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IgA nephropathy (IgAN) and focal segmental necrotizing glomerulonephritis (FSNGN) are characterized by proliferation of native glomerular cells and infiltration by inflammatory cells. Several cytokines act as mediators of kidney damage in both diseases. The aim of the present study was to investigate the role of Th1, Th2 and Treg/T17 cytokines in these types of proliferative glomerulonephritis. Simultaneous measurement of Th1 interleukin (IL-2, IL-12, tumor necrosis factor-alpha [TNF-α], interferon-gamma [INF-γ]), Th2(IL-4, IL-5, IL-6, IL-10, IL-13), Treg/T17 transforming growth factor-beta 1 (TGF-β1, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-17) cytokines and C-C chemokines Monocyte chemoattractant protein-1 (MCP-1, macrophage inflammatory protein-1 [MIP-1]β) was performed in first-morning urine samples, at the day of renal biopsy, using a multiplex cytokine assay. Cytokine concentrations were correlated with histological findings and renal function outcome. Urinary excretion of Th1, Th2 and Treg/Th17 cytokines were significantly higher in FSNGN compared to IgAN patients. In IgAN patients (n = 50, M/F: 36/14, M age: 40.7 [17-67] years), Th1, Th2 and T17 cytokines correlated significantly with the presence of endocapillary proliferation, while in FSNGN patients (n = 40, M/F: 24/16, M age: 56.5 [25-80] years), MCP-1 and TGF-β1 had a positive correlation with severe extracapillary proliferation (P = 0.001 and P= 0.002, respectively). Urinary IL-17 was the only independent parameter associated with endocapillary proliferation in IgAN and with MCP-1 urinary excretion in FSNGN. Response to treatment was mainly predicted by IL-6 in IgAN, and by Th2 (IL-4, IL-6), Treg (GM-CSF) cytokines and MIP-1β in FSNGN. Th1, Th2 and T17 cytokines were directly implicated in renal pathology in IgAN and possibly through MCP-1 production in FSNGN. IL-17 and IL-6 seem to have a central role in inflammation and progression of kidney injury. [ABSTRACT FROM AUTHOR]

Aim. Recent evidence suggests that chronic subclinical inflammation plays a key role in the pathogenesis and progression of diabetic nephropathy. Aim of the present study was to investigate possible correlation between the presence and degree of microalbuminuria and markers of inflammation in patients with type 2 diabetes mellitus (DM). Patients-Methods. Eighty patients were enrolled and clinical and laboratory data were recorded. Albumin-creatinine ratio (ACR) was calculated in first-morning urine samples. Serum and urinary tumor necrosis factor-α (TNF-α) levels were determined by ELISA. Results. Forty-five patients had normoalbuminuria, 33 microalbuminuria, and 2 macroalbuminuria. Patients with microalbuminuria were older, with higher glycosylated hemoglobin levels (HbA1c) and they more frequently had diabetic retinopathy, neuropathy, and cardiovascular disease and were on treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). ACR was significantly correlated with the presence of cardiovascular disease, hypertension, and HbA1c levels and the administration of clopidogrel and ACEi or ARBs. ACR was not correlated with C-reactive protein, fibrinogen, or serum TNF-α levels but had a strong correlation with urinary TNF-α levels. Conclusions. In patients with type 2 DM, urinary, but not serum, TNF-α levels are associated with the presence and severity of microalbuminuria. [ABSTRACT FROM AUTHOR]

Objective: To study the epidemiology of acute poisoning patients presenting to an acute medical service ward in a Greek hospital between January 1998 and December 2000. Design: Prospective case series. Results: A total of 273 patients with self-poisoning were included in the study. This represented 3.8% of the overall admissions to the unit. The mean age of patients was 33, the most frequent age group being that aged 20–30 years (36.2% of total) with a male-to-female ratio of 1:1.97. Sixty per cent of patients was admitted within 4 h. Those from urban areas comprised 76.2% and 23.8% from rural areas. The most frequently ingested agents were psychopharmaceuticals (37.4%) and analgesics/anti-rheumatics (32.6%). Pesticides (7.7% of total) were most frequently used by patients coming from rural areas (32.3% of patients from rural areas). Alcohol was included in the overdose in 8.4%. Of the patients, 16.2% had a previous history of overdose. In this case series, psychiatric assessment suggested that 52% of the patients had a formal psychotic diagnosis, 21% had personality disorder and 27% had taken an overdose in response to stress. The most frequently documented precipitating factors were family problems and disputes (37%). Unusually, the seasonal distribution in these patients suggested a peak in summer (37.5% of presentations) with lower numbers in spring (30.2%), autumn (17.7%) and winter (14.6%). Of the patients, 23.7% presented in July. A total of 73.5% of patients was conscious, 16.4% was somnolent, 4.5% was in precoma and 5.6% was in coma (GCS <8). Patients who received antidotal therapy comprised 17.9%. Evidence of hepatic dysfunction was observed in 8.9% of patients and renal dysfunction in 3.6%. Extracorporeal techniques for drug removal (hemodialysis and hemoperfusion) were used in 2.2% of patients. Intensive care therapy was required in 11.4% of patients. The mean overall hospitalization time was 3.3 days. The mortality rate was 2.9%. Conclusions: This study shows that the epidemiology of self-harm by overdose in Greece is significantly different in terms of the seasonal presentation from other parts of Europe. The agents ingested and other features are similar to northern Europe. Psychiatric diagnoses are more common in our group than in those reported from northern Europe. Human & Experimental Toxicology (2001) 20, 611–617. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the membranous glomerulonephritis complicating ankylosing spondylitis.

Background and aim: The diagnosis of peripheral diabetic neuropathy is based on clinical examination. Nerve conduction study (NCS) enables earlier diagnosis, but it is demanding and requires specialised personnel. In an attempt to simplify the procedure, this study aimed to identify a new electrophysiological index, which might correlate with results obtained on standardised NCS in patients with long-standing type 2 diabetes. Patients and methods: Medical records of type 2 diabetic patients evaluated for neuropathy by NCS were reviewed retrospectively. This analysis included 104 patients (50 men, 54 women) with a mean age of 67.1±5.5 years and mean diabetes duration of 13.1±2.7 years. NCS was performed on radial, ulnar, sural, and peroneal nerves. Neuropathy was defined as impaired NCS. Ratios of neurophysiological parameters from these nerves were calculated and each of them was compared with diagnosis of neuropathy. Results: The sural sensory/radial motor amplitude ratio had the best combination of sensitivity (85%) and specificity (71%) for neuropathy. It also remained the strongest independent predictor of neuropathy in multivariate regression analysis: low levels of this ratio yielded an odds ratio of 7.7 for neuropathy. Conclusions: The sural sensory/radial motor amplitude ratio has a high sensitivity and a moderately high specificity for the diagnosis of neuropathy, low levels being associated with a nearly eightfold increase in the risk for neuropathy. These results encourage further evaluation of this and other electrophysiological indices to enable wider availability of NCS. [ABSTRACT FROM AUTHOR]

Cardiovascular calcifications (CVC) are frequently observed in chronic kidney disease (CKD) patients and contribute to their cardiovascular mortality. The aim of the present study was to investigate the impact of osteoprotegerin (OPG)/Receptor Activator of NF-κΒ (RANK)/RANK ligand (RANKL) pathway in the development and evolution of CVCs in hemodialysis patients. In total, 80 hemodialysis patients were assessed for the presence of vascular (abdominal aorta and muscular arteries) calcifications and results were correlated to serum OPG and RANKL levels and the OPG/RANKL ratio. Traditional cardiovascular risk factors and mineral bone disease parameters were also estimated. The presence of VCs was also evaluated 5 years after the initiation of the study, and results were correlated to the initial serum OPG levels. Age, diabetes mellitus, coronary artery disease and OPG levels ( p < 0.001) were associated with VCs, whereas RANKL levels were not. Multivariate analysis though revealed that only OPG levels were significantly associated with abdominal aorta calcifications ( p = 0.026), but they were not correlated with the progression of VCs. Serum OPG levels are positively and independently associated with VCs in HD patients, but not with their progression. RANKL levels did not show any associations, whereas further studies are needed to establish the significance of OPG/RANKL ratio.

Benzoyl urea insecticides are a class of pesticides used in agriculture for the inhibition of chitin synthesis in pests. These compounds are persistent in environmental samples, and thus their monitoring is necessary to avoid detrimental effects to human health and the environment. Magnet integrated fabric phase sorptive extraction (MI-FPSE) is a recently introduced sample preparation technique that combines sample stirring and analyte extraction into one stand-alone device. However, the applicability and the potential benefits of this technique in environmental analysis remain unexplored. In the present study, MI-FPSE was employed for the first time for the extraction and preconcentration of benzoyl urea insecticides (i.e., diflubenzuron, triflumuron, hexaflumuron, lufenuron and chlorfluazuron) from environmental water samples prior to their determination by high performance liquid chromatography-diode array detection (HPLC-DAD). The main factors affecting the performance of the proposed methodology were thoroughly investigated and optimized and the MI-FPSE-HPLC-DAD method was validated. The proposed method enabled the handling of relatively high sample quantity resulting in high preconcentration factors (501 and 731) and good sensitivity. Under optimum conditions, the limits of detection and the limits of quantification for the benzoyl urea insecticides were 0.06 ng mL -1 and 0.20 ng mL -1 , respectively. Moreover, the relative standard deviations were less than 6.1% for intra-day study and less than 8.2% for inter-day study showing good method precision. After its validation, the herein developed method was successfully employed for the analysis of tap, mineral, river, and lake water samples. In addition, the ComplexGAPI index was used to present the green potential of developed method from the step of MI-FPSE device preparation to final determination. All things considered, MI-FPSE could potentially serve as an efficient tool for the monitoring of pollutants in environmental analysis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus +2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs. -0.67±13.07) and diastolic BP (-3.85±6.34 vs. -0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Sleep apnea syndrome (SAS) is an established cardiovascular risk factor in the general population related to inflammation and oxidative stress and is very common among hemodialysis patients. Cardiovascular disease and its complications is the main cause of death among hemodialysis patients. The aim of the present study was to investigate the role of SAS in the promotion of inflammation and oxidative stress and thus in the augmentation of cardiovascular risk in hemodialysis patients., Methods: Thirty-seven hemodialysis patients underwent an overnight full polysomnography study. The following morning blood samples were obtained and TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), MPO (myeloperoxidase), and oxLDL (oxidized low density lipoprotein) were measured., Findings: We investigated the correlation of patients' markers of inflammation and oxidative stress with their sleep parameters (total sleep time, AHI, apnea/hypopnea index; RDI, respiratory disturbance index; DI, desaturation index, mean and minimum SpO 2 and percentage of sleep time with SpO 2  < 90%). TNF-α correlated positively with BMI (r = 0.510, P < 0.0001) and total sleep time (r = 0.370, P = 0.027). IL-6 correlated positively with age (r = 0.363, P = 0.027), AHI (r = 0.385, P = 0.018), DI (r = 0.336, P = 0.042) and percentage of sleep time with SpO 2  < 90% (r = 0.415, P = 0.012) and negatively with mean SpO 2 (r = -0.364, P = 0.027). Myeloperoxidase correlated positively with AHI (r = 0.385, P = 0.018), DI (r = 0.380, P = 0.02) and percentage of sleep time with SpO 2  < 90% (r = 0.388, P = 0.019). Finally, oxLDL correlated positively with BMI (r = 0.443, P = 0.007), AHI (r = 0.395, P = 0.015), RDI (r = 0.328, P = 0.048) and total sleep time with SpO 2 <90% (r = 0.389, P = 0.019)., Conclusions: These results indicate that, in hemodialysis patients, the severity of SAS and nocturnal hypoxia correlated positively with markers of inflammation and oxidative stress., (© 2017 International Society for Hemodialysis.)

Arterial stiffness and augmentation of aortic blood pressure (BP) measured in office are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of ambulatory brachial BP, central BP, pulse wave velocity (PWV), and heart rate-adjusted augmentation index [AIx(75)] in this population. A total of 170 hemodialysis patients underwent 48-hour ambulatory monitoring with Mobil-O-Graph-NG during a standard interdialytic interval and followed-up for 28.1±11.2 months. The primary end point was a combination of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary end points included: (1) all-cause mortality; (2) cardiovascular mortality; and (3) a combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, coronary revascularization, or hospitalization for heart failure. During follow-up, 37(21.8%) patients died and 46(27.1%) had cardiovascular events. Cumulative freedom from primary end point was similar for quartiles of predialysis-systolic BP (SBP), 48-hour peripheral-SBP, and central-SBP, but was progressively longer for increasing quartiles for 48-hour peripheral-diastolic BP and central-diastolic BP and shorter for increasing quartiles of 48-hour central pulse pressure (83.7%, 71.4%, 69.0%, 62.8% [log-rank P =0.024]), PWV (93.0%, 81.0%, 57.1%, 55.8% [log-rank P <0.001]), and AIx(75) (88.4%, 66.7%, 69.0%, 62.8% [log-rank P =0.014]). The hazard ratios for all-cause mortality, cardiovascular mortality, and the combined outcome were similar for quartiles of predialysis-SBP, 48-hour peripheral-SBP, and central-SBP, but were increasing with higher ambulatory PWV and AIx(75). In multivariate analysis, 48-hour PWV was the only vascular parameter independently associated with the primary end point (hazard ratios, 1.579; 95% confidence intervals, 1.187-2.102). Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not. These findings further support that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis., (© 2017 American Heart Association, Inc.)

Background: Differential diagnosis between primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is sometimes difficult as nephrotic syndrome is the main clinical symptom in both diseases., Objectives: This study has attempted to evaluate the urinary excretion of Th1 and Th2 cytokines as potential biomarkers in distinguishing the two types of nephrotic syndrome, and predicting outcome of renal function., Patients and Methods: Thirty-six patients with FSGS (M/F 22/14, Age; 41.9 ± 17 years, SCr=1.7 ± 0.8 mg/dL, UProt=4.7 ± 5.5 g/24 h), and 21 with MCD (M/F 5/16, Age; 41.4 ± 15 years, SCr = 1 ± 0.4 mg/dL, UProt = 7.9 ± 9.3 g/24 h) were included in the study. Τh1 (IL-2, IL-12, GM-CSF, INF-γ, TNF-α) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were measured by multiple cytokine assay, Luminex technology, in first morning urinary samples collected at the day of renal biopsy., Results: No significant differences in urinary excretion of all cytokines were found between FSGS and MCD patients. In FSGS however, IL-12 urinary levels were independent factor correlated with both global sclerosis (R = 0.5, P = 0.009) and interstitial fibrosis (R = 0.5, P = 0.02). Th1 cytokines (IL-2 and GM-CSF) were significantly increased in FSGS patients who did not respond to treatment ( P = 0.03 and P = 0.007, respectively). Th2 cytokines (IL-4, IL-5, IL-10, IL-13) were significantly increased in MCD patients with frequent relapses ( P = 0.05, P = 0.001, P = 0.01, P = 0.03)., Conclusions: Urinary excretion of Th1 and Th2 cytokines cannot discriminate FSGS from MCD. Th1 cytokines, especially IL-12, IL-2 and GM-CSF, may be involved in pathology and progression of FSGS, while Th2 cytokines are implicated in frequent relapses of nephrotic syndrome in MCD.

We report the case of a 69-year-old man with uncontrolled multidrug-resistant secondary hypertension following a 10 year history of endovascular abdominal aortic aneurysm repair, with suprarenal fixation and concurrent angioplasty with stenting of the left renal artery for atherosclerotic renal disease, and progressive chronic kidney disease. Renal scintigraphy revealed complete loss of the right kidney's and severe reduction of the left kidney's perfusion and function. Following recent evidence and consultation with vascular surgeons regarding the technical difficulties of any procedure, escalation of antihypertensive treatment was initially chosen. Careful drug adjustments significantly improved but did not fully control blood pressure (BP); further, the patient experienced an acute ischaemic stroke and renal function deterioration towards end-stage renal disease within a few months. At this point, revascularization of the left renal artery coupled with three haemodialysis sessions to remove contrast media was justified as rescue therapy against permanent renal replacement therapy. Successful intervention achieved an immediate BP reduction, with BP fully controlled, despite a  > 70% decrease in antihypertensive treatment, while renal function improved at 6 months from 11.5 to 22 ml/min/1.73 m(2). Renal angioplasty confers undisputed benefits in BP control and nephroprotection, and should be offered without delay to patients with renovascular hypertension and/or ischaemic nephropathy.

We report a case of a 51-year-old Caucasian man referred at our department due to acute renal failure (ARF) complicating respiratory failure during hospitalization in a regional hospital. The patient was previously started on steroids due to the suspicion of rapidly progressive glomerulonephritis (RPGN) in the context of Goodpasture syndrome. However, clinical and laboratory findings did not support this diagnosis; instead a careful evaluation limited differential diagnosis of the renal insult to acute tubular necrosis or acute interstitial nephritis (AIN) following respiratory infection. With lung function fully improved but renal function not recovering, a renal biopsy revealed AIN, a finding leading to further diagnostic testing and finally to the diagnosis of Legionnaires' disease as a cause of this patient's pulmonary-renal syndrome. The management consisted of progressive tapering of oral steroids associated with full recovery of the patient's renal function. This is a rare case of Legionnaires' disease causing immune-mediated AIN and highlights the possibility of Legionella infection as a cause of pulmonary-renal syndrome., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Background and Objectives: Wave reflections and arterial stiffness are independent cardiovascular risk factors in ESRD. Previous studies in this population included only static recordings before and after dialysis. This study investigated the variation of these indices during intra- and interdialytic intervals and examined demographic, clinical, and hemodynamic variables related to arterial function in patients undergoing hemodialysis., Design, Setting, Participants, & Measurements: Between February 2013 and May 2014, a total of 153 patients receiving maintenance hemodialysis in five dialysis centers of northern Greece underwent ambulatory BP monitoring with the newly introduced Mobil-O-Graph device (IEM, Stolberg, Germany) over a midweek dialysis session and the subsequent interdialytic period. Mobil-O-Graph is an oscillometric device that records brachial BP and pulse waves and estimates, via generalized transfer function, aortic BP, augmentation index (AIx) as a measure of wave reflections, and pulse wave velocity (PWV) as an index of arterial stiffness., Results: AIx was lower during dialysis than in the interdialytic period of dialysis-on day (Day 1) (mean±SD, 24.7%±9.7% versus 26.8%±9.4%; P<0.001). In contrast, PWV remained unchanged between these intervals (9.31±2.2 versus 9.29±2.3 m/sec; P=0.60). Both AIx and PWV increased during dialysis-off day (Day 2) versus the out-of-dialysis period of Day 1 (28.8%±9.8% versus 26.8%±9.4% [P<0.001] and 9.39±2.3 versus 9.29±2.3 m/sec [P<0.001]). Older age (odds ratio [OR], 1.09; 95% confidence interval [95% CI], 1.02 to 1.15), female sex (OR, 7.56; 95% CI, 1.64 to 34.81), diabetic status (OR, 8.84; 95% CI, 1.76 to 17.48), and higher mean BP (OR, 1.17; 95% CI, 1.09 to 1.27) were associated with higher odds of high AIx; higher heart rate was associated with lower odds (OR, 0.71; 95% CI, 0.63 to 0.80) of high AIx. Older age (OR, 2.04; 95% CI, 1.61 to 2.58) and higher mean BP (OR, 1.15; 95% CI, 1.05 to 1.27) were independent correlates of high PWV., Conclusions: This study showed a gradual interdialytic increase in AIx, whereas PWV was only slightly elevated during Day 2. Future studies are needed to elucidate the value of these ambulatory measures for cardiovascular risk prediction in ESRD., (Copyright © 2015 by the American Society of Nephrology.)

Prevalence of adynamic bone disease (ABD), characterized by low bone turnover and absence or a reduced number of osteoblasts and osteoclasts, is increasing steadily over the last years. We present a dialysis patient, with recurrent bone fractures and biopsy-proven ABD, who was treated with teriparatide. Nine months after initiation of treatment, iPTH plasma levels increased to 520 pg/mL and a second bone biopsy revealed high bone turnover, normal mineralization and normal bone volume. Two years later, iPTH was 250-350 pg/dL and bone metabolism parameters within normal range. The probable utility of teriparatide in the treatment of ABD in dialysis patients is discussed.

Hemodialysis (HD) with the use of vitamin E-coated membrane (VEM) dialyzers is shown to exert anti-inflammatory and antioxidative effects in patients with end-stage renal disease on HD. However, the association of baseline inflammatory status with the antioxidative effects of VEM has not been investigated thus far. Thirty-five stable end-stage renal disease patients treated with VEM for 6 months were enrolled in the present prospective, observational cohort study. For the previous 3 months minimum, 17 (48%) patients were dialyzed with a cellulose, eight (23%) patients with a hemophane, and 10 (29%) patients with a polysulfone 1.2 to 1.5 m(2) hollow fiber dialyzer. The effects of treatment on oxidized low-density lipoprotein (oxLDL) were stratified according to half percentiles of baseline serum logC-reactive protein and interleukin-6, and the association between treatment goal, arbitrarily defined as a minimum 30% decrease in baseline oxLDL, was assessed with the use of logistic regression analysis. The higher C-reactive protein and interleukin-6 half percentiles were independently and additively associated with a higher odds ratio for achieving treatment goal. Adjustment for baseline oxLDL, age, sex, HD duration, smoking, and body mass index did not attenuate the odds ratios, whereas the history of diabetes, as primary renal disease, significantly decreased the odds ratio for achieving treatment goal. Increased baseline C-reactive protein and interleukin-6 are independent, additive factors associated with the effect of VEM on oxLDL in HD patients., (© 2014 International Society for Hemodialysis.)

Objective: Steroids and immunosuppressants can delay progression of renal function in IgAN, but their possible effect in local cytokines has not been studied., Material and Methods: Histology in 53 IgAN patients (M/F 35/18 age 40.5 years (17 - 65)) was evaluated using the Oxford classification system. IL-1β, -2, -4, -5, -6, -10, -12 and -17, INF-γ and MCP-1 were measured subsequently by multiplex cytokine assay in first morning urine samples taken at the day of renal biopsy. After a 6-month course with RAASinhibitors + fish oils (FO), 35/53 patients, Group A, responded and continued on the same treatment, while in 18/53 who did not respond, Group B, steroids + azathiopine were added., Results: The presence of endocapillary proliferation had significant correlation with the urinary excretion of pro-inflammatory and pro-fibrotic cytokines (IL-1β, MCP-1, IL-17, INF-γ, IL-6 and IL-10). Serum creatinine at time of diagnosis had significant correlation with proteinuria (p = 0.02), urinary levels of IL-1β (p = 0.03), IL-2 (p = 0.01) and MCP-1 (p = 0.03). GFR was reduced from 65 ± 29 to 57 ± 34 ml/min, p = 0.005 in Group A and remained stable in Group B patients (GFR from 63 ± 24 to 61 ± 30 ml/min, p = NS). Most of the measured cytokines in the urine predicted deterioration of renal function in Group A, but the urinary excretion of IL-6 seemed to predict renal function outcome in both groups of patients., Conclusion: Several cytokines are excreted in the urine of patients with IgAN, and their levels predict the outcome of the disease. Steroids + aza may exert their beneficial effect through suppression of the production or activation of most cytokines.

Background: Cardiovascular morbidity and mortality remains excessive in patients with chronic kidney disease. The association of vascular changes with regulators of extraosseous calcification in this patient population is still under investigation. The aim of the present study was to investigate the associations of the calcification inhibitor fetuin-A, and the anti-osteoclastic factor osteoprotegerin (OPG) with vascular pathology in chronic hemodialysis patients., Methods: In this cross-sectional study including 81 stable chronic hemodialysis patients, we measured carotid-to-femoral pulse wave velocity (cfPWV) with applanation tonometry, reflecting arterial stiffness, and common carotid intima-media thickness (ccIMT), a surrogate of early atherosclerosis, as well as serum levels of fetuin-A and OPG. Co-morbidities, traditional cardiovascular risk factors, inflammatory markers and mineral-bone disease serology parameters were also recorded., Results: cfPWV correlated inversely with fetuin-A (r=-0.355, p=0.001) and positively with OPG (r=0.584, p<0.001). In multilinear regression analysis including age, gender, diabetes, cardiovascular disease, hypertension, pulse pressure, LDL, logCRP, both fetuin-A and OPG were independently associated with cfPWV (p=0.024 and p=0.041 respectively). ccIMT was negatively associated with fetuin-A (r=-0.312, p=0.005) and positively with OPG (r=0.521, p<0.0001); however these associations lost statistical significance after adjustment for age., Conclusion: In chronic hemodialysis patients both fetuin-A and OPG levels are independently associated with arterial stiffness but not with early atherosclerotic vascular changes.

Background: We investigated the effects of the use of vitamin E-coated membrane (VEM) dialyzer in comparison to simvastatin on markers of chronic inflammation, oxidative stress, and endothelial cell apoptosis in ten patients on chronic hemodialysis (HD), aiming at distinguishing the different treatment effects and their time sequence on these pathogenetic routes., Methods: Ten HD patients were sequentially submitted to a 6-month treatment with the use of VEM and 10 mg of simvastatin daily, interrupted by a 3-month washout period. At baseline, at 3, and 6 months of each trial, serum C-reactive protein (CRP), apolipoprotein (Apo) A1 and B, lipoprotein-a [Lp(a)], high-sensitivity interleukin-6 (hsIL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble Fas (sFas), soluble Fas ligand (sFasL), and plasma oxidized low-density lipoproteins (oxLDL) levels were determined., Results: VEM treatment resulted in a significant decrease in CRP, IL-6, sICAM-1 at 3 months, and oxLDL at 6 months, compared to baseline. Simvastatin resulted in a significant decrease in CRP, which correlated with decreases in both total (r = 0.87, p < 0.05) and low-density lipoprotein cholesterol, IL-6, sICAM-1, sVCAM-1, oxLDL, and sFas at 6 months, compared to baseline. Simvastatin effects on sVCAM-1 (mean difference = 652 ng/mL; 95% CI = 294 to 2686; p < 0.05) and sFas (mean difference = 1284 pg/mL; 95% CI = 510 to 1910; p < 0.05) differed significantly from the corresponding VEM effects., Conclusions: The 6-month use of VEM resulted in more direct and immediate anti-inflammatory effects compared with those caused by the 6-month treatment with simvastatin. Simvastatin caused a more intense decrease in the markers of inflammation, which was in part correlated with its lipid-lowering effects.

Background: Detection of urinary cytokines in pauci-immune focal segmental necrotizing glomerulonephritis (FSNGN) may provide valuable information about disease pathogenesis and prognosis., Methods: Epidermal growth factor (EGF), transforming growth factor (TGF-β1) and vascular endothelial growth factor (VEGF) were measured by ELISA, and Interleukins, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP1β) by a multiplex cytokine assay, in 38 patients with FSNGN. Their levels were correlated with severity of histological findings and renal function outcome in short and long term., Results: The percentage of crescents in renal biopsy had positive correlation with TGF-β1 (p=0.004) and IL-15 urinary excretion (p=0.01), and negative correlation with EGF (p=0.01). Increased urinary excretion of IL-6, IL-15, VEGF and MIP-1β was associated with poor renal function outcome, but increased levels of EGF, IL-2 and IL-9 predicted a favourable prognosis. In multiple regression analysis IL-6 and VEGF urinary levels were independent predictors of no-response at the acute phase (p=0.001 and p<0.0001, respectively), while, IL-6 was the only factor (p=0.03) predicted worse outcome at the end of follow-up (39.4±45 months)., Conclusion: Increased urinary excretion of IL-6, IL-15, VEGF, TGF-β1, MCP-1 and MIP-1β and reduced EGF, IL-2, IL-9 may be associated with histological damage and influence response to treatment in pauci-immune FSNGN., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aim: IgA nephropathy (IgAN) is a very common glomerulonephritis among young adults, but the best therapeutic approach has not been fully elucidated. This study evaluated the effect of two different treatment regimes in IgAN, steroids alone or in combination with azathioprine., Methods: Among 122 patients with primary IgA nephropathy diagnosed in the 2000-2007 period, 22 fulfilled the inclusion criteria for the study: estimated glomerular filtration rate (eGRF) ≥30 ml/min/1.73 m(2), urine protein (Upr) ≥1 g/24 h, blood pressure (BP) <130/80 mmHg, and previous treatment with renin-angiotensin system inhibitors (RAASi) and polyunsaturated fatty acids (PFA) for at least 6 months. Patients were randomized to receive either methylprednisolone alone (MP group) or MP in combination with azathioprine (MP + Aza group) for 12 months, while treatment with RAASi + PFA continued unchanged in both groups., Results: At the completion of the trial, renal function in the MP group remained stable, eGFR from 52 ± 26.7 to 53.6 ± 27.3 ml/min/1.73 m(2), p = NS, and Upr decreased from 2.4 ± 0.9 to 0.8 ± 0.5 g/24 h, p < 0.001. In the MP + Aza group, eGFR slightly increased from 57.4 ± 28.7 to 66 ± 31 ml/min/1.73 m(2), p = NS, and Upr decreased from 2.4 ± 1 to 0.7 ± 0.7 g/24 h, p < 0.001. Four patients from the MP group with partial remission at the end of the trial had a complete response when converted to Aza. Eleven patients (5 from the MP and 6 from the MP + Aza group) relapsed after stopping treatment and were restarted on lower doses., Conclusions: Both, steroid treatment alone and steroids in combination with azathioprine seem to be effective in reducing the severity of proteinuria and stabilizing renal function in IgAN. Patients who do not respond to steroids may have a better response with the combination of steroids and azathioprine.

Aim: We investigated the effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in hyperlipidemic endstage renal disease patients on chronic hemodialysis (HD)., Methods: In 25 hyperlipidemic HD patients who received 10 mg of simvastatin for 6 months and another 25 controls, the extended lipid profile and serum hsIL-6, MCP-1, sICAM-1, sVCAM-1, and sE-selectin, plasma oxLDL, and serum sFas and sFasL levels were determined at baseline, 3 months and 6 months. In 18 patients of the simvastatin group, the expression of CD14, CD16, CD62L and CD64 on monocyfes was determined with flow cytometry., Result: Simvastatin treatment resulted in significant reductions in serum lipid levels at 3 months and beyond, compared to at baseline. Moreover, at 6 months, simvastatin caused a significant reduction in CRP (p < 0.001), which correlated to the decrease in total and LDL cholesterol levels, as well as a significant reduction in IL-6 (p=0.001), sICAM-1 (p < 0.001), sVCAM-1 (p < 0.001), oxLDL (p=0.001), sFas (p=0.02) and CD14 expression (p < 0.001), compared to baseline values. No significant changes in the controls were noticed during the study., Conclusion: In conclusion, in hyperlipidemic HD patients, simvastatin treatment resulted in a significant reduction in markers of endothelial dysfunction, inflammation, oxidative stress, endothelial cell apoptosis and peripheral blood monocyte stimulation. The reduction in CRP appears to be related to the lipid-lowering effects of simvastatin.

Tubulointerstitial renal fibrosis, characterized as a progressive detrimental connective tissue deposition on the kidney parenchyma, appears to be a harmful process leading inevitably to renal function deterioration, independently of the primary renal disease which causes the original kidney injury. Epithelial to Mesenchymal Transition (EMT) of tubular epithelial cells which are transformed to mesenchymal fibroblasts migrating to adjacent interstitial parenchyma constitutes the principal mechanism of renal fibrosis along with local and circulating cells. Proteinuria as well as hypoxia is included among the main mechanisms of EMT stimulation. TGFbeta-1 through the SMAD pathway is considered as the main modulator regulating the EMT molecular mechanism, probably in cooperation with hypoxia inducible factors. Hepatocyte Growth Factor (HGF) and Bone Morphogenetic Factor-7 (BMF-7) are inhibitory to EMT molecules which could prevent in experimental and clinical level the catastrophic process of interstitial fibrosis. Interesting data emerge indicating that HGF and BMF-7 administration prevents the peritoneal fibrosis of mesothelial cells.

Chronic kidney disease (CKD), and particularly kidney failure, is associated with accelerated atherosclerosis and approximately a 20-fold increased risk of cardiovascular death. The majority of these patients die from complications directly attributed to atherosclerosis and their life expectancy is decreased. Established risk factors are involved in the pathogenesis of this phenomenon. Age, gender, smoking, hypertension, dyslipidaemia and diabetes mellitus are among the established risk factors. Inflammation, qualitative lipid disorders (e.g. small dense low density lipoprotein), vascular calcification and oxidative stress represent emerging risk factors. The precise mechanism of atherosclerosis in patients with kidney failure is not yet known. CKD might represent a clinical model of atherogenesis. Thus, the evidence obtained from investigating "renal" atherogenesis could be of interest in improving our understanding of this disease process in the non-renal population. We review the relationship between "renal" and non-renal atherosclerosis focusing on pathogenesis, risk factors and clinical events and how they interact with treatment options. Overall, the "later" stages of CKD may eventually be considered as a coronary heart disease equivalent condition.

Contrast media administration during diagnostic and invasive procedures in high risk patients for nephrotoxicity is a common problem in clinical practice. The mechanisms involved in renal function impairment after contrast media administration are not precisely known but are intensively investigated, and new data have emerged in the literature lately. We present the case of a 72-year old male patient with diabetic nephropathy to whom a new generation iso-osmolar contrast medium (iodixanol) was administered during intravenous pyelography. Due to the contrast agent administration, the patient developed irreversible acute renal failure and became dialysis-dependent. This case suggests that even new generation contrast media (including iodixanol) may be severely nephrotoxic, when administered to high risk patients. Additionally we review the complex mechanisms involved in pathogenesis of contrast media nephrotoxicity.

Background/aims: Cardiovascular disease (CVD) remains the leading cause of increased morbidity and mortality for hemodialysis (HD) patients. The aim of this study was to investigate the predictive values of carotid artery atherosclerotic lesions and endothelial adhesion molecule levels for long-term outcome in non-diabetic HD patients., Methods: 112 HD patients (60 male, mean age 59 years) consecutively entered the study. Atherosclerotic disease was assessed by measuring the mean and maximum intima-media thickness (IMT and IMTmax respectively) of the common carotid arteries using an ultrasound scanner. Circulating intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured by ELISA. Patients were followed for the next 5 years and primary end points on follow-up were all-cause death, death from CVD causes and incidence of a CVD event., Results: Kaplan-Meier analysis showed that survival curves for all-cause mortality, CVD mortality and morbidity differed significantly between the upper and lower tertiles of baseline IMT (p = 0.002, p = 0.01 and p = 0.001 respectively) and IMTmax values (p = 0.0007, p = 0.006 and p = 0.0003 respectively), as well as ICAM-1 (p = 0.008, p = 0.003 and p = 0.02 respectively) and VCAM-1 levels (p = 0.004, p = 0.012 and p = 0.025 respectively). In non-adjusted analysis all-cause mortality and CVD mortality and morbidity were significantly associated with IMT (p = 0.003, p = 0.01 and p = 0.001 respectively) and IMTmax values (p = 0.001, p = 0.007 and p = 0.0007 respectively). After adjusting for other significant covariates, IMT values remained associated only with CVD morbidity (p = 0.03), while IMTmax were associated with both CVD mortality and morbidity (p = 0.03 and p = 0.01 respectively). All-cause mortality and CVD mortality and morbidity were also significantly associated with serum ICAM-1 (p = 0.004, p = 0.005 and p = 0.01 respectively) and VCAM-1 levels (p = 0.008, p = 0.02 and p = 0.03 respectively). After adjusting for the same covariates, the associations between ICAM-1 and all-cause mortality and CVD mortality and morbidity remained significant (p = 0.02, p = 0.01 and p = 0.02 respectively), while serum VCAM-1 levels were independently associated only with all-cause mortality (p = 0.02)., Conclusions: In non-diabetic HD patients, carotid atherosclerosis and adhesion molecule levels are independent predictors of long-term clinical outcomes and may be useful surrogate markers for risk stratification in these patients., (2007 S. Karger AG, Basel)

The interaction between chronic heart failure, chronic kidney insufficiency and anemia, form a vicious cycle, termed as the cardio-renal anemia syndrome. The interaction between these three conditions causes deterioration of the cardiac and renal function and increases anemia. Each of the three can cause or be caused by the others.We herein analyze and speculate the mechanisms involved in the pathophysiology of this new syndrome highlighting the main points of interest that seem to expand upon more than one specialty. The cardio-renal anemia syndrome is emerging in the area of clinical investigation with progressively elevated significance. Additionaly we report the data related to anemia treatment as part of therapeutic perspective concerning the management of patients manifesting the profile of this syndrome.

The role of leptin in humans is not yet precisely established. Nevertheless there is increasing evidence revealing that this molecule is involved in the pathogenesis of atherosclerosis as an independent risk factor. From another point of view, however, leptin is already related to known traditional risk factors for accelerated atherogenesis, like obesity. We herein provide the experimental and clinical data concerning the association between leptin and atherosclerotic disease. Vascular stiffness and calcification, immune response regulation, fibrinolysis, and oxidative stress, are the main fields to be investigated in relation to leptin in the present study. Additionally the description of the main characteristics of leptin and its receptors is included in the introduction of this article, whereas in the end the main clinical data suggesting that this molecule represents an interesting risk factor for atherosclerotic disease are provided.

Rhabdomyolysis constitutes a common cause of acute renal failure and presents paramount interest. A large variety of causes with different pathogenetic mechanisms can involve skeletal muscles resulting in rhabdomyolysis with or without acute renal failure. Crush syndrome, one of the most common causes of rhabdomyolysis presents increased clinical interest, particularly in areas often involved by earthquakes, such as Greece and Turkey. Drug abusers are another sensitive group of young patients prone to rhabdomyolysis, which attracts the clinical interest of a variety of medical specialties. We herein review the evidence extracted from updated literature concerning the data related to pathogenetic mechanisms and pathophysiology as well as the management of this interesting syndrome.

Cardiovascular mortality is significantly increased among patients with end-stage renal disease. The commonly observed vascular calcification in such patients has been considered as one of the causative factors. In patients undergoing dialysis, the incidence of coronary artery calcification is 2-5 times higher compared to patients with normal renal function and angiographically demonstrated coronary artery disease. Moreover, epidemiological studies have revealed a significant correlation of the extent of coronary artery calcification with the severity of underlying atherosclerotic lesions. Vascular calcification was initially considered as a passive process of hydroxyapatite deposition due to elevated plasma concentrations of calcium and phosphate. Nevertheless, there is a growing body of evidence that vascular calcification is an actively regulated and cell-mediated process. This phenomenon includes phenotypic alterations of vascular smooth muscle cells mainly resulting from an imbalance between promoters (such as increased Ca x P product) and inhibitors (fetuin-A, GLA protein, osteoprotegerin) of mineral deposition. With regard to the therapeutic approach, despite the evident effectiveness of both traditional and innovative remedies in the management of metabolic and electrolytic abnormalities of patients with end-stage renal disease, an individualized intervention based on etiopathogenesis is really required.

Interventional Nephrology is a new and emerging subspecialty of Nephrology that mainly deals with ultrasonography of kidneys and ultrasound-guided renal biopsy, insertion of peritoneal dialysis catheters, tunneled dialysis catheters as a vascular access for patients undergoing hemodialysis as well as percutaneous endovascular procedures performed to manage dysfunction of arteriovenous fistulas or grafts in end stage renal disease patients. Traditionally, these procedures have been delegated to a variety of specialists with resultant delays in diagnosis and initiation of therapy. To avoid the delays nephrologists have taken the initiative to perform these procedures themselves. Indeed, recent data have emphasized that nephrologists can safely and successfully perform these procedures with excellent results. The success of nephrologist's role in Interventional Nephrology insures the ideal management of renal patients with effectiveness, safety and lower cost for Public Health System. Certainly nephrologists must have adequate training and develop the necessary skills in the new fields as a prerequisite for the success of the concept.

Magnesium depletion in clinical practice is mainly related to loop diuretics and thiazides. Among patients treated with diuretics more than 1/3 exhibit hypomagnesa. Arrhythmias and sudden death attributed to magnesium depletion could be prevented by Mg administration. Magnesium deficiency in experimental animals promotes atherosclerotic lesions whereas this ion is involved in various stages of myocardial damage after experimental coronary artery occlusion. In humans magnesium administration in the first 24 hours of myocardial infarction was related to beneficial effects in first year mortality rate. Nevertheless more evidence from clinical investigation is needed for permanent conclutions.

Herein we report the case of a patient suffering from renal amyloidosis secondary to Crohn's disease (CD) who presented with anuria and anasarca 8 years after commencement of colchicine treatment. End-stage renal disease was confirmed. Renal imaging prior to hemodialysis showed tumor of the left kidney. Histopathology after nephrectomy revealed secondary amyloidosis as well as the existence of cancer (hypernephroma). We discuss the presence of renal amyloidosis secondary to CD and at the same time renal cancer development, a combination that has not been reported so far, and we emphasize the surprisingly long renal survival of this patient after colchicine treatment.

There are only a few data on the relationship of insulin-like growth factor-1 (IGF-1), implicated in glucose homeostasis, and C-reactive protein (CRP), a measure of subclinical systemic inflammation, in patients with the metabolic syndrome (MetS). The authors investigated, in a cross-sectional design, the correlation between total IGF-1 and CRP in 170 subjects. Among them 123 had the MetS (National Cholesterol Program ATP III definition) and 47 did not, and 136 had type 2 diabetes mellitus (DM) and 34 did not. Anthropometric variables, clinical characteristics, as well as laboratory measurements, including total IGF-1 and CRP, were recorded. CRP levels showed a significant negative correlation with total IGF-1 concentrations, both in the whole study population (r = -0.252, p = 0.001) and the MetS group (r = -0.203, p = 0.025), regardless of the presence of DM. This correlation remained significant after adjusting for age, gender, smoking status, and waist circumference (r = -0.18, p = 0.05). Both low IGF-1 and high CRP levels had an almost linear relationship with the number of MetS components (p = 0.029 and p = 0.020, respectively), suggesting a close relationship of both variables with the cardiovascular disease (CVD) risk involved. The correlation between high CRP and low total IGF-1 might indicate that an increase in CRP levels may well be a key factor for the reduction in IGF-1 concentrations. Both factors are related to an increase in risk for MetS and CVD and this finding might have clinical implications in preventing or treating MetS, DM, and CVD. Given the cross-sectional design of the study, this finding should be confirmed by larger prospective and, it is hoped, interventional studies.

The case of a 65-year-old woman presenting with Guillain-Barré syndrome is herein reported. Tomographic investigation revealed abdominal and retroperitoneal fibromatosis. During her hospitalization, renal involvement ensued, and subsequent renal biopsy demonstrated findings of crescentic pauci-immune glomerulonephritis negative for ANCA antibodies and with characteristics indicative of necrotic angiitis. The simultaneous existence of the three diseases in the same patient as well as the relation between necrotic vasculitis and G-B syndrome is speculated, and the relevant literature is reviewed.

Strumpell's familial spastic paraplegia is a rare hereditary disease, clinically characterized by progressive disturbance of gait. Focal Segmental Glomerulosclerosis (FSGS) is a frequent glomerulopathy, with an extremely rare familial subtype. The cases of two brothers with Strumpell' s disease are reported, who also developed glomerular renal disease, most probably familial FSGS. The genetics of the two disorders, Strumpell's paraplegia and familial FSGS, are discussed, together with the possibility of a parallel transmission.

Lyme disease is a multisystem disorder with protean clinical manifestations that is caused by the tick-transmitted spirochete Borrelia burgdorferi. Infection caused by B burgdorferi is known to induce glomerulonephritis in animals. We report a patient with acute postinfection membranoproliferative glomerulonephritis after the clinical multisystem manifestation of Lyme disease, which was confirmed serologically. Although the patient was dialysis dependent for a protracted period of 5 months, the final outcome was excellent.