Comparison of Comorbidities between Adults and Children with Glycogen Storage Disease Type Ia (GSDIA)

Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023

Incisional Hernia with Loss of Domain as a Consequence of Botulinum Toxin a and the Covid-19 Pandemic

Introduction: Abdominal wall surgery has been one of the major victims of the COVID-19 pandemic, with a large number of patients who have seen their surgery delayed and many are still waiting to be operated on today. On the other hand, botulinum toxin is one of the main protagonists in optimizing abdominal wall surgery, especially important in complex hernia, but we must not forget that it can have adverse effects. Case report: We present the case of a 54-year-old man with a history of obesity, diabetes, hypertension, chronic renal failure and kidney transplant in 2000, who presented a midline incisional hernia as a result of an epigastric hernia operated on in 2006 and subsequently two onlay permanent synthetic mesh in 2010 and 2015. In February 2020 he presented an incisional hernia M2-4W3R3 with a volume of 35%, botox was infiltrated as optimization for surgery and while awaiting placement of a pneumoperitoneum catheter, the surgery was suspended due to the COVID-19 situation. He returns to our clinics in 2022 with a growth of the hernia and a volume of 95%. Weight loss, botulinum toxin and preoperative pneumoperitoneum were indicated. We performed a reconstruction of the abdominal wall with bilateral transversus abdominal release and preperitoneal 45x60cm polyvinylidene fluoride mesh and abdominoplasty. Discussion(s): Botulinum toxin can facilitate abdominal surgery, especially in complex hernias, but we must not forget that blocking the abdominal muscles can have adverse effects. The COVID-19 pandemic has been especially hard on surgical waiting lists, delaying surgeries and aggravating pathologies.

EXPERIENCE IN THE USE OF NEUTRALIZING MONOCLONAL ANTIBODIES IN KIDNEY TRANSPLANT RECIPIENTS WITH COVID-19.

Therapy with neutralizing monoclonal antibodies (mAbs) is particularly relevant during COVID-19 outbreaks in patients at high risk of severe disease, including kidney transplant recipients (KTRs). Objective(s): to evaluate the efficacy and safety of neutralizing mAbs in KTRs with mild to moderate COVID-19. Materials and methods. The retrospective study included 99 KTRs who received inpatient treatment for COVID-19 between September 1 and December 31, 2021. Patients were 52.0 +/- 11.5 years old (M, 47.5%). Bamlanivimab/etesevimab combination drug at a dose of 700/1400 mg was used as mAbs. To evaluate the efficacy of mAbs therapy, two groups of patients were identified. Group 1 consisted of 33 KTRs who received mAbs as one of the therapy components, while group 2 consisted of 66 patients who received no mAbs. Discharge from the hospital or death was considered as the endpoint of follow-up. Results. In group 1, after the use of mAb, progression of pulmonary process was observed less frequently than in the control group with CT1-2 transformation to CT3-4 (9.1% vs. 30.3%, respectively, p < 0.01). Group 1 KTRs differed significantly from group 2 - lower need for ICU and ventilator care (6.1% vs. 27.3% and 3% vs. 19.8%, respectively). The groups were comparable by sex, age, body mass index, Charlson Comorbidity Index (CCI) and time after kidney transplant (KTx) at the onset of the disease and by aseline blood biochemistry parameter values at the time of hospitalization. Only C-reactive protein (CRP) and fibrinogen values were higher in the non-mAbs patients who were hospitalized later in the course of the disease (7.7 +/- 3.2 days versus 4.6 +/- 1.6 days in group 1, p < 0.001). The frequency of prescription of other therapies did not differ between the compared groups. Use of mAbs significantly reduced mortality from 19.7% in KTRs in group 2 to 3% in group 1 without adverse effect on graft function. Conclusion. The use of mAbs therapy in the early stages of COVID-19 in KTRs is safe, it prevents severe COVID-19, and reduces the incidence of adverse outcomes.Copyright © 2023 Russian Transplant Society. 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.

Renal Toxicity Boxed Warnings of Drugs Marketed in the US

Objectives: To assess the characteristics of FDA renal toxicity boxed warnings (formerly called Black Box Warning) included in the labels of drugs approved by the FDA and marked in the US. Method(s): We extracted the labels of human prescription drugs with renal toxicity boxed warnings from the "FDA Label: Full-Text Search of Drug Product Labeling" database, FDA regulatory information from drugs@FDA as of September 1, 2022. We extracted the therapeutic classification from the WHO ATC system. We conducted a descriptive analysis of the data. Result(s): The FDA listed 86 drugs including 72 active ingredients and 14 combinations with a boxed warning mentioning renal toxicity. Three drugs had emergency use authorizations for COVID-19, and all combinations included metformin. There were 8 (8.7%) drugs with renal toxicity boxed warnings approved before 1970, 6 (6.5%) in the 1970s, 14 (15.2%) in the 1980s, 34 (37.0%) in the 1990s, 17 (18.5%) in the 2000s, 9 (9.8%) in the 2010s, and 4 (4.3%) in 2020-Sep 2022. The therapeutic classes with the largest number of renal toxicity boxed warning included anti-infectives for systemic use 24 (26.1%), antineoplastic and immunomodulating agents 22 (23.9%), and alimentary tract and metabolism 17 (18.5%). The most common boxed warnings included renal impairment (n=21, 22.8%), nephrotoxicity (10, 10.9%), and nephrogenic systemic fibrosis (7, 7.6%). Additionally, 9 (9.8%) boxed warnings referred to the potential problems for patients with kidney transplants. Conclusion(s): Most drugs with a boxed warning were approved in the 1990s and 2000s. The therapeutic classes with the highest number of renal toxicity warnings were anti-infective for systemic use, antineoplastic and immunomodulating agents, and alimentary tract and metabolism. The most common warnings were renal impairment, nephrotoxicity, nephrogenic systemic fibrosis, and issues for patients with kidney transplants. Future research could expand the analysis to renal toxicity warnings, interactions, and precautions.Copyright © 2023

Pancreatitis Secondary to Paxlovid-Induced Tacrolimus Toxicity

Introduction: Pancreatitis is a very common gastrointestinal disease that results in hospital admission. Early detection and treatment leads to better outcomes. This is the first reported case of pancreatitis secondary to elevated tacrolimus in a patient with prior renal transplantation after receiving Paxlovid for a COVID-19 infection. Case Description/Methods: A 57-year-old male with past medical history of 4 renal transplants secondary to posterior urethral valves who presented to the emergency room with acute onset epigastric pain for 24 hours. He was on tacrolimus 5 mg every 48 hours monotherapy for his immunosuppression. 10 days prior to his presentation he had developed chills and anxiety. He tested positive for COVID-19 at that time on a home rapid test. His symptoms had not significantly improved and given his immunosuppressed state he was given Paxlovid (Nirmatrelvir/ritonavir). He took 2 days of Paxlovid, however after his second day of treatment he developed severe epigastric pain requiring him to go to the emergency room. On admission his labs were notable for a lipase of 150 U/L (ULN 63 U/L). He underwent a CT scan was notable for an enlarged pancreatic head and neck with peripancreatic fat stranding (Figure). He also had a right upper quadrant ultrasound without any cholelithiasis and only trace sludge noted. His creatinine was noted to be 1.81 mg/dl which was above his baseline of 1.2 mg/dl. His tacrolimus trough level resulted at a level 45.6 ng/ml and later peaked at 82.2 ng/ml. His liver enzymes were normal. He was treated as acute pancreatitis with hydration and his tacrolimus was held with overall clinical improvement. Discussion(s): Tacrolimus is one of the most common medications used in solid organ transplantation. It is a calcineurin inhibitor that inhibits both T-lymphocyte signal transduction and IL-2 transcription. It is metabolized by the protein CYP3A and levels are monitored closely. Paxlovid is currently prescribed as an antiviral therapy for COVID-19 infection. The ritonavir compound in Paxlovid is potent inhibitor of CYP3A. Currently the guidelines do not recommend Paxlvoid as a therapeutic in patients taking tacrolimus as there is concern about increased drug levels. There have been several case reports of pancreatitis in setting of tacrolimus. This case report helps to demonstrate the need for close monitoring of therapeutics levels, especially in medications with high risk of drug to drug interaction to help prevent serious side effects such as tacrolimus induced pancreatitis.

A Rare Cause of Enteritis in an Adult Male

Introduction: IgA vasculitis is more commonly seen in the pediatric population than in adults. Rarely IgA vasculitis is associated with malignancy, most commonly solid tumor malignancies, although there are case reports of association with hematologic malignancies. We report a case of large B-cell lymphoma mimicking IgA vasculitis in a 33-year-old immunosuppressed male with a prior history of IgA vasculitis. Case Description/Methods: A 33-year-old Caucasian male post renal transplant from reflux nephropathy on chronic immunosuppression was hospitalized for postprandial epigastric abdominal pain, nausea, vomiting and diarrhea. Two years prior, he was admitted for the same symptoms, palpable purpura of the lower extremities and elevated serum IgA. Enteroscopy had shown duodenal and jejunal ulceration with biopsies staining positive for IgA, confirming IgA vasculitis. He had complete resolution with a steroid taper. His current presentation had resulted in multiple hospital admissions, but empiric trial of steroids failed to alleviate symptoms. Vitals were normal and exam was notable for epigastric tenderness. Labs were notable for WBC 19.00 x103/cmm with normal differential, hemoglobin 9.2 gm/dL (prior 11.0 gm/dL), CRP 20.7 mg/L, serum creatinine 2.7 mg/dL (prior 1.5 mg/dL), and urinalysis with proteinuria, sterile pyuria, and hematuria. CTA abdomen/pelvis revealed thickening of the duodenum with shotty mesenteric lymph nodes without ischemia. Enteroscopy revealed an erythematous duodenum and jejunum (figure A). Jejunal biopsy (figure B) revealed CD20 positive cells consistent with DLCBL (figure C). He was seen by oncology and treated with R-CHOP but later unfortunately expired due to COVID-19 complications. Discussion(s): Non small cell lung cancer and renal cell carcinoma are most commonly associated with IgA vasculitis. It may also be seen in both Hodgkin and Non-Hodgkin lymphomas in adult patients. If IgA vasculitis occurs after a malignancy is diagnosed, it may indicate that metastasis has occurred. Malignancy associated IgA vasculitis is more likely to have an incomplete response to steroids and requires treatment of the underlying malignancy to achieve remission. Our case illustrates posterior probability error and premature closure cognitive biases. We should consider alternative diagnoses rather than anchor on prior diagnoses even when presentations are similar. Our case also highlights the importance of considering occult malignancy in adults with diagnosis of IgA vasculitis.

Higher Spike Genetic Diversity of Delta/Omicron Variants in Immunocompromised Hosts

Background: Immunocompromised hosts with prolonged SARS-CoV-2 infections have been associated with the emergence of novel mutations, especially in the Spike protein, a key target for vaccines and therapeutics. Here, we conducted a case-control study to measure the genetic diversity of SARSCoV- 2 and to search for immunocompromised-specific minority variants. Method(s): SARS-CoV-2-positive patients with lung/cardiac/kidney transplant, HIV-positive, or treated with high doses of corticosteroids for auto-immune diseases were considered as immunocompromised hosts. SARS-CoV-2-positive healthcare workers with no auto-immune disease were used as controls. Samples were analyzed by RT-qPCR at Pitie-Salpetriere and Bichat Claude-Bernard university hospitals (Paris, France). Samples with Cycle threshold < 30 were selected for SARSCoV- 2 whole-genome sequencing using Oxford Nanopore protocol. Raw sequence data were mapped onto the Wuhan-Hu-1 reference genome, and consensus sequences were produced to determine the lineage. Only sequences covering at least 95% at >=50X depth of the Spike gene were investigated. In-house algorithms were developed to identify all majority and minority mutations in Spike. We defined a minority variant when it was present in >=6% and < 50% of the reads;and a majority variant when it was present in >50%. Result(s): We sequenced SARS-CoV-2 genome from 478 COVID-19- positive immunocompromised patients and 234 controls. More minority non-synonymous mutations in Spike were detected in viruses from immunocompromised hosts, compared to viral genomes from controls, in both Delta (p=0.001) and Omicron (p< 0.001) lineages, but not in Alpha (p=0.66) (Figure 1). Interestingly, among the 52 patients infected with the Delta variant, we concomitantly detected at low frequencies the mutations H655Y, N764K, D796Y, in three patients (associated with different auto-immune disease), that are part of Omicron variants signature mutations. Similarly, some patients (n=7) infected by Omicron BA.1 lineage had R346T at low-frequency, later fixed in Omicron BA.4.6 and BQ.1.1 lineages. None of these mutations were observed in the viral genomes from controls. Conclusion(s): Here, we report a higher genetic diversity in Spike gene among SARS-CoV-2 sequences from immunocompromised hosts for Delta and Omicron lineages. These results suggest that immunocompromised patients are more likely to allow viral genetic diversification and are associated with a risk of emergence of novel SARS-CoV-2 variants. (Figure Presented).

Coronavirus disease 2019 vaccination in patients with chronic kidney diseases.

Patients with chronic kidney disease (CKD) are at high risk for coronavirus disease 2019 (COVID-19). Government agencies or learned societies in many countries recommend prioritizing patients with CKD for COVID-19 vaccines. The immune response rate to the COVID-19 vaccines is lower in hemodialysis patients and kidney transplant recipients compared with that in healthy individuals, and increasing the number of vaccinations each member of these population may improve their immune response rate. There was no significant difference in the incidence of adverse reactions after vaccination between patients with CKD and healthy controls. Patients with stable CKD should be vaccinated against COVID-19 unless there were contraindications to vaccination. The mRNA vaccines, inactivated vaccines, and recombinant protein subunit vaccines are all safe for patients with CKD. Patients with CKD treated with rituximab or high-dose glucocorticoid need to weigh the benefits and risks before vaccination, and COVID-19 vaccines can be given when rituximab treatment ends for more than 6 months or after glucocorticoid reduction.Copyright © 2021 by the Chinese Medical Association.

Patterns And Outcomes Of Covid Positive Donor Utilization For Heart Transplant

Background: The outcomes following COVID positive donor utilization for heart transplant are unknown. Method(s): UNOS database was analyzed for heart transplants performed after the declaration of COVID pandemic on 11th March 2020 until 31st December 2021. The cohort was divided into two groups based on donor COVID antigen and NAAT results. Result(s): Since the onset of pandemic, there were 6855 heart transplants reported. COVID antigen or NAAT results were available in 5529 donors at the time of donation, of which 38 (0.7%) were positive. COVID positive donors (CPD) were accepted for older recipients (age 54 vs 48, p=0.04). Listing status 1 and 2 were similar in both groups (9% vs 5% and 24% vs 23% respectively). Durable mechanical support (LVAD, RVAD, TAH) were similar in both groups pre-transplant (31% vs 33%, p=0.3). There was no difference in days on waitlist (183 vs 176 days, p=0.9). Both groups had similar travel distance (261 vs 239 nautical miles, p=0.4) and ischemic time (3.6 vs 3.5 hours, p= 0.8). Simultaneous renal transplant rates were similar (10% vs 9%, p=0.8). CPD utilization increased with time (figure 1A) and was uniform across most UNOS regions (figure 1B) Post-transplant, there was no difference in length of stay (24 days in both groups) and acute rejection episode prior to discharge (4% vs 8%, p=0.6) or within one year (3% vs 4%). There were no deaths reported in the CPD group during a mean 72 days of follow up (range 0-365 days) (figure 2). Known hospitalization for rejection management were similar (3% vs 4%) post-transplant. Conclusion(s): Active COVID infection in donors did not affect survival or rejection rates in the short-term post-heart transplantCopyright © 2022

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

Clinical and laboratory characteristics of patients who succumbed to COVID-19: a single center experience from a resource poor setting

Introduction: The clinical and laboratory characteristics of patients who died with COVID 19 yet to be elucidated. Aims and objectives: We were aiming at identifying potential contributory factors for the mortality in COVID 19. Method(s): Patients died with COVID 19 at the intensive care unit (ICU), National Hospital, Kandy, Sri Lanka from 01.01.2021 to 31.12.2021 were retrospectively studied. Result(s): 79 deaths were analyzed. Males (44/79);median age 63 years (19, 94). Mean hospital and ICU stay were11 days (interquartile range-IQR:7,14), 7days (IQR: 2.5,9) subsequently. Median of 2 comorbidities (0,5) were present;diabetes(n=43), hypertension(n=43), ischemic heart disease(n=21), chronic kidney disease(n=10), post kidney transplant recipients(n=10), other(n=10). 14/79 had none. Mean systolic blood pressure on admission:130 mmHg (IQR: 115,148), mean SpO2/FiO2 ratio was 147(IQR 95,163), mean serum lactate level was 1.9(IQR: 1.08,2.25). The average heart rate 95(IQR: 81,108);mean respiratory rate was 28(IQR: 22, 33);mean random blood sugar was 229(IQR: 156, 289). 15/79 documented to be vaccinated (one =4/11: two=6/15: three=5/15). C-Reactive protein was available in 72/79;mean=122(IQR: 38, 182). Procalcitonin (PCT) on admission was available in 32/79;median=3.70 (0.01, 96), PCT was >1 in 16/32. 8/18 blood culture samples, 4/12urine culture samples detected bacterial pathogens. 25/46 demonstrated either PCT>1 or blood and/or urine culture positivity. Conclusion(s): Higher proportion of patients were unvaccinated, with multiple comorbidities predominantly diabetes. Hyperinflammation was common and significant proportion had bacterial co-infection.

Impact of Covid-19 Pandemic on Epidemiology of Infections in Pre- and Post-Covid-19 Pandemic a Single Centre Study

Introduction: Infections are the leading cause of death in kidney transplant recipients (KTR) at all time intervals. The non-pharmaceutical interventions (NPIs) taken during the COVID-19 pandemic have reduced almost all kinds of infections in the general population, as shown in the Chunmei Su et al. study. The aim of this study was to investigate the impact of NPIs for the COVID-19 pandemic on infections in KTR patients. Method(s): This was a single-center retrospective observational study conducted at Mumbai's Jaslok Hospital and Research Centre.Samples from symptomatic KTR patients were taken and those who had positive cultures were thought to be infected. The data were analysed and compared between the years 2021 (during the COVID-19 pandemic) and 2019 (before the COVID-19 pandemic). Result(s): A total of 224 patients were enrolled, including 117 patients in 2019 and 107 patients in 2021. In 2019 and 2021, the prevalence of nosocomial infection and community-acquired infection in KTR patients remains unchanged.In 2021, both the number of protective gloves and level 2 PPE kits used per individual, as well as the number of healthcare professionals per patient, have increased dramatically. Regarding the source of infections, no significant change in major infections was observed in respiratory tract infections (12% vs. 10.3%, p = 0.8985), gastrointestinal infections (1.8% vs. 6.5%, p = 0.0786), catheter related blood stream infections (CRBSI) (4.5% vs. 3.7%, p = 0.776), and blood stream infections (11.7% vs. 10.3%, p = 0.73), However, there were increases in urinary tract infections (23% vs. 42.1%;p = 0.0006). The microorganism analysis of respiratory infections shows declines in nocardia and tuberculosis. Gastrointestinal infections show increased Clostridium difficile cases in 2021 compared to 2019, which can be attributed to the overuse of antibiotics. Regarding urinary tract infection, a decline in mixed infection cases and an increase in Enterobacter faecalis and Enterobacter cloacae cases were observed. There were no significant variations in catheter-related nosocomial infections between 2019 and 2021. In comparison to an older study done in the general population by Chunmei Su et al, our study shows no significant change in respiratory, gastrointestinal, and catheter-related blood infections in 2021 compared to 2019 in KTR, despite restrictions being relaxed in general populations beginning in June 2020.Also, there was no significant increase in community acquired pneumonia in 2021, even after reopening public places. Conclusion(s): Our institutional NPIs for KTR patients in the pre-COVID-19 era were shown to be as effective as NPIs for the COVID-19 pandemic in reducing the prevalence of common infections like respiratory, gastrointestinal, blood stream, and catheter-related infections in KTR patients. No conflict of interestCopyright © 2023

Higher pro-inflammatory cytokines are associated with anti-SARS-CoV-2 spike protein-specific seroconversion after two doses of COVAXINTM, COVISHIELDTM vaccination in renal transplant recipients

Introduction: Generating adequate cellular and humoral responses are essential principle of vaccination. Immune system of renal transplant recipient remained compromised and speculated to less likely to develop antibody after vaccination. SARS-CoV-2 neutralizing antibody after anti-SARS-CoV-2 vaccination is required for the protection from subsequent viral infection. During COVID-19 disease, anti-SARS-CoV-2 specific antibody formation was correlated with the inflammatory cytokines level. Although, there is limited informations about serum cytokines and antibody formation after COVAXINTM, COVISHIELDTM vaccination in RTRs. Therefore, in the current study, we have evaluated the inflammatory cytokines response and anti-SARS-CoV-2 specific antibody formation in renal transplant recipient. Method(s): In this study, we have recruited 171 live-related renal transplant recipients vaccinated with two doses of either COVAXINTM (whole inactivated virus-based vaccine) or COVISHIELDTM (Simian adenovirus containing full-length spike protein-based vaccine). A 5 ml blood sample was collected after two weeks of 2nd dose of vaccination. The serum was separated and stored at -200C till the analysis. Anti-SARS-CoV-2 spike protein-specific IgG antibody titer was determined by chemiluminescent microparticle immunoassay methods and Cytokines IL-10, TGF-beta, IFN-gamma, IL-6 were measured by the ELISA techniques. Result(s): The overall anti-SARS-CoV-2 spike protein specific seroconversion after vaccination was observed in 149/171(87.13%) of RTRs with median IgG titer in seroconversion group 1191.90 (IQR, 398.70-2652.45) au/ml. The median and interquartile serum cytokines IL-10 level in seroconversion (n=149) vs non-seroconversion (n=22) group was 88.89 (IQR, 55.5-125.92) vs 92.59 (IQR, 48.14-148.14) pg/ml. The median TGF-beta level in seroconversion vs non-seroconversion group was 692.10 (IQR, 446.05-927.63) vs 1001.31 (IQR, 813.15-1125.65) pg/ml. The median IL-6 level in seroconversion vs non-seroconversion group was 46.66 (33.3-66.66) vs 28.33 (16.66-34.16) pg/ml. The median IFN-gamma level in seroconversion vs non-seroconversion group was 98.0 (IQR, 57.40-111.60) vs 50.0 (IQR, 30.55-52.55) pg/ml. The cytokines IL-6 and IFN-gamma level was positively correlated with anti-SARS-CoV-2 specific protein antibody titer (r=0.192;p=0.012), IFN-gamma (r=0.188;p=0.014). TGF-beta and IL-10 were negatively correlated with anti-SARS-CoV-2 specific protein antibody titer. For IL-10 (r=-0.065;p=0.39), for TGF-beta (r=-0.246;p=0.002). Further IFN-gamma was negatively correlated with TGF-beta (r=-0.268;p<0.001). Conclusion(s): Higher pro-inflammatory cytokines (IL-6, IFN-gamma) levels were associated with anti-SARS-CoV-2 spike protein-specific seroconversion, whereas higher anti-inflammatory cytokines IL-10 and TGF-beta were negatively associated with seroconversion after vaccination in renal transplant recipients. No conflict of interestCopyright © 2023

Association of urinary mitochondrial DNA with COVID-19 related acute kidney injury, mitochondrial stress, and inflammation in renal transplant recipients

Introduction: ACE-receptors are profusely expressed in the renal cell, making it highly susceptible for severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infection. After entering the cells, the virus induces high levels of cytokines, chemokines, and inflammatory responses, resulting neutrophilic infiltration, activation, and profuse reactive oxygen species (ROS) formation, leading to cellular necrosis and acute tubular injury. Proximal convoluted tube cell are rich in mitochondria and susceptible for developing acute kidney injury (AKI) due to mitochondrial stress. Early detection of AKI may helpful in its management, limiting the severity, avoiding nephrotoxic medicines and modifying the drug dose depending on renal function. Therefore, in the current study, we have determined the utility of urinary mitochondrial DNA (umt-DNA) and neutrophil gelatinase-associated lipocalin (NGAL) in predicting COVID-19-associated acute kidney injury (AKI) and mitochondrial stress and demonstrated the inflammatory response of urinary mt-DNA. Method(s): Live-related RTRs(n=66), who acquired SARS-CoV-2 infection and were admitted to a COVID hospital were included and subclassified into AKI (N=19) with > 25% spike in serum creatinine level from the pre-COVID-19 serum creatinine level, and non-AKI (N=47) whose serum creatinine value remained stable similar to the baseline value, or a rise of < 25% of the baseline values of pre-COVID-19. A 50ml urine sample was collected and umt-DNA and N-GAL was determined by the RT-PCR and ELISA methods respectively. A 10ml blood sample from 10 healthy volunteers was also collected for PBMC isolation and inflammatory response demonstration. A 1x106 PBMC was stimulated for 24hrs. with 1microg/ml of urinary DNA or TLR9 agonist CpG oligodeoxynucleotide (5'-tcgtcgttttcggcgc:gcgccg-3') in duplicate. Unstimulated PBMCs served as control. The gene expression of IL-10, IL-6, MYD88 was analyzed by the RT-PCR and IL-6, IL-10 level in supernatants by the ELISA. Result(s): Both the urinary mitochondrial gene ND-1 and NGAL level was significantly higher in AKI group compared to non-AKI. The mean ND-1 gene Ct in AKI group was (19.44+/-2.58 a.u) compared to non-AKI (21.77+/-3.60;p=0.013). The normalized ND-1 gene Ct in AKI was (0.79+/-0.11 a.u) compared to non-AKI (0.89+0.14;P=0.007). The median urinary NGAL level in AKI group was (453.53;range, 320.22-725.02, 95% CI) ng/ml compared to non-AKI (212.78;range, 219.80-383.06, 95%CI;p=0.015). The median urine creatinine normalized uNGAL was 4.78 (0.58-70.39) ng/mg in AKI group compared to 11.26 ng/mg (0.41-329.71) in non-AKI group. The area under curve of ND-1 gene Ct was 0.725, normalized ND-1 Ct was 0.713 and uNGAL was 0.663 and normalized uNGAL was 0.667 for detecting the AKI and mitochondrial stress. The IL-10 gene expression was downregulated in umt-DNA treated PBMCs compared to control (-3.5+/-0.40vs1.02+/-0.02, p<0.001). IL-6 and Myd88 gene expression was upregulated. The culture supernatant IL-10 and IL-6 level in umt-DNA treatment PBMCs vs control was 10.65+/-2.02 vs 30.3+/-5.47, p=0.001;and 200.2+/-33.67 vs 47.6+/-12.83, p=0.001 pg/ml respectively. Conclusion(s): Urinary mt-DNA quantification can detect the Covid19 associated AKI and mitochondrial distress with higher sensitivity than uNGAL in RTRs. Urinary mt-DNA also induces a robust inflammatory response in PBMCs, which may exacerbate the Covid19 associated allograft injury. No conflict of interestCopyright © 2023

Coronavirus infection in immediate post-renal transplant period: A case report

The novel coronavirus (severe acute respiratory syndrome coronavirus;SARS-CoV-2) has spread out to most of the world with the World Health Organization (WHO) classifying it as a global pandemic. There exists very little information on the infectious course of COVID- 19 in immunocompromised individuals, including transplant recipients. We report a case of a young adult who tested positive for SARS-CoV-2 in the immediate post-operative period following renal transplantation.

Psychological Concerns of Children Undergoing Kidney Transplantation and Their Families during the Covid-19 Pandemic

Background The current COVID-19 pandemic has been an anxious time for children and young people (CYP) with end stage kidney disease and their families particularly as they were identified as a vulnerable group. Many transplant programmes closed and reopening brought new concerns for patients and professionals. We report patient experience on being transplanted during the pandemic. Objectives To obtain a better understanding of the concerns and experiences that CYP and families have about receiving a kidney transplant during the pandemic. Methods A questionnaire was sent to patients and families of 10 paediatric patients transplanted in the first six months of reopening our transplant programme. One patient refused transplant and one lacked social support to proceed with the transplant. Results All participants felt that their questions were answered before transplantation and 75% felt well informed about the SARS-CoV-2 effects on transplantation. 62.5% reported feeling nervous 37.5% were anxious 25% scared and 12.5% relaxed about transplantation during the pandemic. The majority of participants reported surgical complications being their biggest fear;two participants were worried about catching SARS-CoV- 2. 87.5% felt that care was delivered safely in inpatient and outpatient setting. 75% of participants found shielding easy. Overall 87.5% of patients were glad to have received a kidney transplant during the pandemic with one patient struggling with feeling isolated. Conclusions Receiving a kidney transplant can be a stressful experience particularly during a pandemic. Our results show that a significant number of patients felt scared that detailed counselling of CYP and families about risks and addressing their concerns related to SARS-CoV-2 contributed to a good patient and family experience on transplantation during the pandemic. Further studies are needed to look into the longterm effects of the pandemic on this vulnerable group of patients and strategies to mitigate them.

Immunogenicity and Safety of Homologous Chadox1 Ncov-19 and Heterologous Prime-Boost of Coronavac and Chadox1 Ncov-19 among Kidney Transplant Recipients: An Observational Prospective Cohort Study

Introduction: Kidney transplant recipients (KTRs) are at risk for substantial morbidity and mortality during COVID-19 infection. Vaccination for this group of patients is reccommended. However, immunogenicity and safety data after COVID-19 vaccination among KTRs remains limited. Method(s): We conducted an observational prospective trial involving KTRs at Chiang Mai University hospital, Chiang Mai, Thailand. The participants were received homologous ChAdOx1 nCoV-19 (AZ-AZ), or the heterologous prime-boost of CoronaVac,followed by AZ (SV-AZ). The immunogenicity was assessed by measuring antibodies against the S1 receptor-binding domain (anti-RBD), and SARS-CoV-2 surrogate virus neutralization test (sVNT) at specific timepoints. The primary outcome was the seroconversion rate of sVNT at day 28 after complete vaccination. The secondary outcomes were the seroconversion rate of sVNT at day 28 after the first dose of vaccination, the level of sVNT and anti-RBD at specific timepoints, and the adverse events of each vaccine regimen. Result(s): A total of 18 KTRs were recruited. Among those, 13 (72.2%), and 5 (27.8%) patients were received AZ-AZ, and SV-AZ regimen, respectively. The seroconversion rate of sVNT at day 28 after the second dose were 23.1%, and 20.0% for AZ-AZ, and SV-AZ, respectively (P>0.99). The level of sVNT and the level of anti-RBD at day 28 after the first and at day 28 after the second dose were not different between groups (Figure 1). There were no serious adverse events reported in any vaccine groups. However, AZ-AZ showed sign of tubular dysfunction demonstrated by increasing of fractional excretion of magnesium after complete course of vaccination which correlated to the trend of urine albumin and urine protein creatinine ratio (r=0.720, P=0.013;and r=0.726, P=0.011, respectively). [Formula presented] [Formula presented] Figure 1 Percentage of neutralization inhibition (a) and level of anti-RBD antibody (b) at each visit of homologous ChAdOx1 nCoV-19 (AZ-AZ), and heterologous prime-boost of CoronaVac, followed by AZ (SV-AZ) regimen Conclusion(s): Immunogenicity after COVID-19 vaccination with either homologous or heterologous prime-boost regimen among KTRs was compromised. Homologous replication-defective viral vectors vaccine regimen seemed to affect renal tubular function, and further follow-up should be warranted. No conflict of interestCopyright © 2023

A Comprehensive Review of 275 Kidney Transplants Performed over 3 1/2 Years;a Single Center Experience

Introduction: Access to kidney transplantation has always been a problem in the African countries with many patients having to travel to other medically advanced countries in Asia, Europe and America. This involves unnecessary excessive expenditure and the travails of journey and stay in an unknown foreign land. To ease this situation and to provide affordable Renal transplant services in their home land, we have made an effort to start the transplant services at our medical facility and have successfully carried out about 275 transplants over a period starting from Nov 2018 till September 2022. Method(s): All the Kidney transplants done between the period Nov 2018- September 2022 (275 cases) were included in the analysis. All the transplants were performed at a single center and the data were collected progressively during their Pre transplant evaluation, perioperative course and post op follow up. All the laboratory and radiological tests were done locally at the center except the HLA cross matches and tissue typing, which were outsourced to Transplant immunology labs outside the country. All the patients with positive DSA titres [about 70%], underwent Plasmapheresis and received IVIg before the transplantation. immunological assessment was done by NGS high resolution, for A B C DP DQ DR loci and X match was done by SAB analysis for class 1 and Class II antigens. All the patients underwent laparoscopic donor nephrectomy. All Patients received vaccinations for Hepatitis B, Pneumonia, Infuenza & Covid. Result(s): A series of 275 kidney transplants were performed over a period of 42 months [ Nov 2018- September 2022] at a private hospital successfully. All the cases were live donor kidney transplants with majority of the donors being 1st or 2nd degree relatives or spousal donors. About 70% of the patients had some degree of sensitization in the form of weakly positive B cell X match, or positive for DSAs at CL I, CLII with MFIs > 1000. All high-risk patients received induction with rabbit Thymoglobulin, and IV methyl prednisolone. Around 50 patients received Basiliximab. Of all patients, 4were HBsAg positive, and 6 were HIV positive,& HCV 1 patient. 8 patients required pretransplant Parathyroidectomy for refractory hyperparathyroidism, 3 patients required simultaneous native kidney nephrectomy at the time of transplant. 25 patients had multiple renal vessels which were double barreled and anastamosed.4 patients had lower urinary tract abnormalities requiring simultaneous/subsequent repair. Overall, 4 patients underwent 2nd transplant. All the donors underwent laparoscopic nephrectomy. Most of the patients had good immediate graft function except in 40 patients, who had delayed graft function;most of them improving over 2 - 6 weeks. 6 Patients had hyperacute rejection and the graft was lost,.4patients had main renal artery thrombosis, Renal allograft biopsy was done in 20 patients. Overall, the Patient survival was 95 %.at 1 year and graft survival 90%. Conclusion(s): Our experience shows that kidney transplantation is a viable and practical option for End stage kidney disease and can be performed even in resource constrained centers in third world countries and the survival rates of patients and the grafts are comparable to other centers across the world. No conflict of interestCopyright © 2023