According to the Croatian Registry for Renal Replacement Therapy in 2011, the incidence of renal replacement therapy was 119.3, while the prevalence was 980 patients per million of inhabitants. According to the 2011 population census, the Medimurje County has 114,414 inhabitants of whom 70-75 have been involved in the chronic hemodialysis program in the last few years.

Chronic renal failure (CRF) results in changes of the concentration of biomarkers used in routine diagnostic procedures of cardiovascular diseases (1, 2). For example, it is known that in these patients we can observe the level of troponin T basically higher than the reference values.

The importance of D-dimer test lies in its negative predictive value for the development of thrombosis and is routinely used to exclude deep venous thrombosis and pulmonary embolism (3, 4). The values of D-dimer can be elevated in different non-thrombotic disorders: in inflammatory diseases, liver diseases, postoperatively, in eclampsia, sickle cell disease crises. The patients with malignancy usually have elevated levels of D-dimer, which are moderately physiologically elevated even during pregnancy and in old age as well.

The decreased activity of von Willebrand factor causes reduced interaction of platelets with the endothelium of blood vessels with reduced adhesive and aggregation capability. Fibrinogen synthesis accompanied by antithrombin III deficiency rises in kidney diseases with the development of nephritic syndrome (5-7).

The purpose of this study was to measure the baseline concentrations of D-dimer in patients on chronic dialysis due to disorders of hemostasis in patients with CRF. We wondered whether CRF impacts the value of the D-dimer test because the D-dimers are the fibrin degradation products containing the transverse link created as a result of FXIII action on fibrin threads at the time of clot formation.

The patients of the Hemodialysis Department of the Cakovec County Hospital with normally functioning native arteriovenous fistula without clinical manifestations of thrombosis or infection in the last six months' period and without anticoagulant therapy during the period when they were not subject to hemodialysis were selected. Patients with permanent or temporary endovenous catheter and patients with artificial fistula — graft were not included in the study.

Samples were collected during the two months’ period with consecutive patients without excluded criteria during the regular terms of dialysis. Blood was taken prior to the procedure of dialysis for the purpose of avoiding heparinization. Blood samples were taken by Vacutainer in 2.7 mL tube with 3.2% sodium citrate. Upon the receipt, the samples were centrifuged at 1,500 g in 15 minutes. Performing the test on the analyzer takes about 5 minutes. All samples were processed in a maximum time of 60 minutes from the receipt (8, 9).

D-dimers were measured in the BCS automatic analyzer by using the Innovance D-Dimer assay (Siemens Healthcare Diagnostics). The principle of the test is the immunoturbidimetric method, whereas 8D3 monoclonal antibodies are bonded to the two epitopes of the D-dimer product to form the aggregation manifested as elevated adsorbency, which allows the calculation of the quantitative values. The values of D-dimer test are expressed as μg/L FEU (Fibrinogen equivalent unit). According to the specifications of the D-dimer Innovance test cut-off is 500 μg/L FEU. The specificity of the test is 35.8-38.2%, sensitivity 98.0-99.4%, while the negative predictive value is 98.6-99.5%. This test is currently widely routinely used.

Transthoracic echocardiography (CV 70 Siemens) was performed in 52 patients according to standard protocol. Left ventricular mass index >131 g/m2 for men and >100 g/m2 for women was taken as a criterion of concentric left ventricular hypertrophy. Left ventricular ejection fraction (EF) was measured by Teicholtz method and Simpson method.

Baseline values of D-dimer were measured in 67 patients (37 women and 30 men) on chronic dialysis at the age from 17 to 80 years (median 66 years) and the length of dialysis treatment from 3 to 216 months (median 94 months). 42 patients with average hemoglobin values of 108 g/L were on the therapy by agents that stimulate erythropoiesis.

In 68.3% of patients the baseline D-dimer concentrations were twice or more above the upper limit of the normal value. The test results were within normal reference limits in 31.6% of patients (Figure 1). We followed-up how the results are related to the patients’ age and sex, the time spent on dialysis treatment, but we found no relation between the age, sex or the influence of the dialysis treatment to the results obtained.

Left ventricular hypertrophy was found by echocardiography in 72.7% of patients, while the mean ejection fraction value was 53.9 ±12%. A small pericardial effusion was found in one of the patients without hemodynamic repercussions. Intracavitary formations were not recorded.

The relatively high prevalence of patients with reduced renal function (11%) observed in epidemiological studies, with an overall prevalence of the third, fourth and fifth stage (glomerular filtration rate lower than 59 to 15 ml/min/1.73 m2) of 8.5% makes this group of patients increasingly important including the specializations which are not nephrology, especially diabetologists and cardiologists.

Chronic renal disease is closely associated with heart diseases, so this comorbidity is their common cause and consequence. There is a fact that has been known from the literature for some time, that multiple abnormalities of the coagulation system are present in patients undergoing hemodialysis, predominantly as a result of endothelial dysfunction, and that the elevated levels of the D-dimer are an independent predictor of the prevalence of ischemic heart disease (10-13).

D-dimers are the reflection of procoagulant condition in patients with chronic renal insufficiency and the elevated values in some patients on dialysis without symptoms of thromboembolic events as determined by the results of this study can be considered to be their baseline values.

In patients on chronic hemodialysis, the value of the D-dimer test in the diagnosis of thromboembolic events has reduced significantly, but the test needs to performed and it is necessary to follow up the dynamics of the results in this specific population as well. The results need to be interpreted according to the principle "cum grano salis — grain of salt".