Serum levels of endocan correlate with the presence and severity of pre-eclampsia.

BACKGROUND: Endocan, a cysteine-rich dermatan sulfate proteoglycan expressed by endothelial cells, is seemed to be a new biomarker for endothelial dysfunction. Pre-eclampsia (PE) is characterized by the new onset of hypertension, proteinuria after 20 weeks of gestation, placental vascular remodeling, systemic vascular inflammation and endothelial dysfunction. The aim of this study was to investigate the relationship of PE and its severity with serum endocan levels. METHODS: A cross-sectional study was performed. Serum was collected from women with PE and normotensive controls. Serum endocan and tumor necrosis factor alpha (TNF-α) concentrations were measured by a specific enzyme linked immunosorbent assay. RESULTS: Patients with PE had significantly higher median (interquartile range) endocan and mean TNF-α concentrations than controls [20.04 (12.26) ng/mL vs 15.55 (6.19) ng/mL, p < 0.001 for endocan; 26.49 ± 12.14 pg/mL vs 14.62 ± 5.61 pg/mL, p < 0.001 for TNF-α; respectively]. Serum endocan concentrations were positively correlated with systolic blood pressure (r = 0.618, p < 0.001), diastolic blood pressure (r = 0.608, p < 0.001), the amount of 24-h proteinuria (r = 0.786, p < 0.001) and TNF-α (r = 0.474, p < 0.001) in women with PE. In subgroup analysis, patients with severe PE had significantly higher endocan concentrations than those with mild PE. Receiver operating characteristic analysis of endocan was used to identify the patients with PE and also discriminating between mild and severe PE. CONCLUSION: Serum endocan concentrations were significantly elevated in women with PE versus normotensive controls, and concentrations seem to be associated with the severity of the disease.

Circulating irisin levels reflect visceral adiposity in non-diabetic patients undergoing hemodialysis.

BACKGROUND: Recent evidence suggests that increased visceral adiposity is a strong independent risk factor for cardiovascular death and all-cause mortality in hemodialysis (HD) patients. Irisin, which is a novel myokine, can play critical roles in diabetes and adiposity. The purpose of our study was to investigate whether serum irisin levels are associated with body mass index, waist circumference (WC), and total fat mass in non-diabetic patients undergoing maintenance HD. METHODS: This cross-sectional study included 108 non-diabetic HD patients and 40 age- and sex-matched apparently healthy subjects. Serum irisin concentrations were determined using an enzyme-linked immunosorbent assay. Body fat composition (TBF-410 Tanita Body Composition Analyzer) was measured and calculated. RESULTS: Serum irisin levels did not differ between HD patients and the healthy controls (523.50 ± 229.32 vs. 511.28 ± 259.74, p = 0.782). Serum irisin levels were associated with age (r = 0.314; p =0.006), HOMA-IR (r = 0.472; p = 0.003), WC (r = 0.862; p < 0.001), and total fat mass (r = 0.614; p < 0.001). In multivariate regression analysis, WC (ß = 1.240, p < 0.001) and total fat mass (ß = 0.792, p = 0.015) were the variables that were significantly associated with irisin concentrations (R(2 )=( )0.684, p < 0.001) after adjusting for confounding factors (age and HOMA-IR). CONCLUSIONS: These results suggest that serum irisin levels are related to visceral adiposity in non-diabetic HD patients.

Serum galectin-3 levels were associated with proteinuria in patients with Familial Mediterranean Fever.

BACKGROUND: The most common and pernicious complication of Familial Mediterranean fever (FMF) is renal amyloidosis, usually affecting the kidneys, leading to end-stage renal failure. FMF-related renal amyloidosis needed to be diagnosed early. Optimal colchicine dose is effective in preventing and reversing renal amyloidosis. Galectin-3, profibrotic mediator, has regulatory functions in inflammation, fibrosis and tumorigenesis. Galectin-3 is a strong prognostic marker for heart failure. Galectin-3 plays role in diabetic nephropathy and chronic kidney disease. The aim of the study is to investigate whether galectin-3 is related to proteinuria and amyloidosis in FMF. METHODS: Seventy-five FMF patients who have no exclusion criteria and healthy controls (n = 36) were included. Serum galectin-3 was measured and morning spot urine was collected for determination of the protein/creatinine ratio (PCR). RESULTS: Serum Galectin-3 levels were significantly higher in FMF patients than the control group [969.66 (3825) pg/mL vs. 238 (921) pg/mL, respectively; P<0.001]. We classified into two groups: Group1 (n = 48) had FMF patients with proteniuria, Group2 (n = 27) had FMF patients without proteinuria. Group1 had higher levels of galectin-3 than Group2 [1106(3812) pg/mL vs. 867.3(1433) pg/mL, P < 0.001]. Galectin-3 levels were correlated with PCR in whole group and FMF group (r = 0.785, P < 0.001 and r = 0.803, P < 0.001). In ROC curve, best cutoff value = 581.50 pg/mL was used to detect proteinuria (sensitivity = 91.7 %, specificity = 71.4 %, AUC = 0.879) and optimal cutoff value = 1458.00 pg/mL was an indicator of nephrotic-range proteinuric (sensitivity = 100 %, specificity = 92.1 %, AUC = 0.983). CONCLUSION: Galectin-3 is associated with proteinuria and renal amyloidosis in FMF. Galectin-3 may play role in pathogenesis of amyloidosis.

Relationship of late arteriovenous fistula stenosis with soluble E-selectin and soluble EPCR in chronic hemodialysis patients with arteriovenous fistula.

BACKGROUND/AIMS: Vascular access dysfunction caused by stenosis is a major complication for hemodialysis (HD) patients. However, physiopathology of late arteriovenous fistula (AVF) stenosis is still under investigation. The aim of the present study was to evaluate the association between plasma soluble EPCR (sEPCR) with serum soluble E-selectin (sE-selectin) concentration and late AVF stenosis in HD patients. METHODS: Plasma sEPCR and serum sE-selectin concentrations were measured in 94 HD patients. Using these data, we studied the association of sEPCR and sE-selectin with the presence and degree of AVF stenosis using ultrasonography and fistulogram. RESULTS: Fifty-one patients have AVF stenosis, and the others (n = 43) have patent AVF. The degree of AVF stenosis was correlated with serum sE-selectin levels (r = 0.351, p = 0.01), but not sEPCR (r = 0.075, p = 0.702). The median level of sE-selectin was statistically higher in the group of AVF stenosis than in the group of patent AVF [463.2 pg/ml (275.4-671.4) vs. 162.5 pg/ml (96.7-285.3), p = 0.001]. Increased sE-selectin levels [OR (OR) = 6.356, p = 0.015] and high levels of LDL (OR = 4.321, p = 0.044) were independent predictors of late AVF stenosis in the multivariate model. CONCLUSIONS: sE-selectin and the LDL were the most important predictors of late AVF stenosis. In addition, sE-selectin correlated with the degree of AVF stenosis. We suggested that atherosclerosis might be contributing factor for development of late AVF stenosis.

Galectin-3 as a new biomarker of diastolic dysfunction in hemodialysis patients.

BACKGROUND: Galectin-3 (gal-3) is an emerging prognostic biomarker in heart failure (HF). Clinical and experimental studies suggest that gal-3 is an important mediator of HF. Here we aimed to examine the relationship between gal-3 and diastolic dysfunction in patients undergoing maintenance hemodialysis (HD). METHODS: We examined the relationship between plasma gal-3 levels and left ventricular diastolic function. Plasma gal-3 was measured in 87 subjects with chronic HD and in 45 healthy controls using biochemical evaluations. Conventional echocardiography and pulsed tissue Doppler assessment were performed in all patients. Left ventricular diastolic dysfunction (LVDD) was defined as E' < 8 cm/s. The E/E' ratio was used as the main determinant of LVDD grade. RESULTS: The mean gal-3 concentrations were: 16.05 ng/ml (13.89-19.75) in healthy controls; 14.54 ng/ml (10.85-17.65) in HD patients with normal diastolic function; and 23.30 ng/ml (20.12-26.87) in HD patients with LVDD (p < 0.01). Plasma gal-3 levels correlated with E/E' (r = 0.933, p < 0.01), left atrial volume index (r = 0.713, p < 0.01), and E' (r = -0.685, p < 0.01). ROC analysis showed that the best gal-3 cut-off point for the diagnosis of LVDD was 20.12 ng/ml with a sensitivity of 67.6 % and specificity of 84.6 % (AUC = 0.803). CONCLUSION: We suggest that gal-3 may be a promising biomarker for the detection of LVDD in HD patients.

Can neutrophil-lymphocyte ratio be independent risk factor for predicting acute kidney injury in patients with severe sepsis?

AIM: Neutrophil-lymphocyte ratio (NLR) is an easily calculated, sensitive, and accurate marker for prognosis and diagnosing sepsis, cardiovascular disease and cancer. As sepsis and septic shock are main causes of acute kidney injury (AKI) intensive care unit (ICU), we investigated whether NLR is an early predictor of AKI in patients with severe sepsis. We compared NLR's predictive power with that of other inflammation-related variables. METHODS: Between December 2011 and November 2013, we enrolled 118 consecutive cases with severe sepsis admitted to ICU in this retrospective study. Levels of C-reactive protein (CRP), NLR, and white blood cell count (WBC) were recorded on admission and patients' renal function was monitored for seven consecutive days. RESULTS: The rate of AKI occurrence 7 days after enrollment was 57.6%. NLR levels were higher in the AKI group (Group 1) than in the non-AKI group (Group 2) on the day of ICU admission (p<0.001). AKI development was independently associated with NLR, Acute Physiology and Chronic Health Evaluation II (APACHE II) and duration of invasive mechanical ventilation (MV) in multivariate logistic regression analysis. The area under the receiver-operating characteristic (ROC) curve of NLR for predicting AKI was 0.986, which was superior to WBC and CRP (p<0.05). The cut-off value of 10.15 for NLR had the highest validity for predicting AKI in patients with severe sepsis. The sensitivity, specificity, negative-predictive value (NPV), and positive-predictive value (PPV), for this cut-off value was 90.2%, 92.9%, 90.4%, and 92.7%, respectively. CONCLUSION: NLR is superior to CRP, and WBC for predicting the development of AKI in patients with severe sepsis.

Association of ambulatory arterial stiffness index with sEPCR in newly diagnosed hypertensive patients.

AIM: Increased arterial stiffness is strongly associated with cardiovascular diseases, while thrombotic events are more common than hemorrhagic events in hypertensive patients. Markers of a hypercoagulable state may also predict future cardiovascular events in hypertensive patients. Here, we speculated that increased arterial stiffness might lead to the development of a hypercoagulable state that can play a role in the thrombotic complications of hypertension. Soluble endothelial protein C receptor (sEPCR) is one such marker of hypercoagulation. The ambulatory arterial stiffness index (AASI) could be accepted as a non-invasive measure of arterial stiffness. The aim of this study was to investigate association of AASI with levels of sEPCR in newly diagnosed hypertensive patients. MATERIALS AND METHODS: The study included 263 newly diagnosed essential hypertensive patients and 55 healthy normotensive controls. All subjects underwent 24 h ambulatory blood pressure monitoring (ABPM); the AASI was derived from ABPM tracings. Plasma sEPCR was measured by ELISA. RESULTS: Hypertensive patients (n = 263) had higher AASI, C-reactive protein (CRP) and sEPCR versus the normotensive healthy group (n = 55). Univariate analysis showed that AASI was positively associated with age (r = 0.212, p < 0.001) body mass index (r = 0.412, p < 0.001), pulse pressure (r = 0.350, p < 0.001), plasma sEPCR (r = 0.894, p < 0.001), 24-h heart rate (r = 0.176, p = 0.001) and inversely related to high-density lipoprotein (HDL) (r = -0.293, p < 0.001). Multivariate analyses revealed that sEPCR and HDL are independently correlated to AASI. CONCLUSION: We suggest that increased AASI is associated with elevated sEPCR. It might be responsible for subsequent thrombotic events in newly diagnosed hypertensive patients.

Relationship between late arteriovenous fistula (AVF) stenosis and neutrophil-lymphocyte ratio (NLR) in chronic hemodialysis patients.

OBJECTIVES: Primary cause of late arteriovenous fistula (AVF) dysfunction is venous stenosis as result of neointimal hyperplasia. The mechanism of AVF stenosis is not exactly understood. But inflammation is a contributing factor for development of AVF stenosis. Neutrophil-lymphocyte ratio (NLR) reflects systemic inflammation, and it was investigated in many diseases. The aim of this study was to investigate the relationship between NLR and AVF stenosis in chronic hemodialysis patients. MATERIALS AND METHODS: Of 593 patients applied to the department of interventional radiology between January 2011 and November 2012, a total of 108 patients meeting the appropriate criteria were included in this study. All patients were assessed with Color Doppler ultrasonography and then digital subtraction angiography was used for the patients with abnormal results. Sixty-four patients were classified as patients with AVF stenosis (group 1) and 44 patients without AVF stenosis (group 2). Routine biochemical and complete blood count values measured six months ago were recorded for all patients. RESULTS: Mean NLR (3.47 ± 0.46 vs. 2.27 ± 0.22; p < 0.001) was higher in group 1 compared to group 2, whereas high-density lipoprotein (HDL; 31.8 ± 12.6 mg/dL vs. 51.5 ± 11.9 mg/dL; p < 0.001) was lower in group 1. NLR level was correlated with degree of AVF stenosis (r = 0.625; p < 0.01). Receiver operating characteristic curve analysis showed that NLR (optimal-cut-off = 2.70) was a useful parameter in prediction of AVF stenosis (AUC = 0.893, sensitivity = 98.4% and specificity = 75%; p < 0.001). NLR level and HDL < 30 mg/dL in logistic regression analysis are independent predictors of AVF stenosis. CONCLUSIONS: For hemodialysis patients with increased level of NLR and decreased level of HDL, regular monitoring with regard to the development of AVF stenosis may be beneficial. Our study suggests that the mechanism of AVF stenosis might have similarities to that of atherosclerosis.

The effectiveness of oral essential aminoacids and aminoacids containing dialysate in peritoneal dialysis.

BACKGROUND/AIM: Oral essential amino acids (AAs) containing supplements (EAS) and AA containing dialysate (ACD) are frequently used in peritoneal dialysis (PD) patients with malnutrition. The present study was conducted to investigate two strategies and compare their effects on the malnutrition status of PD patients. MATERIALS AND METHODS: A total of 31 EAS, 14 ACD patients were enrolled in this study. Serum albumin levels were lower than 3.5 g/dL in all subjects. EAS group patients took five pills containing AAs three times a day with meals. In the other, 2.000 cc of 1.1% ACD was given to patients daily during the study. Demographic and laboratory parameters were analyzed and compared at baseline and 6th month. RESULTS: Significant increases in BMI, albumin, and protein in both groups. Mean albumin levels increased significantly by 0.54 g/dL in ACD group (p < 0.005) and 0.49 g/dL in EAS group (p < 0.001) following 6 months. Mean albumin and delta albumin levels did not differ between two groups. CONCLUSION: These strategies may play an important role in increasing albumin levels and improving the nutritional status of PD patients.

Correlation between iron stores and QTc dispersion in chronic ambulatory peritoneal dialysis patients.

AIM: We aimed to investigate the QT dispersion and corrected QT (QTc) dispersion which are suggested as the signals of ventricular arrhythmias, in patients on maintenance CAPD and to evaluate the correlation between iron stores and these electrocardiographic parameters. MATERIALS AND METHOD: Fifty-eight patients on maintenance CAPD and 19 healthy age- and sex-matched adults without cardiac disease were included. The PD patients were divided into two groups according to whether their computerized measurements of QTc dispersion were longer than 65 ms. RESULTS: Although QT interval was statistically significantly shorter in control group (34 ± 28 vs. 43 ± 34 ms; p < 0.05), there was no significant difference in regards to the QTc, QT dispersion and QTc dispersion between two groups. PD patients with QTc dispersion longer than 65 ms had higher levels of serum ferritin (p = 0.038) and transferrin saturation (TSAT; p = 0.022) than the others. QTc dispersion were positively correlated with ferritin (r = 0.469, p < 0.01) and TSAT (r = 0.430, p < 0.01) in CAPD patients. CONCLUSION: Although prolonged QTc, QT dispersion and QTc dispersion were suggested as the markers of ventricular arrhythmias we did not find any significant difference in regards to these parameters between control patients and CAPD patients. But the high body iron stores in these patients increase the risk of increased QT dispersion. The concern over iron overload in dialysis patients is not only because of its oxidative toxicity, but also its precipitation of arrhythmias, which may be measured by the surrogate marker of QTc dispersion.

Higher thrombin activatable fibrinolysis inhibitor levels are associated with inflammation in attack-free familial Mediterranean fever patients.

BACKGROUND: Coagulation abnormalities have been reported in familial Mediterranean fever (FMF) patients with amyloidosis and nephrotic syndrome; but there is not enough data about the continuity of the thrombogenic activity in FMF patients in clinical remission. The purpose of this study was to assess thrombin activatable fibrinolysis inhibitor (TAFI) levels and its relationship with fibrinolytic activity and also evaluate relationships between mutations and clinical signs in attack-free patients without amyloidosis. METHODS: Seventy-nine FMF patients and 40 healthy adults were included. The study group was divided into five groups as follows: first group, homozygote M694V; second group, homozygote M680I; third group, M694V in one allele, the other allele have other mutations or not; fourth group, other mutations; and fifth group, no mutation. RESULTS: Serum TAFI levels were significantly increased in patients compared with healthy individuals (116.64 ± 21.8 vs. 78.48 ± 19.7 µg/mL, p < 0.001) and a positive correlation was detected between TAFI antigen level and erythrocyte sedimentation rate and C-reactive protein levels (r = 0.247, p = 0.029 and r = 0.252, p = 0.032, respectively). Mean fibrinogen and TAFI levels were significantly higher in Group 1 than the other groups (p = 0.04 and p = 0.001, respectively) and in Group 3 it was higher than Groups 2, 4 and 5 (p = 0.04 and p = 0.001, respectively). CONCLUSIONS: High level of TAFI antigen in attack-free period of FMF disease shows ongoing subclinical inflammation and hypercoagulability. Clinicians should be careful about thrombosis even in patients at clinical remission. Also, genetic tests must be considered to predict clinical outcome and to reduce complications of FMF disease.

CA 125 levels and left ventricular function in patients with end-stage renal disease on maintenance hemodialysis.

PURPOSE: The aim of this study was to analyze associations between serum cancer antigen 125 (CA 125) levels and left ventricular (LV) function in patients with end-stage renal disease on maintenance hemodialysis (HD). METHODS: CA 125 levels, pro-brain natriuretic peptide (pro-BNP) and biochemical parameters were measured, and echocardiography was performed for 110 patients and 47 healthy controls. RESULTS: The mean CA 125 level in patients, 38.78 ± 35.48 U/mL, was significantly higher than that found in healthy controls (9.20 ± 4.55 U/mL; p = 0.003). Patients with elevated CA 125 levels (n = 40) had significantly lower levels of albumin and reduced relative wall thickness, LV ejection fraction (EF) and fractional shortening but significantly higher levels of pro-BNP and a greater left ventricular end-diastolic diameter (LVEDd) and -systolic diameter (LVESd). CA 125 levels were positively correlated with pro-BNP (r = 0.596, p < 0.05) and C-reactive protein (CRP) levels (r = 0.439, p < 0.05), as well as LVEDd (r = 0.599, p < 0.001), LVESd (r = 0.750, p < 0.001) and LV mass index (r = 0.378, p < 0.05). In contrast, serum CA 125 levels were negatively correlated with albumin (r = -0.513, p < 0.05) and hemoglobin (r = -0.475, p < 0.05) as well as the EF (r = -0.878, p < 0.0001). A depressed EF (ß = -1.121, p < 0.0001) and increased CRP levels (ß = 0.247, p = 0.035) were independent predictors of high CA 125 levels in the whole group in the multivariate-model. CONCLUSIONS: Our study is the first to demonstrate an association between serum CA 125 levels and LV systolic dysfunction via inflammation in patients on maintenance HD.

NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury.

We have demonstrated that caspase-1 is a mediator of both cisplatin-induced acute kidney injury (AKI) and ischemic AKI. As caspase-1 is activated in the inflammasome, we investigated the inflammasome in cisplatin-induced and ischemic AKI. Mice were injected with cisplatin or subjected to bilateral renal pedicle clamping. Immunoblot analysis of whole kidney after cisplatin-induced AKI revealed: 1) an increase in apoptosis-associated Speck-like protein containing a caspase recruitment domain (ASC), the major protein that complexes with nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing proteins (NLRP) 1 or 3 to form the inflammasome; 2) an increase in caspase-1 activity, caspase-5, and NLRP1, components of the NLRP1 inflammasome; and 3) a trend toward increased NLRP3. To determine whether the NLRP3 inflammasome plays an injurious role in cisplatin-induced AKI, we studied NLRP knockout (NLRP3(-/-)) mice. In cisplatin-induced AKI, the blood urea nitrogen, serum creatinine, acute tubular necrosis score, and tubular apoptosis score were not significantly decreased in NALP3(-/-) mice compared with wild-type mice. We have previously demonstrated the injurious role of caspase-1 in ischemic AKI. NLRP3, but not ASC or NLRP1, is increased in ischemic AKI. NLRP3(-/-) mice with ischemic AKI had significantly lower blood urea nitrogen, serum creatinine, and acute tubular necrosis and apoptosis scores than the wild-type controls. The difference in protection against cisplatin-induced AKI compared with ischemic AKI in NLRP3(-/-) mice was not explained by the differences in proinflammatory cytokines interleukin (IL)-1ß, IL-6, chemokine (C-X-C motif) ligand 1, or tumor necrosis factor α. NLRP3 inflammasome is a mediator of ischemic AKI but not cisplatin-induced AKI, and further investigation of the NLRP1 inflammasome in cisplatin-induced AKI should prove interesting.

IL-33 exacerbates acute kidney injury.

Inflammation contributes to the pathogenesis of acute kidney injury (AKI). IL-33 is a proinflammatory cytokine, but its role in AKI is unknown. Here we observed increased protein expression of full-length IL-33 in the kidney following induction of AKI with cisplatin. To determine whether IL-33 promotes injury, we administered soluble ST2 (sST2), a fusion protein that neutralizes IL-33 activity by acting as a decoy receptor. Compared with cisplatin-induced AKI in untreated mice, mice treated with sST2 had fewer CD4 T cells infiltrate the kidney, lower serum creatinine, and reduced acute tubular necrosis (ATN) and apoptosis. In contrast, administration of recombinant IL-33 (rIL-33) exacerbated cisplatin-induced AKI, measured by an increase in CD4 T cell infiltration, serum creatinine, ATN, and apoptosis; this did not occur in CD4-deficient mice, suggesting that CD4 T cells mediate the injurious effect of IL-33. Wildtype mice that received cisplatin and rIL-33 also had higher levels of the proinflammatory chemokine CXCL1, which CD T cells produce, in the kidney compared with CD4-deficient mice. Mice deficient in the CXCL1 receptor also had lower serum creatinine, ATN, and apoptosis than wildtype mice following cisplatin-induced AKI. Taken together, IL-33 promotes AKI through CD4 T cell-mediated production of CXCL1. These data suggest that inhibiting IL-33 or CXCL1 may have therapeutic potential in AKI.

Effect of dialysis type on orbital vascular flow in patients with end-stage renal disease.

PURPOSE: To evaluate ocular blood flow dynamics by color Doppler ultrasonography (CDU) in patients with end-stage renal disease (ESRD). Additionally, to investigate the effect of dialysis type on ocular blood flow by comparing the findings of peritoneal dialysis (PD) subjects, hemodialysis (HD) subjects, and healthy controls. MATERIAL AND METHODS: Forty patients (21 HD and 19 PD) and 40 controls were included in the study. CDU and spectral analysis of temporal posterior ciliary artery (TPCA) and central retinal artery (CRA) were performed to evaluate peak systolic flow velocity (PSV), end diastolic flow velocity (EDV), and resistive indices (RIs). Ocular blood flows were examined before and after HD. Post-HD findings were compared with those in PD subjects and healthy controls. RESULTS: PSV and EDV values in CRA and TPCA after HD sessions were found to be significantly decreased when compared with pre-dialysis values. There was no statistically significant difference between the pre-dialysis and post-dialysis RI values of both arteries. Systolic and diastolic blood flows in CRA and TPCA were higher and RI values were lower in PD subjects than in HD and controls. No significant difference was seen between HD subjects and controls. CONCLUSION: After a single HD session, ocular blood flows of patients with ESRD were normalized. But PD subjects show higher systolic and diastolic ocular blood flows than healthy controls, suggesting that HD is more effective than PD for achieving normal ocular blood flow.

Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis.

AIMS: Focal segmental glomerulosclerosis (FSGS) is the common cause of chronic renal disease worldwide. Although there are many etiologic factors which have common theme of podocyte injury conclusive etiology is not clearly understood. In this study, we aimed to explore the role of autophagy in the pathogenesis of podocyte injury, which is the key point in disease progression, and the roles of intrarenal microRNAs and the prorenin receptor (PRR) in the 5/6 nephrectomy and adriamycin nephropathy models of FSGS. MAIN METHODS: For experimental FSGS model, 5/6 nephrectomy and adriamycin nephropathy models were created and characterized in adult Sprague Dawley rats. Microarray analysis was performed on FSGS and control groups that was confirmed by q-RT-PCR. Beclin1, LC3B, PRR, ATG7 and ATG5 expression were evaluated by western blotting and immunohistochemistry. Also, Beclin1 and PRR expression were measured by ELISA. Glomerular podocyte isolation was performed and autophagic activity was evaluated in podocytes before and after transfection with miRNA mimic and antagonists. KEY FINDINGS: Glomerular expression of Beclin1, LC3B, PRR, ATG7 and ATG5 were significantly lower in the 5/6 nephrectomy than adriamycin nephropathy group and in both groups lower when compared to control groups. Western blot results were consistent with immunohistochemical data. Electron microscopy revealed signs of impaired autophagy in FSGS. Autophagic activity decreased significantly after miR-214, miR-132 and miR-34c mimics and increased after transfection with antagonists. SIGNIFICANCE: These results showed that the role of autophagic activity and decreased expression of PRR in FSGS pathogenesis and miR-34c, miR-132 and miR-214 could be a potential treatment strategy by regulating autophagy.

Olmesartan associated with acute renal failure in a patient with bilateral renal artery stenosis.

In patients with renal artery stenosis (RAS), the inhibition of renin-angiotensin-aldosterone system can cause deterioration of renal function. Here we present a 75-year-old man who developed acute renal failure after olmesartan treatment. Following discontinuation of olmesartan, his renal functions normalized. His renal Doppler ultrasonography and renal angiography showed findings consistent with bilateral RAS. In this case, unlike those previously reported, renal failure developed with olmesartan for the first time and after only a single dose, which is thought to be a new, safe, and tolerable antihypertensive agent. This is a well-defined effect of angiotensin-converting enzyme inhibitors, in patients with RAS. Also with the increasing use of angiotensin II receptor blockers (ARBs), renal failure associated with ARBs in patients with RAS is rising. The use of olmesartan also requires caution and close follow-up of renal functions for patients who have risk factors.

The effects of L-carnitine therapy on respiratory function tests in chronic hemodialysis patients.

BACKGROUND: Respiratory functions are affected during hemodialysis. The strength of respiratory muscles, ultrafiltration rate, and acid-base balance have been suggested as important factors. L-carnitine is crucial for energy producing, utilization of fatty acid, and possible amino acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. This study was performed to investigate the chronic effects of L-carnitine treatment on respiratory functions in adults receiving chronic hemodialysis therapy. METHODS: A total of 20 hemodialysis patients were scheduled to take L-carnitine supplementation (20 mg/kg three times/week) (group 1), and the rest of 20 hemodialysis patients served as the control group and were observed without supplementation with L-carnitine (group 2). Pre- and post-dialytic L-carnitine levels and post-dialytic respiratory functions tests were performed in both groups at baseline and after six months. RESULTS: The average concentration of free and total carnitine levels increased significantly after six months of supplementation (p < 0.01). While a statistically significant increase between postdialytic forced expiratory volume in one second/forced vital capacity values after treatment period (77.10 +/- 12.15 and 83.00 +/- 14.49, before and after treatment, respectively, p < 0.05) was observed, the increase of vital capacity, forced expiratory volume in one second, and forced expiratory flow between 25-75% of expired vital capacity were not significant in the treatment group (p > 0.05). CONCLUSION: Intravenous L-carnitine supplementation could contribute to the management of respiratory dysfunction in chronic hemodialysis patients by improving FEV1/FVC. The mechanism by which LC causes these effects merits further investigation.

Phosphate - the silent stealthy cardiorenal culprit in all stages of chronic kidney disease: a systematic review.

BACKGROUND AND AIM: Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on dialysis, the following question arises: At what stage of chronic kidney disease (CKD) does the relationship between elevated phosphate levels, vascular calcification and increased cardiovascular mortality begin? Therefore, the purpose of the current study was to critically review the current literature regarding this issue. METHODS: We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to February 2008 to identify clinical studies examining the effects of plasma phosphate on cardiovascular outcome, mortality and progression of kidney disease in subjects with and without CKD who have not yet received dialysis. The primary outcome measure was the development of CVD, mortality and progression of kidney disease. RESULTS: Twelve clinical trials investigated the role of serum phosphate levels and adverse outcome (9 studies examining CVD outcome and 3 examining progression of kidney disease). After adjustment for risk factors for mortality, adverse cardiovascular outcome and progression of kidney disease, all studies found a graded independent significant association between phosphate levels and mortality, development of CVD and progression of kidney disease. There was no such association with plasma calcium levels. CONCLUSIONS: There is a graded independent association between serum phosphate levels and mortality, mainly cardiovascular events, and the progression of renal disease in subjects with and without definable (loss of glomerular filtration rate) CKD.

Mediators of inflammation in acute kidney injury.

Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is now believed to play a major role in the pathophysiology of AKI. It is hypothesized that in ischemia, sepsis and nephrotoxic models that the initial insult results in morphological and/or functional changes in vascular endothelial cells and/or in tubular epithelium. Then, leukocytes including neutrophils, macrophages, natural killer cells, and lymphocytes infiltrate into the injured kidneys. The injury induces the generation of inflammatory mediators like cytokines and chemokines by tubular and endothelial cells which contribute to the recruiting of leukocytes into the kidneys. Thus, inflammation has an important role in the initiation and extension phases of AKI. This review will focus on the mediators of inflammation contributing to the pathogenesis of AKI.