Search

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.)

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy., (© 2020 Wiley Periodicals LLC.)

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.

Objective: To report the development of the first robot-assisted kidney transplantation (RAKT) programme from deceased donors, examining technical feasibility and early perioperative and functional outcomes at a referral academic centre., Patients and Methods: A RAKT programme was developed in 2016 at our institution following structured modular training. Specific inclusion/exclusion criteria for both living and deceased donors were set. Data from patients undergoing RAKT from January 2017 to April 2018 were prospectively collected in an a priori developed web-based data set. RAKT followed the principles of the Vattikuti Urology Institute-Medanta technique, with specific technical modifications based on clinical recipient characteristics, as well as surgeon's skills and preference during the learning curve. Technical feasibility of RAKT from deceased donors and evaluation of perioperative and early functional outcomes were the main study endpoints., Results: In all, 17 RAKTs were performed during the study period. Of these, six were from living donors and 11 were from deceased donors. All RAKTs were successfully completed without need of conversion. The median (interquartile range [IQR]) console time was 190 (160-220) min and the median (IQR) estimated blood loss was 120 (110-140) mL. The median times to complete venous, arterial and uretero-vesical anastomoses were 21, 22 and 21 min, respectively. The median (IQR) length of stay was 8 (6-12) days. At a median (IQR) follow-up of 8 (6-11) months, five (30%) complications were recorded. Of these, four (24%) were minor (Clavien-Dindo Grade I-II) and one major (Clavien-Dindo Grade IIIb, requiring graft nephrectomy). Overall, two patients were still on dialysis at last follow-up. A significant improvement in graft function was recorded progressively at all postoperative time points., Conclusion: Our preliminary experience outlines that: (i) the development of a RAKT programme is feasible in centres experienced in robotic surgery and open kidney transplantation; (ii) RAKT from deceased donors is feasible from both a technical and logistical perspective; and (iii) RAKT from deceased donors appears to achieve favourable early postoperative and functional outcomes. Larger studies with longer follow-up are needed to confirm these findings and compare the outcomes of RAKT from deceased donors with those from living donors., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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 © 2012 Elsevier Inc. All rights reserved.)

Introduction: The aim of the study was to compare efficacy of cyclosporine (CsA) very low exposure with everolimus high exposure, with respect to CsA standard exposure with enteric-coated mycophenolate sodium (EC-MPS) therapy., Methods: In a randomized, prospective, single-center, open-label study, patients were enrolled to receive either everolimus (C0 (trough level) 8-12 ng/mL) + CsA (C2 (CsA level 2 hours after drug administration) 250-300 ng/mL) + steroids, or EC-MPS (1,440 mg/day) + CsA (C2 500-700 ng/mL) + steroids. Fifty-six patients were enrolled in the everolimus group, 50 in the EC-MPS group. Efficacy was evaluated at 3 and 12 months., Results: Characteristics of groups were similar. Biopsy-proven acute rejection (BPAR) rates were similar in both groups (everolimus 18.8% vs. EC-MPS 18.2%). Everolimus patients had a lower incidence of delayed graft function (DGF) than EC-MPS patients (22.6% vs. 40.9%; p<0.05; relative risk [RR] = 0.65). One-year graft survival was 95% in the everolimus group and 88% in the EC-MPS group (p=NS). CsA dose at 1 year was lower in the everolimus group (1.52 ± 0.67 vs. 2.55 ± 0.79 mg/kg; p<0.0001). Estimated glomerular filtration rate (eGFR; Cockcroft-Gault) was higher in the everolimus group (81.64 ± 32.67 vs. 62.62 ± 22.81 ml/min; p<0.001). Systolic blood pressure was lower in the everolimus group (124.9 ± 14.64 mm Hg vs. 131.1 ± 13.23 mm Hg; p=0.03). Hemoglobin blood levels were slightly lower in the everolimus group (12.62 ± 1.42 vs. 13.01 ± 1.3 g/L; p=NS; for anemia, RR=1.302). Serum cholesterol was similar in both groups (everolimus 219.1 ± 47.20 vs. EC-MPS 207.2 ± 38.8 mg/dL; p=NS), but everolimus patients used more statins (RR=1.49). Twenty-four-hour proteinuria was higher in the everolimus group (519.7 ± 77.31 vs. 296.7 ± 33.42 mg/24 hours; p=0.01)., Conclusions: Everolimus regimen compared with EC-MPS regimen is associated with lower incidence of DGF, slightly better 1-year graft survival rate, a significantly higher GFR and lower systolic blood pressure.

We reviewed available, particularly epidemiological data regarding transplantation of organs from donors positive for hepatitis B core antibodies (HBcAb) to evaluate the possibility of transmitting the disease. For nonhepatic organs, the risk is low: higher for lung but lower for kidneys and heart, according to the quantity of lymphoid tissue. The use of such organs is increasing owing to the worldwide organ shortage. Unfortunately, even if the use of HBcAb-positive donors does not seem to affect patient or graft survival, the United Network for Organ Sharing and United States Renal Data System registries do not have data on hepatitis B incidence after transplantation. Cohort data suggest that the use of such donors is safe if one follows suggested guidelines. In particular, recipients with no evidence of HBsAb should receive prophylaxis with either lamivudine or HB immunoglobulin. Our data show a 15%-20% incidence of HBcAb-positive donors, as in other European countries. The 1-year graft outcomes are good, with a 3% seroconversion rate to HB surface antigen., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Renal transplant recipients (RTRs) patients are at increased risk of cardiovascular morbidity and mortality. We aimed this study to assess reticulated platelets (RP), platelet reactivity and von Willebrand factor (vWF) levels in RTRs patients. In 150 RTRs patients [84 (56%) not on acetylsalicylic acid (ASA) treatment, group A; 66 (44%) on ASA 100 mg treatment, group B] and in 60 healthy control subjects, RP were measured by a Sysmex XE-2100 and were expressed as the percentage of RP of the total optical platelet count (immature platelet fraction; IPF), as the percentage of RP highly fluorescent (H-IPF) and as the absolute number of RP (IPF#). Platelet function was assessed by optical aggregometry (PA) induced by 1 mmol arachidonic acid (AA-PA), 2 and 10 μM ADP (ADP2-PA and ADP10-PA) and 2 μg/ml collagen (Coll-PA). vWF levels were measured by using a miniVidas analyser. Group A and group B showed significant higher values of RP than controls. At a multiple linear regression analysis IPF and IPF# were significantly and positively related to collagen-PA. By analysing group B according to residual platelet reactivity (RPR), we observed a significant higher number of RP among patients with RPR by collagen. Moreover at a multiple logistic regression analysis, IPF# significantly affected the risk of having a RPR by collagen. With regard to vWF, RTRs patients showed higher levels than control subjects. We documented a higher platelet turn-over in both groups of RTRs patients and increased platelet reactivity in RTRs patients not on ASA therapy than controls.

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 possible 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 micromol/L vs 21.2 +/- 11 micromol/L; P < .005. Hyper-Hcy, defined as Hcy levels >15 micromol/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 (c) 2010. Published by Elsevier Inc.)

Preemptive kidney transplantation is performed before the initiation of chronic dialysis. Preemptive transplantation is the best treatment modality for patients reaching end-stage renal disease. The Tuscany region has experienced, in the last years, a marked increase in donation rate. Starting from 2006, the first Italian cadaveric preemptive transplant program was activated. The aim of our study was to investigate the characteristics and preliminary results of this program. Among 163 patients entered on to the waiting list for renal transplantation from October 2006 to October 2008, 120 (73.6%) were on dialysis for 21.3 +/- 17.8 months, whereas 43 patients (26.4%) had not yet been on dialysis (preemptive). Eighty two patients (50.3%) resided in Tuscany and 81 (49.7) outside Tuscany; 36.6% of Tuscany patients and 16% of extraregional patients (P = .003) were listed as preemptive. Fifty-eight of 163 (35.6%) patients were transplanted during the period after a mean waiting time of 10.3 +/- 6.4 months. The estimated overall man waiting time was 17.5 months (confidence interval (CI) = 15.8-19.2). Upon Cox multivariate analysis, the probability of transplantation was similar for preemptive and dialysed patients (relative risk [RR] 1.02, P = NS). According to local allocation policy, only residents of Tuscany showed a significant advantage in both groups (RR = 0.43, CI = 0.24-0.75, P = .003). Two-year graft and patients survivals were similar, but delayed graft function was lower in the preemptive group (13% vs 42%, P = .007). The 1-year serum creatinine was 1.56 +/- 0.43 in the preemptive group and 1.68 +/- 0.92 in the dialysis group (P = NS). No differences were observed concerning rejection rate. The preemptive listing rate for cadaveric renal transplantation was more than 35% for Tuscany patients.

Anti-mTOR may induce proteinuria when utilized after renal transplantation. Little is known about the pathogenesis and composition of proteinuria. To clarify this unresolved aspect, we analyzed urinary protein composition utilizing an integrated proteomics approach, including quantitative assays, 2-dimensional electrophoresis, MALDI-TOF, and Western blots among 48 renal transplant recipients treated with everolimus (EVL; n = 31) or enteric-coated mycophenolic acid (EC-MPA; n = 17). High (>3 g/d) or intermediate levels of proteinuria (1-3 g) developed in 12 EVL patients (39%) compared with 4 subjects (23%) in the EC-MPA group. Proteinuria, which started during the first 2 days after EVL, tended to reduce during the follow-up. Quantitative proteomics showed an increase in low molecular proteins beta2 microglobulin (P < .001) and alpha1 microglobulin (P < .025). Qualitative proteomics showed a marked increase among all urinary components in EVL and EC-MPA patients. Major changes involved typical components of glomerular damage: albumin, Zn-alpha1 glycoprotein, alpha2HS glycoprotein, and leucine-rich alpha2 glycoprotein. In addition, we observed specific biomarkers for EVL: clusters of alpha1-antitrypsin fragments and monoclonal lambda chains. In conclusion, EVL induced proteinuria of a mixed glomerular and tubular origin that correlated with the start of treatment and reached nephrotic ranges in few cases. The specific urinary markers may reflect renal alterations related to the transplant or specific alterations associated with the drug.

Little is known on both the composition and mechanism(s) of proteinuria associated with the use of mTOR inhibitors, in particular of Everolimus (E). We characterized urinary proteins utilizing an integrated proteomics approach (quantitative essays, 2-DE, MALDI-TOF, Western blot) in 48 renal transplant recipients who were alternatively treated with E (n = 31) or with enteric coated mycophenolic acid (EC-MPA) (n = 17). Twelve E patients (39%) developed high (>3 g/day) or intermediate proteinuria (1-3 g) compared to four (23%) of the EC-MPA group. Urinary proteins (p<0.001), β2 microglobulin (p<0.001) and α1microglobulin (p<0.025) were higher in E than in EC-MPA, appeared more rapidly and were inversely correlated with the day of treatment. Proteomics showed a marked increase of all urinary components in E and EC-MPA patients, major changes involving typical components of glomerular damage (albumin, α1-Zn glycoprotein, α2HS glycoprotein, leucin-richα2-glycoprotein) and specific bio-markers for E (clusters of α1-antitrypsin fragments and monoclonal λ chains). Finally, inter-α-trypsin-inhibitor heavy chain H4 precursor was decreased in E and EC-MPA urine compared to normal urine. In conclusion, E induced massive and generalized proteinuria of mixed glomerular and tubular origin that was correlated with the start of treatment and reached a nephrotic range in few cases. Specific urinary markers reflect renal alterations related to the transplant or specific alterations associated with the drug., (Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

According to a k/DOQI work group, chronic kidney disease (CKD) can be present also in subjects with glomerular filtration rate (GFR) >90 mL/min or a serum creatinine (sCr) below 1.3 mg/dL. The aim of this study was to document the prevalence of clinical or biologic abnormalities among 190 cadaveric renal transplant patients with excellent and stable renal function at 6 months after transplantation as well as 5 years later. The recipients were 82 women and 108 men of mean age at transplantation of 44.56 +/- 11.73 years. All patients were on Neoral-based immunosuppression with at least 5-year follow-up. Mean sCr was 1.18 +/- 0.2 mg/dL. Mean GFR was 78.57 +/- 27.06 mL/min. Systolic blood pressure was >130 mm Hg in 56.6%, although 78.3% of patients were on antihypertensive therapy; 34.3% were anemic; 75.4% had serum cholesterol >200 mg/dL; 62.2% had serum triglyceride levels >170 mg/dL. Serum intact parathyroid hormone >100 pg/mL was observed in 38% of patients and 43% were on vitamin D supplementation, and 11.4% had developed posttransplant diabetes mellitus. With respect to controls, von Willebrand factor was higher in 81.2% (P < .0001; RR = 11); serum homocysteine levels in 75% (P < 0.001; RR = 7.61); PAI-1 in 37.5% (P = .0009; RR = 4). At 5 years posttransplantation we observed an overall improvement in these abnormalities. The vast majority of renal transplant patients with excellent graft function belong to stage 1 of CKD being affected by hypertension, dyslipidemia, anemia, and residual hyperparathyroidism. Markers of endothelial dysfunction were largely abnormal, a condition that could predispose to cardiovascular events.

In recent years Italy has experienced a remarkable increase in organ donation and transplant rates for kidney transplantation. The organ donation rate has placed Italy among the European leaders, but a careful comparative evaluation of Italian and international registries data demonstrates that renal transplantations have not shared the same significant growth. In a decisive way donor characteristics have influenced not only the number of renal transplantations, but also the access to transplant for some age groups. We investigated the probability of transplantation from different age groups using the Kaplan-Meier method and the log-rank test. The 7-year probability of transplant was 72% for the 15 to 45 age group, 85.7% for the 46 to 55 age group, and 88.5% for the over 55 years group (P = .0029). Ethical considerations suggest new approaches of innovative promotion of living donor transplants and a revision of organ allocation criteria.

Chronic allograft dysfunction after renal transplantation can be ascribed to different causes, among which are viral infections. The aim of this work was to show the various ways by which different kinds of viruses affect transplant structure and function. Polyoma virus is an example of viruses directly affecting the kidney because of a specific tropism to the uroepitelial cells. Cytomegalovirus (CMV) has been chosen both because of the frequency of this infection and because CMV (as other viruses) can produce transplant vascular sclerosis. Finally, we describe hepatitis C virus (HCV) because of its capacity to induce renal lesions independently from chronic allograft nephropathy. Indeed HCV is likely to determine immunologically mediated nephritis in the transplanted kidney as well in the native one.

To verify the long-term efficacy and safety of Palmaz stent implantation in the treatment of transplant renal artery stenosis (TRAS), we reviewed the charts of 26 patients affected by TRAS and treated by percutaneous transluminal angioplasty (PTA) followed by permanent insertion of a Palmaz stent. The mean follow-up period was 43.31 +/- 33.6 months. The mean blood pressure fell significantly at 1 month after stenting (118 +/- 8.1 vs 101 +/- 7.8 mmHg; P < .0001); then remained stable. Renal artery blood flow, as determined by Doppler ultrasonography, was reduced from 352.5 +/- 56.5 to 157.3 +/- 53.7 cm/sec at 1 month after stenting (P < .0001). Renal function improved after stenting (serum creatinine 2.2 +/- 1.4 mg/dL preinsertion versus 1.72 +/- 1.05 at 3 years). In conclusion, in cases of severe or recurrent TRAS, stenting of the renal artery has proved to be an effective therapeutic tool. This method, which has low procedure costs and an extremely low complication rate has proved to be safe and to offer the potential of preserving luminal patency, improving the long-term efficacy of percutaneous angioplasty.