De novo collapsing glomerulopathy after kidney transplantation: Description of two cases.

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.

Threatening drug-drug interaction in a kidney transplant patient with coronavirus disease 2019 (COVID-19).

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.

Development of a robot-assisted kidney transplantation programme from deceased donors in a referral academic centre: technical nuances and preliminary results.

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.

Good outcomes with cyclosporine very low exposure with everolimus high exposure in renal transplant patients.

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.

High platelet turnover and reactivity in renal transplant recipients patients.

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.

Post-transplant proteinuria associated with everolimus: Definition of main features with proteomics.

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), ß2 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.