Scedosporium Infection in Recipients of Kidney Transplants from Deceased Near-Drowning Donor.

Scedosporium aurianticum infection developed in 2 recipients of kidney transplants in India, acquired from the same deceased near-drowning donor. Given the substantial risk for death associated with Scedosporium infection among solid-organ transplant recipients, safety protocols for organ transplantation from nearly drowned donors should be thoroughly revaluated and refined.

Outcomes after lung resection in renal transplant patients with pulmonary mucormycosis.

BACKGROUND: Pulmonary mucormycosis has been associated with high mortality (reported up to 100%) in renal transplant recipients. METHODS: This was a retrospective analysis of renal transplant patients with pulmonary mucormycosis between April 2014 and March 2020, who underwent surgical resection of the affected lung along with liposomal amphotericin therapy. Patients with lower respiratory illness features underwent chest X-ray, high-resolution computed tomography of the chest, and those with suspicious findings underwent analysis of bronchioloalveolar fluid and transbronchial lung biopsy. Patients with histological or microbiological evidence of mucormycosis were started on liposomal Amphotericin B. Tacrolimus and mycophenolate mofetil were stopped at the time of diagnosis. RESULT: Ten patients underwent combined management, while five patients were managed medically. At last follow up, seven out of ten patients (70%) who underwent combined management and two of the five patients (40%) who were managed medically, had a mean survival of 28.86 months (sd = 15.71, median = 25) and 14.17 months (sd = 12.21, median = 18), respectively, post-diagnosis of pulmonary mucormycosis. CONCLUSION: Surgical resection combined with antifungals in the perioperative period and decreased immunosuppression may improve the outcomes in renal transplant patients with pulmonary mucormycosis.

Risk factors for mortality in kidney transplant recipients with COVID-19: a single centre experience and case-control study.

BACKGROUND: COVID-19 infection is considered to cause high mortality in kidney transplant recipients (KTR). Old age, comorbidities and acute kidney injury are known risk factors for increased mortality in KTR. Nevertheless, mortality rates have varied across different regions. Differences in age, comorbidities and varying standards of care across geographies may explain some variations. However, it is still unclear whether post-transplant duration, induction therapy, antirejection therapy and co-infections contribute to increased mortality in KTR with COVID-19. The present study assessed risk factors in a large cohort from India. METHODS: A matched case-control study was performed to analyze risk factors for death in KTR (N = 218) diagnosed with COVID-19 between April 2020 to July 2021 at the study centre. Cases were KTR who died (non-survivors, N = 30), whereas those who survived were taken as controls (survivors, N = 188). RESULTS: A high death-to-case ratio of 13.8% was observed amongst study group KTR infected with COVID-19. There was a high incidence (12.4%) of co-infections, with cytomegalovirus being the most common co-infection among non-survivors. Diarrhea, co-infection, high oxygen requirement, and need for mechanical ventilation were significantly associated with mortality on regression analyses. Antirejection therapy, lymphopenia and requirement for renal replacement therapy were associated with worse outcomes. CONCLUSIONS: The mortality was much higher in KTR who required mechanical ventilation and had co-infections. Mortality did not vary with the type of transplant, post-transplant duration and usage of depletion induction therapy. An aggressive approach has to be taken for an early diagnosis and therapeutic intervention of associated infections.

Successful re-transplantation in patient with recurrent parvovirus B19 pure red cell aplasia.

Impaired cell-mediated, as well as antibody-mediated immunity predisposes a renal transplant recipient to a wide variety of atypical infection. With an increasing number of re-transplant, the balance between immunosuppression and the risk of recurrent disease poses a clinical and therapeutic challenge. Here, we report a successful re-transplantation in a case of parvovirus B19 infection leading to anaemia and collapsing glomerulopathy in the allograft managed with intravenous immunoglobulin (IVIG) and reduction of immunosuppression. This case emphasizes re-consideration to renal transplant after clearance of the virus in a previous renal allograft lost to PVB19 infection.

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.

Evaluation of oxidant and antioxidant status in living donor renal allograft transplant recipients.

The objective of this study was to evaluate the oxidant and antioxidant status in living donor renal allograft transplant recipients. Ninety-two renal transplant recipients with mean age of 34.75 ± 11.22 years were included in the present study. Venous samples of the recipients were drawn: before the transplant (baseline), 5 min after reperfusion, and 2 weeks after transplant. Samples were processed for the measurement of markers of oxidant and antioxidant status viz. malondialdehyde, catalase, glutathione peroxidase, reduced glutathione, ascorbic acid, and total antioxidant system. The mean baseline levels of reduced glutathione, ascorbic acid, and total antioxidant system were 1.61 ± 0.84 mg/g hemoglobin, 3.64 ± 1.49 mg/dL, and 1.42 ± 0.14 mmol/L which decreased at 5 min after reperfusion to 1.32 ± 0.72 (p = 0.010), 2.96 ± 1.25 (p = 0.002), and 1.36 ± 0.12 (p = 0.042), respectively. The malondialdehyde levels increased from a baseline value of 3.11 ± 1.02 µmol/mL to 3.32 ± 1.09 at 5 min after reperfusion (p = 0.344) and 4.01 ± 1.21 (p = 0.000) at 2 weeks. Glutathione peroxidase level decreased from 68.59 ± 32.79 units/g hemoglobin (baseline) to 63.65 ± 32.92 at 5 min after reperfusion (p = 0.530) and increased significantly at 2 weeks to 86.38 ± 37.18 (p = 0.00). There was no significant change in the catalase level. In living donor renal transplantation, oxidative stress starts after reperfusion and is reflected by fall in antioxidant factors and enzymes in the early period. Over the next 2 weeks, there is increased oxidative stress and simultaneous strengthening of antioxidant system which is implied by increase in malondialdehyde and improvement in the markers of antioxidant status.

Simultaneous Liver and Kidney Transplantation in a Patient With Telomere Biology Disorder: A Case Study.

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.

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.

Pediatric Renal Transplant With Dilated Cardiomyopathy: A Stepwise Hemodynamic Management-A Case Report.

Here we have described the anesthetic management of a 10-year-old patient having uremia-induced dilated cardiomyopathy for a living-related adult to pediatric renal transplant. Maintaining optimal hemodynamics, especially during the reperfusion phase, is crucial for maintaining graft perfusion. However, dilated cardiomyopathy limits indiscriminate fluid administration as it may cause congestive heart failure and pulmonary edema. We have described the fluid therapy algorithm based on the plethysmography variability index and velocity time integral at the left ventricular outflow tract, which was able to limit excessive fluid administration and maintain adequate perfusion pressures.

Outcome of tibio-saphanous arteriovenous fistula in patients with failed upper extremity dialysis access: A report of two cases.

Arteriovenous fistulas (AVF) are the preferred access for hemodialysis in patient with end stage renal disease. Usually, distal vessels of upper limb are preferred. There are situations in which the upper limb cannot be a site for AVFs or graft as in cases of bilateral central venous stenosis or with exhausted sites in upper limb. In these cases, lower limb AVF can be considered. Tibial-saphanous (ankle) fistula should be the preferred site over femoral AVF/graft following the principle of distal to proximal. Also, femoral AVFs are associated with more ischemic and infective complications. The present report describes successful hemodialysis in two patients with tibial-saphanous fistula a site rarely used as an option for HD access. Hemodialysis for over 1 year in one patient and 6 months in the other portrays the success of this approach.

Impact of a trained vascular access coordinator on a vascular access program in India.

BACKGROUND: Native AV fistulas are the ideal access for hemodialysis but require monitoring and multiple interventions in some patients to keep them functioning. The aim of the study was to assess the impact of the appointment of a trained vascular access coordinator (VAC) for fistula monitoring, on the evolution of the vascular access program at our institute. METHOD: Data was retrieved from the departmental database for the baseline year 2014 and compared with the data from 2018. Initial review showed that appointment of the VAC in 2015 resulted in a steady increase in the number of AV fistula interventions over 2 years to a plateau in 2018 which was chosen as the comparison year. The number of AVF's created, number of salvage procedures performed, and follow-up data were compared. Other parameters like number of operation theatre hours, surgeons, and nursing staff remained constant during this period. RESULT: Total numbers of AVFs increased from 511 to 713 (39.3%). The number of follow-up visits to surgeons reduced from an average of 4-0.25 visits per patient during this period. Follow up Doppler examinations increased from 761 to 1296 (70%) indicating improved follow up. The salvage procedures increased from 44 to 161 (272%) with early detection of fistula dysfunction. Primary and secondary patency rates of 86% and 92% at 3 months could be achieved whereas limited follow-up data was available for 2014. CONCLUSION: Appointment of trained VAC increased the number of vascular access procedures, improved follow-up care, and led to early detection and intervention for access dysfunction while reducing the workload of surgeons.

First case of subcutaneous infection by Talaromyces marneffei in a renal transplant recipient from India and review of literature.

Talaromyces marneffei is one of the endemic mycoses prevalent in South-East Asian region. The infection, which was once considered to be opportunistic infection in HIV-positive patients, is establishing foothold in transplant and immunocompetent population. We report a case of a 41-year-old post-renal transplant female with a travel history to Assam two years back presenting with a subcutaneous lesion on right side of scalp associated with pain and blurring of vision in right eye. Fine-needle aspiration from the scalp lesion showed yeast cells with transverse septation in cytological examination and culture grew Talaromyces marneffei, which was confirmed by sequencing of ITS region. Patient was successfully managed with oral itraconazole 200 mg twice daily for ten months without subsequent recurrence. To our knowledge, this is the first case of subcutaneous infection by T. marneffei in a renal transplant recipient from India.

Mesenchymal Stromal Cells Mediate Clinically Unpromising but Favourable Immune Responses in Kidney Transplant Patients.

BACKGROUND: Allograft rejection postkidney transplantation (KTx) is a major clinical challenge despite increased access to a healthcare system and improvement in immunosuppressive (IS) drugs. In recent years, mesenchymal stromal cells (MSCs) have aroused considerable interest in field of transplantation due to their immunomodulatory and regenerative properties. This study was aimed at investigating safety, feasibility, and immunological effects of autologous MSCs (auto-MSCs) and allogeneic MSCs (allo-MSCs) as a complement to IS drug therapy in KTx patients. METHODS: 10 patients undergoing KTx with a living-related donor were analysed along with 5 patients in the control group. Patients were given auto-MSCs or allo-MSCs at two time points, i.e., one day before transplant (D-0) and 30 days after transplant (D-30) at the rate of 1.0-1.5 × 106 MSCs per kg body weight in addition to immunosuppressants. Patients were followed up for 2 years, and 29 immunologically relevant lymphocyte subsets and 8 cytokines and important biomarkers were analysed at all time points. RESULTS: Patients displayed no signs of discomfort or dose-related toxicities in response to MSC infusion. Flow cytometric analysis revealed an increase in B regulatory lymphocyte populations and nonconventional T regulatory cells and a decrease in T effector lymphocyte proportions in auto-MSC-infused patients. No such favourable immune responses were observed in all MSC-infused patients. CONCLUSION: This study provides evidence that auto-MSCs are safe and well tolerated. This is the first ever report to compare autologous and allogeneic MSC infusion in KTx patients. Importantly, our data demonstrated that MSC-induced immune responses in patients did not completely correlate with clinical outcomes. Our findings add to the current perspective of using MSCs in KTx and explore possibilities through which donor/recipient chimerism can be achieved to induce immune tolerance in KTx patients.

Challenges in Brain-Death Certification in India.

The determination of Brain Death (BD)/Death by neurological criteria (DNC) is now widely accepted among various international societies following the World Brain Death project recommendation. As per the World Brain Death project, ancillary testing should be performed when standard brain-death examination components are inconclusive or cannot be performed. BD was defined legally in 1994 under the Transplantation of Human Organs Act (THOA). However, even after 27 years of the formulated law, there are no guidelines in the THOA regarding the determination of BD using ancillary tests. The present brief report describes two instances where ancillary tests like four-vessel angiography and transcranial doppler-aided brain-death certification were done. It is the first available literature from our country where ancillary tests aided in confirmation of BD when the standard clinical components of DNC could not be performed.

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.

Impact of COVID-19-associated Mucormycosis in Kidney Transplant Recipients: A Multicenter Cohort Study.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is a recently emerging entity. There is a lack of reports of CAM in organ transplant recipients. METHODS: We conducted a multicenter (n = 18) retrospective research in India during November 2020 to July 2021. The purpose of this study was to explore the clinical spectrum, outcome and risk factors for mortality of CAM in kidney transplant recipients (KTRs). RESULTS: The incidence of CAM was 4.4% (61/1382 COVID-19-positive KTRs) with 26.2% mortality. The median age of the cohort was 45 (38-54) y. Twenty (32%) were not hospitalized and 14 (22.9%) were on room air during COVID-19. The proportion of postdischarge CAM was 59.1%, while concurrent CAM was reported in 40.9%. The presentation of CAM was 91.8% rhino-orbital-cerebral mucormycosis and 8.2% pulmonary with 19.6% and 100% mortality, respectively. In the univariable analysis, older age, obesity, difficulty of breathing, high-flow oxygen requirement, and delay in starting therapy were significantly associated with mortality. In the multivariable logistic regression analysis, patients requiring high-flow oxygen therapy [odds ratio (95% confidence interval) = 9.3 (1.6-51); P = 0.01] and obesity [odds ratio (95% confidence interval) = 5.2 (1-28); P = 0.05] was associated with mortality. The median follow-up of the study was 60 (35-60) d. CONCLUSIONS: We describe the largest case series of CAM in KTRs. Morality in pulmonary CAM is extremely high. Severe COVID-19 pose extra risk for the development of CAM and associated mortality. Our report will help in better understanding the conundrum and management of CAM.

Xanthogranulomatous cholecystitis: case series in a rural area, clinicopathological study and review of literature.

Xanthogranulomatous cholecystitis is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. We are reporting two of such rare cases in female patients attending our institute. In both patients xanthogranulomatous cholecystitis was diagnosed on histopathology.

Deceased Donor Renal Transplantation: A Single Center Experience.

INTRODUCTION: Deceased donor kidney transplant are still not common across India. This study was done to assess various measures taken at a single center level to increase organ donation rate and to analyse the outcomes of transplants performed from these donors. METHODS: All deceased donor renal transplants performed from November 2011 to February 2017 were analysed for patient and death censored graft survival, rate of delayed graft function, rate of rejection and mortality. Kaplan Meir analysis for Survival Curves was used. RESULTS: Organ donation rate at our center improved from one donation every alternate year in 2004 to a peak of 44 donations in 2017. Patient survival was 93.42%, 89.44%, 85.53%, and death censored graft survival was 94.07%, 88.21%, and 82.86% at 1, 2 and 3 years respectively. Mean duration of hemodialysis pre transplantation was 34.6 ± 27.43 months. CONCLUSIONS: This study has shown that steps taken at a single center level alone can also significantly improve organ donation rates. Employment of dedicated professionals including transplant surgeons and coordinators, developing a protocol-based approach for referral, and early counseling in triage along with regular audits can help to establish deceased donor program with acceptable outcomes elsewhere in the country.

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.