Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss. To uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of peripheral blood mononuclear cells (PBMCs) and, separately, of CD4(+) T lymphocytes isolated from CAMR patients, compared to kidney transplant recipients with normal graft function and histology. We enrolled 29 patients with biopsy-proven CAMR, 29 stable transplant recipients (controls), and 8 transplant recipients with clinical and histological evidence of interstitial fibrosis/tubular atrophy. Messenger RNA and microRNA profiling of PBMCs and CD4(+) T lymphocytes was performed using Agilent microarrays in eight randomly selected patients per group from CAMR and control subjects. Results were evaluated statistically and by functional pathway analysis (Ingenuity Pathway Analysis) and validated in the remaining subjects. In PBMCs, 45 genes were differentially expressed between the two groups, most of which were up-regulated in CAMR and were involved in type I interferon signalling. In the same patients, 16 microRNAs were down-regulated in CAMR subjects compared to controls: four were predicted modulators of six mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signalling. To further confirm this result, we investigated the transcriptomic profiles of CD4(+) T lymphocytes in an independent group of patients, observing that the activation of type I interferon signalling was a specific hallmark of CAMR. In addition, in CAMR patients, we detected a reduction of circulating BDCA2(+) dendritic cells, the natural type I interferon-producing cells, and their recruitment into the graft along with increased expression of MXA, a type I interferon-induced protein, at the tubulointerstitial and vascular level. Finally, interferon alpha mRNA expression was significantly increased in CAMR compared to control biopsies. We conclude that type I interferon signalling may represent the molecular signature of CAMR. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). In the previous years, novel insights in the pathophysiology of CKD progression suggested a causal link between AKI and CKD due to a maladaptive repair after severe and repeated injury.

BACKGROUND: Arteriovenous fistula (AVF) stenosis is the major cause of vascular access failure in hemodialysis. Adventitial remodeling has been suggested to play a role in the pathogenesis of AVF stenosis. This study aimed to evaluate adventitial fibrosis in stenotic AVF and investigate the underlying molecular mechanisms. METHODS: Forty-four patients undergoing surgery for AVF creation were examined; ten presented AVF failure, with histological-proven AVF stenosis. RESULTS: In stenotic AVF we observed a significant increase of adventitia extracellular matrix deposition and alpha-smooth muscle actin (α-SMA)+ cell numbers; most of these cells were myofibroblast (α-SMA+/vimentin+). Phosphorylated platelet-derived growth factor β receptor (p-PDGFRβ) was significantly increased within the adventitia of stenotic compared to native AVF, along with a marked increase in the phosphorylation of Akt and ERK, two key kinases in PDGFRβ signalling. Myofibroblasts were the main cell type associated with the activation of p-PDGFRβ. At the same time, we observed a significant adventitial vessels rarefaction in stenotic AVF, as demonstrated by a reduced CD34 expression. This event was associated with a marked reduction in the expression of KDR/fetal liver kinase-1, the main vascular endothelial growth factor receptor. The degree of adventitial fibrosis was directly correlated with the extent of adventitial α-SMA and inversely associated with adventitial CD34 expression. Finally, we observed an increase in CD34+/α-SMA+ cells within the adventitia of failed AVF. CONCLUSION: This study suggests that AVF failure is associated with an increased adventitial fibrosis, myofibroblast activation and capillary rarefaction, potentially linked with endothelial-to-mesenchymal transition. In this scenario, our data suggest that PDGF may play a pathogenic role.

PURPOSE: Patients with end-stage renal disease (ESRD) have an increased risk of developing renal cell carcinoma (RCC). This retrospective study compared clinical and pathological outcomes of RCC occurring in native kidneys of patients with ESRD (whether they underwent kidney transplantation or not) with those of renal tumors diagnosed in the general population. METHODS: The study included a total of 533 patients with RCC. The ESRD cohort included 92 patients with RCC in native kidneys. Of these, 58 and 34 cases were identified before (pre-Tx group) and after kidney transplantation (post-Tx group), respectively. The control group was composed of 441 RCCs diagnosed in the general population. Variables were compared by chi-square and Student's t tests. Cancer-specific survival was assessed by Kaplan-Meier and Cox methods. RESULTS: The ESRD groups had smaller (P = 0.001), lower-grade, and lower-stage tumors than the non-ESRD group (P = 0.001). The papillary RCC rate was higher in the ESRD groups (P = 0.01). Ten-year cancer-specific survivals were 94.5, 87.9, and 74.6 % in pre-Tx, post-Tx, and non-ESRD patients, respectively (P = 0.003). Mean follow-up was 90.2 months. At multivariate analysis, tumor size (HR = 1.10), pathological stage (HR = 1.46), presence of nodal (HR = 2.22) and visceral metastases (HR = 3.49), and Fuhrman grade (HR = 1.48) were independent adverse prognostic factors for cancer-specific survival. CONCLUSIONS: Native kidney RCCs arising in ESRD patients are lower stage and lower grade as compared to RCCs diagnosed in the general population, and these tumors exhibit favorable clinical and outcome features.

Klotho is an anti-aging factor mainly produced by renal tubular epithelial cells (TEC) with pleiotropic functions. Klotho is down-regulated in acute kidney injury in native kidney; however, the modulation of Klotho in kidney transplantation has not been investigated. In a swine model of ischemia/reperfusion injury (IRI), we observed a remarkable reduction of renal Klotho by 24 h from IRI. Complement inhibition by C1-inhibitor preserved Klotho expression in vivo by abrogating nuclear factor kappa B (NF-kB) signaling. In accordance, complement anaphylotoxin C5a led to a significant down-regulation of Klotho in TEC in vitro that was NF-kB mediated. Analysis of Klotho in kidneys from cadaveric donors demonstrated a significant expression of Klotho in pre-implantation biopsies; however, patients affected by delayed graft function (DGF) showed a profound down-regulation of Klotho compared with patients with early graft function. Quantification of serum Klotho after 2 years from transplantation demonstrated significant lower levels in DGF patients. Our data demonstrated that complement might be pivotal in the down-regulation of Klotho in IRI leading to a permanent deficiency after years from transplantation. Considering the anti-senescence and anti-fibrotic effects of Klotho at renal levels, we hypothesize that this acquired deficiency of Klotho might contribute to DGF-associated chronic allograft dysfunction.

NADPH oxidase plays a central role in mediating oxidative stress during heart, liver, and lung ischemia/reperfusion injury, but limited information is available about NADPH oxidase in renal ischemia/reperfusion injury. Our aim was to investigate the activation of NADPH oxidase in a swine model of renal ischemia/reperfusion damage. We induced renal ischemia/reperfusion in 10 pigs, treating 5 of them with human recombinant C1 inhibitor, and we collected kidney biopsies before ischemia and 15, 30, and 60 min after reperfusion. Ischemia/reperfusion induced a significant increase in NADPH oxidase 4 (NOX-4) expression at the tubular level, an upregulation of NOX-2 expression in infiltrating monocytes and myeloid dendritic cells, and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis along with a marked upregulation of NADPH-dependent superoxide generation. This burden of oxidative stress was associated with an increase in tubular and interstitial expression of the myofibroblast marker α-smooth muscle actin (α-SMA). Interestingly, NOX-4 and NOX-2 expression and the overall NADPH oxidase activity as well as α-SMA expression and 8-oxo-7,8-dihydro-2'-deoxyguanosine synthesis were strongly reduced in C1-inhibitor-treated animals. In vitro, when we incubated tubular cells with the anaphylotoxin C3a, we observed an enhanced NADPH oxidase activity and α-SMA protein expression, which were both abolished by NOX-4 silencing. In conclusion, our findings suggest that NADPH oxidase is activated during ischemia/reperfusion in a complement-dependent manner and may play a potential role in the pathogenesis of progressive renal damage in this setting. Copyright © 2014 Elsevier Inc. All rights reserved.

CA 15-3, CA 125 and β-2 microglobulin are three common tumor markers currently used for diagnosis, prognosis, assessment of therapeutic response, and/or to evaluate recurrence in breast and ovarian cancer and malignant lymphoproliferative disorders, respectively. In the present prospective study we assessed the role of these three serum proteins as biomarkers for renal cell carcinoma (RCC), as well as any association between tumor marker levels and clinical-pathological parameters. CA 15-3, CA 125, and β-2 microglobulin were preoperatively measured in 332 patients who underwent nephrectomy for RCC. Estimates of cancer-specific survival (CSS) was calculated according to the Kaplan-Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS. Preoperatively, 35.2% (n = 117), 9.6% (n = 32) and 30.4% (n = 101) of the patients had abnormal levels of CA 15-3, CA 125 and β-2 microglobulin, respectively. Statistically significant differences resulted between CA 15-3, CA 125 and β-2 microglobulin values and tumor size, Fuhrman grade, presence of lymph node, and visceral metastases. CSS was significantly decreased for patients with high levels of CA 15-3, CA 125, and β-2 microglobulin (P < 0.0001, P < 0.0001, and P = 0.001, resp.). At multivariate analysis only age, the presence of visceral metastases, and high levels of CA 15-3 were independent adverse prognostic factors for CSS.

Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of the major complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra-glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial-to-mesenchymal transition (EndMT). Gram-negative bacteria and their cell wall component lipopolysaccharides (LPSs) are frequently involved in the pathogenesis of AKI. The host recognition of LPS requires a specific receptor, which belongs to the Toll-like receptor (TLR) family of proteins, called TLR4, and two carrier proteins, namely the LPS-binding protein (LBP) and cluster of differentiation 14 (CD14). In particular, LBP is released as a consequence of Gram-negative infection and maximizes the activation of TLR4 signalling. Recent findings regarding the emerging role of LBP in mediating sepsis-induced AKI, and the possible beneficial effects resulting from the removal of this endogenous adaptor protein, will be discussed in this review.

The pathophysiology of endotoxemia-induced acute kidney injury (AKI) is characterized by an intense activation of the host immune system and renal resident cells by lipopolysaccharide (LPS) and derived proinflammatory products. However, the occurrence of renal fibrosis in this setting has been poorly investigated. The aim of the present study was to investigate the possible association between endothelial dysfunction and acute development of tissue fibrosis in a swine model of LPS-induced AKI. Moreover, we studied the possible effects of coupled plasma filtration adsorption (CPFA) in this setting.

Background. Increasing evidence demonstrates a phenotypic plasticity of endothelial cells (ECs). Endothelial-to-mesenchymal transition (EndMT) contributes to the development of tissue fibrosis. However, the pathogenic factors and signalling pathways regulating this process in ischaemia/reperfusion (I/R) injury are still poorly understood. Methods. We investigated the possible role of complement in the induction of this endothelial dysfunction in a swine model of renal I/R injury by using recombinant C1 inhibitor in vivo. Results. Here, we showed that I/R injury reduced the density of renal peritubular capillaries and induced tissue fibrosis with generation of CD31+/α-SMA+ and CD31+/FPS-1+ cells indicating EndMT. When we inhibited complement, the process of EndMT became rare, with preserved density of peritubular capillaries and significant reduction in renal fibrosis. When we activated ECs by anaphylatoxins in vitro, C3a and C5a led to altered endothelial phenotype with increased expression of fibroblast markers and decrease expression of specific endothelial markers. The activation of Akt pathway was pivotal for the C3a and C5a-induced EndMT in vitro. In accordance, inhibition of complement in vivo led to the abrogation of Akt signalling, with hampered EndMT and tissue fibrosis.

Acute rejection is still a common complication of kidney transplantation. IL-17 is known to be associated with allograft rejection but the cellular source and the role of this cytokine remains unclear. We investigated IL-17 graft expression in renal transplant recipients with acute antibody-mediated rejection (ABMR), acute T-cell-mediated rejection (TCMR), interstitial fibrosis and tubular atrophy (IFTA) and acute tubular damage due to calcineurin-inhibitor toxicity (CNI). In acute ABMR, tubular IL-17 protein expression was significantly increased compared to TCMR, where most of the IL-17⁺ cells were CD4⁺ graft infiltrating lymphocytes, IFTA and CNI control groups. The tubular expression of IL-17 in acute ABMR colocalized with JAK2 phosphorylation and peritubular capillaries C4d deposition. In addition, IL-17 tubular expression was directly and significantly correlated with the extension of C4d deposits. In cultured proximal tubular cells, C3a induced IL-17 gene and protein expression along with an increased in JAK2 phosphorylation. The inhibition of JAK2 abolished C3a-induced IL-17 expression. The use of steroids and monoclonal antibodies reduced IL-17 expression, JAK2 phosphorylation and C4d deposition in acute ABMR patients. Our data suggest that tubular cells represent a significant source of IL-17 in ABMR and this event might be mediated by the complement system activation featuring this condition.

Malignancies represent the third leading cause of post-transplant mortality worldwide. The main challenge for transplant physicians is a timely diagnosis of this condition. The aim of the study was to identify a soluble diagnostic marker for monitoring the development of post-transplant malignancies.

Type I interferons are pivotal in the activation of autoimmune response in systemic lupus erythematous. However, the pathogenic role of interferon-alpha in patients affected by lupus nephritis remains uncertain. The aim of our study was to investigate the presence of a specific interferon signature in lupus nephritis and the effects of interferon-alpha at renal level.

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomised to either have Coupled Plasma Filtration and Adsorption (CPFA) added to the standard care (n=35) or not (n=35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria and CD80 expression in Gram- sepsis, a swine model of LPS-induced AKI was set up. 3-hours after LPS infusion, animals were treated or not with CPFA for 6-hours. Treatment with CPFA significantly reduced serum cytokines, CRP, procalcitonin and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.

Abstract BACKGROUND: The aim of this study was to investigate neutrophil activation and its role in long pentraxin-3 (PTX3) release and oxidative stress generation during haemodialysis (HD) and to correlate neutrophil PTX3 and oxidant expression with endothelial dysfunction. METHODS: Forty-seven uraemic patients on stable HD, 12 healthy subjects and 15 patients with congestive heart failure (New York Heart Association classes III and IV) were enrolled. Neutrophil PTX3 protein expression was evaluated by confocal microscopy. l-selectin expression, intracellular PTX3 localization and reactive oxygen species (ROS) generation in human neutrophils were measured by flow cytometry. NADPH-dependent superoxide generation was investigated by chemiluminescence. PTX3 plasma concentrations were measured by ELISA. Endothelial dysfunction was studied by flow-mediated dilation (FMD). RESULTS: The low baseline levels of FMD significantly improved after HD, but worsened by 24 h. A significant up-regulation of PTX3 protein expression, localized within secondary granules, was detected in neutrophils isolated at 30 and 240 min of HD, along with an increase in l-selectin expression. The up-regulation in intracellular PTX3 in neutrophils was associated with a significant increase in PTX3 plasma concentrations at 240 min. HD increased ROS production and NADPH oxidase activity in neutrophils. In a univariate analysis, pre-treatment with FMD was inversely correlated with PTX3 expression and ROS generation in neutrophils. In a multivariate analysis, both circulating pre-HD PTX3 and intracellular ROS generation by neutrophils were independent predictors of abnormal FMD. CONCLUSIONS: Neutrophil overexpression of PTX3 is associated with ROS overproduction and endothelial dysfunction and may represent an emerging marker of vascular damage progression in HD patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The renal assist device (RAD) is a blood purification system containing viable renal tubular epithelial cells (TECs) that has been proposed for the treatment of acute kidney injury (AKI) and multiple organ failure. Perfluorocarbons (PFCs) are oxygen carriers used for organ preservation in transplantation. The aim of this study was to investigate the effect of PFCs on hypoxia- and sepsis-induced TEC injury and on renal CD133+ progenitor differentiation in a microenvironment similar to the RAD.

Genetic mutations in complement components are associated with the development of atypical hemolytic uremic syndrome (aHUS), a rare disease with high morbidity rate triggered by infections or unidentified factors. The uncontrolled activation of the alternative pathway of complement results in systemic endothelial damage leading to progressive development of renal failure. A previously healthy 8-month-old boy was referred to our hospital because of onset of fever, vomiting, and a single episode of nonbloody diarrhea. Acute kidney injury with preserved diuresis, hemolytic anemia, and thrombocytopenia were detected, and common protocols for management of HUS were followed without considerable improvement. The persistent low levels of complement component C3 led us to hypothesize the occurrence of aHUS. In fact, the child carried a specific mutation in complement factor H (Cfh; nonsense mutation in 3514G>T, serum levels of Cfh 138 mg/L, normal range 350-750). Given the lack of response to therapy and the occurrence of kidney failure requiring dialysis, we used eculizumab as rescue therapy, a monoclonal humanized antibody against the complement component C5. One week from the first administration, we observed a significant improvement of all clinical and laboratory parameters with complete recovery from hemodialysis, even in the presence of systemic infections. Our case report shows that complement inhibiting treatment allows the preservation of renal function and avoids disease relapses during systemic infections.

Urinary tract infections (UTIs) after kidney transplantation are associated with significant morbidity. However, data on the impact of UTI on graft survival are controversial. We conducted a retrospective cohort study of 380 kidney transplant patients. Recipients with symptomatic UTIs during the first year after transplantation were categorized into three groups: early (< 3 episodes from months 1st to 6th), late (< 3 episodes during months 7th to 12th) and recurrent (≥ 3 episodes throughout the whole first year). Graft function at three years was considered the primary outcome. Symptomatic UTIs occurred in 184 (48.4%) kidney transplant recipients during the first year; 83 (21.8%) patients developed early UTIs, 50 (13.2%) late UTIs and 51 (13.4%) recurrent UTIs. We observed a significant improvement in graft function after three years in all patients (P < 0.001) except those who had recurrent UTIs. A Kaplan-Meier analysis showed that recipients with recurrent UTIs had worse graft outcome (eGFR value < 60 mL/min/1.73 m2) (P = 0.01). Recurrent UTIs was an independent predictor of graft function at three years in a model adjusted for DGF and episodes of acute rejection (Hazard Ratio, 2.2; 95% CI, 1.3 to 3.5; P = 0.001). Recurrent symptomatic UTIs during the first year after transplantation have negative impact on long-term graft function.

Acute kidney injury (AKI) following major heart surgery (MHS) is associated with early decrease in renal blood flow and worsened prognosis. Doppler-derived renal resistive index (RRI), which reflects renal vascular resistance, may predict the development of AKI in patients undergoing MHS.

Angioedema (AE) is related to the activation of the contact phase system—kallikrein and generation of bradykinin. Different types of AE are recognized: hereditary or acquired deficit of the C1 inhibitor, drug-related, or idiopathic. Treatment of idiopathic nonhistaminergic AE (IAE) is difficult because corticosteroids, antihistamine drugs, and adrenalin are inefficacious. We describe a patient with an IAE and an acute attack of facial AE that was successfully treated with the bradykinin receptor antagonist icatibant. This case report strengthens the relevance of bradykinin formation in IAE and underlines the effectiveness of icatibant as a therapeutic option in acute IAE. Angioedema (AE) is characterized by recurrent attacks of nonpruritic swelling of subcutaneous and submucosal tissues not associated to urticaria. The pathogenesis of AE is linked to an activation of the contact phase system—kallikrein, which leads to the ultimate generation of bradykinin as the main vasopermeabilizing substance [1]. Different clinical forms of AE are recognized: paradigmatic is hereditary AE (HAE), due to a congenic defect of the complement C1 inhibitor (C1 inh) with an autosomal transmission. In type I HAE, antigenic and functional levels of C1 inh are less than 50% of normal values. Less commonly, there is a dysfunctional C1 inh protein with normal antigenic levels but reduced activity on C1 esterase (HAE type II). Angioedema with a typical appearance of recurrent attacks of dermis and mucosae may occur late in life as an acquired condition, with reduced antigenic and functional C1 inh. Acquired AE is associated to malignancies or lymphoproliferative disorders, monoclonal gammopathies, or other conditions [2]. Angioedema may also represent adverse effects of drugs such as angiotensin-converting enzyme inhibitors, estrogens, or nonsteroidal anti-inflammatory drug. In this latter case, levels of C1 inh are generally not altered or only minimally affected. Finally, in some patients, the occurrence of AE attacks with a clinical onset after the third to fourth decade of life is not associated to C1 inh alteration and absence of other clinical accompanying conditions or drugs (idiopathic AE [IAE]). Bradykinin seems also to play a relevant pathogenic role in IAE. For treatment of AE, corticosteroids, epinephrine, and antihistamine drugs are ineffective, whereas concentrate of plasma-derived C1 inh has long been proved efficacious. Recently, a specific bradykinin B2 receptor antagonist, icatibant, has been introduced for the treatment of HAE attacks [3]. Perhaps, although plasma-derived C1 inh concentrate is very effective in those conditions characterized by reduced or dysfunctional C1 inh such as HAE and acquired AE, it is completely inefficacious in those conditions with normal levels of C1 inh, such as angiotensin-converting enzyme inhibitor–related AE or IAE. Although some beneficial effects have been reported with tranexamic acid in preventing attacks of IAE, at the moment, there is not specific therapy for this disabling condition. We report a case of the successful treatment of a facial AE attack in a patient with IAE. The patient, a 50-year-old white man, complained of the recent appearance of recurrent attacks of AE, involving mainly the facial region. The attacks started about 1 year before, without any precipitating condition and with an increasing frequency reaching 2 to 3 attacks per month. Angioedema attacks were nonpruritic, not associated to urticaria, lasted about 36 hours, and resolved spontaneously. Antihistamine drugs and corticosteroids were almost completely ineffective. The patient was also prescribed a prophylactic dose of levocetirizin (5 mg twice a day) for about a month without any beneficial effect on frequency and severity of AE attacks. Physical examination did not show any relevant sign. Laboratory investigation showed normal levels of C1 inh, C3 and C4, i

Dendritic cells (DCs) have a pivotal role in the autoimmune response of systemic lupus erythematosus. Plasmacytoid DCs infiltrate the kidney of patients with lupus nephritis, but factors regulating their recruitment to the kidney are unknown. Chemerin is the recently identified natural ligand of ChemR23, a receptor highly expressed by plasmacytoid DCs. We performed immunohistochemical and immunofluorescence analysis to study the ChemR23/Chemerin axis in renal biopsies from patients with lupus nephritis. We found ChemR23-positive DCs had infiltrated the kidney tubulointerstitium in patients with severe lupus nephritis. Chemerin association with tubular epithelial cells and renal lymphatic endothelial cells was found in patients with lupus nephritis but not in normal kidneys. Proximal tubular epithelial cells produced Chemerin in vitro, which was significantly down-modulated by added tumor necrosis factor (TNF)-α and interferon-γ as measured by quantitative PCR and enzyme-linked immunosorbent assay. Interestingly, TNF-α was capable of inducing a functionally active form of renal Chemerin, resulting in an efficient transendothelial migration of plasmacytoid DCs measured in transwell systems. Thus, the ChemR23/Chemerin axis may have a role in the recruitment of DCs within the kidney in patients affected by lupus nephritis.

Ischemia-reperfusion injury is the major cause of delayed graft function in transplanted kidneys, an early event significantly affecting long-term graft function and survival. Several studies in rodents suggest that the alternative pathway of the complement system plays a pivotal role in renal ischemia-reperfusion injury. However, limited information is currently available from humans and larger animals. Here we demonstrated that 30 minutes of ischemia resulted in the induction of C4d/C1q, C4d/MLB, and MBL/MASP-2 deposits in a swine model of ischemia-reperfusion injury. The infusion of C1-inhibitor led to a significant reduction in peritubular capillary and glomerular C4d and C5b-9 deposition. Moreover, complement-inhibiting treatment significantly reduced the numbers of infiltrating CD163(+), SWC3a(+), CD4a(+), and CD8a(+) cells. C1-inhibitor administration led to significant inhibition of tubular damage and tubular epithelial cells apoptosis. Interestingly, we report that focal C4d-deposition colocalizes with C1q and MBL at the peritubular and glomerular capillary levels also in patients with delayed graft function. In conclusion, we demonstrated the activation and a pathogenic role of classical and lectin pathways of complement in a swine model of ischemia-reperfusion-induced renal damage. Therefore, inhibition of these two pathways might represent a novel therapeutic approach in the prevention of delayed graft function in kidney transplant recipients.

Coagulation and complement activation represent key events in ischaemia-reperfusion-induced renal injury leading to delayed graft function (DGF). It is still unclear whether the coagulation cascade may also influence the acquired immunity. The aim of the present study was to investigate the expression of protease-activated receptor 1 (PAR-1), the main thrombin receptor, by graft-infiltrating dendritic cells (DCs), and to evaluate whether thrombin may influence DCs complement production and T-cell response.

The occurrence of pregnancy in patients with chronic kidney disease (CKD) has been considered a dangerous event both for the mother and for the fetus. However, increasing evidence shows that the stage of CKD is the leading factor that can predict possible acceleration in the declining of renal function and complications of pregnancy. This review summarizes recent data on pregnancy in patients with CKD, dialysis and kidney transplantation. Copyright (C) 2011 S. Karger AG, Basel

Urinary tract infection (UTI) represents the most common infection after kidney transplantation; it is associated with an increased risk for acute kidney rejection and impaired graft function in the early post-transplant period. Kidney transplant recipients with UTIs are often clinically asymptomatic due to the immunosuppressive therapy; however, asymptomatic bacteriuria may progress to acute pyelonephritis, bacteremia and urosepsis, particularly in the early post-transplant period, that are independent risk factors for short and long-term graft and patient survival. This article reviews the definitions, incidence, risk factors and the management of UTI in kidney transplant recipients; furthermore, the main controversial and still unanswered questions, regarding the causes of recurrent UTIs, adequate use of antibiotics to avoid antibiotic resistance, dosing and timing for prophylaxis and treatment of symptomatic infections, are also discussed. The emerging definition of urinary microbiota introduces new concepts in understanding the complexity of the disease and might represent the future target for therapeutic interventions.