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Double kidney transplantation allows the use of marginal kidneys with a significant improvement in the recovery of renal function expected after transplantation, although with a greater anesthesiologic and surgical risk. One-sided positioning, more cautious in the event of functional exhaustion, can be complex due to vascular anomalies. We report the case of 2 double unilateral kidney transplants with vascular reconstructions. The first is a double kidney transplant from a 83-year-old donor. Both kidneys (score 5) had 2 arteries and the arterial patch was not usable. A cryopreserved arterial graft was used for the packaging of an arterial axis with which a single T-L anastomosis was performed; the 2 veins were also joined with the packaging of a single anastomosis. The second case is a double kidney transplant from a cadaveric donor performed on a recipient suffering from severe diffuse atheromasia. The right kidney had 2 arteries and the left kidney had 3 arteries (both score 5). The aortic patches and veins of the 2 kidneys were joined together and a single arterial and venous anastomosis was performed. The course has been uneventful. In both cases there were no perioperative vascular complications. The use of marginal organs is an increasingly common reality. Bench vascular reconstructions can further increase donation resources, safely enhancing the transplantation of already marginal organs that would otherwise not be usable and allowing the contralateral vascular axis to be kept intact. [ABSTRACT FROM AUTHOR]

Tubulo-interstitial nephritis (TIN) in patients affected by inflammatory bowel disease, both ulcerative colitis and Crohn's disease, is usually considered as drug-associated to aminosalicylate. We report a rare case of granulomatous active tubulo-interstitial nephritis in a young patient with a recent diagnosis of ulcerative colitis naïve to aminosalicylate treatment. The patient has been successfully treated with steroids administration. Our purpose is to sensitize that TIN should always to be considered in differential diagnosis an extra-intestinal manifestation of bowel disease. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) infection remains a major cause of morbidity, graft failure, and death in kidney transplant recipients. We describe a case of a 53-year-old CMV-seronegative man who underwent renal transplant from a CMV-positive donor and who developed ganciclovir- (GCV-) resistant CMV infection. Foscarnet was started while immunosuppressive therapy was modified with the introduction of everolimus minimizing tacrolimus dosage. Only two weeks after the start of this treatment regimen was the patient’s viral load negative. At two-year follow-up the patient has no clinical or laboratory signs of CMV infection and a good and stable renal function or graft survival. In our case, administration of an mTOR inhibitor combined with foscarnet led to rapid and persistent viral clearance without compromising short- and medium-term graft function. This combination therapy supports the need for the kidney transplant community to individualize a target therapy for each type of GCV-resistant CMV infection. [ABSTRACT FROM AUTHOR]

• During the first 14 days of Direct oral anticoagulant (DOAC) therapy, a slight increase in serum levels of tacrolimus and cyclosporine can be found; • Serum Levels and concentration/dose ratio of Tacrolimus and cyclosporin were stable at 18 months follow-up in patients treated with DOAC; • DOACS have a similar safety and efficacy profile when compared to antagonist of vitamin K and no difference in terms of bleeding, thromboembolic events and renal function decline was found. direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed. [Display omitted] [ABSTRACT FROM AUTHOR]

• Patients undergoing kidney transplant were screened for Leishmania. • Test combination was used to better identify asymptomatic Leishmania infection. • Polymerase chain reaction, serology, and whole blood assay were carried out. • Fifty out of 120 patients (42%) were tested positive on one or more tests. • Multiple tests efficiently identified asymptomatic Leishmania infection. In immunocompromised patients, asymptomatic Leishmania infection can reactivate, and evolve to severe disease. To date, no test is considered the gold standard for the identification of asymptomatic Leishmania infection. A combination of methods was employed to screen for Leishmania infection in patients undergoing kidney transplant (KT). We employed polymerase chain reaction for the detection of parasitic DNA in peripheral blood, Western blot to identify serum immunoglobulin G and whole blood assay to detect cytokines/chemokines after stimulation of whole blood with parasitic antigen. One-hundred twenty patients residing in Italy were included in the study at the time of KT. Each patient that tested positive to at least one test was considered as Leishmania positive. Fifty out of 120 patients (42%) tested positive for one or more tests. The detection of specific cell-mediated response (32/111, 29%) was the most common marker of Leishmania infection, followed by a positive serology (24/120, 20%). Four patients (3%) harbored parasitic DNA in the blood. Our findings underline the high prevalence of asymptomatic Leishmania infection in patients undergoing KT in Italy, who are potentially at-risk for parasite reactivation and can benefit from an increased vigilance. Understanding the clinical relevance of these findings deserves further studies. [ABSTRACT FROM AUTHOR]

Summary: Donation after circulatory death (DCD) is a potential source of reducing organ demand. In Italy, DCD requires a 20‐min no‐touch period that prolongs warm ischemia and increases delayed graft function (DGF) risk and graft loss. We report here our preliminary experience of sequential use of normothermic regional perfusion (NRP), as standard procedure, and hypothermic oxygenated perfusion (HOPE), as an experimental technique of organ preservation, in 10 kidney transplants (KT) from five DCD Maastricht III with extensive functional warm ischemia time (fWIT) up to 325 min. During NRP, renal function tests were evaluated to accept organs which were retrieved according to standard fashion with biopsy. While waiting for pathology and cross‐match results, organs were preserved with HOPE through pressure‐ and temperature‐controlled arterial pulsatile flow. All grafts with Karpinski score ≤4 were used for conventional single KT with mean cold ischemia time of 584 ± 167 min and mean fWIT of 151 ± 132 min. At the end of HOPE, lactate levels increased significantly in all cases with DGF (P = 0.0095), which were 3/10 (30%). No primary nonfunctions were recorded, and all patients had sCr < 1.5 mg/dl at 6‐month post‐KT. NRP and HOPE for DCD may overcome fWIT limits safely, and lactate during HOPE predicts DGF. [ABSTRACT FROM AUTHOR]

Kidney transplantation is a lifesaving procedure for patients with end-stage kidney disease (ESKD). Organs derived from donation after cardiac death (DCD) are constantly increasing; however, DCD often leads to ischaemia-reperfusion (IR) and Acute Kidney Injury (AKI) events. These phenomena increase kidney cell turnover to replace damaged cells, which are voided in urine. Urine-derived renal epithelial cells (URECs) are rarely present in the urine of healthy subjects, and their loss has been associated with several kidney disorders. The present study aimed to characterize the phenotype and potential applications of URECs voided after transplant. The results indicate that URECs are highly proliferating cells, expressing several kidney markers, including markers of kidney epithelial progenitor cells. Since the regulation of the immune response is crucial in organ transplantation and new immunoregulatory strategies are needed, UREC immunomodulatory properties were investigated. Co-culture with peripheral blood mononuclear cells (PBMCs) revealed that URECs reduced PBMC apoptosis, inhibited lymphocyte proliferation, increased T regulatory (Treg) cells and reduced T helper 1 (Th1) cells. URECs from transplanted patients represent a promising cell source for the investigation of regenerative processes occurring in kidneys, and for cell-therapy applications based on the regulation of the immune response. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients is associated with poorer antibody response (AbR) compared with non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) has yet to be assessed. Methods Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV-2 vaccination during a 1-year period (February 2021 – January 2022), end of follow-up April 2022. Patients were tested for AbR at multiple time points. The primary end-point was BI (laboratory-confirmed SARS-CoV-2 infection ≥14 days after the second dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization, and BI states were obtained for each type of graft and vaccination sequence using multistate survival analysis. Then, multivariable logistic regression was performed to analyze the risk of BI related to AbR levels. Results 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received 3 vaccine doses. The first 2 consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively. For the third dose, mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed the lowest probability of immunization (0.418) and the highest of BI (0.323); all mRNA-1273 vaccine sequences showed the highest probability of immunization (0.732) and the lowest of BI (0.098). Risk of BI was higher for non–high-level AbR, younger age, and shorter time from transplant. Conclusions SOT patients with non–high-level AbR and shorter time from transplantation and heart recipients are at highest risk of BI. [ABSTRACT FROM AUTHOR]

Neutrophil gelatinase-associated lipocalin (NGAL), a protein belonging to the lipocalin superfamily initially found in activated neutrophils, is expressed by several cell types, including kidney tubule. The increase in NGAL production and release from tubular cells in response to various insults has been proven to predict acute kidney injury (AKI). For this reason, it has emerged as a valuable noninvasive biomarker of AKI in clinical nephrology. Also in the renal transplant setting, different studies have indicated NGAL as a valuable tool, especially in the early postoperative period, since the currently available clinical and laboratory parameters remain poorly sensitive to monitor immediate posttransplant graft function. This is an analysis of the recent literature to assess the utility of plasma and urinary NGAL, exosomal mRNA for NGAL, and NGAL levels in the perfusate of machine-perfused kidneys for the prediction of graft function recovery in the early postsurgery phase after renal transplantation. We found that NGAL appears as a promising troponin-like biomarker to detect short-term impairment of graft function after renal transplant, but there are still some limitations in its clinical application, essentially related to its low specificity. Moreover, comparing NGAL assayed in serum, urine, machine-perfusate, or as exosomal mRNA, each one has shown limitations and benefits in terms of predictive performance for DGF, according to various existing studies, feasibly due to different cut-off levels, designs and patient sample sizes. [ABSTRACT FROM AUTHOR]

Background A long-standing effort is dedicated towards the identification of biomarkers allowing the prediction of graft outcome after kidney transplant. Extracellular vesicles (EVs) circulating in body fluids represent an attractive candidate, as their cargo mirrors the originating cell and its pathophysiological status. The aim of the study was to investigate EV surface antigens as potential predictors of renal outcome after kidney transplant. Methods We characterized 37 surface antigens by flow cytometry, in serum and urine EVs from 58 patients who were evaluated before, and at 10–14 days, 3 months and 1 year after transplant, for a total of 426 analyzed samples. The outcome was defined according to estimated glomerular filtration rate (eGFR) at 1 year. Results Endothelial cells and platelets markers (CD31, CD41b, CD42a and CD62P) in serum EVs were higher at baseline in patients with persistent kidney dysfunction at 1 year, and progressively decreased after kidney transplant. Conversely, mesenchymal progenitor cell marker (CD1c, CD105, CD133, SSEEA-4) in urine EVs progressively increased after transplant in patients displaying renal recovery at follow-up. These markers correlated with eGFR, creatinine and proteinuria, associated with patient outcome at univariate analysis and were able to predict patient outcome at receiver operating characteristics curves analysis. A specific EV molecular signature obtained by supervised learning correctly classified patients according to 1-year renal outcome. Conclusions An EV-based signature, reflecting the cardiovascular profile of the recipient, and the repairing/regenerative features of the graft, could be introduced as a non-invasive tool for a tailored management of follow-up of patients undergoing kidney transplant. [ABSTRACT FROM AUTHOR]

In LDKT, right kidneys and kidneys with anomalous vascularization are often deferred because of concerns on complications and vascular reconstructions. To date, only few reports have examined renal vessel extension with cryopreserved vascular grafts in LDKT. The aim of this study is to investigate the effect of renal vessel extension on short-term outcomes and ischemia times in LDKT. From 2012 to 2020, recipients of LDKT with renal vessels extension were compared with standard LDKT recipients. Subset analysis of rights grafts and grafts with anomalous vascularization, with or without renal vessel extension, was performed. Recipients of LDKT with (n = 54) and without (n = 91) vascular extension experienced similar hospital stays, surgical complications and DGF rates. For grafts with multiple vessels, renal vessel extension granted a faster implantation time (44±5 vs. 72±14 min), which resulted comparable to that of standard anatomy grafts. Right kidney grafts with vascular extension had a faster implantation time compared to right kidney grafts without vascular lengthening (43±5 vs. 58±9 min), and a comparable implantation time to left kidney grafts. Renal vessel extension with cryopreserved vascular grafts allows faster implantation time in right kidney grafts or grafts with anomalous vascularization, maintaining similar surgical and functional outcomes. [ABSTRACT FROM AUTHOR]

Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate's lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. [ABSTRACT FROM AUTHOR]

Background: The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear. Methods: Systematic literature search retrieving observational studies comparing solid organ transplant (SOT) recipients with culture‐positive PF versus culture‐negative PF. The quality of included studies was independently assessed according to the ROBINS‐I tool for observational studies. Meta‐analysis was performed using Mantel‐Haenszel random‐effect models. Graft site arteritis within 180 days from transplant was selected as the primary outcome. Results: Twenty‐one observational studies (N = 2208 positive PF vs. 4458 negative) were included. Among positive PF, 857 (38.8%) were classified as high‐risk group pathogens and 1351 (61.2%) as low‐risk pathogens. Low‐risk and negative PF showed similar odds ratios. A significant higher risk of graft arteritis was found in SOT recipients with a PF yielding a high‐risk pathogen (odds ratio [OR] 18.43, 95% confidence interval [CI] 7.83–43.40) compared to low‐risk and negative PF, with low heterogeneity (I2 = 2.24%). Similar results were found considering separately high‐risk bacteria (OR 12.02, 95%CI 4.88‐29.60) and fungi (OR 71.00, 95%CI 28.07–179.56), with no heterogeneity (I2 = 0%), and in the subgroup analyses of the liver (OR 16.78, 95%CI 2.95–95.47) and kidney (OR 19.90, 95%CI 4.78–82.79) recipients. However, data about diagnostic features of graft arteritis were very limited, indeed for only 11 of the 93 events histological or microbiological results were reported. Conclusions: Our results may support the performance of PF culturing and a preemptive diagnostic or therapeutic management upon isolation of high‐risk pathogens. Further studies based on a reliable diagnosis of graft arteritis are needed. [ABSTRACT FROM AUTHOR]

Although most patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) experience respiratory manifestations, multi-organ dysfunction is frequent. Almost 20% of hospitalized patients with SARS-CoV-2 infection develop acute kidney injury (AKI). The pathophysiology of AKI is a result of both the direct and indirect effects of SARS-CoV-2 infection, including systemic inflammatory responses, the activation of the renin-angiotensin-aldosterone system (RAAS), and endothelial and coagulative dysfunction. Underlying SARS-CoV-2 infection-associated AKI, an immunological hyper-response with an unbalanced innate and adaptative response defined as a "cytokine storm" has emerged. Numerous agents have been tested in an effort to mitigate the cytokine storm, and a range of extracorporeal cytokine removal techniques have been proposed as potential therapeutic options. In the present review, we summarize the main pathogenetic mechanisms underlying COVID-19-related AKI in order to provide an appropriate individual therapeutic strategy to improve clinical outcomes and limit the progression of early disease. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a complex and multifactorial disease, and one of the most prevalent worldwide. Chronic kidney disease–mineral bone disorders (CKD–MBD) with biochemical and hormonal alterations are part of the complications associated with the progression of CKD. Pathophysiology of CKD–MBD focused on abnormalities in serum levels of several biomarkers (such as FGF-23, klotho, phosphate, calcium, vitamin D, and PTH) which are discussed in this review. We therefore examine the prognostic association between CKD–MBD and the increased risk for cardiovascular events, mortality, and CKD progression to end-stage kidney disease (ESKD). Lastly, we present specific treatments acting on CKD to prevent and treat the complications associated with secondary hyperparathyroidism (SHPT): control of hyperphosphatemia (with dietary restriction, intestinal phosphate binders, and adequate dialysis), the use of calcimimetic agents, vitamin D, and analogues, and the use of bisphosphonates or denosumab in patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients' outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient's outcome. [ABSTRACT FROM AUTHOR]

Diabetes is the leading cause of kidney failure and specifically, diabetic kidney disease (DKD) occurs in up to 30% of all diabetic patients. Kidney disease attributed to diabetes is a major contributor to the global burden of the disease in terms of clinical and socio-economic impact, not only because of the risk of progression to End-Stage Kidney Disease (ESKD), but also because of the associated increase in cardiovascular (CV) risk. Despite the introduction of novel treatments that allow us to reduce the risk of future outcomes, a striking residual cardiorenal risk has been reported. This risk is explained by both the heterogeneity of DKD and the individual variability in response to nephroprotective treatments. Strategies that have been proposed to improve DKD patient care are to develop novel biomarkers that classify with greater accuracy patients with respect to their future risk (prognostic) and biomarkers that are able to predict the response to nephroprotective treatment (predictive). In this review, we summarize the principal prognostic biomarkers of type 1 and type 2 diabetes and the novel markers that help clinicians to individualize treatments and the basis of the characteristics that predict an optimal response. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology. Background: Rhabdomyolysis is a syndrome characterized by muscle necrosis and the subsequent release of intracellular muscle constituents into the bloodstream. Although the specific cause is frequently evident from the history or from the immediate events, such as a trauma, extraordinary physical exertion, or a recent infection, sometimes there are hidden risk factors that have to be identified. For instance, individuals with sickle cell trait (SCT) have been reported to be at increased risk for rare conditions, including rhabdomyolysis. Moreover, there have been a few case reports of SARS-CoV-2 infection-related rhabdomyolysis. Case Report: We present a case of a patient affected by unknown SCT and admitted with SARS-CoV-2 pneumonia, who suffered non-traumatic non-exertional rhabdomyolysis leading to acute kidney injury (AKI), requiring acute hemodialysis (HD). The patients underwent 13 dialysis session, of which 12 were carried out using an HFR-Supra H dialyzer. He underwent kidney biopsy, where rhabdomyolysis injury was ascertained. No viral traces were found on kidney biopsy samples. The muscle biopsy showed the presence of an "open nucleolus" in the muscle cell, which was consistent with virus-infected cells. After 40 days in the hospital, his serum creatinine was 1.62 mg/dL and CPK and Myoglobin were 188 U/L and 168 ng/mL, respectively; therefore, the patient was discharged. Conclusions: SARS-CoV-2 infection resulted in severe rhabdomyolysis with AKI requiring acute HD. Since SARS-CoV-2 infection can trigger sickle-related complications like rhabdomyolysis, the presence of SCT needs to be ascertained in African patients. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) may be associated with worse outcome in solid organ transplant (SOT) recipients. We performed a prospective cohort study of hospitalized patients with confirmed diagnosis of COVID‐19, from March 15 to April 30, 2020, at two tertiary hospitals in Emilia‐Romagna Region. SOT recipients were compared with non‐SOT patients. Primary endpoint was all‐cause 30‐day mortality. Relationship between SOT status and mortality was investigated by univariable and multivariable Cox regression analysis. Patients were assessed from COVID‐19 diagnosis to death or 30‐day whichever occurred first. Study cohort consisted of 885 patients, of them 24 SOT recipients (n = 22, kidney, n = 2 liver). SOT recipients were younger, had lower BMI, but higher Charlson Index. At admission they presented less frequently with fever and respiratory failure. No difference in 30‐day mortality between the two groups (19% vs 22.1%) was found; however, there was a trend toward higher rate of respiratory failure (50% vs 33.1%, P =.07) in SOT recipients. Superinfections were more represented in SOT recipients, (50% vs 15.5%, P <.001). At multivariate analysis adjusted for main covariates, there was no association between SOT and 30‐day mortality HR 1.15 (95% CI 0.39‐3.35) P =.79. Our data suggest that mortality among COVID‐19 SOT recipients is similar to general population. [ABSTRACT FROM AUTHOR]

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7–14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management. [ABSTRACT FROM AUTHOR]

With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT. [ABSTRACT FROM AUTHOR]

Background: Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation are becoming popular in Italy, with the purpose of reducing the risk of primary non function and delayed graft function due to the prolonged warm ischemia time. Potential complications related to these procedures are currently under investigation and are continuously emerging with the increasing experience. Post-operative infections - in particular graft arteritis - are a rare complication but determine high risk of mortality and of graft loss. The acute onset of the arterial complications makes it very difficult to find an effective treatment, and early diagnosis is crucial for saving both patient and graft. Prevention of such infections in this particular setting are advisable.Case Presentation: We present a patient with an acute arterial rupture after transplantation of a DCD graft treated in-vivo hypothermic oxygenated perfusion. The cause was a severe arteritis of the renal artery caused by Candida krusei and Pseudomonas aeruginosa. We discussed our treatment and we compared it to the other reported series.Conclusion: Fungal infections in DCD transplant may be treacherous and strategies to prevent them should be advocated. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) has become one of the most frequent non-infectious comorbidities in the aging HIV-infected population on long-standing combination antiretroviral therapy (cART). Methods: We conducted a retrospective, cross-sectional study including HIV-infected adult patients attending our HIV outpatient clinic during the years 2017 and 2018 to assess prevalence and associated risk factors of CKD. Estimated glomerular filtration rate (eGFR) was measured by Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. CKD was diagnosed and classified according to the National Kidney Foundation guidelines. Logistic regression was employed to identify factors associated with CKD. Results: We enrolled 2339 HIV-infected patients (91% were Caucasian) with a mean age of 45.3 years and a mean current CD4 lymphocyte count of 531 cells/mm3. CKD was diagnosed in 311 subjects (13.3%). Overall, 294 (12.6%) patients had albuminuria, 108 (4.6%) had eGFR < 60 mL/min/1.73 m2, and 78 (3.3%) had albuminuria plus eGFR < 60 mL/min/1.73 m2. Stages 4–5 of CKD were documented in 23 (1%) cases. Age greater than 50 years, male gender, hypertension, diabetes mellitus, high triglycerides, nadir CD4 cell count < 200 cells/mm3, current use of tenofovir disoproxyl fumarate (TDF) and of TDF plus a ritonavir-boosted protease inhibitors were independently associated with CKD, while current use of abacavir plus one integrase inhibitor was associated with a reduced risk of CKD. Conclusion: There is a significant prevalence of CKD among HIV-infected persons in association with both traditional and HIV-specific risk factors, requiring a careful periodic monitoring of renal function in these patients. [ABSTRACT FROM AUTHOR]

The article focuses on Urine-derived Renal Epithelial Cells (URECs) from transplanted kidneys, which have shown promising immunomodulatory properties that could be valuable in kidney transplantation and regenerative medicine, potentially aiding in the regulation of the immune response.

A case study is presented of a 61-year-old woman presented with renal thrombotic microangiopathy. Renal biopsy showed thrombotic microangiopathy; adverse events associated with the use of cabozantinib drug for the treatment of metastatic medullary thyroid cancer such as diarrhoea, nausea and hypertension; and use of appropriated strategies for the treatment of the same.

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is characterized by an increased fracture risk. Bone marrow mesenchymal stromal cells (BMSCs) may be involved in the pathogenesis of bone disease and, in view of their promising potential applications in bone tissue engineering, the effect of uremia on BMSCs regenerative potential represents a central issue. The present study evaluated in vitro the effect of a serum pool from hemodialysis patients on BMSCs to observe its influence on osteogenic differentiation. Besides alterations in spatial organization and cytotoxicity along with hyperproliferation, gene expression analysis suggested an impairment in the osteogenic differentiation. More importantly, Receptor activator of nuclear factor kappa-B ligand (RANKL) was upregulated with a mild reduction in osteoprotegerin levels. In summary, uremic environment seems to impair BMSCs osteogenic differentiation. Moreover BMSCs themselves may enhance osteoclastogenesis, feasibly contributing to the altered bone remodeling in CKD-MBD patients. J. Cell. Physiol. 232: 2201-2209, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Chemotherapy and extracorporeal treatment reduce serum free light chains (FLCs) allowing the recovery of acute kidney injury (AKI) caused by myeloma cast nephropathy (MCN). We report the first case of recovery from AKI in a patient with MCN who underwent the removal of FLCs using the PEPA filter, with an undisclosed cut‐off, combined with chemotherapy for multiple myeloma (MM). [ABSTRACT FROM AUTHOR]

Different arterial wall properties can significantly increase the risk of blood turbulent fluxes leading to complications such as atherosclerosis. Since the mechanical properties of arterial vessels are influenced by age, we investigated, in a retrospective study, the effects on renal artery stenosis of an age difference >15 years between donor and recipient in a cohort of 164 patients undergoing renal transplantation between 1981 and 1991. The age difference between donor and recipient was ≤15 years in 87 patients (53.0%) (Group A) and >15 years in 77 patients (47.0%) (Group B, p=ns). None of the Group A patients developed an anastomotic arterial stenosis, whereas 8/77 Group B patients (10.4%) had an anastomotic arterial stenosis (p<0.001). This study shows that an age difference >15 years is significantly linked to the risk of developing arterial stenosis after renal transplantation. Indeed, different wall properties can significantly increase the risk of generation of blood turbulent fluxes and involve, in the arterial vessels, the development of complications such as atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Renal transplantation represents the therapeutic gold standard in patients with end stage renal disease (ESRD). Still the role of pre-transplant dialysis in affecting time to transplantation has yet to be determined. We wanted to verify whether the type of renal replacement therapy (hemodialysis vs. peritoneal dialysis) affects time to transplantation and to identify clinical features related to the longer time to transplantation. Methods: We performed a retrospective single-center observational study on patients who had received a transplant in the Bologna Transplant Unit from 1991 to 2019, described through the analysis of digital transplant list documents for sex, age, body mass index (BMI), blood group, comorbidities, underlying disease, serology, type of dialysis, time to transplantation, Panel Reactive Antibodies (PRA) max, number of preformed anti Human Leukocyte Antigens (HLA) antibodies. A p-value < 0.05 was considered statistically significant. Results: In the 1619 patients analyzed, we observed a significant difference in time to transplant, PRA max and Preformed Antibodies Number between patients who received Hemodialysis (HD) and Peritoneal dialysis (PD). Then we performed a multiple regression analysis with all the considered factors in order to identify features that support these differences. The clinical variables that independently and directly correlate with longer time to transplantation are PRA max (p < 0.0001), Antibodies number (p < 0.0001) and HD (p < 0.0001); though AB blood group (p < 0.0001), age (p < 0.003) and PD (p < 0.0001) inversely correlate with time to transplantation. Conclusions: In our work, PD population received renal transplants in a shorter period of time compared to HD and turned out to be less immunized. Considering immunization, the type of dialysis impacts both on PRA max and on anti HLA antibodies. [ABSTRACT FROM AUTHOR]

Background. Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis.Methods. One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality.Results. RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS [intermittent (I-RLS) vs continuous (C-RLS)]. Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality.Conclusions. This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality. [ABSTRACT FROM AUTHOR]

Among the causes of in-hospital acute renal failure, contrast-induced nephropathy ranks third in prevalence. Although it represents a condition of renal impairment with spontaneous recovery, contrast nephropathy should always be considered, because it prolongs hospitalization and it may become a severe complication requiring dialysis. The purposes of this study are: (i) to determine if the application of the most effective contrast-induced nephropathy prevention strategies in the Cardiology Intensive Care Unit can prove to be successful in reducing nephropathy risk; and (ii) to identify which of the involved risk factors persist after the preventive treatment. We examined the patients who had a coronarography at the Bentivoglio hospital from April 2007 to April 2008 who required at least 3 days of permanence in hospital due to the presence of potential risk factors; 136 out of 784 patients were included. Among the selected patients, 21 (15.44%) developed a renal impairment compatible with contrast-induced nephropathy. The risk factors that seemed to display the best correlation with risk of contrast nephropathy were advanced age and an ventricular failure (ejection fraction <40%); however, the critical condition did not appear to be due to a single risk factor, but it resulted from the association of more contextual risk factors. Particularly, the concomitant presence of ventricular failure, anemia, diabetes, previous myocardial infarction and advanced age (>70 years) determined a threefold increased risk of contrast nephropathy. Our data suggest that the development of contrast nephropathy following coronarography is associated with worse renal function during hospitalization and at discharge. [ABSTRACT FROM AUTHOR]

There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation. Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion ( n = 6) or cold storage ( n = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5′-triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation. The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys. The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT. [ABSTRACT FROM AUTHOR]

Background: Here, we isolated, expanded and functionally characterized regulatory T cells (Tregs) from patients with end stage kidney and liver disease, waiting for kidney/liver transplantation (KT/LT), with the aim to establish a suitable method to obtain large numbers of immunomodulatory cells for adoptive immunotherapy post-transplantation.Methods: We first established a preclinical protocol for expansion/isolation of Tregs from peripheral blood of LT/KT patients. We then scaled up and optimized such protocol according to good manufacturing practice (GMP) to obtain high numbers of purified Tregs which were phenotypically and functionally characterized in vitro and in vivo in a xenogeneic acute graft-versus-host disease (aGVHD) mouse model. Specifically, immunodepressed mice (NOD-SCID-gamma KO mice) received human effector T cells with or without GMP-produced Tregs to prevent the onset of xenogeneic GVHD.Results: Our small scale Treg isolation/expansion protocol generated functional Tregs. Interestingly, cryopreservation/thawing did not impair phenotype/function and DNA methylation pattern of FOXP3 gene of the expanded Tregs. Fully functional Tregs were also isolated/expanded from KT and LT patients according to GMP. In the mouse model, GMP Tregs from LT or KT patient proved to be safe and show a trend toward reduced lethality of acute GVHD.Conclusions: These data demonstrate that expanded/thawed GMP-Tregs from patients with end-stage organ disease are fully functional in vitro. Moreover, their infusion is safe and results in a trend toward reduced lethality of acute GVHD in vivo, further supporting Tregs-based adoptive immunotherapy in solid organ transplantation. [ABSTRACT FROM AUTHOR]