Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury.

Sepsis-associated acute kidney injury (SA-AKI) severely impacts morbidity and mortality in surgical patients with sepsis. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) have an important role in pathophysiology of sepsis but they have been unexplored in SA-AKI. We aimed to investigate the role of MMP-9 and TIMP-1 in septic surgical patients with SA-AKI and to evaluate them as diagnostic biomarkers of SA-AKI. This prospective observational study compared 53 major abdominal surgery patients with sepsis divided into SA-AKI (n = 37) and non-SA-AKI (n =16) group to 50 controls without sepsis matched by age, gender, comorbidities and type of surgery. Blood and urine samples from septic patients were collected on admission to ICU and 24, 48, 72 and 96 h later and once from the controls. The levels of MMP-9, TIMP-1, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, urea and creatinine were measured. MMP-9/TIMP-1 ratio and disease severity scores, such as Sequential Organ Failure Assessment (SOFA), were calculated. Septic patients with SA-AKI had higher serum TIMP-1 levels and lower serum MMP-9 levels and lower MMP-9/TIMP ratio, compared to septic patients without SA-AKI and controls. The levels of these biomarkers did not change significantly over time. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio correlated with urea, creatinine, NGAL, and SOFA scores. Moreover, using the area under ROC curve, we showed that TIMP-1 and MMP-9/TIMP-1 ratio, but not MMP-9, were good diagnostic biomarkers of SA-AKI. We report for the first time the potential diagnostic value of TIMP-1 and MMP-9/TIMP-1 ratio in SA-AKI.

Inflammatory markers as mortality predictors in continuous ambulatory peritoneal dialysis patients.

BACKGROUND/AIM: Besides peritonitis, the most common complication, indicators of chronic inflammation are also present in patients treated by peritoneal dialysis. The aim of this study was to analyze the predictive value of inflammatory parameters on mortality of continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Eighty-seven patients (57 males), aged from 30 to 85 [62.92 (10.61)] years who had been treated by a chronic program of CAPD for 3-113 months were analyzed. The basal period lasted 3 months with a follow-up of 30 months. Clinical parameters, dialysis adequacy and laboratory parameters including some inflammatory markers: serum amyloid-A (SAA), high sensitive C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR) and leukocytes were determined for each patient. Cox regression analysis selected the parameters of univariate and multivariate survival analysis. RESULTS: During the follow-up period, 37 patients (42.5%) died. Univariate analysis selected the following potential mortality predictors (p<0.10): age, months on CAPD, residual urine output, presence of cerebrovascular insult (CVI), KT/V, serum urea and albumin concentrations, SAA, hs-CRP, fibrinogen and ESR. In the multivariate survival analysis four models were created, each with a single inflammatory parameter. In all of these models, besides the age and CVI, inflammatory parameters were the most significant mortality predictors. When the inflammatory markers were analyzed altogether, multivariate analysis established that independent mortality predictors in this group of patients were: SAA, age and CVI. CONCLUSION: It may be concluded that in this studied group treated by CAPD, SAA was the most significant independent mortality predictor among the analyzed inflammatory markers.

Predictive value of echocardiography and its relation to Kt/V and anthropometric parameters in hemodialysis patients.

BACKGROUND: In order to evaluate the predictive value of echocardiograph parameters for mortality of hemodialysis patients and their relation to Kt/V and anthropometry, a prospective, single center study was analyzed post-hoc. METHODS: This analysis encompassed 106 patients on maintenance hemodialysis monitored for 108 months from 1996 to 2004. spKt/V was calculated using the Daugirdas formula. Anthropometric measurements included mid-arm muscle measurements (MAMC) and percentage of body fat (%fat). Echocardiography included the estimations of left ventricular wall thickness, dimensions and volumes (EDV, ESV), systolic LV function (ejection fraction - EFLV, fractional shortening - VCF, stroke volume - SV) and diastolic LV function (E/A, VTI-A wave of transmitral flow velocity), left atrial diameter, as well as assessment of clinical and biochemical parameters. The Cox proportional hazard model was used to estimate predictive values of echocardiograph parameters. RESULTS: Kt/V correlated significantly with left ventricular systolic and diastolic volumes and function, septal and posterior wall thickness and left atrium dimension. MAMC and %fat also correlated with many echocardiograph parameters. Multivariate Cox regression selected age [HR 1.07; CI (1.03-1.12); p < 0.01], albumin [HR 0.88; CI (0.79-0.97); p < 0.05] and left atrium dimension - binary [values > 4 cm were marked as "1" and others "0" - HR 3.76; CI (1.56-9.03); p < 0.01] as independent predictors of death. CONCLUSION: Left atrium dimension was the most important predictor of mortality among the echocardiograph parameters. Many of these parameters were related to Kt/V and anthropometric measurements and could be the combined consequence of hypervolemia and hypertension.

Association of small, dense low-density lipoprotein cholesterol and galectin-3 in patients with chronic kidney disease.

BACKGROUND: Dyslipidemia is a common feature of chronic kidney disease (CKD). Although it has been observed that the pattern of lipid abnormalities can vary according to the stage of CKD, there is lack of data concerning the distribution of lipoprotein subclasses at various stages of the disease. In addition, association of proatherogenic small, dense low-density lipoprotein (sdLDL) subclasses with markers of inflammation, such is galectin-3, is not sufficiently explored. The aim of this study was to analyze concentrations and relative proportions of sdLDL-cholesterol (sdLDL-C) and galectin-3 in patients with CKD, with respect to the stage of the disease. Also, we sought possible independent associations of galectin-3 and sdLDL-C. METHODS: The study involved 100 hemodialysis (HD) and 50 pre-dialysis patients, together with 94 healthy individuals. SdLDL-C was measured by heparin-magnesium precipitation method. Galectin-3 was measured by ELISA technique. RESULTS: Galectin-3 levels were higher in pre-dialysis and HD patients than in the control group (p < 0.01). The concentration of sdLDL-C was highest in the pre-dialysis group and lowest in HD patients (p < 0.01). CKD patients with increased galectin-3 concentrations had significantly higher relative proportions of cholesterol in sdLDL (% sdLDL-C) than their counterparts with lower galectin-3 levels (p < 0.05). Relative proportion of sdLDL-C was shown to be an independent determinant of galectin-3 concentration. CONCLUSIONS: Our results demonstrated alterations in concentrations and proportions of sdLDL-C according to the stages of CKD. The observed independent associations of % sdLDL-C and galectin-3 provide further insight into their complex interaction during the progression of atherosclerosis in CKD.

A comparison of markers of myocardial injury and their relation to nutritional parameters in hemodialysis patients.

BACKGROUND: Serum cardiac troponin T (cTnT) is a valuable marker of ischemic heart disease (IHD) and left ventricular hypertrophy, as well as a mortality predictor in hemodialysis populations. We compared the value of cTnT, creatinine kinase (CK)-MB mass and myoglobin as mortality predictors in our hemodialysis patients and evaluated their relation to nutritional status. METHODS: A total of 118 hemodialysis patients were prospectively studied from January 2004 to April 2013. Clinical and laboratory evaluations during the 12-month baseline period included the history of IHD, signs of left ventricular hypertrophy (LVH), Kt/V and serum cardiac markers together with the percentage of body fat (%fat), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), triceps skinfold (TSF) and BMI. RESULTS: Underweight patients had significantly higher cTnT values (Mann-Whitney, p<0.05). Correlation analysis (Spearman) showed an inverse association between cTnT and TSF (ρ=-0.22, p<0.05), as well as between CK-MB mass and TSF (ρ=-0.26, p<0.01). In men cTnT also correlated inversely with %fat (ρ=-0.27, p<0.05) and BMI (ρ=-0.33, p<0.05). In addition, myoglobin was correlated significantly with MAC, MAMC and albumin. Among cardiac markers cTnT was the only independent variable predicting mortality (Multivariate Cox regression, HR=1.04 CI (1.01-1.07); p<0.01; measurement units 0.01 µg/L). CONCLUSION: Troponin T and CK-MB mass were significantly elevated in the underweight patient group. Troponin T was the only independent cardiac marker predictor of all cause mortality in our hemodialysis patients.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

BACKGROUND: The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. METHODS: We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. RESULTS: Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. CONCLUSIONS: NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Association of multiple retinal nodular hamartomas and "confetti" skin lesions with end-stage renal disease in patients with tuberous sclerosis.

PURPOSE: The main purpose of this study is to explore characteristics of patients with chronic kidney disease in tuberous sclerosis (TSC) and to underline differences in clinical characteristics between end-stage renal disease (ESRD) patients and patients in earlier stages of chronic kidney disease. METHODS: This multicentric, retrospective study included data for 48 patients from seven South-Eastern European countries (Albania, Bosnia and Herzegovina, Croatia, Greece, Montenegro, Serbia, Slovenia) in the period from February to August 2020. Researchers collected data from local and national nephrological and neurological registries and offered clinical and laboratory results from medical histories in follow-up periods. RESULTS: This study enrolled 48 patients with a median age of 32.3 years (range, 18-46 years), and predominant female gender (60.45%). The percentage of patients with chronic kidney disease (CKD) diagnosis of the total number of patients was 66.90%, with end-stage renal disease development in 39.6%. The most prevalent renal lesions leading to chronic kidney disease were angiomyolipomas (AMLs) in 76.6%, while multiple renal cysts were present in 42.6% of patients. Nephrectomy was performed in 43% of patients, while the mTOR inhibitors were used in 18 patients (37.5%). The majority of patients had cutaneous manifestations of tuberous sclerosis-83.30% had hypomelanotic cutaneous lesions, and 68.80% had angiofibromas. Multiple retinal nodular hamartomas and "confetti" skin lesions were more frequent in end-stage renal disease (ESRD) than in patients with earlier stages of chronic kidney disease (p-0.033 and 0.03, respectively). CONCLUSION: Our study has also shown that retinal hamartomas and "confetti" skin lesions are more frequent in end-stage renal diseases (ESRD) patients than in other chronic kidney disease (CKD) patients. Usage of mTOR inhibitors can also reduce the number of complications and associated with tuberous sclerosis, such as dermatological manifestations and retinal hamartoma, which are more common in the terminal stage of chronic kidney disease.

Risk factors associated with coronary artery calcification should be examined before kidney transplantation.

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.

The fractal and textural analysis of glomeruli in obese and non-obese patients.

Background Fractal dimension is an indirect indicator of signal complexity. The aim was to evaluate the fractal and textural analysis parameters of glomeruli in obese and non-obese patients with glomerular diseases and association of these parameters with clinical features. Methods The study included 125 patients mean age 46 ±â€¯15.2 years: obese (BMI ≥ 27 kg/m2-63 patients) and non-obese (BMI < 27 kg/m2-62 patients). Serum concentration of creatinine, protein, albumin, cholesterol, trygliceride, and daily proteinuria were measured. Formula Chronic Kidney Disease Epidemiology Colaboration (CKD-EPI) equation was calculated. Fractal (fractal dimension, lacunarity) and textural (angular second moment (ASM), textural correlation (COR), inverse difference moment (IDM), textural contrast (CON), variance) analysis parameters were compared between two groups. Results Obese patients had higher mean value of variance (t = 1.867), ASM (t = 1.532) and CON (t = 0.394) but without significant difference (P > 0.05) compared to non-obese. Mean value of COR (t = 0.108) and IDM (t = 0.185) were almost the same in two patient groups. Obese patients had higher value of lacunarity (t = 0.499) in comparison with non-obese, the mean value of fractal dimension (t = 0.225) was almost the same in two groups. Significantly positive association between variance and creatinine concentration (r = 0.499, P < 0.01), significantly negative association between variance and CKD-EPI (r = -0.448, P < 0.01), variance and sex (r = -0.339, P < 0.05) were found. Conclusions Variance showed significant correlation with serum creatinine concentration, CKD-EPI and sex. CON and IDM were significantly related to sex. Fractal and textural analysis parameters of glomeruli could become a supplement to histopathologic analysis of kidney tissue.

The predictive value of anthropometric parameters on mortality in haemodialysis patients.

BACKGROUND: Since protein-calorie malnutrition is a common factor influencing morbidity and mortality of haemodialysis patients, assessing their nutritional status is important. The aim of this study was to investigate the predictive value of anthropometric parameters on mortality and their interrelationship. METHODS: The study included a cohort of 242 patients. The analysis involved baseline data obtained during the first calendar year after the patients entered the study (1994-2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and included skinfolds, mid-arm circumference (MAC), body height and weight. The percentage of body fat (%fat) was calculated from triceps (TSF), biceps, subscapular and suprailiac skinfolds (Disease Outcomes Quality Initiative (DOQI) guidelines) and mid-arm muscle circumference (MAMC) from MAC and TSF. Body mass index (BMI), Kt/V, normalized protein catabolic rate (NPCR) and cardiovascular co-morbidity were also determined and laboratory analyses undertaken. RESULTS: Strong correlations were found among the anthropometric parameters. Extended Cox regression analysis selected %fat, MAC, MAMC and TSF in addition to age, ischaemic heart disease, congestive heart failure, Kt/V, haemoglobin, creatinine, albumin and NPCR as potential predictors of mortality. The same anthropometric parameters were found to be independent mortality predictors in corresponding models. The most predictive anthropometric factor was MAC. BMI was not a risk factor. CONCLUSION: Percentage of body fat, MAC, MAMC and TSF were independent predictors of mortality of haemodialysis patients, and MAC was the most predictive one.

Factors associated with hepcidin-25 levels in maintenance hemodialysis patients.

This study aimed to investigate the factors that are independently associated with hepcidin-25 and its relationship with doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron in stable maintenance hemodialysis patients (smHD) stratified by ESAs administration. In 103 adult smHD (ESAs therapy (N = 64) and ESAs-free (N = 39)), median values of biologically active hepcidin-25 (chemiluminescent direct ELISA assay) and ferritin levels were significantly higher whereas red blood cell count, hemoglobin, and hematocrit values were lower in ESAs therapy compared to ESAs-free group (P < .001, for all). Our results suggest that ESAs-independent smHD exhibit supposedly normal hepcidin-25 levels and preserved iron homeostasis, with a lower degree of anemia. The results of our multivariable model indicate that hepcidin-25 levels are independently and positively associated with iron stores and inflammation, and inversely with active erythropoiesis, regardless of ESAs administration. Maintenance ESAs and the intravenous iron dose were not related to hepcidin-25 levels.

Assessment of positive iron balance in end-stage renal disease: Could hepcidin-25 be useful?

INTRODUCTION: The aim of our study was to examine the relationship of hepcidin-25 with red blood cell and reticulocyte indices and to evaluate the diagnostic properties of hepcidin-25 in the assessment of positive iron balance in end-stage renal disease (ESRD) patients. METHODS: Eighty anemic ESRD patients (hemoglobin < 110 g/L) were classified as having iron deficiency (ID, N = 20), iron sufficiency (IS, N = 29), and positive iron balance (PB, N = 31) using the conventional biomarkers for iron status evaluation. Hepcidin-25 was determined by a chemiluminescent direct ELISA. RESULTS: Hepcidin-25 was significantly negatively correlated with the proportion of hypochromic erythrocytes (%HYPO) (P = .034) and immature reticulocyte fraction (P = .010) in ID and with the absolute reticulocyte concentration in ID (P = .048) and PB (P = .040). In multivariate models, hepcidin-25 was independently negatively associated with the mean reticulocyte hemoglobin content (CHr; ß = -0.493, P = .004) and red blood cell size factor (RSf) (ß = -0.334, P = .036) only in the PB group. The best hepcidin-25 value to exclude PB was 66.13 µg/L, showing a sensitivity of 61.3%, a specificity of 75.5%, and an AUC of 0.808. CONCLUSION: Our results suggest that hepcidin-25 levels are independently negatively associated with the iron demand for the most recent erythropoiesis only in PB. Hepcidin-25 performed acceptable in discriminating anemic ESRD patients with positive iron balance and may prove to be a useful additional tool in the evaluation of iron status.

Serum Resistin, Adenylate Cyclase-Associated Protein 1 Gene Expression, and Carotid Intima-Media Thickness in Patients with End-Stage Renal Disease and Healthy Controls.

BACKGROUND: Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. AIMS: We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. METHODS: This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. RESULTS: Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). CONCLUSION: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.

Polyneuropathy in diabetic and nondiabetic patients on CAPD: is there an association with HRQOL?

BACKGROUND: It is well known that patients with uremia, as well as patients with diabetes mellitus, develop polyneuropathy. OBJECTIVES: The signs of polyneuropathy in diabetic and nondiabetic patients on continuous ambulatory peritoneal dialysis (CAPD) and their relation with age, duration of dialysis, biochemical parameters, dialysis adequacy, and health-related quality of life (HRQOL) were analyzed in the present study. PATIENTS AND METHODS: 65 CAPD patients (37 men, age 29-85 years, duration on dialysis 3 months to 14 years) were divided into two groups: group 1 was comprised of 20 diabetic patients (mean age 50.1+/-13.2 years); group 2 was comprised of 45 nondiabetic patients (mean age 62.3+/-9.7 years). Biochemical parameters, dialysis adequacy, and clinical signs were determined. Motor conduction velocity on the peroneal and tibial nerves and sensitive conduction velocity on the sural nerve were measured. The Kidney Disease Quality of Life Short Form (KDQOL-SF) was used to measure the CAPD patients' self-assessment of functioning and well-being using 4 component scores: physical component summary (PCS), mental component summary (MCS), kidney disease target issues, and patient satisfaction. RESULTS: Subjective symptoms were more intense in the diabetic patients and correlated with changes in peroneal and tibial distal motor latency (DML). Diabetic patients were significantly younger, had lower creatinine and higher glucose levels, and all analyzed pathological neurophysiological parameters were higher. Nondiabetic patients had prolonged latency of the F-wave on the peroneal nerve and the tibial nerve and reduced sensitive conduction velocity on the sural nerve. Significant correlations were found between the analyzed neurophysiological parameters and duration of dialysis and diabetes, glucose concentration, and dialysis adequacy in diabetic patients, and between neurophysiological parameters and age and dialysis adequacy in nondiabetic patients. Analysis of the 4 component scores of the KDQOL-SF revealed that diabetic patients had significantly better scores for PCS and MCS, which can be explained by their younger age. Patient satisfaction was worse in diabetic patients and correlated with duration of diabetes. In addition, significant correlations were established between PCS, MCS, and tibial DML (late neuropathic changes) in diabetic patients, and between MCS and tibial F-wave (early neuropathic changes) in nondiabetic patients. CONCLUSION: Polyneuropathy was significantly worse in diabetic than in nondiabetic patients on CAPD. DML on the tibial nerve correlated with glucose concentration, dialysis adequacy, PCS, and MCS in diabetic patients, whereas in nondiabetic patients, dialysis adequacy and azotemia correlated with F-waves on the peroneal nerve and the tibial nerve but MCS only with F-wave on the tibial nerve.

Serum amyloid-A rather than C-reactive protein is a better predictor of mortality in hemodialysis patients.

The most frequent cause of death in hemodialysis patients is cardiovascular disease with chronic inflammation being an epidemiologically proved risk factor. Many studies have shown C-reactive protein (CRP) as the strongest predictor of long-term mortality of hemodialysis patients, while other reports have indicated acute phase proteins as potential predictors of the mortality. The present study therefore aimed to evaluate the prevalence of chronic inflammation in hemodialysis patients and the role of acute phase proteins together with lipids and divalent ions for predicting mortality in hemodialysis patients. Chronic inflammation was defined, based on the serum level of high sensitive CRP > 8.4 mg/L and/or serum amyloid-A (SAA) > 8.9 mg/L. Acute phase proteins are defined as one whose plasma concentration increase (positive) or decreases (negative) by at least 25% during inflammation. High sensitive CRP and SAA were positive acute phase proteins measured, while albumin and fetuin-A, a calcification inhibitor, were selected as negative acute phase proteins. This prospective 36-month follow-up study included 130 patients (60 males and 70 females, aged 55.1 +/- 12.9 years) maintained by hemodialysis for 107.2 +/- 54.72 months at a Nephrology Clinic in Belgrade. The prevalence of chronic inflammation was 35.4% (46 patients). During the follow-up period, 24 patients (18.5%) died and 2 patients received transplants. In multivariate analysis, potential independent predictors of mortality in hemodialysis patients are hyperphosphatemia, hypoalbuminemia, and high SAA. Considering that assays for SAA are widely used, we propose that SAA is the best predictor for outcomes of end-stage renal disease.

Health-related quality of life, treatment efficacy, and hemodialysis patient outcome.

The aim of the study was to examine the influence of improved treatment of hemodialysis (HD) patients on their health-related quality of life (HrQoL) and to assess the predictive value of HrQoL dimensions on patient outcome. The prospective cohort study involved 102 HD patients, and their clinical and laboratory parameters and HD adequacy indices were followed from 2001 to 2007. HrQoL was measured using KDQOL-SF Version 1.3 in 2001, 2004, and 2007. During a six-year period, quality of HD and anemia treatment improved and resulted in significant increase of mean Kt/V (1.2-1.56) and hemoglobin levels (86.5-115.6 g/L). All four HrQoL dimensions (i.e., physical, mental health, kidney disease target issues, and patient satisfaction) remained unchanged, but significant improvement in several HrQoL physical health domains and the effects of kidney disease domain was found. Mortality rate decreased from 18.6% to 7.14% per year. Age was associated positively, but kidney disease target issue score negatively, with patient death. Improved HD adequacy and anemia treatment in HD patients were followed with maintenance of all four HrQoL dimensions unchanged over six years. Moreover, an improvement in several physical health domains and the effects of kidney disease domain was found. Age and kidney disease target issue appeared as significant predictors of patients' death.

Associations of Common Variants in HFE and TMPRSS6 Genes with Hepcidin-25 and Iron Status Parameters in Patients with End-Stage Renal Disease.

BACKGROUND: Influence of TMPRSS6 A736V and HFE (C282Y and H63D) polymorphisms on serum hepcidin-25 levels and iron status parameters in end-stage renal disease (ESRD) patients stratified according to gender has not been previously investigated. In addition, we aimed to evaluate the diagnostic accuracy of the parameters to separate iron-deficiency anemia (IDA) from anemia of chronic disease. MATERIALS AND METHODS: Iron status parameters and genetic analysis were performed in 126 ESRD patients and in 31 IDA patients as the control group. RESULTS: ESRD patients had significantly higher ferritin and hepcidin-25 (<0.001) relative to IDA patients. Cut-off values with the best diagnostic accuracy were found for hepcidin ≥9.32 ng/mL, ferritin ≥48.2 µg/L, transferrin saturation ≥16.8%, and MCV ≥81 fL. Interaction between gender and HFE haplotypes for the hepcidin-25 and ferritin levels in ESRD patients (p = 0.005, partial eta squared = 0.09; p = 0.027, partial eta squared = 0.06, respectively) was found. Serum transferrin was influenced by the combined effect of gender and TMPRSS6 A736V polymorphism in ESRD patients (p = 0.002, partial eta squared = 0.07). CONCLUSION: Our findings could contribute to the further investigation of mechanisms involved in the pathophysiology and important gender-related involvement of the TMPRSS6 and HFE polymorphisms on anemia in ESRD patients.

Serum Lactate As Reliable Biomarker of Acute Kidney Injury in Low-risk Cardiac Surgery Patients.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) frequently occurs in patients assessed as low-risk for developing CSA-AKI. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1) and lactate are promising biomarkers of CSA-AKI but have not yet been explored in low-risk patients. AIM: To evaluate urinary NGAL (uNGAL), KIM-1 and lactate as biomarkers of CSA-AKI in patients with low-risk for developing CSA-AKI. METHODS: This prospective, observational study included 100 adult elective cardiac surgery patients assessed as low-risk for developing CSA-AKI. UNGAL, KIM-1 and lactate were measured preoperatively, at the end of cardiopulmonary bypass (CPB) and 3, 12, 24 and 48 h later. RESULTS: Fifteen patients developed CSA-AKI. Patients with CSA-AKI had significantly higher lactate but similar uNGAL and KIM-1 levels compared to patients without CSA-AKI. Unlike uNGAL and KIM-1, postoperative lactate was good biomarker of CSA-AKI with the highest odds ratio (OR) 2.7 [1.4-4.9] 24 h after CPB. Peak lactate concentration ≥ 4 mmol/L carried dramatically higher risk for developing CSA-AKI (OR 6.3 [1.9-20.5]). CONCLUSIONS: Unlike uNGAL and KIM-1, postoperative lactate was significant independent predictor of CSA-AKI with the highest odds ratio 24 h after CPB.

Nerve conduction studies and prediction of mortality in hemodialysis patients.

BACKGROUND: The electrophysiological aspects of uremic neuropathy have been studied extensively, but never for prediction of mortality. In order to assess the parameters of nerve conduction study (NCS) as predictors of mortality in hemodialysis patients, a post hoc analysis of a prospective observation study was made. METHODS: We examined conventional electrophysiological parameters (motor nerve conduction velocity [MCV], terminal latency [TL], and F wave latency of the peroneal nerve, as well as sensory nerve conduction velocity [SCV] of the sural nerve) in 75 nondiabetic patients. Hemodialysis modality (bicarbonate dialysis and biocompatible membranes), Kt/V, comorbidity (ischemic heart disease and congestive heart failure), and clinical and laboratory parameters were also evaluated. Survival was analyzed using the Cox proportional hazard model. RESULTS: SCV was significantly higher (t-test, p < 0.01) in the group of patients treated with polysulfone compared to those using cuprophane membranes. On the other hand, MCV significantly correlated with Kt/V (Pearson, r = 0.388; p < 0.01). Multivariate Cox regression revealed only MCV as a significant predictor of mortality in this group of hemodialysis patients (HR = 0.92; CI (0.86-0.99); p < 0.05). CONCLUSION: Only MCV was a significant mortality risk predictor among NCS parameters. This parameter correlates significantly with dialysis dose. SCV was related to the use of biocompatible membranes, indicating the complexity of polyneuropathy in dialysis patients.

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery.

BACKGROUND: The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in sepsis after major abdominal surgery and sepsis-associated organ dysfunction is unexplored. MATERIALS AND METHODS: Fifty-three patients with sepsis after major abdominal surgery were compared to 50 operated and 50 nonoperated controls. MMP-9, TIMP-1, biomarkers of inflammation, kidney and liver injury, coagulation, and metabolic disorders were measured daily during 96 h following diagnosis of sepsis and once in controls. MMP-9/TIMP-1 ratios and disease severity scores were calculated. Use of vasopressors/inotropes, mechanical ventilation, and survival were recorded. RESULTS: Septic patients had lower MMP-9 and MMP-9/TIMP-1 ratios but higher TIMP-1 levels compared to controls. AUC-ROC for diagnosis of sepsis was 0.940 and 0.854 for TIMP-1 and 0.924 and 0.788 for MMP-9/TIMP-1 ratio (sepsis versus nonoperated and sepsis versus operated controls, resp.). Lower MMP-9 and MMP-9/TIMP-1 ratio and higher TIMP-1 levels were associated with shorter survival. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio correlated with biomarkers of inflammation, kidney and liver injury, coagulation, metabolic disorders, and disease severity scores. Use of vasopressors/inotropes was associated with higher TIMP-1 levels. CONCLUSIONS: MMP-9, TIMP-1, and MMP-9/TIMP ratio were good diagnostic or prognostic biomarkers of sepsis after major abdominal surgery and were linked to sepsis-associated organ dysfunction.