Aida Hamzić-Mehmedbašić

Serum cystatin C - marker of inflammation and cardiovascular morbidity in chronic kidney disease stages 1-4.

Aim: The aim of the research was to compare the relationship between inflammatory biomarkers and procoagulants with kidney function assessed by using cystatin C, serum creatinine, and eGFR and determine the sensitivity of cystatin C, serum creatinine and eGFR to total cardiovascular morbidity in patients with CKD stages 1-4. Methods: The research included 120 patients older than 18 years with CKD stages 1-4 monitored over a period of 24 months. Results: Serum cystatin C correlates with fibrinogen (p<0.01), serum albumin (p<0.01), D-dimer (p<0.05), antithrombin III (p<0.01) strongly in relation to the evaluation of kidney function based on serum creatinine and eGFR. By following cystatin C, creatinine and eGFR with comparison of ROC to total cardiovascular morbidity, the highest sensitivity in relation to the presence of cardiovascular morbidity shows cystatin C, then eGFR and the lowest, creatinine, with a significant difference between cystatin C and serum creatinine (p<0.05). Conclusion: Serum cystatin C is more strongly correlated with some biomarkers (fibrinogen, serum albumin, D-dimer, antithrombin III), while simultaneously showing a stronger sensitivity in relation to total cardiovascular morbidity compared with the assessment of kidney function based on serum creatinine and eGFR.

Clinical analysis of etiology, risk factors and outcome in patients with acute kidney injury.

Introduction: Acute kidney injury is characterized by a rapid loss of renal excretory function with the increase of nitrogen compounds in the blood and with different outcome. Objective: Since descriptions of the risk factors and sequelae of acute kidney injury (AKI) remain relatively limited, the objective of this study was to determine etiology and clinical characteristics of AKI, as well as risk factors for adverse outcome of renal function and death in AKI patients. Methods: We retrospectively studied a cohort of 84 adult AKI patients admitted to Nephrology Clinic in University Clinical Centre Sarajevo during period 2012-2014. Demographic, laboratory and clinical parameters were retrieved. The in-hospital and 6 months mortality were recorded. Renal function outcome was defined 3 months following discharge. Results: Majority of patients were older (median age 73.5 years) with great severity of AKI (Stage III in 78.5% of cases) and high burden of comorbidities (mean Charlson comorbidity index, CCI score 6.4±3.05). The most common causes of AKI were acute interstitial nephritis (16.7%), heart failure (15.5%), gastroenterocolitis (13.1%), and sepsis (12%). Renal function recovery was recorded in 48.8% of patients, with prevalence of 10.7% of intrahospital mortality and 37.3% of 6 months mortality. Risk factors for poor outcome of renal function and mortality in AKI patients were increasing age and higher CCI score, while protective factor was higher diuresis. Sepsis proved to be risk factor for death.

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.

Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events

Introduction: Inflammatory markers have been identified as potential indicators of future adverse outcome after acute cardiac events. Aim: This study aimed to analyze baseline inflammatory cytokines levels in patients with acute heart failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The main objective was to identify risk factors for mortality after an episode of AHF and/or ACS. Methods: In this prospective longitudinal study 75 patients with the diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18) levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were determined. The primary outcome was in-hospital mortality while secondary outcome was six-month mortality. Results: Median serum and urine IL-6 levels, serum and urine IL-18 levels, as well as median concentrations of plasma BNP and serum cystatin C, were significantly increased in deceased in comparison to surviving AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL-6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for mortality after an episode of AHF and/or ACS. Multivariate Cox regression analysis revealed that only serum IL-6 is the independent risk factor for mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018). Conclusion: Present study demonstrated the strong prognostic value of serum IL-6 in predicting mortality of patients with AHF and/or ACS.

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.

Biomarkers of Cardiovascular Remodeling in Patients on Peritoneal Dialysis

Objectives: The purpose of this study was to determine endothelin (ET)-1 and nitric oxide (NO) serum concentration levels at baseline and after 1 year of peritoneal dialysis (PD) treatment. A further aim was to evaluate the association between ET-1 and NO with parameters of echocardiography and the common carotid artery (CCA) ultrasound, and to assess their impact on cardiovascular remodeling. We also aimed to evaluate the influence of dialysis adequacy and residual renal function (RRF) on cardiovascular remodeling. Methods: This study included 40 PD patients in whom we measured serum ET-1 and NO concentrations, echocardiography and CCA ultrasound parameters. Results: ET-1 decreased and NO serum concentration levels increased (p < 0.01) after 12 months of PD treatment compared to baseline values. Left ventricular (LV) hypertrophy was observed in 77.5% of patients at baseline with significant reduction in LV mass index (LVMI), CCA intima media thickness (IMT) and plaque score after 12 months of PD treatment (p < 0.001). The dialysis adequacy and RRF were significantly associated with LVMI and CCA IMT after 12 months on PD. Conclusion: In our study, ET-1 significantly decreased while NO increased during PD treatment and both were independently related to the cardiovascular remodeling parameters in PD patients.

Predictors of Hospitalization for Heart Failure Decompensation in 18-months Follow-up After Index Hospitalization for Acute Heart Failure

Introduction: Heart failure (HF) has very high rate of repeat hospitalizations due to HF decompensation (HHFD), sometimes very shortly after discharge for acute HF. Aim: The aim of this paper is to investigate rate of HHFD and to identify their possible predictors. Patients and Methods: Total amount of 222 patients hospitalized at Clinic for heart and vessel disease and rheumatism in acute HF were followed for next 18 months for occurrence of HHFD. During hospitalization were collected demographic data, risk factors, routine laboratory tests and admission BNP (brain natriuretic peptide), discharge BNP, percentage change of BNP during hospitalization, high sensitive troponin I, CA125 (cancer antigen125) and cystatin C. Results: In next 18 months 129 patients (58.11%) reached end-point HHFD- mean time of its occurrence was 2.2 (95% CI=1.67-2.7) months. Patients with HHFD had more often arterial hypertension (HTA) (p=0.006), had higher BMI (p=0.035) and had higher values of bilirubin, admission BNP (p=0.031), discharge BNP (p <0.001), CA125 (p=0.023) and cystatin C (p=0.028). There was no difference in troponin values (p=0.095), while % reduction of BNP during hospitalization was lower (p<0.001) in group with HHFD. In univariate Cox hazard analysis HTA was positively and BMI negatively correlated with HHFD, while in multivariate Cox hazard analysis independent predictors were HTA (HR 1.6; 95% CI=1.1-2.2; p=0.018) and BMI<25 (HR 1.6; 95% CI=1.1-2.3; p=0.007). In univariate Cox hazard analysis admission BNP, discharge BNP, rise of BNP during hospitalization, CA125 and bilirubin were positively correlated, while sodium was negatively correlated with HHFD. In multivariate Cox hazard analysis there was only one independent predictor of HHFD - discharge BNP (HR 6.05; 95% CI=1.89-19.4; p=0.002). Conclusion: Arterial hypertension, BMI>25 and discharge BNP are independent predictors of HHFD. This could help us to identify high-risk patients for readmission who should be monitored more frequently and treated with sophisticated drug and device therapy.