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.

Management and standardization of hemodialysis centers in lockdown areas under the epidemic of coronavirus disease 2019.

Maintenance hemodialysis patients need to return to hospital 3 times a week for routine hemodialysis treatment. In the case of coronavirus disease 2019 (COVID-19) and regional lockdown, a set of management systems and standardizations has been established in our hemodialysis center, including forward movement of the critical nodes of treatment, specialists pooling program for hemodialysis technology, and dynamic bubble personnel management, to implement dynamic prevention and control strategies, precise management of inpatient wards and closed-loop management of outbreaks. While improving the management of our own hemodialysis center, it is recommended to strengthen multi-center collaboration to build a municipal grid management system for hemodialysis and explore different dialysis strategies for end-stage renal disease to meet the treatment needs and safety management of maintenance hemodialysis patients in lockdown areas under the epidemic.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Health-related quality of life, mental health and caregiver burden in children with autosomal recessive polycystic kidney disease (ARPKD)

Objective: To examine whether established patient-reported outcome measures are suitable for capturing the impact of ARPKD in children and their families. Method(s): We assessed 44 children with ARPKD (40 families) with respect to patients' health-related quality of life ((hr- QOL) using PedsQLTM ESRD module) and mental health (strength and difficulties questionnaire (SDQ)) as well as family and caregiver burden (Impact on family score (IFS) und Ulm inventory of parental caregiver QOL (ULQIE)) and compared them to published data and 36 healthy control children matched for age and time. Result(s): Patients were aged 9.5 +/- 5.9 years (vs. controls 8.8 +/- 5.0, p = ns) and 21 (48%) were female (vs. 19 controls (53%), p = ns). Mean eGFR was 81 ml/min*1.73m2 (range 4 - 165);7 received dialysis and 11 had functioning kidney transplants (KTX, 2 combined with liver transplants). Eight patients had developmental delay secondary to medical complications, while chronic illness was an exclusion criterion for healthy controls. 61 caregivers of affected children had same gender-distribution (61% vs. 60% mothers) and age (both 42 +/- 7 years) and number of dependent children (1.8 +/- 0.9 vs. 2.0 +/- 0.8) as 57 caregivers of healthy children. The mean proxy reported PedsQL Total score was 77.5 +/- 10.6 (range 59 - 96). It correlated significantly to eGFR (r = 0.5, p < 0.01, (also within the subpopulations pre- and post-KTX)). Parents reported greater mental health problems in affected than in control children with a higher SDQ total score mainly due to higher scores in the hyperactivity and peerinteraction subscales. ULQIE revealed that parents of affected children had significantly lower levels of physical functioning, self-fulfillment and general QOL, but despite higher emotional burden scores they indicated similar satisfaction with family life. Impact on family scores were in a similar range to those of children with moderate to severe disabilities. Conclusion(s): The good spread of PedsQLTM ESRD-scores and their correlation to renal function indicates that it captures significant aspects of ARPKD, however, it may need further adjustment to include liver complications. All four chosen instruments revealed significant impact of ARPKD on hrQOL and mental health of affected children as well as family life and parental wellbeing in comparison to healthy controls. More problems with peer-interactions may also be due to more stringent shielding of chronically ill children from social contacts during the COVID pandemic compared to healthy children.

Trends in Covid-19 and Atrial Fibrillation: A National Inpatient Sample Trend from 2020

Background: Atrial fibrillation (AF) is the most common arrhythmia in the United States. Concomitant Covid-19 infection and the outcomes of AF are unknown. Objective(s): The study's goals were to analyze the outcomes of AF during the Covid-19 pandemic. Method(s): We conducted a retrospective cohort study based on the 2020 National Inpatient Sample (NIS) of Adults (>18 years) hospitalized for AF as the primary admitting diagnosis based on the ICD-10 codes and stratified these groups into concomitant covid-19 infection vs. non-covid-19 infection. All-cause mortality was our primary outcome, while the rate of ICU admission, length of stay, hospital charges were our secondary outcomes. Temporal trends were assessed using logistic regression. Result(s): In 2020, there were 1,994,985 admissions for atrial fibrillation, out of whom 104,495 (5.3%) had concomitant Covid-19. In the 104,495 AF admissions with covid-19, the mean age was 75y and 56.8% were males. Our results, image 1, showed AF with and without concomitant Covid-19 had similar rates of comorbid conditions including HTN, DM, OSA, CAD. HFrEF, and ESRD. AF patients with Covid-19 infection had a lower prevalence of smoking (31.83% vs. 39.4%, p<.001) and alcohol use (2% vs. 4.2%, p<.001). AF patients from both groups had similar rates of stroke (1.6% vs. 1.0%, p<.001). New AF patients with concomitant Covid-19 had worsening in-hospital outcomes such as shock (12.8% vs. 3.7%, p<.001), admission to the ICU (18.1% vs. 6.4%, p<0.001), higher all-cause mortality (21.8% vs. 3.9%, p<0.001), a longer length of stay (9.96 days vs 6.08 days, p<.001), and total hospital costs ($114,387 vs. $85,830, p<.0001). The incidence of AF catheter ablation on initial hospital admission for AF Covid-19 was lower compared to the AF non-covid-19 patients (.08% vs. 1.39%, p<.001). Conclusion(s): In 2020, Covid-19 infection was an independent predictor of higher all-cause mortality, length of stay, and costs in patients admitted for atrial fibrillation. In addition, these patients were less likely to get catheter ablation on hospital admission. [Formula presented]Copyright © 2023

Immunogenicity and safety of COVID-19 BNT162b2 booster vaccine in end-stage kidney disease patients receiving haemodialysis in Yogyakarta, Indonesia: a cohort prospective study.

BACKGROUND: A significant decrease in antibody titres several months after COVID-19 primary vaccination in end-stage kidney disease (ESKD) patients receiving maintenance haemodialysis has recently been reported. The waning in antibody titres has led to the recommendations for a booster dose to increase the antibody titres after vaccination. Consequently, it is crucial to analyse the long-term humoral immune responses after COVID-19 primary vaccination and assess the immunogenicity and safety of booster doses in haemodialysis (HD) patients. METHODS: Patients on maintenance haemodialysis who received the primary vaccine of CoronaVac (Sinovac) vaccine were administered with BNT162b2 (Pfizer-BioNTech) as the booster dose. The immunogenicity was assessed before (V1), one month (V2) and eight months (V3) after the primary vaccination, as well as one month after the booster dose (V4). Patients were followed up one month after the booster dose to assess the adverse events (AEs). RESULTS: The geometric mean titre (GMT) of anti-SARS-CoV-2 S-RBD IgG antibody at 8 months after the primary vaccination increased significantly to 5,296.63 (95%CI: 2,930.89-9,571.94) U/mL (p = < 0.0001) compared to before the primary vaccination. The GMT also increased significantly to 19,142.56 (95% CI: 13,489.63-27,227.01) U/mL (p < 0.0001) 1 month after the booster vaccine. Meanwhile, the median inhibition rate of neutralizing antibodies (NAbs) at 8 months after the primary vaccine and 1 month after the booster dose were not significantly different (p > 0.9999). The most common AEs after the booster dose included mild pain at the injection site (55.26%), mild fatigue (10.53%), and swelling at the injection site (10.53%). No serious AEs were reported. CONCLUSIONS: The majority of ESKD patients on haemodialysis mounted a good antibody response to the BNT162b2 booster vaccination with tolerable adverse events.

Management and standardization of hemodialysis centers in lockdown areas under the epidemic of coronavirus disease 2019

Maintenance hemodialysis patients need to return to hospital 3 times a week for routine hemodialysis treatment. In the case of coronavirus disease 2019 (COVID-19) and regional lockdown, a set of management systems and standardizations has been established in our hemodialysis center, including forward movement of the critical nodes of treatment, specialists pooling program for hemodialysis technology, and dynamic bubble personnel management, to implement dynamic prevention and control strategies, precise management of inpatient wards and closed-loop management of outbreaks. While improving the management of our own hemodialysis center, it is recommended to strengthen multi-center collaboration to build a municipal grid management system for hemodialysis and explore different dialysis strategies for end-stage renal disease to meet the treatment needs and safety management of maintenance hemodialysis patients in lockdown areas under the epidemic.Copyright © 2022, Second Military Medical University Press. All rights reserved.

COVID-19 in hemodialysis patients

Objective. Evaluation of clinical observation, the course, the risk factors, and treatment options for SARS-CoV-2 infection in hemodialysis patients with end-stage chronic kidney disease. Material and methods. The retrospective, single-center, uncontrolled study involved 231 patients (132 M/99 W) aged 61.7+/-14.7 years with COVID-19 diagnosed. The SPSS software package was used for statistical analysis. Results. 72 (31.2%) of patients died, 68 (94.4%) of them had ARDS as the main cause of death. Comparative analysis in groups with favorable and unfavorable outcomes of the disease showed that age (68.1+/- 13.2 years vs 58.7+/-14.5 years, p<0.0001) and the comorbidity index (8.8+/-2.2 vs 6.2+/-2.6, p<0.0001) were significantly higher in those who have died compared to survivors. According to CT data, they were more likely to have 3rd or 4th-degree lung damage (72.2 vs 36.5%, p<0.0001), and the minimum oxygen saturation index: 67.6+/-12.8 and 87.8+/-10.9%, respectively (p<0.0001). Somorbidity index and the need for invasive ventilation were independent predictors of the fatal outcome of COVID-19. Early administration of monoclonal antibodies to IL-6 (in the first 3 days after hospitalization) in patients with a low prevalence of the pulmonary process (CT stage 1-2) was associated with a significantly lower frequency of fatal outcome. Conclusions. SARS-CoV-2 infection in HD patients is characterized by a high rate of mortality. Predictors of severe disease in this population are comorbidity index and the need for invasive ventilation.Copyright © Infectious Diseases: News, Opinions, Training.

Taiwan's national strategies and actions toward HCV elimination before 2025

In 1990, the seroprevalence of antibody against hepatitis C virus (anti- HCV) in Taiwan was first documented to be 0.95% in volunteer blood donors, 90% in hemophiliacs, and 81% in parenteral drug abusers. The risk factors for HCV infection in Taiwan include iatrogenic transmission (medical injection, hemodialysis, acupuncture, and blood transfusion), tattooing, and sexual transmission. The long-term risk of hepatic and non-hepatic diseases has been well-documented by REVEL-HCV study. A national program of antiviral therapy for chronic viral hepatitis was launched in Taiwan in 2003. Mortality rates of end-stage liver diseases decreased continuously from 2000-2003 to 2008-2011 in all age and gender groups. When the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis in 2016, National program to eliminate hepatitis C was very carefully evaluated. It became a consensus to reach the WHO's 2030 goals in 2025. Taiwan Hepatitis C Policy Guideline 2018-2025 was approved and published at the beginning of 2019. There are triple focuses of hepatitis C elimination in Taiwan including (1) therapy spearheads prevention, (2) screening supports therapy, and (3) prevention secures outcome. A total of US$1.7 billion will be allocated from 2017 to 2025 for the elimination of HCV. The coverage of HCV screening and treatment has been increasing significantly since 2017. The HCV screening coverage was almost 100% for dialytic patients, 96% for HIV-infected patients, 65% for patients under opioid substitution treatment, 63% for patients in the pre-end-stage renal disease care program, 57% for patients in the early chronic kidney disease care program, 52% for patients in diabetes care program, 39% for prisoners, and 38% for adults aged 45-79 years old in the general population by April 30, 2020. The budget to cover the cost of DAA increased from US$101 million in 2017 to US$219 million in 2019. The number of chronic hepatitis C patients receiving DAA therapy increased from 9,538 in 2017, 19,549 in 2018, to 45,806 in 2019. However, the number of DAA-treated CHC patients reduced to 36,159 in 2020 and 20,559 in 2021 due to the COVID-19 pandemic. The cure rate based on SVR12 was 96.8% in 2017, 97.4% in 2018, over 98.6% after 2019. It is expected that Taiwan will achieve WHO's HCV elimination goal by 2025.

Esophageal Mucosal Calcinosis: A Rare Site of Calcium Deposition in End-Stage Renal Disease

Introduction: Calciphylaxis, otherwise known as calcium uremic arteriolopathy, is defined as calcium deposition around blood vessels in skin and fat tissue which occurs in 1-4% of patients with end-stage renal disease (ESRD). Calcium deposition in the esophagus is extremely rare;to date, there have been only 4 cases reported worldwide. We report the fifth case of esophageal mucosal calcinosis occurring in a young male with ESRD. Case Description/Methods: A 37-year-old Thai man with ESRD on peritoneal dialysis since 2005 presented with generalized weakness and odynophagia due to oral ulcers, resulting in poor PO intake. He denied drinking alcohol, illicit drug use, or smoking. On exam his abdomen was soft, non-distended, non-tender, without any guarding. Past medical history included hypertension and COVID-19 in January 2022. Laboratory tests revealed neutropenia and pancytopenia, hyperphosphatemia, and hypocalcemia. EGD revealed distal esophageal esophagitis and hemorrhagic erosive gastropathy. Biopsy showed ulcerative esophagitis with dystrophic calcification, consistent with esophageal mucosal calcinosis .No intestinal metaplasia was noted. Immunohistochemistry was negative for CMV, HSV1, and HSV2. The patient was treated with pantoprazole 40mg IV every 12 hours, Magic Mouthwash 5ml qid, and Carafate 10mg qid. He was transferred to a cancer center where he had a bone marrow biopsy formed which was negative. His symptoms resolved and the patient was discharged to home (Figure). Discussion(s): Esophageal mucosal calcinosis is extremely rare. It is due to a combination of factors involving acidosis and the phenotypic differentiation (and apoptosis) of vascular smooth muscle cells (VSMC) into chondrocytes or osteoblast-like cells. These changes, along with the passive accumulation of calcium and phosphate, induce calcification. Acidosis is well-known to promote inflammation of the arterial walls, releasing cytokines that induce vascular calcification. The benefits of treatment with sodium thiosulfate remain unclear. An ample collection of cases should help devise standardized treatment options and establish management guidelines for this condition.

Rates of Hypoglycemia with Reduced- vs. Standard-Dose Insulin for Hyperkalemia Treatment in Renal Insufficiency

Objective: The primary objective was to assess the difference in rates of hypoglycemia (blood glucose (BG) <=70 mG/dL) when using reduced-dose (5 units) vs. standard-dose (10 units) of IV regular insulin for hyperkalemia treatment in renal insufficiency. Secondary objectives include the efficacy of insulin dose on potassium reduction and evaluating the difference in rates of severe hypoglycemia (BG <=54 mG/dL) between the groups. Method(s): This was a retrospective chart review of patients with renal insufficiency treated with IV regular insulin for hyperkalemia at a tertiary care teaching hospital from June 2020 to June 2021, with institutional review board approval. Inclusion criteria encompassed patients aged 18 years and older with elevated baseline potassium (>=5.5 mEq/L), estimated glomerular filtration rate < 30 mL/min/1.73m2, end stage renal disease, or presence of acute kidney injury, having received either 5 or 10 units of IV regular insulin for hyperkalemia, and had documented glucose and potassium levels after insulin administration. Patients who were pregnant, had diabetic ketoacidosis, or a baseline BG <=70 mG/dL were excluded. Data collection included patient demographics, diabetes history, relevant labs at time of elevated potassium, doses of insulin and dextrose administered for hyperkalemia treatment, presence of coronavirus-19 infection, glucose levels within 6 hours and first potassium level within 24 hours following insulin administration, concurrent use of potassium-lowering agents, insulin outside of hyperkalemia treatment, or steroids, and mortality. Result(s): Out of 409 patients included, 92 were in the 10-unit group and 317 in the 5-unit group. The rate of hypoglycemia in the 5-unit arm vs. the 10-unit arm was 6.9% vs. 8.7% (p=0.649), respectively. The rate of severe hypoglycemia between the 5-unit arm and the 10-unit arm was 3.2% vs 5.4% (p=0.682), respectively. The percent normalization of potassium was not statistically different between the 5-unit group and the 10-unit group (59% vs. 68%;p=0.115), with the same mean reduction in potassium from baseline (0.8 mEq/L (p=0.947)). Administration of concurrent treatments for hyperkalemia was similar between the groups, with dialysis being the only one with statistical significance in normalization of potassium. Patient characteristics that could have an impact on risk of hypoglycemia were studied and analyzed, including pre-treatment BG, history of diabetes mellitus, insulin naive, and patient weight. In patients with hypoglycemia (n=30) vs. those without hypoglycemia (n=379), there was a significantly different mean pre-treatment BG (113 mG/dL vs. 178 mG/dL, p<0.001). Discussion/Conclusion: There was no significant difference in rates of hypoglycemia and severe hypoglycemia between the 5-unit vs. 10-unit groups. There was no significant change in potassium normalization between the two insulin doses. Because of the small number of hypoglycemia events, larger studies are needed to better understand if 5 units of regular insulin is a safer option for the treatment of hyperkalemia in renal insufficiency.Copyright © 2023

Diazoxide in the Treatment of Asymptomatic Refractory Hypoglycemia in End Stage Renal Disease

Introduction: Diabetic patients with end-stage renal disease (ESRD) treated with insulin or any other diabetic agent show high variations in their glucose metabolism, lower insulin clearance level, and uncertain accuracy of glycemic control measurements. Therefore, these patients are at a greater risk of developing hypoglycemia. Diazoxide use in the treatment of spontaneous and refractory hypoglycemia in this population has not been well documented. We report a case of a young diabetic male that has been successfully treated with diazoxide for his asymptomatic refractory hypoglycemic episodes. Case Description: A young man with type 2 diabetes mellitus complicated by diabetic nephropathy, on hemodialysis for ESRD, presented with shortness of breath due to COVID pneumonia. After resolution of his infection, he was noted to have recurrent asymptomatic hypoglycemic episodes, although he has been off his diabetes medications for the past few years due to worsening of his kidney function. His oral intake was adequate and there was no concern for malnutrition, or any substance use. From the testing performed, we were able to exclude exogenous insulin or insulin secretagogues use and the presence of insulin antibodies. Insulin and noninsulin (insulin-like growth factor) mediated mechanisms were also ruled out. Since he was having recurrent and refractory asymptomatic hypoglycemic episodes and to minimize the need for supplemental dextrose containing fluids, he was started on diazoxide at 3 mg/kg/day. Knowing the risk of fluid retention with diazoxide, this patient on hemodialysis tolerated it well. Diazoxide helped reduce his episodes of hypoglycemia and he was then safely discharged on it. Discussion(s): In ESRD, hypoglycemia can be explained by the impaired contribution of the kidneys to gluconeogenesis and glucose release, as well as the higher insulin levels caused by insulin resistance and decrease in insulin clearance. When his hypoglycemia persisted even after the resolution of his infection, further testing and work-up was done and other causes of hypoglycemia were ruled out. Generally, diazoxide is used as a treatment to manage the symptoms of hypoglycemia in congenital hyperinsulinism, insulinomas and post bariatric surgery cases of hyperinsulinemic hypoglycemia. However, it has not been the optimal treatment when it comes to treating hypoglycemia in ESRD patients because of its side effects;specifically, fluid retention, and electrolyte imbalances. In our case, the patient was treated with diazoxide as a last resort, despite its known side effects and the limited documentation of its use in ESRD patients. Actually, a few other case reports, have also shown promising results with the use of diazoxide for that purpose with no or minimal side effects. However, there are not enough studies that have shown the benefits or risks of long-term treatment of diazoxide in ESRD patients, an area of growing interest.Copyright © 2023

Anti-S-Rbd Titer and Risk of Clinical Progression in Patients with Covid-19 Pneumonia

Background: Antibodies (Ab) against the receptor-binding-domain of the spike protein (anti-S-RBD) elicited by SARS-CoV-2 infection or vaccination are deemed to be a correlate of protection. We aimed at assessing whether anti-S-RBD titer is associated with the outcome of subjects hospitalized with COVID-related pneumonia. Method(s): Adults hospitalized between Jul 2021 and Jul 2022 for COVID-19 with respiratory failure (SpO2 < 93% on room air) or radiological evidence of pneumonia were included if anti-S-RBD titer was measured within 72h of admission. Time between admission and death/need for intubation was described using Kaplan-Meier curves. Cox Regression analysis, stratified by vaccination status, was used to explore the association between anti-S-RBD titer and survival. Age, gender, days since symptom onset, immunosuppressive conditions and use of monoclonal Ab (mAb) were explored as possible confounders. Result(s): 534 patients were enrolled. Their mean age was 71 years, 63% were male and 61% vaccinated;42% had >=1 immunosuppressive condition among hematological or solid malignancy, HIV, diabetes, end-stage renal failure, liver cirrhosis, organ transplant or immunosuppressive treatment. Antibody titer was significantly higher among vaccinated than among unvaccinated patients (1166 vs 158 BAU/ml;p< 0.001). Among vaccinated subjects, lower titer of anti-S-RBD were measured among those with hematological malignancies (1282 vs 471 BAU/mL;p< 0.001) or who were receiving immunosuppressive therapy (1287 vs 537 BAU/ml;p< 0.001). Older age, shorter time between onset of symptoms and hospitalization and immunosuppressive conditions were associated with higher rates of death or intubation (Fig 1). Using Cox regression stratified for vaccination, a significant association between anti-S-RBD titer and risk of death/intubation was observed (per log2 BAU/ml increase, HR 0.93;95%CI 0.88-0.99;p=0.020), independently of age (per year increase, HR 1.03;95%CI 1.01-1.04), male gender (HR 1.00;95%CI 0.70-1.42) and presence of immunosuppressive conditions (HR 1.46;95%CI 1.01-2.10). Adjustment for mAb treatment did not change the results to a significant Extent. Conclusion(s): Low anti-S-RBD titer was associated with poor outcome among patients hospitalized for COVID19-related pneumonia, regardless of vaccination. In addition, older age and presence of immunosuppressive conditions remain important predictors of mortality. Kaplan-Meier Curves for intubation-free survival according to age, days from symptoms' onset, presence of immunosuppressive conditions and anti-S-RBD titer. (Figure Presented).

From Covid to Bovid to Ovid: A Case of Disseminated Cryptococcus Neoformans

Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.

Partial recovery of SARS-CoV-2 immunity after booster vaccination in renal transplant recipients

The pandemic caused by the SARS-CoV-2 coronavirus has been especially detrimental to patients with end-stage renal disease. History with other vaccines suggests that patients with renal disease may not respond adequately to the SARS-CoV-2 vaccine. The aim of this study is to evaluate the immunity to SARS-CoV-2 mRNA vaccines in renal patients. Post SARS-CoV-2 vaccination first, and after the booster dose, antibodies and cellular immunity were studied in patients on hemodialysis (N = 20), peritoneal dialysis (N = 10) and renal transplantation (N = 10). After the two doses of vaccine, there was an effective immunity in dialysis patients, with 100% seroconversion and 87% detection of cellular immunity (85% in hemodialysis and 90% in peritoneal dialysis). In contrast, in renal transplant recipients there was only 50% seroconversion and cellular immunity was detected in 30% of patients. After the booster dose, all dialysis patients achieved a cellular and antibody immunity, whereas in transplant patients, despite improvement, 20% did not produce antibodies and in 37.5% cellular immunity could not be detected. The mRNA vaccine plus booster performs excellently in dialysis patients, whereas in kidney transplant recipients, despite the booster, complete immunization is not achieved.Copyright © 2022

The Effect Of Covid-19 Infection On Sirolimus Metabolism In Heart Transplant

Introduction: Limited knowledge exists regarding the effect of Covid-19 on heart transplant recipients. Monitoring immunosuppressant levels is an important management strategy concerning the risk of graft rejection. Furthermore, how Covid-19 and its treatment affect sirolimus metabolism in solid organ transplants is not well understood. Here, we present a case of a heart transplant recipient with elevated sirolimus levels following Covid-19 infection. The elevated sirolimus levels occurred after previously being therapeutic on a steady dose and persisted despite significant dose reductions and no other known drug-drug interactions. Case Presentation: The patient is a 58-year-old male with a history of ischemic cardiomyopathy;status post orthotopic heart transplantation on 8/17/2009. The postoperative course was complicated by atrial tachycardia without rejection status post-ablation in 8/2020 and end-stage renal disease on hemodialysis. In January of 2022, the patient was instructed to present to the ER after missing dialysis due to Covid-like symptoms including generalized weakness, nausea, and shortness of breath. Covid-19 PCR returned positive. Before infection, the patient had been maintained on a steady dose of sirolimus 0.5 mg daily for 5 months with associated trough levels between the goal range of 4-8 ng/mL. At the time of infection, the patient's sirolimus was held due to elevated trough levels, and he was subsequently maintained on a dose of 0.5 mg every other day for the next few days. Seeing no improvement, the dose was then decreased to 0.25 mg every other day for the remainder of his admission. He expired on 2/09/2022 from Covid-19. Figure 1 shows the sirolimus trough:dose ratio before and after diagnosis of Covid-19. Discussion(s): To our knowledge, this is the first case presented of a heart transplant recipient with altered sirolimus metabolism status post Covid-19 infection without apparent drug-drug interactions. This may suggest a relationship between SARS-COV-2 viremia with sirolimus metabolism.Copyright © 2022

WCN23-1206 Glomerulopathies Biobank in Uruguay. Description of the first 110 patients enrolled

Introduction: The incidence of glomerular diseases varies across different countries and criteria for kidney biopsy has changed over time. In Uruguay, glomerular diseases (GD) are a frequent cause of end stage kidney disease (ESKD) and renal replacement therapy with an annual incidence of 25.0 patients per million population according to data from the Uruguayan Dialysis Registry (UDR, year 2020). Since 1970, the Uruguayan Registry of Glomerulopathies has been recording the incidence, epidemiology and evolution of patients with GP in our country. In 2018, the Glomerulopathies Biobank (GB) began to operate including all patients with a native kidney biopsy performed at the Nephrology Department of the teaching hospital Hospital de Clinicas in Montevideo, Uruguay. The purpose of the BG is to record the phenotype (clinical and paraclinical) of patients with GD diagnosed by renal biopsy and at the same time store blood, urine, renal tissue and DNA samples. The aim of this report is to communicate the first 110 patients enrolled in the BG, which started in February 2018. Method(s): The BG protocol includes the collection of patronymic data, personal history, and clinical and paraclinical features of renal pathology. Plasma, urine and cell samples are stored for subsequent DNA extraction at the time of the kidney biopsy. In our country, all renal biopsies are performed by nephrologists. The Glomerular Biobank project is funded by the Nephrology Research Fund (School of Medicine, University of the Repubic) and was approved by the Ethics Committee of the Hospital de Clinicas and the Regulatory Verification Unit of the National Institute of Donation and Transplantation. The results are presented as mean and standard deviation (SD) for the continuous variables;and qualitative variables are described with percentages. Result(s): Patient recruitment began in February 2018 and we have recruited 110 patients. The mean age at the time of biopsy was 38.3+/-16.1 (min:16;max:78) years. Regarding sex distribution, the female sex slightly predominated (55.3%). Plasma creatinine was 2.1+/-1.45 mg/dL, proteinuria was 3.1+/-3.7 gr/dL and albuminaemia was 3.2+/-1.0 mg/dL. Microhaematuria was present in 61% of patients in the sediment study. Figure 1 shows the negative impact of the COVID 19 pandemic on the incidence of patients undergoing kidney biopsy. IgA nephropathy (13,8%)was the most frequent primary glomerular disease, followed by d focal and segmental glomerulosclerosis and membranous nephropathy. Consernig the glomerulopathies secondary to a systemic disease, the most frequent diagnosis was lupus nephritis (34,5%) followed by vasculitis, amyloidosis and diabetes. Conclusion(s): Having a prospective cohort of patients with glomerular disease, including reliable data and biological samples, will allow us to perform clinical and epidemiological analyses quickly and reliably in the future. The data and aliquots of biological material are available to any local nephrologist who proposes a hypothesis and has the approval of the corresponding ethics committee. The medium-term objective is to incorporate other national reference institutions in the care of patients with glomerular diseases. The data collected by the Glomerular Biobank will be a valuable input to the process of continuous improvement, and will serve as a basis for future nephrological research of excellence. No conflict of interestCopyright © 2023

Effect of Lymphocyte Phenotypic Alterations on the Humoral Response to Vaccination Against SARS-COV-2 in Dialysis Patients.

Background: The response to vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies depending on comorbidities. This study evaluated the clinical and immunological factors affecting the humoral response of patients with end-stage renal disease (ESRD) to the BNT162b2 vaccine. Methods: Humoral immunity was evaluated in 54 ESRD patients using serum levels of anti-receptor-binding domain (RBD) and neutralizing antibodies (NAbs), measured by a chemiluminescent immunoassay 30 (T1), 60 (T2), and 120 (T3) days after the second vaccine dose. The results were correlated to baseline patient T- and B-lymphocyte subpopulations determined by flow cytometry. Results: The proportion of seroconverted patients based on the NAb titer decreased from 83.3% at T1 to 53.7% at T3. Age was negatively correlated to the NAb titer at T1 and T2. Patients receiving hemodiafiltration had higher NAb titers at T3. Diabetes was associated with a lower response rate at T3. Univariate analysis revealed a positive correlation between the naïve CD4 T-lymphocyte population and RBD titer at T1 and the NAb titer at T3, with no association observed with naïve CD8 T lymphocytes. NAb titers at T3 were significantly correlated with late-differentiated CD4 T lymphocytes and terminally differentiated effector memory cells re-expressing CD45RA (TEMRA) CD8 T lymphocytes. RBD levels were positively correlated with naïve and memory B-lymphocyte counts at T3. Conclusions: Age, diabetes, and hemodialysis prescription had significant impacts on the response to vaccination. T- and B-lymphocyte phenotypes are major determinants of the humoral response potency to SARS-CoV-2 vaccination with BNT162b2 in patients with ESRD.

Factors Related to Quality of Life of Hemodialysis Patients during the COVID-19 Pandemic.

Taiwan had the second highest number globally of end-stage renal disease patients undergoing treatment in 2018. A meta-analysis of Chen et al. (2021) showed the incidence and mortality rates of COVID-19 were 7.7% and 22.4%, respectively. Few studies have explored the effects of patients' self-participation and perceptions of hemodialysis on their quality of life. This study aimed to explore the factors related to hemodialysis patients' quality of life during the COVID-19 pandemic. This study was a descriptive correlational study. Patients were recruited (n = 298) from the hemodialysis unit of a medical center in northern Taiwan. Variables included patients' sociodemographic, psychological, spiritual, and clinical characteristics (i.e., perceived health level, comorbidities, hemodialysis duration, weekly frequency, transportation, and accompaniment during hemodialysis), perceptions of hemodialysis, self-participation in hemodialysis, and health-related quality of life (KDQOL-36 scale). Data were analyzed using descriptive and bivariate and multivariate linear regression. Multivariate linear regression, after adjusting for covariates, showed that anxiety, self-perceived health status, two vs. four comorbidities, and self-participation in hemodialysis were significantly associated with quality of life. The overall model was significant and accounted for 52.2% (R2 = 0.522) of the variance in quality of life during hemodialysis (adjusted R2 = 0.480). In conclusion, the quality of life of hemodialysis patients with mild, moderate, or severe anxiety was poorer, whereas that of patients with fewer comorbidities, higher self-perceived health status, and higher self-participation in hemodialysis was better.

Prospective Analysis of B Lymphocyte Subtypes, before and after Initiation of Dialysis, in Patients with End-Stage Renal Disease.

End-stage renal disease (ESRD) is followed by alterations in adaptive immunity. The aim of this study was to evaluate B lymphocyte subtypes in ESRD patients before and after hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: CD5, CD27, BAFF, IgM and annexin were evaluated by flow cytometry on CD19+ cells in ESRD patients (n = 40), at time of initiating HD or CAPD (T0) and 6 months later (T6). RESULTS: A significant reduction in ESRD-T0 compared to controls was noticed for CD19+, 70.8 (46.5) vs. 171 (249), p < 0.0001, CD19+CD5-, 68.6 (43) vs. 168.9 (106), p < 0.0001, CD19+CD27-, 31.2 (22.1) vs. 59.7 (88.4), p < 0.0001, CD19+CD27+, 42.1 (63.6) vs. 84.3 (78.1), p = 0.002, CD19+BAFF+, 59.7 (37.8) vs. 127.9 (123.7), p < 0.0001 and CD19+IgM+ cells, 48.9 (42.8) vs. 112.5 (81.7) (K/µL), p < 0.0001. The ratio of early/late apoptotic B lymphocytes was reduced (16.8 (10.9) vs. 110 (25.4), p = 0.03). CD19+CD5+ cells were the only cell type with an increased proportion in ESRD-T0 patients (2.7 (3.7) vs. 0.6 (1.1), p < 0.0001). After 6 months on CAPD or HD, CD19+CD27-(%) and early apoptotic lymphocytes were reduced further. The HD patients also showed a significant increase in late apoptotic lymphocytes, from 1.2 (5.7) to 4.2 (7.2) K/mL, p = 0.02. CONCLUSIONS: B cells and most of their subtypes were significantly reduced in ESRD-T0 patients compared to controls, the only exception being CD19+CD5+ cells. Apoptotic changes were prominent in ESRD-T0 patients and were exacerbated by HD.

Acute Kidney Injury after Covid 19 Infection in Chronic Kidney Disease Patients of Bangladesh: Retrospective Study

Introduction: COVID 19 pandemic has caused unprecedented devastation worldwide. Spectrum of Covid 19 illness is wide and variable. Risk of mortality is increased in chronic kidney disease patients, during coronavirus disease. CKD is an independent risk factor for poor outcome. AKI is also common in COVID-19 patients who are hospitalized. This study was undertaken to see the outcome of Covid-19 infection in CKD patients. Method(s): This retrospective observational study was carried out in the Kidney Foundation Hospital and Research Institute, Bangladesh from January 2021 to July 2022. One hundred CKD patients who were on regular follow up in the outpatient department and developed COVID-19 as confirmed by reverse transcription polymerase chain reaction (RT-PCR) test underwent chart review after they consented to be part of the study. Their clinical parameters, treatment regiments and laboratory investigations were noted in a data collection sheet. Data was analyzed by Statistical Analysis Software. Result(s): The mean age of the patients was 55.2 years. Of them 43% were female. Diabetes mellitus was the most common comorbidity, seen in 65% of the patients. 24% were CKD stage 4 or 5 prior to the onset of COVID-19, rest were of earlier stage. Hospitalization was required in 65.3% patients;41.1% required oxygen, steroid given in 19.8% patients,8.4% required ICU transfer. 7 patients died, all of respiratory failure. Treatment with antiviral, biologics like Tocilizumab and plasma exchange was not commonly done. AKI developed in 28% of the patients during the course of the illness. Males were more prone to develop AKI (p = 0.23). People with longer duration of symptoms had higher incidence of AKI (p < 0.0001). AKI incidence did not vary according to baseline eGFR (p = 0.16). Among those who developed AKI, 17.9% required temporary dialysis and 7.1% went on to develop end stage kidney disease. Interim outcomes such as hospitalization, oxygen requirement, ICU transfer and death did not vary according to development of AKI. Conclusion(s): People with chronic kidney disease and other comorbid conditions are at higher risk for more serious COVID-19 illness. In our study it has been shown that a significant proportion of CKD patients developed AKI after COVID 19 infection of which a number of patients develop end stage kidney disease and required renal replacement therapy. No conflict of interestCopyright © 2023