CHARACTERISTICS OF PATIENTS WHO RECEIVED BIOLOGICAL TREATMENT AFTER KIDNEY TRANSPLANTATION AND THE INCIDENCE OF SERIOUS INFECTIONS: A MULTICENTER STUDY

BackgroundKidney transplant patients due to both primary kidney involvement of chronic/autoimmune inflammatory diseases and end-stage kidney disease related to amyloidosis are followed up in rheumatology clinics. Biological agents one of the treatment options in kidney transplant recipients with chronic/autoimmune inflammatory disease.ObjectivesHowever, there is insufficient data on the development of infection in kidney transplant recipients who received biological treatment. Herein, we aimed to determine the incidence of serious infections in patients with kidney transplant recipients who are received biological therapy.MethodsKidney transplant recipients who are received biological agents due to rheumatologic disease were included in the study. Patients' demographic features, transplantation data, biological treatment, development of infection and severity of infection were screened retrospectively. Infections that requiring hospitalization were defined as severe infections.ResultsA total of 31 patients were included in the study, 14 (45%) of whom were female and mean age was 41 ±9 years. Twenty-five patients (80%) of them were non-preemptive kidney transplant and mean duration of hemodialysis before the transplantation was 40 ±40 months. Twenty-three patients (74%) had end stage kidney failure due to FMF-amyloidosis(Figure-1-). Seventeen patients (54%) received anakinra, 11 patients (35%) received canakinumab and 3 patients (10%) received etanercept with other immunosuppressive treatment. Mean treatment duration of biological agents was 4.2±2.6 years. Two patients developed solid organ malignancy and one patient developed hematological malignancy after transplantation. Sixteen of the patients (52%) were hospitalized at least once due to infection and 4 patients (13%) died due to infection. The cause of decease in two patients was COVID-19.ConclusionRheumatic diseases are an important cause of end-stage renal disease and definitive treatment is kidney transplantation. Kidney transplant recipients due to rheumatological disease also use biological agents in the post-transplantation period. Kidney transplant recipients have higher risk for the development of infection since they receive immunosuppressive therapy and use of biologic agents may further increase the risk for development infection. Meyer et al reported that infection developed in 54 of 187 solid organ transplant recipients using biological agents.[1] Mean treatment duration of biological agents was 12 months in this study. The incidence of infection was 54% in our study. Mean treatment duration of biological agent was 4.2 year was considered main reason for higher incidence of infection in our study.Reference[1]Meyer F, Weil-Verhoeven D, Prati C, Wendling D, Verhoeven F. Safety of biologic treatments in solid organ transplant recipients: A systematic review. Semin Arthritis Rheum. 2021 Dec;51(6):1263-1273. doi: 10.1016/j.semarthrit.2021.08.013. Epub 2021 Aug 26. Erratum in: Semin Arthritis Rheum. 2022 Aug;55:152015. PMID: 34507811.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

A rare case of central diabetes insipidus unmasked after renal transplantation in a young male

Background: The diagnosis of central Diabetes insipidus (DI) requires intact renal function to manifest polyuria. Therefore, it may not become evident in patients with oliguric or anuric renal failure such as in chronic kidney disease (CKD) or end stage renal disease (ESRD). This might get manifested after renal transplantation, however there are only 5 cases reported so far of Central DI post renal transplantation. Here we report a case of central DI that was unmasked in a patient with CKD after kidney transplantation leading to polyuria. Case Report: RV, 26-year-old male had one episode of febrile illness with hematuria at age of 20 years and was diagnosed IgA nephropathy by renal biopsy following which he recovered completely. Hypertension was detected in Feb 2021, and he has been on Cilnidipine 10 mg OD, Clonidine 0.1 mg TDS, Metoprolol XL 40 mg OD. At age of 25 years, he had covid illness and his kidney function deteriorated to ESRD for which he was started on twice weekly hemodialysis for 8 months and then underwent live donor renal transplantation in October 2021. Two months later, he was admitted for polyuria, polydipsia, and nocturia. After renal transplantation, his urine volume increased to 9-10 L/ d, while it had been less than 500 mL/day before the transplantation. His serum creatinine level improved from 3.2 mg/dL prior to transplant to 0.8 mg/dL after transplant. He had not been diagnosed with diabetes before, and his blood glucose levels were within the normal range. He showed no symptoms of polyuria or polydipsia before transplantation and had no history of head trauma or neurosurgery. Diagnosed to have primary hypothyroidism in Feb 2021 during pre-transplant workup, for which he was started on levothyroxine 50 ug and was euthyroid. The patient received prednisolone, tacrolimus, mycophenolate mofetil, and sulfamethoxazole/trimethoprim after the transplantation. During evaluation for polyuria, urine volume was >100 ml/kg in 24 Hour. Serum osmolality of 295 mOsm/kg, urine osmolality of 101 mOsm/kg, and serum sodium of 138 mEq/L, RBS 86 mg/dl, Urea 24 mg/dl. Anterior pituitary hormone profile workup was normal. To evaluate the cause of polyuria, water deprivation test was performed which confirmed complete central diabetes insipidus. He was started on oral desmopressin 120 ug in divided doses. His urine output subsequently decreased to about 2.5 L/d with resolution of excessive thirst and nocturia. MRI sella revealed normal anterior pituitary, infundibulum and diminished posterior pituitary bright spot in the T1-weighted image. Patient is continued on desmopressin therapy at 6 months with marked improvement in symptoms. Conclusion: In this case, the water deprivation test and diminished posterior pituitary bright spot-on MRI and the responsiveness to desmopressin therapy confirm the diagnosis of central DI. Hence, any case of polyuria after renal transplantation must be evaluated for Central Diabetes Insipidus.

Sotrovimab-Flashes of Safety in COVID-19 Patients: An International Journal of Medical Toxicology and Drug Experience

Introduction: Sotrovimab is a monoclonal therapy authorized for emergency use (EUA) on May 26, 2021, by the US (FDA) for treatment of mild-to-moderate coronavirus disease (COVID-19) in adults and children > 12 years old). The drug showed positive viral testing in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, reduced risk for progressing to severe COVID-19, including hospitalization or death1. Objective: This paper reviewed published data on safety of Sotrovimab 500mg in COVID-19 patients. Methods: The study based on reviewing published literature. Pubmed and FDA web was searched for data on Safety of Sotrovimab use in COVID-19 patients (May2021-May2022). Results: Gupta A et al2 reported among (n = 291 Sotrovimab group, n = 292 placebo group) mild diarrhea occurred in 5 cases (1%) in Sotrovimab group, compared to 1 case of moderate diarrhea, while diarrhea occurred in 3 patients in placebo group. One patient who received Sotrovimab had moderate dyspnea, an infusion-related reaction that was related to Sotrovimab. Hospitalization adverse events occurred in 2% of Sotrovimab group and in 6% in placebo group. No death or serious adverse events e.g., hematological disorders or liver damage were related to Sotrovimab. Further study by Gupta A et al3 for Sotrovimab (n = 528) or placebo (n = 529) reported that adverse events were infrequent and are similar between two groups (22% for Sotrovimab vs 23% for placebo);the most common events were diarrhea with Sotrovimab (n = 8;2%) and COVID-19 pneumonia with placebo (n = 22;4%). Kreuzberger N et al4 reported treatment with Sotrovimab may reduce the number of participants with oxygen requirement weaned in 3 days and risk of all-cause hospitalization or death without exhibiting significant adverse reaction. Fernandes G et al5 observed that following administration of Sotrovimab to kidney transplant recipients infected with Omicron variant, two patients required hospitalization for oxygen therapy. None were admitted to the intensive care unit or died. Conclusion: This review found limited number of safety studies of Sotrovimab in COVID-19, which reflects low numbers of publications. This is probably because of the Emergency utilization of drug and limitation of use in many countries. Lately, FDA US announced Sotrovimab is no longer authorized to treat COVID-19 in US due to increases in the proportion of COVID-19 cases caused by the Omicron variants6. Further data is needed to evaluate Sotrovimab safety in COVID-19 patients and examine risk-benefit, adverse events, and risk correlation to disease severity in patients with various risk factors.

COVID-19 Vaccine Mandates in U.S. Transplant Centers

While the previous survey focused primarily on operational challenges, the purpose of this new survey was "to better inform clinicians, policy makers, and the public about the prevalence, rationale, and scope of vaccine mandate policies instituted (or not) by solid organ transplant centers" (p. 1). The most common reasons given for a vaccine mandate were organ stewardship responsibilities (64%), the responsibility to promote the public health (52%), and the desire to reduce the risk of transmission to health care workers (40%) and to other patients and family members (40%). Additionally, "despite evidence of hypo- responsiveness to COVID-19 vaccination in patients with end-stage kidney disease, very few centers with a vaccine mandate required additional testing to prove sufficient immune responsiveness to COVID-19 vaccination as a condition of active listing" (p. 4). Discussion The authors noted that despite widespread agreement concerning the efficacy of vaccination in decreasing the risk of severe illness and death in recipients of solid organ transplants, their "study confirms the challenges and complexity in deciding whether a transplant center should mandate COVID-19 vaccination for actively listed waitlisted candidates" (p. 4).

Immunosuppression reduction when administering a booster dose of the BNT162b2 mRNA SARS-CoV-2 vaccine in kidney transplant recipients without adequate humoral response following two vaccine doses: protocol for a randomised controlled trial (BECAME study)

IntroductionInadequate antibody response to mRNA SARS-CoV-2 vaccination has been described among kidney transplant recipients. Immunosuppression level and specifically, use of antimetabolite in the maintenance immunosuppressive regimen, are associated with inadequate response. In light of the severe consequences of COVID-19 in solid organ transplant recipients, we believe it is justified to examine new vaccination strategies in these patients.Methods and analysisBECAME is a single-centre, open-label, investigator-initiated randomised controlled, superiority trial, aiming to compare immunosuppression reduction combined with a third BNT162b2 vaccine dose versus third dose alone. The primary outcome will be seropositivity rate against SARS-CoV-2. A sample size of 154 patients was calculated for the seropositivity endpoint assuming 25% seropositivity in the control group and 50% in the intervention group. A sample of participants per arm will be also tested for T-cell response. We also plan to perform a prospective observational study, evaluating seropositivity among ~350 kidney transplant recipients consenting to receive a third vaccine dose, who are not eligible for the randomised controlled trial.Ethics and disseminationThe trial is approved by local ethics committee of Rabin Medical Center (RMC-0192-21). All participants will be required to provide written informed consent. Results of this trial will be published;trial data will be available. Protocol amendments will be submitted to the local ethics committee.Trail registration numberNCT04961229.

Persistent Neutropenia after ABOi Kidney Transplantation: A Case Report

Post-transplant neutropenia (PTN) is frequently reported in the first-year after transplantation. Although prevalence and clinical consequences are widely described, there are no guidelines to manage diagnosis and treatment. We report here a case of persistent PTN occurred in a patient undergoing a kidney transplant from an AB0-incompatible living donor. The desensitization protocol consisted of Rituximab administration and immunoadsorption while the pre-transplant protocol, which was initiated 14 days before the transplant, included Tacrolimus, Mofetil Mycophenolate (MMF), antimicrobial and antiviral prophylaxis. Induction therapy consisted of anti-thymocyte globulins and steroids, while maintenance after transplantation consisted of steroid, tacrolimus and MMF. When the first occurrence of leukopenia was observed six weeks after the transplant, firstly antimicrobial/antiviral prophylaxis was stopped and later also MMF treatment was interrupted but severe neutropenia relapsed after MMF resuming treatment. Immunological and virological causes were excluded. The patient was treated with Filgrastim. Bone marrow biopsy, which was performed to exclude a hematological cause of severe persistent neutropenia, revealed a bone marrow hypoplasia with neutrophils maturation interrupted at the early stages. This case highlights the need to establish diagnostic and therapeutic guidelines for PTN which take in consideration all the therapeutic steps including the pre-transplant phase in particular in the context of AB0i where immunosuppression is more consistent.

Multi Organ Involvement in a Kidney Transplant Recipient, A Case Report

A 22-year old man underwent kidney transplant two years ago. Following fever and cough, epigastric pain, convulsion, vomiting and PO intolerance he had been brought to the emergency room. During evaluation in addition to pulmonary involvement with SARS-COVID-19, brain, stomach and pancreas involvements with COVID-19 infection also were detected. Hemodialysis and specific treatments were initiated. After 16 days he could be discharged ultimately.

Using statistical analysis and logistic regression to study the effect of CoViD-19 on hospital activities of the C.O.U. general surgery and kidney transplants

Due to the Sars-Cov-2 pandemic, the entire health sector in all countries around the world had to reorganize. It was not only a question of increasing the number of intensive care places, but all other medical specialties also had to rewrite their protocols. In this context, it is interesting to investigate whether these new measures have changed the volume of activity and the way hospital departments work. The aim of this study is precisely to verify what has happened to the Transplantation and Related Surgery Centre of the "San Giovanni di Dio e Ruggi d'Aragona"University Hospital of Salerno. For this reason, data were collected on patients who were admitted in 2019 (pre-pendemic) and 2020. The statistical analysis carried out showed that nothing had changed in this department in 2020. © 2021 ACM.

National study on the risks of COVID-19 for paediatric renal transplant recipients

IntroductionFrom the start of the COVID-19 pandemic, evidence emerged that children were less affected by SARS-CoV-2 PCR DNA COVID-19 positive infections, with increasing evidence showing immunosuppressed children were less at risk compared to immunosuppressed adults. The aim of our study was to investigate how COVID-19 infections affected paediatric renal transplant recipients in the UK.MethodsQuestionnaires regarding patient demographics, renal transplant information, COVID-19 infection data and care of patients during the COVID-19 pandemic were sent out to all 13 UK paediatric nephrology centres.Results54 patients (69% male;50% Black, Asian and minority ethnic [BAME];57% living donors) aged 4–19 (median 11) years and between 2 months – 15 years (median 3 years 1 month) post-transplantation from nine centres tested positive for SARS-CoV-2 PCR DNA. Four centres had no positive patients. 48% presented with the classical COVID-19 symptoms (37% fever, 11% continuous cough and 4% loss of sense of taste or smell);atypical presentations included diarrhoea (13%) and headache (8%). 37% of patients were asymptomatic. 28% were hospitalised (median stay 2 days) which included asymptomatic patients admitted for other reasons. Of those admitted, one patient required oxygen;however, no patients required ventilation or intensive care admission. One child had a rejection episode as a complication of the infection and one adolescent had ongoing cardiorespiratory symptoms for six months. There was evidence of AKI with renal transplant dysfunction in 31% of patients, with increase in mean baseline plasma creatinine from 80.6µmol/l to 171.7µmol/l, but no patients required CVVH or dialysis.Conclusion9% of the UK paediatric renal transplantation population have had documented SARS-CoV-2 PCR DNA infections with 28% required hospitalisation. There was increased prevalence of AKI, particularly after the first wave of the COVID-19 pandemic, possibly due to different variants, although there is no specific virological data to support this.

Better outcome of COVID-19 positive kidney transplant recipients during the unremitting stage with optimized anticoagulation and immunosuppression.

INTRODUCTION: COVID-19 is an ongoing pandemic with high morbidity and mortality and with a reported high risk of severe disease in kidney transplant recipients (KTR). AIM: We aimed to report the largest number of COVID-19-positive cases in KTR in a single center and to discuss their demographics, management, and evolution. METHODS: We enrolled all the two thousand KTR followed up in our center in Kuwait and collected the data of all COVID-19-positive KTR (104) from the start of the outbreak till the end of July 2020 and have reported the clinical features, management details, and both patient and graft outcomes. RESULTS: Out of the one hundred and four cases reported, most of them were males aged 49.3 ± 14.7 years. Eighty-two of them needed hospitalization, of which thirty-one were managed in the intensive care unit (ICU). Main comorbidities among these patients were hypertension in 64.4%, diabetes in 51%, and ischemic heart disease in 20.2%. Management strategies included anticoagulation in 56.7%, withdrawal of antimetabolites in 54.8%, calcineurin inhibitor (CNI) withdrawal in 33.7%, the addition of antibiotics in 57.7%, Tocilizumab in 8.7%, and antivirals in 16.3%. During a follow-up of 30 days, the reported number of acute kidney injury (AKI) was 28.7%, respiratory failure requiring oxygen therapy 46.2%, and overall mortality rate was 10.6% with hospital mortality of 13.4% including an ICU mortality rate of 35.5%. CONCLUSION: Better outcome of COVID-19-positive KTR in our cohort during this unremitting stage could be due to the younger age of patients and early optimized management of anticoagulation, modification of immunosuppression, and prompt treatment of secondary bacterial infections. Mild cases can successfully be managed at home without any change in immunosuppression.