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Background: Antineutrophil cytoplasmic antibody associated vasculitis (AAV) is a group of diseases associated in most cases with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs). Rituximab- based remission induction has been proven effective in ANCA associated vasculitis but scarce data exist in forms with severe renal involvement. In this case series, we report the outcomes in patients with de novo or recurrent MPO-AAV and severe renal involvement treated with rituximab without cyclophosphamide (CYC).Methods: In this single centre retrospective study, we analysed patients with a clinical diagnosis of de novo or recurrent AAV who met the following criteria: detection of P-ANCA, creatinine clearance lower than 30 ml/min, induction of remission therapy with rituximab without concomitant CYC and a follow up period of at least 6 months. The primary outcomes were complete remission after induction therapy, renal function recovery and mortality after the induction treatment.Results: Eight patients met the inclusion criteria. The M:F ratio was 1:7, the average age was 54 years old and the median follow up was 10 months (7-72); in 2 patients there was a MPA renal limited vasculitis. A renal biopsy was performed in 7 patients. The median BVAS score at rituximab induction was 14(range 6-21). Two patients required haemodialysis before the induction treatment. Four patients developed end stage renal disease (ESRD) that required haemodialysis. These data show a remission of the disease, associated with a stabilization of the kidney function in 50% of patients. In 3 patients who did not show a response, there was also no response to CYC.Conclusions: This study shows a partial efficacy of rituximab in renal function recovery and a low risk of infectious complications in patients with MPO vasculitis with severe renal involvement, in particular in the short term. The optimal treatment in this subgroup of patients still has to be established because data are lacking. [ABSTRACT FROM AUTHOR]

Abstract: Squamous cell carcinoma of the skin (SCC) is the most frequent cancer in renal transplant recipients. Conversion to mammalian target of rapamycin inhibitors after diagnosis of SCC may reduce the incidence of recurrence of skin cancer. This retrospective study evaluated the outcome of renal transplant recipients followed by the Renal Unit with posttransplant diagnosis of SCC treated with conversion from calcineurin inhibitors (CNIs) to Everolimus (EVR) associated with low-dose cyclosporine. Eleven patients developed SCC at a median time from renal transplantation of 107 months (range 36–264). Five patients with creatinine clearance (CCl) below 40 mL/min before conversion developed end stage renal disease (two cases) or further deterioration of renal function (two cases); only one patient in this group maintained a stable renal function. The remaining six patients with a CC1 greater than 40 mL/min and proteinuria below 0.8 g/24 hours maintained a stable renal function after conversion to EVR at a median follow-up of 22 months (range 15–75). Conversion from CNIs to EVR has been proven safe, effective, and associated with low recurrence of SCC in patients with a CCl >40 mL/min. In the case of preexisting deterioration of renal function or significant proteinuria, conversion to EVR should be carefully evaluated. [Copyright &y& Elsevier]

Abstract: Renal transplant recipients are at increased risk of infectious diseases and subject to cutaneous infections because of the effects of immunosuppressive therapy. Some long-term descriptive follow-up studies confirm that skin infections are common among renal transplant recipients. We report the development of subcutaneous nodules among patients receiving renal transplantations from 1991 to 2009. Transplant recipients were followed by the Nephrology Unit at control visits according to the American Society Nephrology guidelines. Between 1991 to 2009, subcutaneous nodules were identified in 7 out of 774 renal transplant recipients. The male:female ratio was 5:2; median age at renal transplantation was 52 years (range 28–59). Subcutaneous nodules were identified at a median 3 years after transplantation. The 7 patients had the following diagnoses: systemic scedosporiasis (n = 1); Mycobacterium avium complex infection (n = 2) disseminated tuberculosis (n = 2) Sporothrix schenckii infection (n = 1); Trichophyton rubrum infection (n = 1). Four patients died due to sepsis from disseminated infection. Subcutaneous nodules may reflect a systemic infectious pathology. In some cases, the investigation of cutaneous lesions is important to reach a definitive diagnosis for possible future disseminated infections. [Copyright &y& Elsevier]

Abstract: Cardiovascular disease (CVD) is the main cause of morbidity and mortality in renal transplant recipients. The incidence of CVD in this setting is approximately 5-fold greater than in age- and and gender-matched subjects. This excess cardiovascular risk is not completely explained by traditional cardiac risk factors. It has been well documented that these patients show greatly increased prevalence of both fasting and postmethionine-loading hyperhomocysteinemia (hHcy) compared with the general population. An immunosuppressive therapy based on everolimus has been demonstrated to reduce the incidence major adverse coronary events at 4 years compared with azathioprine among heart transplant recipients. In contrast, scarce data are available on the impact of everolimus on emerging risk factors, such as homocysteine (Hcy), in renal transplant recipients. The aim of this study was to evaluate the possibile impact of everolimus compared with other immunosuppressive regimes among 132 stable recipients, including 91 men and 41 women who were at least 1 year after transplant with stable renal function and no clinical evidence of acute or chronic renal graft rejections. We compared 31 subjects on everolimus immunosuppressive therapy (group A) versus 101 on immunosuppressive therapy based on cyclosporine, steroids, and mycophenolate. The Hcy levels were significantly lower among group A patients compared with group B: 16.5 ± 5 μmol/L vs 21.2 ± 11 μmol/L; P < .005. Hyper-Hcy, defined as Hcy levels >15 μmol/L, was diagnosed in 18 out of 31 patients (51%) of group A and in 82 out of 101 patients (81%) of group B. This preliminary study demonstrates a favorable impact of everolimus on a marker of atherothrombosis which is associated with a worse vascular prognosis. [Copyright &y& Elsevier]

We compared retrospectively the level of hemoglobin and the percentage of patients with anemia among 59 kidney transplant recipients receiving everolimus, cyclosporine, and corticosteroids and 128 treated with cyclosporine, mycophenolic acid, and corticosteroids. We also compared age at the time of transplantation, sex and ferritine, serum creatinine, creatinine clearance, folic acid, cyanocobalamine levels, use od recombinant erythropoietin, mean corpuscolar volume at the last ambulatory control. Statistical analysis included Student t test, χ 2 test, and logistic regression. The analysis was performed using SPSS software. We observed no difference in terms of hemoglobin levels in patients treated with everolimus (12.9 ± 1.6 vs 12.7 ± 1.5 g/dL). Anemia (defined as hemoglobin <13 g/dL in men and <12 g/dL in women, or need to use erythropoietin) was found in 49% and 45% of patients in the 2 groups respectively ( P = .6). The other parameters evaluated were similar except for the mean corpuscular volume, which was significantly lower in the everolimus group. In the multivariate analysis only serum creatinine and estimated glomerular filtration rate influenced the level of hemoglobin. We observed no differences in terms of development of anemia in renal transplanted patients treated with everolimus-based regimen. [ABSTRACT FROM AUTHOR]

In this retrospective study, we compared the outcome of renal transplanted patients who received everolimus (EVR) (C0: 8–12 ng/mL) + cyclosporine (CsA) (C2: 150–300 ng/mL) + steroids, vs those who received enteric-coated mycophenolate sodium (EC-MPS) (1,440 mg/d) + CsA (C2: 500–700 ng/mL) + steroids. Efficacy was evaluated at 5 years. We found a nonsignificant trend toward a better 5-year graft survival (81.2% vs 68.6%) and better graft function (estimated glomerular filtration rate 71.8 ± 35.7 vs 60.0 ± 26.2 mL/min, P = .114) in favor of the EVR group. In our experience, EVR with a very low dose of CsA was associated with a nonstatistical trend toward better renal function and graft survival compared to a standard regimen of CsA and EC-MPS. [ABSTRACT FROM AUTHOR]

Abstract: We prospectively studied the potential value of contrast-enhanced ultrasound (CEUS) to characterize complex acquired cystic kidney disease (ACKD) or suspected solid renal masses, avoiding the risk of inducing acute kidney injury in 138 renal transplant recipients by contrast-enhanced computed tomography (CT). Forty-three cases (31%) had ACKD; 15 ACKD patients (35%) showed suspicious or nondiagnostic ultrasound. The latter subgroup underwent CEUS and, if the suspicion was confirmed, a contrast-enhanced CT. Thirty five lesions were identified in the 15 patients studied by CEUS. According to the Bosniak classification, 27 cysts were type I (BI), four type II (BII), two type III (BIII) with enhancement at the level of thickened septa; we also identified two solid enhancing lesions (BIV). We followed the BI and BII lesions with serial CEUS, while the remaining four cases underwent contrast-enhanced CT showing two solid lesions and two complex cysts with contrast enhancement in the septea. The four patients underwent surgical resection yielding three renal cell carcinomas one papillary carcinoma as the pathological findings. This preliminary study characterized solid nodules and BIII lesions for further evaluation by CT. CEUS seems to correctly characterize BI and BII cysts that are not clearly defined by standard ultrasound. [Copyright &y& Elsevier]

Abstract: Renal transplant recipients (RTRs) are at increased risk of cardiovascular complications. An altered hemorheological profile may determine both cardiovascular complications and progression of renal failure in RTRs. We performed this study to evaluate the rheologic status in 239 RTRs at least 12 months after transplantation with stable and normal renal function compared with 90 control subjects. In RTRs, a significantly higher hematocrit-adjusted, but not native, whole blood viscosity was found (P < .0001). Moreover, plasma viscosity and red blood cell deformability were significantly higher in patients than in control subjects (P < .0001), whereas no difference in erythrocyte aggregation between patients and control subjects was observed (P = .5). Fibrinogen, but not hematocrit, significantly increased in RTRs (P = .001). This preliminary study provides evidence of an altered hemorheologic profile in RTRs. [Copyright &y& Elsevier]

Abstract: Introduction: Renal transplant recipients are at increased risk of cardiovascular morbidity and mortality. We assessed platelet reactivity and reticulated platelets (RPs) in 90 recipients, 51 (56.6%) of whom were not receiving acetylsalicylic acid (ASA) therapy (group A) and 39 (43.3%) who were receiving ASA therapy, 100 mg (group B), and in 60 healthy controls (group C). Methods: Reticulated platelets were measured using a hematology automated analyzer (XE-2100; Sysmex Corp, Kobe, Japan) and were expressed as the percentage of RPs in the total optical platelet count (immature platelet fraction [IPF]), as the percentage of highly fluorescent RPs, and as the absolute number of RPs (IPF#). Platelet function was assessed using optical aggregometry (platelet aggregation) induced using 1 mmol/L of arachidonic acid, 2 or 10 μmol/L of adenosine diphosphate, or 2 μg/mL of collagen. Results: Group A demonstrated significantly higher values of RP compared with group B or group C. Group B demonstrated a substantially higher percentage of RPs compared with group C, which was significant only for the IPF parameter. Multiple regression analysis demonstrated that IPF and IPF# were significantly and positively related to collagen-induced platelet aggregation. Conclusion: We documented the presence of higher concentrations of RPs in transplant recipients compared with a control population, and a significant association between RPs and platelet function. [Copyright &y& Elsevier]

Background: Thrombotic microangiopathy (TMA) is a pathological syndrome characterized by a combination of three key features: microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ damage, primarily affecting the kidneys. There are several drugs known to have a definite or probable causal association with TMA, and carfilzomib, a second-generation irreversible proteasome inhibitor (PI), approved for the treatment of multiple myeloma (MM), is one of them. In the medical literature, there have been a growing number of reports describing this serious adverse event occurring in MM patients. The precise mechanisms underlying the development of PI-induced TMA are not yet fully understood. Significant improvements in both renal and hematological aspects have been documented following the administration of eculizumab., Recent Findings: In this report, we present two cases of MM patients who developed TMA while undergoing carfilzomib therapy. These cases were successfully treated at the Haematology Unit, Careggi Hospital in Florence. In our cases as well, the introduction of eculizumab resulted in rapid enhancements in renal function and platelet count, ultimately leading to the discontinuation of hemodialysis after 4 and 2 weeks, respectively., Discussion and Conclusion: We assessed 91 patients who received carfilzomib-based therapies at our Haematology Department, during which we identified two cases of DITMA (2.2% incidence). Additionally, we conducted a literature review and discovered a total of 75 documented cases of carfilzomib-induced TMA. Our experience aligns with the cases reported in literature: this adverse event can manifest at any point during treatment, regardless of the specific drug combinations used alongside carfilzomib. The initial and most crucial step in its management involves discontinuing carfilzomib therapy; therefore, recognizing TMA in a timely manner is of utmost importance. Eculizumab could play a role in improving and expediting the resolution of this potentially fatal adverse event, but further studies are needed. In a MM patient receiving carfilzomib, presenting with anemia, thrombocytopenia, and impaired renal function, a carfilzomib-induced TMA should be suspected in order to discontinue the causative agent., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: 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)., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The use of kidneys from "expanded criteria" donors after brain death (ECD) and uncontrolled donors after circulatory death (uDCD) has been warranted to increase the pool of donors for kidney transplantation (KT). However, there is lack of evidence on the feasibility and safety of KT from such donors in the Italian setting., Methods: We queried our prospectively KT database to select patients undergoing KT from deceased donors (uDCDs, ECDs, and standard-criteria donors [SCD] after brain death) from January 2017 to December 2020, comparing the perioperative and mid-term functional outcomes., Results: Overall, 172 KTs were included. The donor's profile was different among the study groups, while recipients' characteristics were similar expect for median age. Grafts from uDCDs and ECDs had longer median cold ischemia times as compared to grafts from SCDs. The proportion of patients experiencing DGF, the median hospitalization, as well as the overall and major complications rate, were significantly higher among recipients from uDCDs. The proportion of patients needing dialysis at last follow-up was significantly higher among recipients from uDCDs (33.3% vs. 8.5% vs. 5.4%, P<0.001). However, the median eGFR at the last follow-up was lower for recipients from ECDs compared to those from uDCDs and SCDs, respectively (P<0.001)., Conclusions: While "marginal" donors represent a relevant source of organs, KTs from uDCDs carry higher risks of major surgical complications, DGF, and worse graft survival as compared to KT from both ECDs and SCDs. As such, the use of grafts from uDCDs should be carefully assessed balancing the potential benefits with the risk of primary no function and the subsequent immunological sensitization.

Background: Among different forms of de novo focal segmental glomerulosclerosis (FSGS), which can develop after kidney transplantation (KTx), collapsing glomerulopathy (CG) is the least frequent variant, but it is associated with the most severe form of nephrotic syndrome, histological findings of important vascular damage, and a 50% risk of graft loss. Here, we report two cases of de novo post-transplant CG., Clinical Presentation: A 64-year-old White man developed proteinuria and worsening of renal function 5 years after KTx. Before the KTx, the patient was affected by an uncontrolled resistant hypertension, despite multiple antihypertensive therapies. Blood levels of calcineurin inhibitors (CNIs) were stable, with intermittent peaks. Kidney biopsy showed the presence of CG. After introduction of angiotensin receptor blockers (ARBs), urinary protein excretion progressively decreased in 6 months, but subsequent follow-up confirmed a progressive renal function decline. A 61-year-old White man developed CG 22 years after KTx. In his medical history, he was hospitalized twice to manage uncontrolled hypertensive crises. In the past, basal serum cyclosporin A levels were often detected above the therapeutic range. Low doses of intravenous methylprednisolone were administered due to the histological inflammatory signs shown on renal biopsy, followed by a rituximab infusion as a rescue therapy, but no clinical improvement was seen., Discussion and Conclusion: These two cases of de novo post-transplant CG were supposed to be mainly caused by the synergic effect of metabolic factors and CNI nephrotoxicity. Identifying the etiological factors potentially responsible for de novo CG development is essential for an early therapeutic intervention and the hope of better graft and overall survival., Competing Interests: The authors have no conflict of interest to declare. Figure 1.Light microscopy of patient A. Two glomeruli show segmentary sclerosis of the flocculus. Focal aspect of collapse of glomerular capillaries is shown in a glomerulus with some hyperplastic epithelial cells containing drops of protein reabsorption (collapsing lesion). No signs of endocapillary hypercellularity or glomerulitis.Figure 2.Clinical course after transplantation. eGFR = estimated glomerular filtration rate; KTx = kidney transplantation; RBx = renal biopsy., (© Dustri-Verlag Dr. K. Feistle.)

Introduction: Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS)., Methods: We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months., Results: A total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles., Conclusion: Three different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN)., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: Aims of this SR were to assess the association of Periodontitis (PD) with Chronic Kidney Disease (CKD) and with different CKD stages., Materials and Methods: MEDLINE, Cochrane Central Register of Trials and EMBASE, up to April 4, 2021 were searched. RCTs, prospective and retrospective cohort studies, case-control studies and cross-sectional studies were considered. JBI's Critical Appraisal Tool for risk of bias assessment was used. The risk of PD was calculated using the Mantel-Haenszel odds ratios (MH-OR); weighted mean difference for clinical attachment level (CAL) and periodontal probing depth (PPD) were also evaluated., Results: Out of 1949 titles screened, 142 full texts were evaluated and 17 studies were included. CKD was associated to higher risk of PD (MH-OR = 2.36, [95% C.I. 1.25, 4.44]; p = 0.008), higher mean CAL (WMD = 0.41 mm [95% C.I. 0.22, 0.60]; p < 0.0001) and mean PPD (WMD = 0.25 mm [95% C.I. 0.03, 0.47]; p = 0.02) compared to healthy individuals. Severe CKD (stages 4-5 vs 2-3) resulted at higher risk of PD (MH-OR = 2.21, [95% C.I. 1.07, 4.54]; p = 0.03). Heterogeneity and risk of bias were high., Conclusions: An association between PD and CKD was found. It could be appropriate to consider PD a frequent CKD comorbidity., (© 2021 Wiley Periodicals LLC.)

Background: Multiple myeloma (MM) is a malignant neoplasm associated with kidney involvement in nearly half of the patients. Cast nephropathy, monoclonal immunoglobulin deposition disease (MIDD), and light chain (AL) amyloidosis are the most common monoclonal immunoglobulin-mediated causes of renal injury. Cardiac involvement is also present in MM, characterized by restrictive cardiomyopathy generated by light chain deposit or amyloid. Thromboembolic complications such as deep vein thrombosis or pulmonary embolism are also described., Case Presentation: We present an unusual multidisciplinary case of a woman with a newly diagnosed MM associated with severe proteinuria and high natriuretic peptide. A renal and fat pad biopsy with Congo red staining were performed but amyloid deposition was not discovered. While immunofluorescence on fresh frozen unfixed tissue was not contributory, the immunofluorescence on fixed tissue and electron microscopy revealed the correct diagnosis. During subsequent investigations, two intracardiac right-sided masses and massive pulmonary embolism were also detected., Conclusions: This case highlights that multiple organ involvement in patients with MM may result from a combination of paraprotein-dependent and -independent factors. Moreover, renal diseases induced by monoclonal gammopathies are a group of complex and heterogeneous disorders. Their subtle presentation and their potential multiorgan involvement require the expertise of a multidisciplinary team able to provide the most appropriate diagnostic and therapeutic assessment., (© 2022. The Author(s).)

Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease, providing a better survival rate and quality of life compared to dialysis. Despite the progress in the medical management of KT patients, from a purely surgical standpoint, KT has resisted innovations during the last 50 years. Recently, robot-assisted KT (RAKT) has been proposed as an alternative approach to open surgery, especially due to its potential benefits for fragile and immunocompromised recipients. It was not until 2014 that the role of RAKT has found value thanks to the pioneering Vattikuti Urology Institute-Medanta collaboration that conceptualized and developed a new surgical technique for RAKT following the Idea, Development, Exploration, Assessment, Long-term follow-up recommendations for introducing surgical innovations into real-life practice. During the last years, mirroring the Vattikuti-Medanta technique, several centers developed RAKT program worldwide, providing strong evidence about the safety and the feasibility of this procedure. However, the majority of RAKT are still performed in the living donor setting, as an "eligible" procedure, while only a few centers have realized KT through a robotic approach in the challenging scenario of cadaver donation. In addition, despite the spread of minimally-invasive (predominantly robotic) surgery worldwide, many KTs are still performed in an open fashion. Regardless of the type of incision employed by surgeons, open KT may lead to non-negligible risks of wound complications, especially among obese patients. Particularly, the assessment for KT should consider not only the added surgical technical challenges but also the higher risk of postoperative complications. In this context, robotic surgery could offer several benefits, including providing a better exposure of the surgical field and better instrument maneuverability, as well as the possibility to integrate other technological nuances, such as the use of intraoperative fluorescence vascular imaging with indocyanine green to assess the ureteral vascularization before the uretero-vesical anastomosis. Therefore, our review aims to report the more significant experiences regarding RAKT, focusing on the results and future perspectives., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing-remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

Background: Fabry's disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A, and is difficult to diagnose. Although parapelvic cysts (PC) were previously associated with FD, their prevalence and significance are unclear., Methods: The present study aimed to: (i) evaluate, by renal ultrasound, the real prevalence of PC and of their determinants in a multicentre, nationwide cohort of FD patients (n = 173, Study 1) and (ii) ascertain whether a greater accuracy of PC detection improved their identification, in FD patients from a single centre (n = 67, Study 2). In both studies, for each FD patient, an age- and renal function-matched subject was selected for comparison (1:1)., Results: In Study 1, PC were detected in 28.9% of FD subjects and in only 1.1% of control subjects (P < 0.001). The presence of other renal abnormalities did not differ between the groups, nor differences exist in the main demographic and laboratory parameters between the groups. In Study 2, the greater accuracy of ultrasound increased PC prevalence from 29.8% to 43.3% in the same subjects (P < 0.05). In both studies, no correlation was detected between PC and the main demographic, clinical and biochemical parameters, including use of enzyme replacement therapy (P < 0.1, minimum value). Finally, no difference existed between FD patients with and without PC., Conclusions: The present study suggests that the presence of PC in renal patients should alert physicians to consider the diagnosis of FD, primarily in subjects with an unclear family history of renal disease and in the presence of other stigmata of the disease., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Interferon-beta (IFN-beta) is one of the most widely prescribed medications for relapsing-remitting multiple sclerosis (RRMS). IFN-related thrombotic microangiopathy (TMA) is a rare but severe complication, with a fulminant clinical onset and a possibly life-threatening outcome that may occur years after a well-tolerated treatment with IFN. Most patients evolve rapidly to advanced chronic kidney disease and eventually to renal failure., Methods: We performed a retrospective analysis of TMA cases diagnosed and managed in our Nephrology Department from 2010 to 2015, and performed a literature review of IFN-beta-induced TMA., Results: Three cases of TMA among patients treated with IFN-beta were identified who did not show any renal improvement following conventional therapy: IFN withdrawal and plasma exchange (PE, range 8-18) sessions. All of them responded favourably to eculizumab, with progressive clinical and renal improvement, allowing dialysis discontinuation, without recurrence of TMA during a long-term follow-up (range 1-5 years)., Conclusions: TMA is a recognized severe complication in RRMS patients treated with IFN-beta. Withdrawal of IFN and treatment with PE, steroids or rituximab did not improve the poor renal prognosis in our three patients and in all the previously described cases in the literature. In our experience, eculizumab had a strikingly favourable effect on renal recovery, suggesting a role of IFN-beta as a trigger in complement-mediated TMA. Neurologists and nephrologists should be vigilant to this complication to prevent possibly irreversible renal damage.

Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25-Dihydroxyvitamin-D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus-associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2-D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2-D3 circulating levels., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The role of anti-human leukocyte antigens DQ region (HLA-DQ) in transplantation is historically less studied than HLA-DR and HLA class I regions, but several studies are demonstrating that anti HLA-DQ antibodies are among the most frequent anti HLA antibodies that develop after transplantation and can have great influence on the developing of humoral rejection and graft loss. In this article we review the gene structure and nomenclature of the HLA-DQ region, the role of anti HLA-DQ antibodies after and before transplantation and briefly the associations of particular HLA-DQ alleles and other diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Atypical haemolytic uraemic syndrome (aHUS) is a rare disease characterized by thrombocytopenia, microangiopathic haemolytic anaemia and renal impairment. Mutations in genes encoding inhibitors of the alternative pathway of the complement system are involved in ∼50% of the cases. Thrombomodulin (THBD) gene mutations occur in ∼3-5% of the cases. The risk of aHUS recurrence after kidney transplantation depends on the complement abnormality involved. In all three cases of THBD mutation reported to date, aHUS recurred after kidney transplantation (KT) with early graft loss. No data exist about therapeutic approaches before kidney transplantation to reduce the risk of recurrence in patients carrying this mutation. Favourable data on the use of eculizumab have been reported, in terms of plasmatherapy withdrawal and renal function recovery in aHUS recurrence after KT. To our knowledge, this case report presents the first case of successful kidney transplantation in a patient with aHUS due to THBD mutation who was treated with a single plasma-exchange immediately before surgery without recurrence of the disease 12 months after transplantation.

Background: The reliability of kidney biopsy as the sole means for assessing kidneys from extended-criteria donors (ECDs) to be allocated to single or dual transplantation is still a matter of debate., Methods: We compared retrospectively 3 years graft survival and renal function in 44 recipients of a single kidney graft from a marginal donor with good renal function and a Karpinski histological score of ≤ 3 and 56 recipients of a single transplant with a Karpinski score of 4 or 5. The donors' and recipients' characteristics were compared by means of Wilcoxon's rank-sum test and Fisher's exact test, and survival was analysed using the log-rank test and Cox regression survival analysis., Results: The donors with the worse histological scores were slightly younger (68.0 ± 4.74 versus 71.3 ± 4.6 years, P < 0.01) and had a higher glomerular filtration rate (85.8 ± 28.2 versus 76.3 ± 26.53 mL/min, P = 0.013), but there was no difference in serum creatinine levels (0.83 ± 0.24 versus 0.85 ± 0.30 mg/dL, P = 0.381). Three years after transplantation, there was no difference between the two groups in terms of recipient serum creatinine levels (1.94 ± 0.69 versus 1.74 ± 0.49 mg/dL, P = 0.134), estimated glomerular filtration rate (eGFR, 45.6 ± 21.1 versus 51.7 ± 22.0 mL/min, P = 0.331) or the rates of graft loss (27.3 versus 35.7%, P = 0.47), delayed graft function or acute rejection., Conclusions: In our experience, provided the donor has a normal renal function, a difference in the pre-transplant histological score of kidneys from marginal cadaveric donors do not have a significant influence on the outcome 3 years after transplantation. Our findings might represent a basis for designing a randomized controlled trial of using a higher histological score threshold for the DKT allocation of grafts from ECDs with a normal renal function.

Background: There are limited published data concerning the effects of different immunosuppressive regimens on the development of polyomavirus (BKV) viremia. We examined the risk of developing BKV viremia in kidney transplant recipients receiving everolimus (EVR) or mycophenolic acid (MPA) as maintenance therapy., Methods: We observationally analyzed 296 patients who underwent renal transplantation at our center between 2005 and 2010: 58 were treated with EVR and low-dose cyclosporine (LD-CyA) (group 1) and 238 with MPA and standard-dose CyA (group 2). All of the patients received induction therapy with basiliximab and maintenance steroids. BKV viremia (a whole-blood viral load of >850 copies/mL) was measured by means of real-time polymerase chain reaction at least once a month during a 12-month follow-up period., Results: BKV viremia was detected in 57 patients (19%), five (9%) in group 1 and 52 (22%) in group 2. Kaplan-Meier analyses showed that freedom from BKV viremia was significantly more frequent in group 1. The mean time of onset of BKV viremia was about four months after transplantation in both groups. The median viral load was greater in group 2 (12.5 ± 6.1 vs. 2.5 ± 1.8 × 10(4) copies/mL; p = 0.01). After the onset of BKV viremia, graft function significantly declined in group 2: 11 patients developed polyomavirus-associated nephropathy (PVAN) and four presumptive PVAN; nine experienced an acute rejection after the discontinuation of MPA, and 11 (21%) lost their graft. There was no graft loss in group 1., Conclusion: These findings suggest that in comparison with MPA and Cya, an EVR and LD-CyA regimen lowers the risk of BKV viremia after kidney transplantation and favorably alters outcomes., (© 2013 John Wiley & Sons A/S.)

We report the case of a 50-year-old woman who was admitted to the hospital for acute abdominal pain with nephrotic proteinuria, rapidly progressive renal failure, and moderate anemia. Laboratory tests showed mild Bence Jones (λ) proteinuria with negative serum immunofixation and a mild increase in λ free light chains. A bone marrow biopsy and a fat tissue aspirate showed multiple myeloma and amyloidosis. Because of the end-stage renal disease, the patient began regular dialysis treatment and was started on bortezomib 1.3 mg/m2 plus dexamethasone 40 mg on days 1, 4, 8 and 11 of 21-day cycles. Ten days later she complained of a new episode of abdominal pain with jaundice. A CT scan and an MRI scan ruled out all secondary causes of cholangitis including cancer. Acute intrahepatic cholestasis due to amyloid deposition was then hypothesized. After 4 well tolerated cycles of bortezomib and dexamethasone, blood tests showed a complete hematological response with full reversal of cholestasis. After three months, a new episode of abdominal pain occurred and this time the patient was operated on and found to have an intestinal volvulus. Because of the jaundice, a transjugular liver biopsy was performed showing no evidence of amyloid deposits. Two months later the patient died of septic shock. Although no autopsy was performed and the ultimate cause of the cholestasis could not be ascertained, amyloidosis remains the major culprit in this unfortunate case.

Background: Skin cancer (SC) is the most frequent malignancy after renal transplantation (RT), especially squamous and basal cell carcinoma. The observation that angiotensin II is a potent angiogenic and growth factor raises the possibility that blocking its effects could reduce the incidence of skin cancer., Objectives: To evaluate the incidence of keratinocyte cancer in RT recipients, the timing of occurrence of the skin events after RT; to compare the incidence of SC in our RT recipients and in RT patients on angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers therapy (ARBs) and their combination. Risk factors were also evaluated., Results: During follow up, 52 of 565 patients (9.2%), 38 males 14 females, developed SC at a median time of 59 months (range 29 - 74) after RT. 12 of 52 patients (23%) with SC were on ACEi, ARBs therapy or their combination. The incidence was significantly lower in user patients compared to non user (5.6% and 11.4% respectively). BCC was the most frequent type of keratinocyte cancer in non users and in users. No association with incidence of BCC or SCC was observed for other classes of antihypertensive drugs (calcium antagonists, beta-blockers, alpha-blockers)., Conclusion: This study confirms that RT patients are at high risk of SC. The use of ACEi or ARBs is associated with an approximately two-fold reduced risk of Keratinocyte cancers compared to non users in RT recipients. We did not observe an association between the incidence of SC and the use of other classes of antihypertensive drugs. Any chemoprotective effect of these agents may reflect inhibition of the growth factor activity of angiotensin II. Use of ACEi or ARBs, when this is possible, should be considered in RT patients with multiple risk factors.