Peritoneal dialysis related peritonitis: insights from a long-term analysis of an Italian center.

BACKGROUND: Peritonitis is a common and severe complication of peritoneal dialysis (PD). For comparative analysis standardized definitions as well as measurements and outcomes are crucial. However, most PD-related peritonitis studies have been using heterogenous definitions and variable methods to measure outcomes. The ISPD 2022 guidelines have revised and clarified numerous definitions and proposed new peritonitis categories and outcomes. METHODS: Between 1st January 2009 and 31st May 2023, 267 patients who started PD at our institution were included in the study. All PD-related peritonitis episodes that occurred in our unit during the study period were collected. The new definitions and outcomes of ISPD 2022 recommendations were employed. RESULTS: The overall peritonitis rate was 0.25 episode/patient year. Patient cumulative probability of remaining peritonitis-free at one year was 84.2%. The medical cure and refractory peritonitis rates were equal to 70.3 and 22.4%, respectively. Culture-negative peritonitis accounted for 25.6% of all specimens. The rates of peritonitis associated death, hemodialysis transfer, catheter removal and hospitalization were 6.8%, 18.3%, 18.7% and 64.4%, respectively. Relapsing, repeat, recurrent and enteric peritonitis accounted for 7.8%, 6.8%, 4.1% and 2.7% of all episodes, respectively. Catheter insertion, catheter related and pre-PD peritonitis were 4.2, 2.1 and 0.5%. CONCLUSIONS: The implementation of PD-related peritonitis reports using standardized definitions and outcome measurements is of paramount importance to enhance clinical practice and to allow comparative studies.

Update on current and potential application of extracellular vesicles in kidney transplantation.

Kidney transplantation (KT) is the best treatment for end-stage kidney disease. However, early diagnosis of graft injury remains challenging, mainly because of the lack of accurate and noninvasive diagnostic techniques. Improving graft outcomes is equally demanding, as is the development of innovative therapies. Many research efforts are focusing on extracellular vesicles, cellular particles free in each body fluid that have shown promising results as precise markers of damage and potential therapeutic targets in many diseases, including the renal field. In fact, through their receptors and cargo, they act in damage response and immune modulation. In transplantation, they may be used to determine organ quality and aging, the presence of delayed graft function, rejection, and many other transplant-related pathologies. Moreover, their low immunogenicity and safe profile make them ideal for drug delivery and the development of therapies to improve KT outcomes. In this review, we summarize current evidence about extracellular vesicles in KT, starting with their characteristics and major laboratory techniques for isolation and characterization. Then, we discuss their use as potential markers of damage and as therapeutic targets, discussing their promising use in clinical practice as a form of liquid biopsy.

New Frontiers in Sepsis-Induced Acute Kidney Injury and Blood Purification Therapies: The Role of Polymethylmethacrylate Membrane Hemofilter.

Acute kidney injury (AKI) is a common consequence of sepsis with a mortality rate of up to 40%. The pathogenesis of septic AKI is complex and involves several mechanisms leading to exacerbated inflammatory response associated with renal injury. A large body of evidence suggests that inflammation is tightly linked to AKI through bidirectional interaction between renal and immune cells. Preclinical data from our and other laboratories have identified in complement system activation a crucial mediator of AKI. Partial recovery following AKI could lead to long-term consequences that predispose to chronic dysfunction and may also accelerate the progression of preexisting chronic kidney disease. Recent findings have revealed striking morphological and functional changes in renal parenchymal cells induced by mitochondrial dysfunction, cell cycle arrest via the activation of signaling pathways involved in aging process, microvascular rarefaction, and early fibrosis. Although major advances have been made in our understanding of the pathophysiology of AKI, there are no available preventive and therapeutic strategies in this field. The identification of ideal clinical biomarkers for AKI enables prompt and effective therapeutic strategy that could prevent the progression of renal injury and promote repair process. Therefore, the use of novel biomarkers associated with clinical and functional criteria could provide early interventions and better outcome. Several new drugs for AKI are currently being investigated; however, the complexity of this disease might explain the failure of pharmacological intervention targeting just one of the many systems involved. The hypothesis that blood purification could improve the outcome of septic AKI has attracted much attention. New relevant findings on the role of polymethylmethacrylate-based continuous veno-venous hemofiltration in septic AKI have been reported. Herein, we provide a comprehensive literature review on advances in the pathophysiology of septic AKI and potential therapeutic approaches in this field.

Enhancing Immune Protection in Hemodialysis Patients: Role of the Polymethyl Methacrylate Membrane.

End-stage renal disease (ESRD) is characterized by deep disorders in both innate and adaptive immune systems that imply unbalance deactivation and immunosuppression. The central, widely recognized factors responsible for this immune dysregulation are uremia, uremic toxin retention, hemodialysis membrane biocompatibility, and related cardiovascular complications. Recently, several studies strengthened the concept that dialysis membranes are not considered as a simple diffusive/adsorptive device but as a platform to personalize a dialysis approach to improve the quality of life of ESRD patients. Therefore, understanding of the molecules associated with altered immune response is crucial and could lead to therapeutically intervention or adaptation of the dialysis procedure itself for the management of immunological dysfunction of ESRD patients. The polymethyl methacrylate (PMMA)-based membrane is characterized by a symmetrical structure with large-sized pores, providing a better hydrophobic and cationic adsorption capacity compared to the other synthetic membranes. Together with hydrophobic interactions, the high adsorption rate of cytokines (i.e., IL-6) can also be enhanced by the size of nano-pores placed on the membrane surface. PMMA membranes exhibit adsorptive properties for a large amount of uremic toxins including p-cresol and indoxyl sulfate, as well as ß2-microglobulin characterized by higher molecular weight, maintaining the diffusive clearance of small molecules like urea with a great biocompatibility. Besides exerting a strong anti-inflammatory effects in line with the improvement of immune responses in patients undergoing dialysis, PMMA also plays a role in modulating adaptive immune response, i.e., can clear blood from soluble CD40, a natural antagonist of the CD40/CD40L signaling that acts inhibiting immunoglobulin production by B cells. This review provides an overview of the main concepts and current understanding of immune dysfunction in hemodialysis and summarizes the recent findings regarding PMMA-based dialysis as potential strategy to restore immune balance in ESRD patients.

Unraveling the Link between Interferon-α and Systemic Lupus Erythematosus: From the Molecular Mechanisms to Target Therapies.

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease with a wide range of clinical expressions. The kidney is often affected, usually within 5 years of the onset of SLE, and lupus nephropathy (LN) carries a high risk for increased morbidity. The clinical heterogeneity of the disease is accompanied by complex disturbances affecting the immune system with inflammation and tissue damage due to loss of tolerance to nuclear antigens and the deposition of immune complexes in tissues. Several studies have reported that in human SLE, there is an important role of the Type-I-interferons (INF) system suggested by the upregulation of INF-inducible genes observed in serial gene expression microarray studies. This review aims to describe the transduction pathways of Type-I-interferons, in particular INFα, and its immune-regulatory function in the pathogenesis of SLE and, in particular, in LN. In addition, recent novelties concerning biologic therapy in LN will be discussed.

Allograft Vesicoureteral Reflux after Kidney Transplantation.

Allograft vesicoureteral reflux (VUR) is a leading urological complication of kidney transplantation. Despite the relatively high incidence, there is a lack of consensus regarding VUR risk factors, impact on renal function, and management. Dialysis vintage and atrophic bladder have been recognized as the most relevant recipient-related determinants of post-transplant VUR, whilst possible relationships with sex, age, and ureteral implantation technique remain debated. Clinical manifestations vary from an asymptomatic condition to persistent or recurrent urinary tract infections (UTIs). Voiding cystourethrography is widely accepted as the gold standard diagnostic modality, and the reflux is generally graded following the International Reflux Study Committee Scale. Long-term transplant outcomes of recipients with asymptomatic grade I-III VUR are yet to be clarified. On the contrary, available data suggest that symptomatic grade IV-V VUR may lead to progressive allograft dysfunction and premature transplant loss. Therapeutic options include watchful waiting, prolonged antibiotic suppression, sub-mucosal endoscopic injection of dextranomer/hyaluronic acid copolymer at the site of the ureteral anastomosis, and surgery. Indication for specific treatments depends on recipient's characteristics (age, frailty, compliance with antibiotics), renal function (serum creatinine concentration < 2.5 vs. ≥ 2.5 mg/dL), severity of UTIs, and VUR grading (grade I-III vs. IV-V). Current evidence supporting surgical referral over more conservative strategies is weak. Therefore, a tailored approach should be preferred. Properly designed studies, with adequate sample size and follow-up, are warranted to clarify those unresolved issues.

Prevalence and Risk Factors of Abnormal Glucose Metabolism and New-Onset Diabetes Mellitus after Kidney Transplantation: A Single-Center Retrospective Observational Cohort Study.

Background and objectives: New-onset diabetes after transplantation (NODAT) represents a primary cause of morbidity and allograft loss. We assessed prevalence and risk factors for NODAT in a population of Italian kidney transplant (KT) recipients. Methods: Data from 522 KT performed between January 2004 and December 2014 were analyzed. Participants underwent clinical examination; blood and urine laboratory tests were obtained at baseline, one, six, and 12-month of follow-up to detect glucose homeostasis abnormalities and associated metabolic disorders. An oral glucose tolerance test (OGTT) was performed at six months in 303 subjects. Results: Most patients were Caucasian (82.4%) with a mean age of 48 ± 12 years. The prevalence of abnormal glucose metabolism (AGM) and NODAT was 12.6% and 10.7%, respectively. Comparing characteristics of patients with normal glucose metabolism (NGM) to those with NODAT, we found a significant difference in living donation (16.6% vs. 6.1%; p = 0.03) and age at transplant (46 ± 12 vs. 56 ± 9 years; p = 0.0001). Also, we observed that patients developing NODAT had received higher cumulative steroid doses (1-month: 1165 ± 593 mg vs. 904 ± 427 mg; p = 0.002; 6-month:2194 ± 1159 mg vs. 1940 ± 744 mg; p = 0.002). The NODAT group showed inferior allograft function compared to patients with NGM (1-year eGFR: 50.1 ± 16.5 vs. 57 ± 20 mL/min/1.73 m2; p = 0.02). NODAT patients were more likely to exhibit elevated systolic blood pressure and higher total cholesterol and triglyceride levels than controls. Conclusions: The prevalence of NODAT in our cohort was relatively high. Patient age and early post-transplant events such as steroid abuse are associated with NODAT development.

Laser capture microdissection on formalin-fixed and paraffin-embedded renal transplanted biopsies: Technical perspectives for clinical practice application.

Renal biopsy (RBx) is an essential tool in the diagnostic and therapeutic process of most native kidney diseases and in the renal transplanted graft. Laser capture microdissection (LCM), combined with molecular biology, might improve the diagnostic power of RBx. However, the limited amount of available renal tissue is often an obstacle for achieving a satisfactory qualitative and quantitative analysis. In our work we present a method which allows us to obtain good quality and quantity of RNA from formalin-fixed and paraffin-embedded (FFPE) renal tissue derived from RBx performed in transplanted patients. Histology, immunohistochemistry, LCM, pre-amplify system and qRT-PCR of biomarkers related to tubular damage, inflammation and fibrosis on FFPE RBx were performed. Glomeruli, tubules and interstitium of three RBx (RB-A: no alteration; RB-B and -C: the progressive rise of creatinine) were compared. The method proposed, could well be useful in future clinical practice. It is quick, easy to perform and allows the analyses of many biomarkers. In addition, it could be extended to all types of RBx without any limitation on the sample amount. Nevertheless, the need for a higher number of well-trained technicians might represent some limitation, counterbalanced by the opportunity to elaborate more accurate diagnosis and, consequently, more targeted therapies.

Impact of hepatitis C virus and direct acting antivirals on kidney recipients: a retrospective study.

Hepatitis C virus (HCV) in kidney transplanted patients (KTx-p) carries a high risk for a worse outcome. This retrospective study evaluates the impact of HCV and of the new direct acting antivirals (DAAs) on patient and graft outcomes in KTx patients. Forty (6.5%) of the 616 KTx-p, who received a kidney transplantation (KTx) in our Centre had antibodies against HCV: 13 were positive for HCV RNA and received DAAs (Group A); 11 were HCV RNA positive and did not receive any treatment (Group B; n = 11); 16 were negative for HCV RNA (Group C). All Group A patients had HCV RNA negativity after 12 weeks of treatment, and 12 (92.30%) achieved a sustained virological response (SVR). Only two patients, who had proteinuria greater than 500 mg/day showed a worsening of proteinuria after antiviral therapy in Group A. Liver enzyme elevation and death were significantly more frequent in Group B than other groups. Our results support the notion that active HCV infection negatively affects kidney recipients and that DAA have a high safety and efficacy profile after KTx with no significant negative effect on allograft function, particularly in well-functioning renal grafts.

Uremic Patients with Increased Vascular Calcification Score Have Serum with High Calcific Potential: Role of Vascular Smooth Muscle Cell Osteoblastic Differentiation and Apoptosis.

BACKGROUND/AIMS: Uremic patients experience premature vascular ageing that causes cardiovascular morbidity. In this study, we investigated the relationship between uremic serum calcific potential induced by high phosphate (Pi) and vascular calcification score (VCS). METHODS: Vascular smooth muscle cells (VSMCs) were cultured with 3.5 mM Na3PO4 (Pi) with 10% uremic serum and calcium deposition, markers of osteoblastic transformation, and apoptosis were evaluated. RESULTS: Culture with uremic serum and high-Pi significantly induced calcification (0.21 ± 0.03 vs. 8.05 ± 0.6; ctr vs. Pi; OD/mg protein; p < 0.01). We next stratified patients with respect of the degree of VCS in 2 groups: absence of vascular calcification (VC) "no VC group" and presence of VC "VC group". We found that there was a significant correlation between VCS and uremic serum calcific potential induced by high Pi in vitro (p < 0.01). Interestingly, uremic sera of the "VC group" were more effective than sera from the "no VC group", in downregulating α-actin and SM22α, after treatment with high-Pi (41.3 ± 4.7 vs. 23.3 ± 2.9 and 25.6 ± 6.8 vs. 8.14 ± 2.3; VC vs. no VC group, α-actin and SM22α respectively; Δ intensity area; p < 0.01). Similarly, sera from "VC group" were more effective than sera from "no VC group" in adjuvanting the high-Pi effect of increasing osteoblastic markers, such as bone morphogenic protein 2 (BMP2), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2; 39.1 ± 11.3 vs. 5.0 ± 2.6 BMP2; 12.2 ± 4.2 vs. 1.7 ± 0.3 OC; 2.9 ± 0.4 vs. 1.2 ± 0.2 RUNX2; VC vs. no VC group respectively; p < 0.05). We found a similar pattern with significantly higher apoptosis and necrosis induction by sera from the "VC group" compared to the "no VC group" (2.05 ± 0.33 vs. 1.29 ± 0.13 and 54.1 ± 19.5 vs. 27.4 ± 10.6; Pi; VC group vs. no VC group; enrichment factor of apoptotic or necrotic fragments, respectively; p < 0.05). CONCLUSIONS: We conclude that VCS of end-stage renal disease patients significantly correlates with serum-calcific potential induced by high Pi. In addition, uremic patients with higher VCS have sera with a higher potential to induce VSMC osteoblastic trans-differentiation, apoptosis, and necrosis.

The Importance of Adherence in the Treatment of Secondary Hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) is a frequent condition in the presence of chronic kidney disease (CKD). In CKD patients, SHPT is reported to increase both morbidity and mortality, especially cardiovascular. The difficulty in the treatment of SHPT in clinical practice is frequently encountered from a not always adequate conduct of the clinicians and a common non-compliance to the therapy of CKD patients. In this review, the greatest difficulties from clinicians and CKD-patients' point of view in the treatment of SHPT will be addressed, with particular attention to those related to dialysis features, nutritional habits, and medical therapy.

FGF23 and Fetuin-A Interaction and Mesenchymal Osteogenic Transformation.

Recently, we found a strict bone association between Fibroblast growth factor 23 (FGF23) and Fetuin-A, both involved in cardiovascular and mineral bone disorders. In this study, an uninvestigated bone marrow positivity for both was found. Though the role of exogenous FGF23 on mesenchymal cells (MSCs) was reported, no information is as yet available on the possible production of this hormone by MSCs. To further analyze these uninvestigated aspects, we studied human primary cells and mouse and human cell lines by means of immunostaining, qRT-PCR, enzyme linked immunosorbent assays, chromatin immunoprecipitation, transfection, and a streamlined approach for the FGF23⁻Fetuin-A interaction called Duolink proximity ligation assay. Mesenchymal cells produce but do not secrete FGF23 and its expression increases during osteo-differentiation. Fibroblast growth factor 23 is also involved in the regulation of Fetuin-A by binding directly to the Fetuin-A promoter and then activating its transcription. Both FGF23 overexpression and addition induced an upregulation of Fetuin-A in the absence of osteo-inducer factors. Fibroblast growth factor 23 and Fetuin-A promoter were increased by osteo-inducer factors with this effect being abolished after FGF23 silencing. In conclusion, both FGF23 and Fetuin-A are present and strictly linked to each other in MSCs with FGF23 driving Fetuin-A production. This mechanism suggests a role for these two proteins in the osteoblast differentiation.

NeuroD Expression in Podocytes and Interrelationships with Nephrin at Both Nuclear and Cytoplasmic Sites.

Background/Aims The research of genes implicated in kidney glomerular function, eliciting cell fate program, is always at the forefront in nephrological studies. Several neurological molecules have been recently the object of study not only for their involvement in the central nervous system differentiation but also for their importance in the functionality of other organs and for mature phenotype, as in kidney. NeuroD, in CNS, is related to two functional roles, the early survival and the differentiation. The aim of our study was to ascertain the presence of NeuroD transcription factor in glomeruli and to understand which targets and mechanisms NeuroD controls. METHODS: We used immunofluorescence (IF) studies on both human and mice renal tissues and on cultured podocytes to describe NeuroD distribution; then we investigated NeuroD binding to the nephrin promoter region in cultured podocytes by chromatin-immuno-precipitation (ChIP) assay. The overexpression of NeuroD in podocytes was used to establish first its role in nephrin synthesis, evaluated by real-time quantitative (RTq) PCR and western-blot (WB) and successively to determine the recovery of cell morphology after adriamycin injury, measuring foot processes length. RESULTS: We identified NeuroD transcription factor in glomeruli, in the same cells positive for WT1 and synaptopodin, namely podocytes; subsequently we observed a differentiation dependent NeuroD distribution in cultured podocytes, and a consistent link of NeuroD with the Nephrin promoter leading to the regulation of Nephrin translation and transcription. Our data also describes NeuroD expression in cytoplasm as phosphoprotein linked to nephrin and actinin4. Preliminary experiments seem to indicate NeuroD involved in dynamics of cell shape regulation after adriamycin injury. CONCLUSION: we propose that NeuroD possess in podocytes a dual ability acting in the nucleus as a transcription factor and in cytoplasm stabilizing cell shape.

Metabolic acidosis in renal transplantation: neglected but of potential clinical relevance.

Chronic metabolic acidosis (CMA) is a common complication of the more advanced stages of chronic kidney diseases (CKD), and is associated with morbidity and mortality of CKD patients and possibly with the progression of renal disease. Nevertheless, there is limited evidence or information on the prevalence, the potential causal factors, the clinical impact and the effects of correction of CMA in kidney transplant recipients. In this review, we briefly look at the more relevant, though scanty, studies which have, over time, addressed the above-mentioned points, with the hope that in the future the interest of transplant nephrologists and surgeons will grow towards this unreasonably neglected issue.

Discoidin domain receptor-1 and periostin: new players in chronic kidney disease.

The incidence and prevalence of chronic kidney disease represents an important problem for public health. In renal diseases, the main histologic alterations derive from the development of renal fibrosis which results from the loss of the balance between pro- and anti-fibrotic factors. Tyrosine kinase receptors (RTKs) and matricellular proteins (MPs) are nowadays studied as potential modulators of renal injury. RTKs regulate cell cycle, migration, metabolism and cellular differentiation. Discoidin domain receptor-1 (DDR-1) is an RTK that has been extensively studied in cancer, and lung and renal diseases. It modulates inflammatory recruitment, extracellular matrix deposition and fibrosis; in renal diseases, it appears to act independently of the underlying disease. MPs regulate cell-matrix interactions and matrix accumulation, cellular adhesion and migration, and expression of inflammatory cells. Periostin is an MP, mainly studied in bone, heart, lung and cancer. Several studies demonstrated that it mediates cell-matrix interactions, migration of inflammatory cells and development of fibrosis. Recently, it has been reported in several nephropathies. In this review, we discuss the potential pathological roles of DDR-1 and periostin focussing on the kidney in both experimental models and human diseases.

Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice.

Excessive recruitment of monocytes and progression of fibrosis are hallmarks of chronic kidney disease (CKD). Recently we reported that the expression of connexin 43 (Cx43) was upregulated in the kidney during experimental nephropathy. To investigate the role of Cx43 in the progression of CKD, we interbred RenTg mice, a genetic model of hypertension-induced CKD, with Cx43+/- mice. The renal cortex of 5-month-old RenTgCx43+/- mice showed a marked decrease of cell adhesion markers leading to reduced monocyte infiltration and interstitial renal fibrosis compared with their littermates. In addition, functional and histological parameters such as albuminuria and glomerulosclerosis were ameliorated in RenTgCx43+/- mice. Interestingly, treatment with Cx43 antisense produced remarkable improvement of renal function and structure in 1-year-old RenTg mice. Similar results were found in Cx43+/- or wild-type mice treated with Cx43 antisense after obstructive nephropathy. Furthermore, in these mice, Cx43 antisense attenuated E-cadherin downregulation and phosphorylation of the transcription factor Sp1 by the ERK pathway resulting in decreased transcription of type I collagen gene. Interestingly, Cx43-specific blocking peptide inhibited monocyte adhesion in activated endothelium and profibrotic pathways in tubular cells. Cx43 was highly increased in biopsies of patients with CKD. Thus, Cx43 may represent a new therapeutic target against the progression of CKD.

Relationship between number of daily exchanges at CAPD start with clinical outcomes.

BACKGROUND: Peritoneal dialysis (PD) continues to be demanding for patients affected by kidney failure. In kidney failure patients with residual kidney function, the employment of incremental PD, a less onerous dialytic prescription, could translate into a decrease burden on both health systems and patients. METHODS: Between 1st January 2009 and 31st December 2021, 182 patients who started continuous ambulatory peritoneal dialysis (CAPD) at our institution were included in the study. The CAPD population was divided into three groups according to the initial number of daily CAPD exchanges prescribed: one or two (50 patients, CAPD-1/2 group), three (97 patients, CAPD-3 group) and four (35 patients, CAPD-4 group), respectively. RESULTS: Multivariate analysis showed a difference in term of peritonitis free survival in CAPD-1/2 in comparison to CAPD-3 (hazard ratio (HR): 2.20, p = 0.014) and CAPD-4 (HR: 2.98, p < 0.01). A tendency towards a lower hospitalisation rate (CAPD-3 and CAPD-4 vs. CAPD-1/2, p = 0.11 and 0.13, respectively) and decreased mortality (CAPD-3 and CAPD-4 vs. CAPD-1/2, p = 0.13 and 0.22, respectively) in patients who started PD with less than three daily exchanges was detected. No discrepancy of the difference of the mean values between baseline and 24 months residual kidney function was observed among the three groups (p = 0.33). CONCLUSIONS: One- or two-exchange CAPD start was associated with a lower risk of peritonitis in comparison to three- or four-exchange start. Furthermore, an initial PD prescription with less than three exchanges may be associated with an advantage in term of hospitalisation rate and patient survival.

Kidney transplantation in patients with ANCA-associated vasculitis is associated with a high incidence of post-transplant cancer.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease with limited data on outcomes after transplantation. METHODS: In this single-center retrospective cohort study, we describe the outcomes of kidney transplant patients with AAV transplanted at our institute from February 2006 to January 2022. RESULTS: We identified 9 patients among 1026 with a pre-transplant diagnosis of AAV; all patients had received previous treatment with cyclophosphamide. Maintenance immunosuppression after transplantation was tacrolimus-based in 89% of the patients. At the end of a mean follow-up of 132 ± 61.1 months after transplantation, only one case of extrarenal vasculitis relapse was observed. The relapse rate was 0.01 per patient per year, which is comparable to that reported in the literature. However, seven patients were diagnosed with cancer after a mean follow-up of 81.4 months after transplantation; six had skin cancer and three had renal cell carcinoma (RCC) of the native kidneys (cumulative incidence of 78%). One patient died from metastatic squamous cell carcinoma. CONCLUSION: In this study, we found a noticeable decrease in disease relapse (1 relapse in the present cohort vs 7 relapses in 19 patients in the previous cohort) in kidney transplant patients with AAV compared with previous data from our group (December 1987-January 2006). Conversely, we found a high incidence of post-transplant cancer. This result could be attributed to reduced immunosurveillance due to immunosuppression therapy before and after transplantation. Therefore, constant cancer early diagnosis and prevention is mandatory during the post-transplant follow-up of AAV patients.

Tunnel ultrasound can guide the use of peritoneal dialysis catheter exit site relocation by external splicing and cuff removal in refractory tunnel infection.

BACKGROUND: Peritoneal dialysis (PD) catheter related infections continue to be a major cause of morbidity and transfer to hemodialysis (HD) in PD patients. The treatment of tunnel infection (TI) could be challenging, especially when the infection involves the superficial cuff requiring the removal of the catheter. To spare the patient the loss of the catheter and the transfer to HD, several mini-invasive surgical techniques have been proposed as rescue therapy. Furthermore, nowadays, the rapid growth of digital technology has enormously increased the diagnostic sensibility of the echo signal allowing to accurately defines the extent of the infectious process along the PD catheter tunnel. METHODS: Between 1st January 2020 and 31st December 2021 seven patients who underwent exit-site relocation by external splicing and cuff removal at our institution due to refractory TI were included in the study. All patients were followed until 12 months after the procedure. As soon as TI was defined refractory to the medical therapy, an ultrasonographic examination of the catheter tunnel was performed to define the extent of the infectious episode. RESULTS: Among the 7 infectious episodes, 4 were caused by P. aeruginosa, and 3 by S. aureus. Around the superficial cuff the hypo/anechoic collections detected by ultrasounds showed a mean diameter of 3.05 ± 0.79 mm. The exit-site relocation by external splicing and cuff removal was successful in all cases (7/7, 100%). CONCLUSIONS: In our experience the use of exit site relocation by external splicing and cuff removal as rescue therapy for TI with positive ultrasounds for TI limited to superficial cuff involvement and without secondary peritonitis, yielded to promising results with a success rate of 100%. This preliminary experience underlines the paramount usefulness of tunnel echography in accurately defining the extent of TI and, consequently, guiding the choice of the therapeutical approach in refractory TI.

Crosstalk mechanisms between glomerular endothelial cells and podocytes in renal diseases and kidney transplantation.

The glomerular filtration barrier (GFB), composed of endothelial cells, glomerular basement membrane, and podocytes, is a unique structure for filtering blood while detaining plasma proteins according to size and charge selectivity. Structurally, the fenestrated endothelial cells, which align the capillary loops, are in close proximity to mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and are separated from the endothelial compartment by the glomerular basement membrane. Podocyte-endothelial cell communication or crosstalk is required for the development and maintenance of an efficient filtration process in physiological conditions. In pathological situations, communication also has an essential role in promoting or delaying disease progression. Podocytes and endothelial cells can secrete signaling molecules, which act as crosstalk effectors and, through binding to their target receptors, can trigger bidirectional paracrine or autocrine signal transduction. Moreover, the emerging evidence of extracellular vesicles derived from various cell types engaging in cell communication has also been reported. In this review, we summarize the principal pathways involved in the development and maintenance of the GFB and the progression of kidney disease, particularly in kidney transplantation.