Circulating "Neutrophils extra-cellular traps" during the early post-renal transplant period and correlation with graft dysfunction and rejection.

BACKGROUND: Neutrophil extracellular traps (NETs) have a role in infection, autoimmunity, autoinflammation, thrombosis, ischemia-reperfusion injury (IRI), epithelial-mesenchymal transition, vasculitis, and metabolic diseases. However, its role in early graft injury and graft outcome has not been elucidated till now. We evaluated the circulating NETs during early post-transplant periods and their correlation with graft outcome and IRI. METHODS: Prospectively, thirty kidney transplants recipient (KTR) were recruited and grouped into non-dysfunction (Group-A) and dysfunction groups (Group-B). Serum levels of circulating NETs were estimated by measuring myeloperoxidase-DNA complex at three-time points: pre-transplant, 8 h post-transplant, and 18 h post-transplant; and correlated with early graft outcome. Malondialdehyde (MDA), a marker of oxidative stress or IRI, was also measured to assess its relation with NETs and early graft outcome. RESULTS: Circulating NETs were significantly increased in both non-dysfunctional [Median OD: 0.11 (0.01-0.19) to 0.51 (0.22-0.91); p = 0.001] and dysfunctional [Median OD: 0.16 (0.12-0.27) to 0.38 (0.19-0.68); p = 0.047] KTR during first 8 h of transplant followed by fall at 18 h post-transplant [0.25 (0.18-0.72) and 0.35 (0.26-0.36) respectively]; however, no significant difference were observed between two groups at any time points. Isolated biopsy-proven graft rejection KTR also had higher circulating NETs during the early post-transplant period [Median OD: 0.16 (0.13-0.31) to 0.38 (0.28-1.5); p > 0.05] but no significant difference compared to non-dysfunctional KTR. MDA also displayed similar trends with an early significant rise [9.30 (7.74-12.56) µM to 17.37 (9.11-22.25) µM; p = 0.03 in group-A, and 8.7 (6.04-10.30) µM to 14.66 (13.39-21.63) µM; p = 0.01in group-B] followed by fall at 18 h in both groups [10.21 (7.64-13.90) µM and 11.11 (9.15-17.54) µM respectively]. Despite similar trends of both NETs and MDA, there was no significant correlation between these; however, creatinine exhibits a significant inverse correlation with NETs and MDA both. CONCLUSION: Circulating NETs are significantly increased during the early post-transplant period in KTR irrespective of early graft outcome. Similar dynamics of MDA indicate that the early rise of NETs might be a part of IRI. However, molecular studies with large sample sizes and longer follow up are required to reach more defined conclusions.

Application of Ex Vivo Normothermic Machine Perfusion in Deceased Donors With Acute Kidney Injury With Successful Renal Transplantation: A Preliminary Experience.

Ex vivo normothermic machine perfusion (NMP) has improved organ preservation and viability assessment among heart, liver, and lung transplantation. However, literature regarding the application of NMP in human clinical kidney transplantation remains limited. Numerous kidneys, especially from donors with stage 3 acute kidney injury (AKI), are not utilized concerning the high rate of delayed graft function (DGF) and primary nonfunction. The present study investigated the impact of NMP (135-150 min) on short-term outcomes after kidney transplantation from deceased donors with AKI. Methods: Graft outcomes of NMP kidneys were compared with contralateral kidneys stored in static cold storage (SCS) from the same donor with AKI during December 2019-June 2021. The study's primary aim is to assess the safety and feasibility of NMP in deceased donors with AKI. The primary outcome was DGF. Secondary outcomes were duration of DGF, biopsy-proven rejection, postoperative intrarenal resistive index, postoperative infections, hospital stay duration, primary nonfunction, and kidney function estimated glomerular filtrate rate at discharge, 3 mo, and 1 y. Results: Five pairs of AKI kidneys (NMP versus SCS) were included in the final analysis. The results show no statistically significant differences in clinical outcomes between NMP versus SCS kidneys; however, NMP kidneys demonstrated slightly improved estimated glomerular filtrate rate at 3 mo (59.8 ± 5.93 [59] versus 75.20 ± 14.94 [74]) mL/min/1.73 m2 (P < 0.065) and at the last follow-up (12-29 mo) (72.80 ± 10.71 [75]) versus (94 ± 22.67 [82]) mL/min/1.73 m2 (P < 0.059) as compared with SCS kidneys. A higher proportion of NMP kidneys had normal intrarenal resistive index (0.5-0.7) and mild acute tubular injury on protocol biopsy, suggesting NMP is safe and feasible in deceased donors with acute kidney injury. Conclusions: NMPs of AKI donor kidneys are safe and feasible. A larger cohort is required to explore the reconditioning effect of NMP on AKI kidneys.

A Multicenter Cohort Study From India of 75 Kidney Transplants in Recipients Recovered After COVID-19.

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.

Poor allograft outcome in Indian patients with post-transplant C3 glomerulopathy.

BACKGROUND: Complement 3 glomerulopathy (C3G) results from dysfunction of the alternative complement pathway (ACP). No data are available on post-transplant C3G in South Asia. METHODS: In this study, renal allograft biopsies of C3G patients performed from 2012 to 2017 were analysed for ACP functional assay (APFA), serum complement levels, complement factor H (CFH), complement factor B (CFB) and autoantibodies to CFH and CFB. Limited genetic screening for CFH/CFHR5 genes was carried out. All study patients were also followed up. RESULTS: A total of 21 cases of C3G were included, of which 11 had native C3G disease (that is, recurrent C3G). Of these 11 recurrent cases, 7 presented with allograft dysfunction and 4 with proteinuria and renal dysfunction. Early post-transplant recurrence (<1 month) was noted in six patients, whereas recurrence in five patients occurred within 8-17 months of transplant. Biopsies showed mild focal mesangial expansion with or without endocapillary proliferation and thrombotic microangiopathy. Rejection was also noted in six patients. APFA/C3 levels were low in all cases. Serum CFH levels were low [dense deposit disease (DDD), 44%; C3 glomerulonephritis (C3GN), 25%], whereas CFB levels were normal. Autoantibodies to CFH, CFB and C3 nephritic factor were present in 11, 0 and 44% of DDD cases, respectively, and in 17, 17 and 33% of C3GN cases, respectively. Genetic analysis revealed only non-pathogenic CFH gene variants (93%). No novel mutation was found. At follow-up (140 months), stable graft was noted in 28% of cases, progressive renal failure in 19%, graft loss in 34%, and 19% of patients died. CONCLUSION: Post-transplant C3G can present with graft dysfunction and/or proteinuria. Subtle histological findings demand careful interpretation of immunofluorescence results. Autoantibodies to complement pathway regulatory proteins are common, and no novel mutation has been found from limited genetic workup. Clinical outcome is poor.

Esophageal tuberculosis with coexisting opportunistic infections in a renal allograft transplant recipient.

We report a renal allograft transplant recipient with esophageal tuberculosis (TB) coinfected with herpes simplex virus (HSV) and Candida. The patient presented with oropharyngeal candidiasis and was started on fluconazole. Upper gastrointestinal endoscopy showed whitish patches with mucosal ulcers in the esophagus. Histopathological examination confirmed TB and HSV infection. The patient recovered after antiviral, antifungal, and anti-tubercular therapy with reduction in immunosuppression. In a TB-endemic zone, TB can coexist with opportunistic infections in an immunocompromised host.