Senija Rašić

Inflammatory Markers and Procoagulants in Chronic Renal Disease Stages 1-4.

Introduction: Starting from the point that the chronic kidney disease (CKD) is chronic, inflammatory and hypercoagulable state characterized by an increase in procoagulant and inflammatory markers high cardiovascular morbidity and mortality in these patients could be explained. Aim: The aim of the research was to monitor inflammatory markers and procoagulants in various stages of kidney disease (stage 1-4). Materials and Methods: The research included 120 subjects older than 18 years with CKD stages 1-4 examined and monitored in Clinic of Nephrology, University Clinical Centre Sarajevo over a period of 24 months. The research included determining the following laboratory parameters: serum creatinine, serum albumin, C-reactive protein, leukocytes in the blood, plasma fibrinogen, D-dimer, antithrombin III, coagulation factors VII (FC VII) and coagulation factor VIII (FC VIII). Results: With the progression of kidney disease (CKD stages 1-4), there was a significant increase of inflammatory and procoagulant markers: CRP, fibrinogen and coagulation factor VIII, and an increase in the average values of leukocytes and a reduction in the value of antithrombin III, but without statistical significance. Also, there were no significant differences in the values of D-dimer and coagulation factor VII. Conclusion: The progression of kidney disease is significantly associated with inflammation, which could in the future be useful in prognostic and therapeutic purposes. Connection of CKD with inflammation and proven connection of inflammation with cardiovascular risk indicates the potential value of some biomarkers, which could in the future identify as predictors of outcome and could have the benefit in the early diagnosis and treatment of cardiovascular disease in CKD.

The Effect of Preserved Residual Renal Function on Left Ventricular Structure in Non-Anuric Peritoneal Dialysis Patients

Background/Aims: Residual renal function (RRF) has been shown to influence survival of peritoneal dialysis (PD) patients. This study examined the relations between RRF and left ventricular hypertrophy (LVH) before switching on dialysis treatment and observed during 18 months on PD treatment. Methods: A prospective longitudinal study was performed in 50 non-anuric (defined as >200 mL urine output in a 24-hour period) PD patients. Echocardiography, RRF and other known risk factors for the increase of LV mass index (LVMi) were determined at study baseline and the end of follow-up. Results: There was 78% patients with LVH in end-stage renal disease (ESRD) baseline and 60% at the end of follow-up. RRF at the start of the study showed no significant difference between patients with normal and increased LVMi, as well as in daily collection of urine. After 18 months, patients with decreased LVMi had better RRF, lower CRP and better Kt/V compared to patients with increased LVMi (p < 0.001). Patients with better preserved RRF not only had significantly higher total Kt/V, but were less anemic and hypoproteinemic and lesser presence of LVH. Conclusions: PD in non-anuric ESRD patients the first 18 months has a positive effect on the preservation of RRF and partial regression of left ventricular remodeling.

Prognostic indicators of adverse renal outcome and death in acute kidney injury hospital survivors.

Introduction: Data regarding prognostic factors of post-discharge mortality and adverse renal function outcome in acute kidney injury (AKI) hospital survivors are scarce and controversial. Objectives: We aimed to identify predictors of post-discharge mortality and adverse renal function outcome in AKI hospital survivors. Patients and Methods: The study group consisted of 84 AKI hospital survivors admitted to the tertiary medical center during 2-year period. Baseline clinical parameters, with renal outcome 3 months after discharge and 6-month mortality were evaluated. According survival and renal function outcome, patients were divided into two groups. Results: Patients who did not recover renal function were statistically significantly older (P < 0.007) with higher Charlson comorbidity index (CCI) score (P < 0.000) and more likely to have anuria and oliguria (P = 0.008) compared to those with recovery. Deceased AKI patients were statistically significantly older (P < 0.000), with higher CCI score (P < 0.000), greater prevalence of sepsis (P =0.004), higher levels of C-reactive protein (CRP) (P < 0.017) and ferritin (P < 0.051) and lower concentrations of albumin (P<0.01) compared to survivors. By multivariate analysis, independent predictors of adverse renal outcome were female gender (P =0.033), increasing CCI (P =0.000), presence of pre-existing chronic kidney disease (P =0.000) and diabetes mellitus (P =0.019) as well as acute decompensated heart failure (ADHF) (P =0.032), while protective factor for renal function outcome was higher urine output (P =0.009). Independent predictors of post-discharge mortality were female gender (P =0.04), higher CCI score (P =0.001) and sepsis (P =0.034). Conclusion: Female AKI hospital survivors with increasing burden of comorbidities, diagnosis of sepsis and ADHF seem to be at high-risk for poor post-discharge outcome.

Renal Function Outcome Prognosis in Septic and Non-septic Acute Kidney Injury Patients.

Aim: The objective of this study was to evaluate prognostic impact of clinical factors on outcome of renal function in septic and non-septic acute kidney injury (AKI) patients. Methods: The prospective, observational, clinical study was performed at Nephrology Clinic and Clinic for Infectious Diseases, University Clinical Centre Sarajevo. One hundred patients with diagnosis of AKI were enrolled in the study, and divided into two groups: septic and non-septic AKI patients. Clinical parameters included causes and type of AKI, pre-existing comorbidities and different treatment modalities. Patients were followed up until discharge or death. Renal function outcome was defined by creatinine clearance values at discharge. Results: Septic AKI patients had significantly longer hospital stay (p=0.03), significantly worse renal function outcome (p<0.001), and higher burden of comorbidities (70.6% vs. 60.6%), compared to non-septic patients. Septic AKI patients were almost three times less likely to receive renal replacement therapy (8.8% vs. 24.4%) and they had significant delay in initiation of dialysis (p=0.03). By multivariate analysis, sepsis (95% CI 0.128-0.967, p=0.043) and hypertension (95% CI 0.114-0.788, p=0.015) were independent predictors of adverse renal function outcome in AKI patients. Postrenal type of AKI was independent predictor of renal function recovery in non-septic AKI patients (95% CI 1.174-92.264, p=0.035), while Failure, as third class of AKI, was independent predictor of non-recovered renal function only in septic AKI patients (95% CI 0.026 to 0.868, p=0.034). Conclusion: Septic AKI patients are clinically distinct compared to non-septic AKI patients with different prognostic factors and poorer renal function outcome.

Valvular calcification and left ventricular modifying in peritoneal dialysis patients

Abstract Background: Cardiac valve calcification (CVC) and left ventricular (LV) alterations are frequent complication in end-stage renal disease (ESRD). We determined the prevalence of CVC and LV hypertrophy (LVH) in ESRD patients before renal replacement therapy and 12 months after peritoneal dialysis (PD). Methods: A prospective longitudinal of 50 incident PD patients was studied. Demographic and clinical data were recorded and blood assayed at baseline and after 1-year of follow-up. CVC and LVH were evaluated by M-mode two-dimensional echocardiography. Results: CVC of the mitral and aortic valves and of both valves were noted in 30, 18 and 10% of patients, respectively. After 12 months of PD regimen, 20% patients had aortic, 24% mitral and 8% had calcification of both valves. After one year of PD, LVH was 62 and 36% in patients with and without CVC, respectively (p < 0.05). Endothelin-1 is an independent predictor of CVC at the baseline, while nitric oxide is inversely an independent predictor at the end of follow-up. Conclusions: CVC is associated with LVH in PD patients. These findings identified a potential role for monitored markers to be incorporated into therapeutic strategies aimed at detection and treatment of cardiovascular complications and prevention strategies.

High prevalence of early chronic kidney disease in high risk outpatients.

Introduction: Chronic kidney disease (CKD) is a significant public health problem. The aim of this study was to determine the presence of early stages of renal disease in hypertensive and diabetic outpatients without previously diagnosed renal damages. Methods: In this cross-sectional study we studied a random sample of outpatients with essential hypertension and/or diabetes mellitus type 2 in the general practice ambulance of city Sarajevo. Renal function was evaluated by using MDRD (Modification of Diet in Renal Disease) equation and with measurement of renal biomarkers. K/DOQI classification was used to define the stages of CKD. Results: The study included 200 patients, of whom 75 (37.5%) were females, mean age of 54.81 ± 6.1 years, and 125 (62.5%) male, mean age 52.46 ± 8.2 years. More than half of respondents (54.0%) were hypertensive during the follow up period. Early CKD was detected in 52% respondents. Higher prevalence of early CKD was verified in the group of patients who had hypertension associated with diabetes mellitus type 2 (59.6% vs. 47.2% in hypertension group vs. 54,0% in diabetic group, p<0.05). Significant negative correlation was found between estimated glomerular filtration rate and presence of albuminuria (p<0.001), duration of hypertension (p=0.003), duration of type 2 diabetes mellitus (p=0.021), stages of hypertension (p=0.012), female gender (p<0.001) and older age of subjects (p=0.040). Conclusion: Our results confirmed high prevalence of CKD and the importance of early detection of CKD in high risk groups of patients in order to prevent the progression of the same. Prevention of chronic kidney disease in our country is still not carried out satisfactorily. Required is a much greater collaboration between primary care health givers and nephrologists.

Influence of endothelin-1 and nitric oxide on left ventricular remodelling in patients on peritoneal dialysis

Abstract Background: Left ventricular hypertrophy is the most common structural cardiac alteration in chronic dialysis patients. The aim of this study was to determine the possible association of endotelin-1 (ET-1) and nitric oxide (NO) with parameters of echocardiography in order to assess their participation in left ventricular (LV) remodeling in patients on peritoneal dialysis (PD). Methods: This prospective longitudinal study included 40 PD patients. Serum levels of ET-1 and NO baseline and after 12 months of PD treatment were measured and compared with echocardiography parameters done at the same time of PD treatment. Linear regression analysis was used to detect independent correlations of variables. Results: Mean ET-1 serum concentration decreased significantly after 12 months of PD treatment compared to baseline values (p < 0.01). NO serum concentration increased significantly 12 months after treatment compared to baseline values (p < 0.01). Left ventricular hypertrophy (LVH) was observed in 72.5% of patients at baseline with significant reduction in LV mass index after 12 months of PD treatment (p < 0.001). On linear regression analysis serum concentration of ET-1 was independent predictors of LV mass index, as well as NO at the end of observed period. Conclusions: According to our data ET-1 and NO are independently related to the process of left ventricular remodeling in PD patients

Influence of Malondialdehyde and Matrix Metalloproteinase-9 on Progression of Carotid Atherosclerosis in Chronic Renal Disease with Cardiometabolic Syndrome

Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase-9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients (P < 0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (P < 0.05) and plaque score on CA in these patients (P < 0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS.

Role of Hypertension and Anaemia in Left Ventricular Remodelling in Patient with Renal Allograft in the First Post-transplant Year.

Background: Hypertension (HT) and renal anaemia (RA) are well-established markers of cardiovascular risk in patients with chronic kidney disease (CKD). They appear to be the stimuli for left ventricular hypertrophy (LVH), who significantly participates in cardiac complications in uremic patients. Hypertension is extremely common after kidney transplantation (KTx) and it has been observed in up to 75% of patients. The prevalence of post-renal transplant anaemia (PTA) is variable (up to 30%) and several factors such as graft function contribute towards its pathophysiology. Aim: The aim of this study was to analyze the impact of blood pressure and anaemia on LV remodelling in first year after transplantation comparing echocardiographic findings before and twelve months after transplantation had done. Methods: In five years retrospective-prospective study we followed up 30 patients with renal allograft in first post-transplant year. During the study values of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), blood hemoglobin (Hgb), serum creatinine and creatinine clearance were monitored monthly. Results: Before transplantation (Tx) 86% of patients had HT, and RA was confirmed in all patients. Normal echocardiographic findings had 33% of patients and 67% of patients had echocardiographic sings of LVH. Before renal transplantation group with LVH had statistically higher the mean values of blood pressure (MBP) (p=0.053) compared to group with diastolic (LVDDF) (p=0.0047) and systolic-diastolic dysfunction (LVSDDF) (p=0.0046). The values of SBP and DBP positively correlated with LV mass index (LVMI) in the group of patients with LVH (p=0.0007 and p=0.0142). The values of Hgb was statistically higher in group with normal LV mass index compared to LVH (p=0.019), with negative correlation between LVMI and values of Hgb in the patients group with LV hypertrophy (p=0.009). After the first year of transplantation, 63% of patients showed normal LV mass index and 37% remained with echocardiographic findings of the LVH. The values of SBP and values of Hgb in both groups, as well as values of DBP in group of LVH were statistically different in compare with data before transplantation (p<0.05). The positive echocardiographic remodelling of LV significantly correlated with the increase of Hgb values (p=0.05), but without significant correlation with the decrease of the mean SBP and DBP. Conclusion: These results confirmed that positive echocardiographic remodelling of left ventricle after successful renal transplantation is complex process depended on many risk factors and elimination of uremia- related factors is a priority.

Alteration of cardiovascular structure and function in patients undergoing peritoneal dialysis.

Aims: Cardiovascular alterations contribute to a high mortality rate in patients with end-stage renal disease (ESRD). The aims of the present study are to evaluate left ventricular (LV) function and common carotid artery (CCA) parameters and to determine risk factors associated with these changes in patients undergoing peritoneal dialysis (PD). Methods: This longitudinal prospective study was conducted in 50 ESRD patients in whom PD had been initiated and who were observed for 18 months after the commencement of dialysis treatment, with echocardiography and CCA ultrasound parameter evaluation. Results: LV hypertrophy was observed in 78% of patients at baseline and in 60% after 18 months of PD treatment. LV systolic and diastolic function was found to be significantly better after 18 months of PD treatment. Examining predictors of LV systolic function, it was found that total cholesterol was an independent positive predictor and endothelin-1 (ET-1) an independent negative predictor of LV systolic function after 18 months of treatment with PD (p < 0.001). Independent negative predictors of diastolic LV function were hemoglobin and type 2 diabetes mellitus, and daily collection of urine was an independent positive predictor (p < 0.001). Female gender was an independent negative predictor of CCA intima-media thickness, whereas body mass index, ET-1 and C-reactive protein were independent positive predictors (p < 0.001). Conclusions: The results suggest several novel modifiable mechanisms related to the short-term effects of dialysis that are potentially implicated in the development of uremic cardiomyopathy.