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.

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.

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.

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.

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.

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.

Association Between Superoxide Dismutase Isoenzyme Gene Expression and Total Antioxidant Status in Patients with an End-Stage Renal Disease

Background: Chronic renal failure, particularly end-stage renal disease, is a serious health problem associated with a high mortality rate. Uremic syndrome leads to increased oxidative stress, inflammation, and dyslipidemia. Aims: To examine superoxide dismutase isoenzyme gene expression in peripheral blood mononuclear cells of patients on hemodialysis and to determine the associations between superoxide dismutase isoenzyme gene expression, oxidative stress, and non-enzymatic antioxidative protection. Study Design: Case control study. Methods: This study included 33 patients on hemodialysis (age, 55.33±15.31 years old) and 33 apparently healthy controls (age, 45.37±8.92 years old). Superoxide dismutase isoenzyme messenger ribonucleic acid levels were determined by real-time polymerase chain reaction. General biochemical parameters, high sensitivity C-reactive protein, total antioxidant status, thiobarbituric acid-reactive substances, and the superoxide anion radical were also determined. Results: Normalized Cu/Zn superoxide dismutase and Mn superoxide dismutase messenger ribonucleic acid levels were significantly higher in patients than controls (p<0.001 and p=0.011). A significant negative correlation was detected between normalized Cu/Zn superoxide dismutase messenger ribonucleic acid levels and total protein, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total antioxidant status. Normalized Mn superoxide dismutase messenger ribonucleic acid levels were negatively correlated with total protein and total antioxidant status. A multiple regression analysis revealed independent associations between total antioxidant status and normalized Cu/Zn superoxide dismutase (p=0.038) and between total antioxidant status and normalized Mn superoxide dismutase messenger ribonucleic acid levels (p=0.038 and p=0.018, respectively). Conclusion: The superoxide dismutase isoenzyme gene is expressed at a higher rate in patients with end-stage renal failure, probably due to increased oxidative stress and attenuated antioxidative defense. The plasma total antioxidant status is an independent predictor of normalized superoxide dismutase isoenzyme messenger ribonucleic acid levels.

Activity of paraoxonase 1 (PON1) on HDL2 and HDL3 subclasses in renal disease.

INTRODUCTION: Cardiovascular complications, as the main cause of mortality in renal patients, are followed with altered lipoproteins composition. Considering that paraoxonase-1 (PON1) is an anti-oxidative enzyme located mainly on HDL particles, the current study has aim to investigate whether failure of kidney function leads to changes in the distribution of PON1 activity between different HDL subclasses. MATERIALS AND METHODS: In 77 renal patients (21 chronic kidney disease (CKD) and 56 end stage renal disease (ESRD) patients on dialysis) and 20 healthy subjects PON1 activity on HDL2 and HDL3 subclasses was determined by zymogram method that combines gradient gel electrophoresis separation of HDL subclasses and measurement of PON1 activity in the same gel. RESULTS: Serum paraoxonase (p<0.01) and arylesterase activity (p<0.001) of PON1 as well as its concentration (p<0.01) were significantly lower in CKD and ESRD patients compared to controls. Relative proportion of HDL3 subclasses was higher in ESRD patients than in healthy participants, while HDL2 subclasses was significantly decreased in CKD (p<0.05) and ESRD (p<0.001) patients, as compared to controls. Furthermore, control subjects had higher PON1 activity on HDL2 (CKD and ESRD patients p<0.001) and HDL3 (CKD p<0.05; ESRD patients p<0.001) subclasses in comparison with the both patients groups. Also, significant negative correlation was found between paraoxonase activity of PON1 in serum and creatinine concentration (ρ=-0.373, p<0.01). CONCLUSIONS: This study showed that altered HDL subclasses distribution, changed PON1 activities on different HDL subclasses as well as diminished anti-oxidative protection could be important factors in atherosclerosis development in CKD and ESRD 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.

Association of Dyslipidemia, Oxidative Stress, and Inflammation With Redox Status in VLDL, LDL, and HDL Lipoproteins in Patients With Renal Disease.

Some cardiovascular complications in patients with chronic kidney disease and end-stage renal disease may be caused by structurally and functionally modified lipoproteins. Redox status (advanced oxidation protein products [AOPPs]), prooxidant-antioxidant balance, total protein sulfhydryl (SH-groups), and paraoxonase 1 (PON1) activity were assessed in 77 renal patients and 20 controls. Lipoproteins were isolated using ultracentrifugation. PON1, PON3, and pentraxin-3 concentration were determined by enzyme-linked immunosorbent assay (ELISA). Dyslipidemia-Oxy-Inflammation (DOI) score was calculated as a sum of dyslipidemia, oxidative stress, and inflammation scores. The dyslipidemia score ( P < .001), oxy score ( P < .01), inflammation score (P < .001), and the DOI score ( P < .001) were higher in patient groups compared with controls. The very-low-density lipoprotein (VLDL) fraction contained the highest amount of AOPP ( P < .001) compared with other lipoprotein fractions in all groups. The low-density lipoprotein (LDL) fraction contained elevated AOPP in all groups compared with the high-density lipoprotein (HDL) fraction ( P < .001). Significant positive correlation was observed between AOPP in LDL fraction and DOI score (ρ = 0.510, P < .01). Dyslipidemia, oxidative stress, and inflammation play an interactive role in renal disease and are mutually associated with redox status in VLDL, LDL, and HDL lipoproteins in plasma of renal patients.

The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015: a summary.

BACKGROUND: This article summarizes the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry's 2015 Annual Report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries. METHODS: In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined. RESULTS: In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006-10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9-50.1).

Association of Pentraxin-3, Galectin-3 and Matrix Metalloproteinase-9/Timp-1 with Cardiovascular Risk in Renal Disease Patients.

Inflammation, apoptosis and extracellular remodeling play significant roles in cardiovascular disease (CVD) underlying the major causes of mortality in renal patients. In 19 pre-dialysis patients, 21 dialysis patients and 20 control subjects, the concentrations of pentraxin-3, galectin-3, MMP-9 and TIMP-1 were determined by ELISA. CVD risk was calculated according to the Framingham risk score algorithm. Pentraxin-3 was increased in renal patients compared to healthy controls (p<0.001). In contrast, galectin-3 was reduced in hemodialysis patients compared to pre-dialysis patients and controls (p<0.001). In addition, MMP-9 and TIMP-1 were elevated in renal patients compared to controls (p<0.01 and p<0.001, respectively). Logistic regression analyses disclosed associations of galectin-3, MMP-9, pentraxin-3 and glomerular filtration with calculated CVD risk score. Combined testing of pentraxin-3, galectin-3, MMP-9 and glomerular filtration rate can discriminate renal patients with high and low risk of a coronary event.

Oxidative stress and hemoglobin-cholesterol adduct in renal patients with different LDL phenotypes.

PURPOSE: Unfavorable lipid profile is a major risk factor for cardiovascular disease in renal pathology. In this study, we compared chronic renal patients and healthy controls with different LDL phenotypes (A or B) in respect of various biochemical parameters related to cardiovascular disease. METHODS: Oxidative stress and anti-oxidative defense parameters [thiobarbituric acid-reacting substances (TBARS), total oxidative status (TOS), total anti-oxidative status (TAS), total protein sulfhydryl (-SH) groups], as well as red blood cell cholesterol distribution were assessed in 40 renal patients and 40 control subjects by standardized assays. LDL particle diameters were determined by polyacrylamide gradient gel electrophoresis. LDL particles are subdivided according to their size into large LDL A phenotype (diameter >25.5 nm) and small LDL B phenotype (diameter ≤25.5 nm). RESULTS: Renal patients with LDL A phenotype had increased oxidative stress (TOS: p < 0.01, and TBARS: p < 0.001) and decreased total SH- groups (p < 0.001) compared to controls with the same LDL phenotype. A notable decrease in hemoglobin-cholesterol adduct was detected in patients with LDL A phenotype (p < 0.001) and LDL B phenotype (p < 0.05) compared with appropriate controls. LDL B phenotype was characterized with increased TBARS (p < 0.05) compared with LDL A phenotype in control group. CONCLUSION: Increased oxidative stress, decreased anti-oxidative defense followed with unfavorable changes in hemoglobin-cholesterol binding capacity, could have important influence on cardiovascular disease risk in renal patients regardless of LDL phenotype.

Downregulation of AdipoR1 is Associated with increased Circulating Adiponectin Levels in Serbian Chronic Kidney Disease Patients.

BACKGROUND: Since the rise in plasma adiponectin levels in chronic kidney disease (CKD) patients has not yet been elucidated, we sought to investigate if patients on hemodialysis (HD) have altered expression of adiponectin receptors in peripheral blood mononuclear cells (PBMCs) compared to healthy subjects. METHODS: This study included 31 patients with chronic kidney disease on HD and 33 healthy subjects (CG). Circulating adiponectin levels were measured by ELISA while AdipoR1 and AdipoR2 mRNA levels in PBMCs were determined by real-time PCR. RESULTS: Plasma adiponectin levels were significantly higher in patients compared to control group (P=0.036). After adjustment for age, BMI and creatinine, this difference became even more significant (P=0.004). In both groups adiponectin correlated with creatinine (CG: r=-0.472, P=0.006; HD: r=-0.375, P=0.038), triglycerides (CG: r=- 0.490, P=0.004; HD: r=-0.488, P=0.005), insulin (CG: r=-0.386, P=0.038; HD: r=-0.506, P=0.012) and high density lipoprotein cholesterol (HDL-C) (CG: r=-0.672, P<0.001; HD: r=-0.584, P=0.001). Significantly lower expression of PBMCs AdipoR1 mRNA was found in patients compared to CG (P=0.034), while AdipoR2 mRNA levels were similarly expressed in PBMCs in both groups. CONCLUSIONS: Complex pathological processes in CKD cause downregulation of AdipoR1 which could ultimately influence AdipoR1 protein levels leading to a state of ≫adiponectin resistance≪.

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.

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.

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.

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.