AND METHODS: Study included 118 CKD patients. All patients underwent transthoracic echocardiography. Diastolic function based on E and A, E/A ratio and pulmonary vein flow velocities as well as EF%, deceleration time, RA, LA volume were assessed. In dialysis patients examination was carried out before and after dialysis. RESULTS: In CKD patients the stage of renal failure was associated with the significant increase in LV mass (268.0 ±47.6 CKD I/II vs. 432.7 ±122.4 CKD V/dialysis, p < 0.0001), systolic LV (37.3 ±4.5 vs. 51.2 ±8.9, p < 0.0001) and diastolic LV (CKD I-II 44.7 ±4.1 vs. CKD III 48.5 ±6.7 vs. CKD IV 47.1 ±5.6; p = 0.004) dimensions and in the size of the LA (40.4 ±2.0 vs. 41.9 ±2.7 vs. 42.3 ±3.2 vs. 44.8 ±3.1; p < 0.0001). The increase the E/E' ratio between groups of patients (6.7 ±1.5 vs. 8.9 ±2.4 vs. 11.5 ±4.0 vs. 13.5 ±5.0; p < 0.0001) was seen in this study. The reduction in deceleration time (247.2 ±34.5 in CKD I/II vs. 197.4 ±61.0 in CKD IV, p = 0.0005) along with the decrease in estimated glomerular filtration rate was also observed in this study. CONCLUSIONS: Early identification of factors involved is necessary to prevent this devastating process. Many indexes of contractility are used and each of them has imperfections. It seems that TVI, E, E/A and E/E' are good instruments for the early detection of left ventricular hypertrophy and diastolic dysfunction.

Acute coronary syndromes in patients with chronic kidney disease.

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality. The available data suggest that efforts to reduce mortality in the CKD population should be focused on treatment and prevention of, among others, coronary artery disease and congestive heart failure. Accelerated atherosclerosis present in CKD patients also leads to a decline in renal function. Definite data concerning the treatment of heart failure in CKD patients are lacking, because patients with significant renal impairment have mostly been excluded from randomized studies. Nevertheless, it seems that CKD patients should receive similar cardiovascular treatment to that used in patients with normal kidney function, but the doses of drugs ought to be titrated to achieve an optimal effect while avoiding adverse events. Several studies have also shown that despite the high risk, in patients with acute coronary syndrome (ACS), revascularization procedures in patients with CKD appear to be advantageous in the long run and are therefore justified. However, large clinical trials are needed to confirm the benefits and to identify possible disadvantages associated with various methods of treatment.

Treatment of non-ST-elevation myocardial infarction and ST-elevation myocardial infarction in patients with chronic kidney disease.

Renal dysfunction is frequent in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Chronic kidney disease (CKD) is associated with very poor prognosis and is an independent predictor of early and late mortality and major bleeding in patients with NSTE-ACS. Patients with NSTE-ACS and CKD are still rarely treated according to guidelines. Medical registers reveal that patients with CKD are usually treated with too high doses of antithrombotics, especially anticoagulants and inhibitors of platelet glycoprotein (GP) IIb/IIIa receptors, and therefore they are more prone to bleeding. Drugs which are excreted mainly or exclusively by the kidney should be administered in a reduced dose or discontinued in patients with CKD. These drugs include enoxaparin, fondaparinux, bivalirudin, and small molecule inhibitors of GP IIb/IIIa inhibitors. In long-term treatment of patients after myocardial infarction, anti-platelet therapy, lipid-lowering therapy and ß-blockers are used. Chronic kidney disease patients before qualification for coronary interventions should be carefully selected in order to avoid their use in the group of patients who could not benefit from such procedures. This paper presents schemes of non-ST and ST-segment elevation myocardial infarction treatment in CKD patients in accordance with the current recommendations of the European Society of Cardiology (ESC).

Prevention of sudden cardiac death in patients with chronic kidney disease.

Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients' prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient.