Soluble urokinase plasminogen activator receptor (suPAR) in children with obesity or type 1 diabetes as a marker of endothelial dysfunction: a cross-sectional study.

Pediatric obesity and type 1 diabetes mellitus (T1DM) represent two common chronic diseases associated with chronic inflammation, endothelial dysfunction and long-term complications. The aim of the present study was to assess the possible diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation and impaired endothelial function, in children with the diseases. In this cross-sectional study, children and adolescents with T1DM (N = 41) or obesity (N = 37), aged < 18 years old, and without proteinuria were included, together with children of similar age and without evident morbidity that served as controls (N = 42). Serum samples were obtained during standard outpatient follow up and the urokinase-type plasminogen activator receptor (suPAR) concentrations were measured using a commercially available sandwich ELISA kit (DUP00, R&D systems). Clinical and biochemical indices that were also assessed include body mass index (BMI) z-score, Tanner stages, glycosylated haemoglobin (HbA1c), fasting lipid profile and serum creatinine. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls. Also, serum suPAR levels showed a negative correlation with age (Spearman rho -0.359, p < 0.001) and serum creatinine levels (Spearman rho -0.334, p = 0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p = 0.009) in the whole cohort.  Conclusion: Serum suPAR may be a useful predictive marker of inflammation or endothelial dysfunction for children with obesity and T1DM, as well as a promising therapeutic target. Further studies are needed in order to clarify whether the reported differences in suPAR levels could reflect a greater impairment of the inflammation status and endothelial function in children with obesity compared to children with T1DM. What is Known: • Paediatric obesity and type 1 diabetes are characterised by chronic inflammation and metabolic dysregulation. • Urokinase plasminogen activator receptor (uPAR) has been proposed as a useful biomarker for chronic inflammation and cardiovascular risk in adults. What is New: • Serum suPAR levels were increased in children and adolescents with obesity compared to those with T1DM and healthy controls; thus, obesity may affect the inflammatory status and endothelial function to a higher degree than T1DM during childhood. • Serum suPAR may serve as a diagnostic and predictive marker of inflammation and endothelial dysfunction for children and adolescents with obesity and T1DM.

Keratin Expression in Podocytopathies, ANCA-Associated Vasculitis and IgA Nephropathy.

Keratins are the main components of the cell cytoskeleton of epithelial cells. Epithelial cells under stressful stimuli react by modifying their keratin expression pattern. Glomerular diseases are pathological conditions that may lead to loss of kidney function if not timely diagnosed and treated properly. This study aims to examine glomerular and tubular keratin expression in podocytopathies, ANCA-associated vasculitis, and IgA nephropathy and how this expression correlates to clinical outcomes. We included 45 patients with podocytopathies (minimal change disease and focal segmental glomerulosclerosis), ANCA-associated vasculitis, and IgA nephropathy, with or without crescentic lesions, and healthy controls. All tissues were assessed by photon microscopy and immunohistochemistry. Biopsy sections were examined for keratins 7, 8, 18, and 19 expression in the glomerular and tubulointerstitial areas separately. Moreover, we examined how keratin expression was correlated with long-term kidney function outcomes. All four studied keratins had significantly increased glomerular expression in patients with ANCA vasculitis compared to controls and MCD patients. Tubular expression of keratins 7, 8, and 19 was related to kidney outcome in all groups. Patients with crescents had higher expression of all keratins in both glomeruli and tubulointerstitium. The presence of tubular atrophy, interstitial fibrosis, mesangial hyperplasia, and interstitial inflammation did not affect keratin expression. Keratins, an abundant component of renal epithelial cells, have the potential to be featured as a biomarker for kidney function prognosis in patients with glomerular diseases.

Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

BACKGROUND: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. METHODS: Thirty-three patients with stage I-IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1ß, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. RESULTS: Patients with stage I-IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. CONCLUSION: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.

Body composition indices as predictors of humoral response to mRNA vaccination against COVID-19 in patients on maintenance hemodialysis.

INTRODUCTION: Patients on maintenance hemodialysis show lower serological response to mRNA vaccines. Main causes that contribute to this phenomenon are uremic milieu and older age. However, there are no data on the impact of body composition parameters to humoral response. MATERIALS AND METHODS: In this retrospective study, we used data from adult patients on maintenance hemodialysis who received vaccination with 2 doses of BNT162b2. Quantitative determination of antibodies to SARS-CoV-2 spike (S) protein receptor binding domain was performed using the Elecsys immunoassay. Antibody levels higher than 0.8 and 264 U/mL were considered positive and protective, respectively. Body composition parameters were assessed using multifrequency bioelectrical impedance spectroscopy. RESULTS: Overall, 49 patients were included in the study. Three weeks after the 1st vaccination, 34% of patients, and 3 weeks and 3 months after the 2nd vaccination, 100% of patients had detectable titers. Protective titer was developed in 43% of patients 3 weeks after the 2nd vaccination and then decreased to 24% 3 months after the 2nd vaccination. More years on dialysis were correlated to the absence of protective titers. Higher prediction marker values correlated to poor antibody response, and phase angle was negatively associated with the development of protective titers. Patients with protective titers at 3 months after the 2nd vaccination had significantly lower prediction marker and higher phase angle values. CONCLUSION: Parameters of body composition correlate and affect antibody response in patients on hemodialysis. The main observation is that immunogenicity of mRNA vaccines is influenced by phase angle and prediction marker.

A Prospective Study of Eplerenone in the Treatment of Patients with Glomerulonephritis.

BACKGROUND: High aldosterone levels contribute to kidney disease progression, while spironolactone in combination with ACEi or ARBs can potentially reduce proteinuria and ameliorate kidney function deterioration. However, evidence on the impact of eplerenone in patients with glomerulonephritis is scarce. METHODS: In this prospective observational study, we assessed the effects of eplerenone in patients with biopsy-proven glomerulonephritis who were already treated with ACEi or ARBs. Patients received either eplerenone (25 mg daily) on top of ACEi or ARBs or standard treatment alone. Proteinuria (24 h total protein excretion), kidney function, blood pressure and serum K+ levels were assessed at 3, 6 and 12 months after the initiation of treatment. RESULTS: Sixty-six patients were included in the study. Eplerenone was administered in 30 patients, while 36 received only ACEi or ARB. Proteinuria decreased from 1768 to 1152 mg/24 h after 1 year of eplerenone treatment, while it remained stable in controls. Eplerenone showed significant impact on proteinuria in those with baseline proteinuria of >1000 mg/24 h. Patients who received eplerenone showed a reduction in systolic blood pressure, while eGFR and serum K+ levels remained stable. CONCLUSIONS: Addition of eplerenone has a beneficial effect on proteinuria in patients with glomerulonephritis and significant baseline proteinuria.

Normal saline versus balanced crystalloids in patients with prerenal acute kidney injury and pre-existing chronic kidney disease.

INTRODUCTION: Normal saline (N/S) and Ringer's-Lactate (L/R), are administered in everyday clinical practice. Despite that, N/S increases the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R has lower sodium content, significantly less chloride and contains lactates. In this study we compare the efficacy of L/R versus N/S administration in patients with prerenal acute kidney injury (AKI) and pre-established chronic kidney disease (CKD). METHODS: In this prospective open-label study we included patients with prerenal AKI and previously known CKD stage III-V without need for dialysis. Patients with other forms of AKI, hypervolemia or hyperkalemia were excluded. Patients received either N/S or L/R intravenously at a dose of 20 ml/kg body-weight/day. We studied kidney function at discharge and at 30 days, duration of hospitalization, acid-base balance and the need for dialysis. RESULTS: We studied 38 patients and 20 were treated with N/S. Kidney function improvement during hospitalization and at 30 days after discharge, was similar between the two groups. Duration of hospitalization was also similar. Anion-gap improvement as expressed with Δanion-gap between discharge and admission day was higher in those patients that received L/R in comparison to those that received N/S and pH increase (ΔpH) was slightly higher in the L/R group. No patient required dialysis. CONCLUSIONS: Administration of L/R or N/S to patients with prerenal AKI and pre-established CKD had no significant difference in short or long term kidney function but L/R showed a better profile in acid-base balance improvement and Cl- overload in comparison to N/S.

NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes.

Chronic Kidney Disease (CKD) is considered as a major public health problem as it can lead to end-stage kidney failure, which requires replacement therapy. A prompt and accurate diagnosis, along with the appropriate treatment, can delay CKD's progression, significantly. Herein, we sought to determine whether CKD etiology can be reflected in urine metabolomics during its early stage. This is achieved through the analysis of the urine metabolic fingerprint from 108 CKD patients by means of Nuclear Magnetic Resonance (NMR) spectroscopy metabolomic analysis. We report the first NMR-metabolomics data regarding the three most common etiologies of CKD: Chronic Glomerulonephritis (IgA and Membranous Nephropathy), Diabetic Nephropathy (DN) and Hypertensive Nephrosclerosis (HN). Analysis aided a moderate glomerulonephritis clustering, providing characterization of the metabolic fluctuations between the CKD subtypes and control disease. The urine metabolome of IgA Nephropathy reveals a specific metabolism, reflecting its different etiology or origin and is useful for determining the origin of the disease. In contrast, urine metabolomes from DN and HN patients did not reveal any indicative metabolic pattern, which is consistent with their fused clinical phenotype. These findings may contribute to improving diagnostics and prognostic approaches for CKD, as well as improving our understanding of its pathology.

Validation of the International IgA Nephropathy Prediction Tool in the Greek Registry of IgA Nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology. METHODS: We validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination ( R D 2 ) for model fit, and the regression coefficient of the linear predictor (ßPI), respectively. RESULTS: The study included 264 patients with a median age of 39 (30-51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The R D 2 for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported R D 2 for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (<16th, ~16 to <50th, ~50 to <84th, and >84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model. CONCLUSIONS: The two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.

Favorable effects of peritoneal dialysis in patients with refractory heart failure and overhydration.

BACKGROUND: Patients with refractory to optimal pharmacological treatment heart failure (HF) require frequent hospitalization. Peritoneal dialysis (PD) has been part of the management of such patients mainly for promoting ultrafiltration and management of overhydration independently of kidney function. The aim of this study was to evaluate the efficacy of PD, especially the use of icodextrin solutions and intermittent PD, in the hospitalization rate and cardiac functional status of patients with HF. METHODS: We conducted a retrospective study involving patients with New York Heart Association (NYHA) class IV HF and preserved renal function (estimated glomerular filtration rate (eGFR) > 25 ml/min), who were refractory to conservative treatment. Clinical data on weight loss, hospitalization rate before and after PD initiation, cardiac functional status, and technique complications during a 6-month observational period were analyzed. RESULTS: PD treatment was performed in 32 patients with a mean age of 63.8 ± 11.9 years and a follow-up of 20.78 ± 14.24 months. Hospitalizations were significantly reduced from 20.7 ± 13.7 to 7.7 ± 8.9 days/patients at 6 months. All patients showed improvement in NYHA class as well as in left ventricular ejection fraction. Overall, eGFR showed a significant decrease but only six patients reached end-stage renal disease. Complications included 18 cases of peritonitis. PD was well tolerated and no patient dropped out of the method. Survival rate reached 72% at 12 months but mortality rate was high with 23 patients dying at 16.65 ± 12.3 months after the initiation of treatment. Patients survival was not influenced by the type of PD modality or weight reduction achieved. CONCLUSIONS: PD showed to be a viable option for the treatment of patients with refractory HF leading to a better cardiac functional status and diminishing the number of hospital admissions.

Treatment of Mixed Dyslipidemia With Alirocumab in a Kidney Transplant Recipient: A Case Report.

Dyslipidemia is common in kidney transplant recipients owing to the disturbance of lipid metabolism caused by chronic kidney disease and the effect of immunosuppression on lipid metabolism. Patients receiving treatment with mammalian target of rapamycin inhibitors show more prominent lipid disorders, which are attributed mainly, but not only, to adipocyte lipid uptake disruption, lipolysis promotion and lipogenic gene expression enhancement. Dyslipidemias in kidney transplant recipients predispose these patients to an increased risk of developing cardiovascular disease; thus, current guidelines recommend treatment initiation with a statin, regardless of low-density lipoprotein cholesterol (LDL-C) concentration, with ezetimibe as a secondary option for patients who do not tolerate such therapy or for those with inadequate response. Treatment with pro-protein convertase subtilisin/kexin type 9 inhibitors such as alirocumab, although effectively reducing LDL-C in patients with chronic kidney disease, has not been evaluated in kidney transplant recipients. In this case report, we present a case of a female kidney transplant recipient who developed substantial dyslipidemia after everolimus initiation. This case was resistant to treatment with simvastatin/ezetimibe combination, and the patient subsequently received alirocumab. Our patient showed a mean reduction of 46.6% in LDL-C during an 18-month period after alirocumab initiation, which is comparable to the results of studies on patients with or without renal impairment. Furthermore, treatment with alirocumab proved to be well tolerated without adverse effects or interactions with the immunosuppression regimen.

Safety and Efficacy of Long-Term Administration of Dipeptidyl peptidase IV Inhibitors in Patients With New Onset Diabetes After Kidney Transplant.

OBJECTIVES: The appearance of new onset diabetes is common after kidney transplant. Treatment options are limited because of renal function-related contraindications, interactions with immunosuppressive drugs, and side effects. We investigated the long-term safety and efficacy of dipeptidyl peptidase IV inhibitors in renal transplant recipients with new onset diabetes. MATERIALS AND METHODS: We treated 12 patients with dipeptidyl peptidase IV inhibitors, and 5 patients received insulin monotherapy as initial treatment of new onset diabetes after kidney transplant. All patients were followed for 12 months after diagnosis. Glycosylated hemoglobin A1c, estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight were measured during outpatient visits. Effects of dipeptidyl peptidase IV inhibitors and insulin on the aforementioned parameters were measured to compare values at time of diagnosis versus mean values of the last 6 months of follow-up. RESULTS: Patients were treated with linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients), and alogliptin (2 patients). Patients had a mean age of 59.4 ± 12 years and a mean glycosylated hemoglobin A1c of 6.6% at diagnosis, which was decreased to 6.1% (P = .03) at 1 year of follow-up. Renal function remained stable, and plasma tacrolimus levels did not appear to be affected. No significant differences were shown in serum total, low-density lipoprotein, and high-density lipoprotein cholesterol levels aftertreatment. Nevertheless,triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dL; P = .0039). A decrease in body weight was also observed. Finally, patients treated with dipeptidyl peptidase V inhibitors achieved better glycosylated hemoglobin A1c levels than those treated with insulin. CONCLUSIONS: Dipeptidyl peptidase IV inhibitors appear to be a safe, effective, and hypoglycemia-free option fortreatment of new onset diabetes in renaltransplant recipients and possibly provide better diabetes control than insulin therapy.

Case Report: Kidney Transplantation in a Patient With Acquired Agammaglobulinemia and SLE. Issues and Challenges.

Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased frequency of infections and neoplasms. However, if the observed immunity dysregulation is secondary and pharmaceutically induced or there is a pre-existing, primary immunodeficiency that shares common pathogenetic pathways with SLE's autoimmunity is not always clear. Herein, we present the case of a 39-year-old woman, that reached ESKD due to lupus nephritis. After an upper respiratory cytomegalovirus (CMV) infection and concomitant CMV reactivations the investigation revealed significant immunodeficiency. Not long after the initiation of intravenous immunoglobulin (IVIG) administration, patient received a cadaveric kidney transplant. IVIG was continued along with standard immunosuppression so that both recurrent infections and allograft rejection are avoided. Patient is closely monitored, and her post-transplant course is remarkably satisfying so far. ESKD patients with immunodeficiency syndromes should not be excluded by definition from kidney transplantation.

Malnutrition as a risk factor for cardiac valve calcification in patients under maintenance dialysis: a cross-sectional study.

PURPOSE: Cardiac valve calcification (CVC) is a significant risk factor for cardiovascular morbidity and mortality in patients with chronic kidney disease on maintenance hemodialysis. The aim of this study was to investigate the association of several risk factors and particularly of malnutrition on CVC. METHODS: In this cross-sectional cohort study, we included stable adult patients on maintenance hemodialysis. Calcification of cardiac valves was evaluated using two-dimensional echocardiography. Nutritional assessment and body composition measurements were performed using the MQSGA clinical tool and bioelectrical impedance analysis, respectively. Biochemical parameters such as serum calcium, phosphorus, iPTH, 1.25 hydroxy-vitamin-D, triglycerides, total cholesterol, HDL-C, LDL-C, total proteins, albumin, creatinine and CRP were assessed as potentially risk factors. The receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic ability of the aforementioned variables on severe degree CVC. Binary logistic regression analysis was also performed to identify independent variables of severe CVC. RESULTS: Overall, 42 patients were included in the study with half of them exhibiting mitral calcification, 38% aortic valve calcification, and 16.7% calcification in both valves. ROC analysis indicated that aging (p = 0.011), increased CRP (p = 0.038) and decreased value of serum albumin to total proteins ratio (p = 0.012) were positive prognostic factors for moderate to severe degree cardiac valve calcification. Low phase angle was also associated with CVC, although with moderate specificity. CONCLUSION: Aging, inflammation, low serum albumin to total proteins ratio and low phase angle values as indicators of malnutrition are predictors of severe CVC in end-stage renal disease patients on hemodialysis.

The Effect of Dialysis Modality and Membrane Performance on Native Immunity in Dialysis Patients.

Chronic Kidney Disease (CKD) is characterized by immune activation with development of chronic inflammation. However, immune deficiency also exists in CKD patients. The number and the activity of Natural Killer cells (NK-cells) are influenced by the biocompatibility of various dialysis membranes. In this study we investigated the effect of dialysis modality and membrane type on NK-cell number and on phagocytic activity of neutrophils in patients on different dialysis methods. Sixty patients were included in the study and divided in three groups of 20 patients each. Patients on conventional hemodialysis using Low Flux membrane (cHD-LF) were included in Group I, patients on conventional dialysis using High Flux membrane (cHD-HF) were included in Group II and patients treated by on-line hemodiafiltration with High Flux polysulphone membrane (on-line HDF) were included in Group III. Native immunity was investigated using the number of NK-cells and the phagocytic activity of neutrophils. NK-cells count was significantly lower (p<0.001) in the three groups of dialyzed patients in comparison to healthy subjects. However, no significant difference was observed in the NK-cells count among patients treated by conventional dialysis using Low or High Flux membrane and patients treated by on-line hemodiafiltration. Similarly, although the phagocytic activity of neutrophils was significantly decreased in all patients on dialysis (p<0.001), no difference related to the dialysis modality or membrane performance was observed. A strong positive correlation was recognized between parathormone blood levels and number of NK-cells (r=0.305, p<0.01). In conclusion, an impairment of the native immunity represented by NK cell number and phagocytic activity of neutrophils is observed in patients on dialysis. Dialysis modality and membrane performance do not influence the native immunity of dialyzed patients. However, parathormone blood levels are possibly involved in the development of immune system disturbances in such patients.

The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial.

PURPOSE: Vascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its activation is vitamin K dependent. The aim of this study is to investigate the role of oral vitamin K2 supplementation in the prevention of VC progression in haemodialysis patients. METHODS: We conducted a prospective randomized interventional study in patients on hemodialysis. Patients were randomly assigned to either receiving orally 200 µgr of vitamin K2 (vitamin K2/MK-7, Solgar) every day for 1 year or no treatment. Uncarboxylated MGP (uc-MGP) concentrations were quantified using ELISA at randomization, at 3 and at 12 months. Aortic calcification was evaluated using Agatston score after an abdominal computed tomography scan that was performed at the beginning and at 12 months of follow-up. RESULTS: There were 102 patients that were randomized. After 1 year of follow-up, 22 patients from the vitamin K2 group and 30 patients from the control group were included in the analysis. After 3 months of treatment, uc-MGP values remained unchanged in the vitK2 group but after 1 year were reduced by 47% (p = 0.005). Furthermore, uc-MGP at 1 year was increased by 12% in the control group. At 1 year, vitK2 group had significantly lower values of uc-MGP in comparison to controls (p = 0.03). Agatston score was increased significantly both in vitamin K2 and control group at 1 year with no difference between groups. CONCLUSIONS: Oral administration of vitamin K2 in patients on haemodialysis reduced serum uc-MGP levels but did not have an effect in the progression of aortic calcification.

Impact of Arteriovenous Fistula on Cardiac Size and Function in Kidney Transplant Recipients: A Retrospective Evaluation of 5-Year Echocardiographic Outcome.

OBJECTIVES: The effect of a functioning arteriovenous fistula on cardiac function in kidney transplant recipients has not been thoroughly investigated. MATERIALS AND METHODS: We retrospectively evaluated cardiac function in 99 renal transplant recipients using transthoracic echocardiography, with available follow-up at baseline and 2 and 5 years posttransplant. Patients were divided into 2 groups: a control group (n = 47) with no functioning arteriovenous fistula immediately after transplant and an arteriovenous fistula group (n = 52) with a functioning arteriovenous fistula for at least 5 years after transplant. Left ventricular ejection fraction, diastolic thickness of the interventricular septum, and left ventricular end-diastolic diameter were assessed. RESULTS: In our study, patients (62.6% men, 7.1% with diabetes, mean age of 55.6 ± 11.5 years), we observed no significant differences with respect to baseline left ventricular ejection fraction and interventricular septum; however, in the arteriovenous fistula group, baseline left ventricular end-diastolic diameter was marginally higher than that shown in the control group (50.6 ± 5.4 vs 48.6 ± 4.4 mm; P = .054). In multivariate analysis, functioning fistula and peripheral arterial disease were negatively associated with left ventricular ejection fraction at 5 years posttransplant, whereas baseline left ventricular ejection fraction had a minimal positive effect: B (95% confidence interval) of -2.186 (-4.312 to -0.061) (P = .044), -5.304 (-9.686 to -0.922) (P = .018), and 0.247 (0.047 to 0.446) (P = .016), respectively. Functioning fistula also emerged as associated with larger left ventricular end-diastolic diameter at 2 and 5 years posttransplant: B (95% confidence interval) of 3.047 (1.470-4.625) (P < .001) and 2.122 (0.406-3.838) (P = .016), respectively. CONCLUSIONS: Maintenance of a functioning fistula in kidney transplant recipients may be associated with adverse long-term effects on left ventricular ejection fraction and left ventricular end-diastolic diameter.

Circulating anti-phospholipase A2 receptor antibodies as a diagnostic and prognostic marker in Greek patients with idiopathic membranous nephropathy - a retrospective cohort study.

INTRODUCTION: Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy. METHODS: Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity. RESULTS: Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse. CONCLUSIONS: Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.

Recent developments in endovascular interventions to sustain vascular access patency in haemodialysis patients.

There is amassed evidence regarding the use of endovascular procedures for the treatment of vascular access stenosis and thrombosis. A review was conducted based on available randomized trials, cohort studies and retrospective analyses published after 2000 on endovascular treatment of dysfunctional and thrombosed vascular access, with an aim to illustrate the available device and procedural options. The use of paclitaxel-coated balloons, cutting balloons and covered stents is described in the field of vascular access stenosis. The broad spectrum of available devices and endovascular declotting procedures ranging from thrombolysis to thrombectomy is also discussed. Overall, in this review we demonstrate the increasing role of endovascular procedures in vascular access treatment and the improved patency outcomes provided by the implementation of novel endovascular devices. Moreover, the improvement of post-intervention primary patency rates after endovascular declotting procedures and the shift to more thrombectomy-dependent procedures over time is also highlighted. In conclusion, endovascular treatment of dialysis access stenosis and thrombosis has an established role, owing to the implementation of sophisticated devices, allowing, when needed, the simultaneous treatment of thrombosis and the underlying stenosis.

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go.

The traditional chronic kidney disease (CKD) biomarkers (eGFR based on serum creatinine, sex and age and albuminuria) cannot predict a patient's individual risk for developing progressive CKD. For this reason, it is necessary to identify novel CKD biomarkers that will be able to predict which patients are prone to develop progressive disease and discriminate between disease processes in different parts of the nephron (glomeruli or tubules). A good biomarker should change before or simultaneously with lesion development and its changes should correlate strongly with lesion development. Also, there should be a close relationship between severity of injury and amount of detectable biomarker and its levels should decrease with diminishing injury. Among the large number of molecules under investigation, we have reviewed the most promising ones: NGAL and KIM-1, MCP-1, MMP-9, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1 and suPAR. All these, have been studied as biomarkers for prediction of CKD progression in cohorts of patients with chronic kidney disease of different stages and various aetiologies (proteinuric and non-proteinuric, glomerulonephritides, diabetic, hypertensive and polycystic kidney disease). There is evidence that these molecules could be useful as biomarkers for progressive chronic kidney disease, however, the available data are not enough to draw final conclusions. Further studies with large cohorts and long follow-up are required to identify appropriate biomarkers, that will be able to accurately and reliably define the risk for progressive chronic kidney disease.

Membranoproliferative glomerulonephritis in a patient with chronic brucellosis.

Brucellosis is the most common zoonotic disease in Greece, with an endemic distribution and can affect any organ. Infiltration of the renal parenchyma causes acute and chronic interstitial nephritis with granulomas, whereas renal glomeruli are rarely affected. The disease has been sporadically reported, and it causes various histopathologic patterns. Herein, we describe the case of a 39-year-old stock breeder with a history of recurrent episodes of bacteremia caused by Brucella melitensis over a period of 3 years. Two months after the last episode of bacteremia, he presented with mild renal insufficiency, nephrotic range proteinuria, and microscopic hematuria. A renal biopsy revealed membranoproliferative glomerulonephritis with a pattern of focal-segmental nodular sclerosis and moderate tubulointerstitial fibrosis. The patient received antimicrobial and corticosteroid therapy with partial remission of the nephrotic syndrome.