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1. Outcomes of kidney transplantation in patients with IgA nephropathy based on induction: A UNOS data analysis

   https://doi.org/10.1111/ctr.15225  

   Aydin‐Ghormoz, Emmanuel Albert; Perlmutter, Jason; Koizumi, Naoru; Ortiz, Jorge; Faddoul, Geovani (January 2024, Clinical Transplantation)

   Abstract IntroductionIgA nephropathy (IgAN) can cause end‐stage kidney disease (ESKD). This study assesses the impact of induction and maintenance immunosuppression on IgAN recurrence, graft survival, and mortality in living and deceased donor kidney transplants (LDKT and DDKT). MethodsRetrospective analysis of the UNOS database in adults with ESKD secondary to IgAN who received kidney transplants between January 2000 and June 30, 2022. Patients with thymoglobulin (ATG), alemtuzumab, or basiliximab/daclizumab induction with calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) with or without prednisone maintenance were analyzed. Multivariate logistic regression was performed to identify factors correlated with IgA recurrence. Multivariable Cox regression analyses were performed for clinically suspected risk factors. Kaplan Meir Analysis was utilized for overall graft survival. ResultsCompared to ATG with steroid maintenance, alemtuzumab with steroid increased the odds of IgAN recurrence in DDKTs (OR 1.90,p <.010, 95% CI [1.169–3.101]). Alemtuzumab with and without steroid increased the odds of recurrence by 52% (p = .036) and 56% (p = .005), respectively, in LDKTs. ATG without steroids was associated with less risk of IgAN recurrence (HR .665,p = .044, 95% CI [.447–.989]), graft failure (HR .758,p = .002, 95% CI [.633–.907]), and death (HR .619,p <.001, 95% CI [.490–.783]) in DDKTs. Recurrence was strongly associated with risks of graft failure in DDKTs and LDKTs and death in LDKTs. ConclusionIn patients with IgAN requiring a kidney transplant, Alemtuzumab induction correlates with increased IgAN recurrence. Relapse significantly affects graft survival and mortality. ATG without steroids is associated with the least graft loss and mortality. 

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2. Cold Storage Followed by Transplantation Induces Immunoproteasome in Rat Kidney Allografts: Inhibition of Immunoproteasome Does Not Improve Function

   https://doi.org/10.34067/KID.0000000000000368  

   Bhattarai, Dinesh; Lee, Seong-ok; Joshi, Neelam; Jun, Se-Ran; Lo, Sorena; Jiang, Li; Gokden, Neriman; Parajuli, Nirmala (February 2024, Kidney360)

   Background:It is a major clinical challenge to ensure the long-term function of transplanted kidneys. Specifically, the injury associated with cold storage of kidneys compromises the long-term function of the grafts after transplantation. Therefore, the molecular mechanisms underlying cold-storage–related kidney injury are attractive therapeutic targets to prevent injury and improve long-term graft function. Previously, we found that constitutive proteasome function was compromised in rat kidneys after cold storage followed by transplantation. Here, we evaluated the role of the immunoproteasome (iproteasome), a proteasome variant, during cold storage (CS) followed by transplantation. Methods:Established in vivo rat kidney transplant model with or without CS containing vehicle or iproteasome inhibitor (ONX 0914) was used in this study. Theiproteasome function was performed using rat kidney homogenates and fluorescent-based peptide substrate specific to β5i subunit. Western blotting and quantitative RT-PCR were used to assess the subunit expression/level of theiproteasome (β5i) subunit. Results:We demonstrated a decrease in the abundance of the β5i subunit of theiproteasome in kidneys during CS, but β5i levels increased in kidneys after CS and transplant. Despite the increase in β5i levels and its peptidase activity within kidneys, inhibiting β5i during CS did not improve graft function after transplantation. Summary:These results suggest that the pharmacological inhibition of immunoproteasome function during CS does not improve graft function or outcome. In light of these findings, future studies targeting immunoproteasomes during both CS and transplantation may define the role of immunoproteasomes on short- and long-term kidney transplant outcomes. 

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3. Initiation of Continuous Glucose Monitoring Is Linked to Improved Glycemic Control and Fewer Clinical Events in Type 1 and Type 2 Diabetes in the Veterans Health Administration

   https://doi.org/10.2337/dc22-2189  

   Reaven, Peter D.; Newell, Michelle; Rivas, Salvador; Zhou, Xinkai; Norman, Gregory J.; Zhou, Jin J. (February 2023, Diabetes Care)

   OBJECTIVETo determine the benefit of starting continuous glucose monitoring (CGM) in adult-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) with regard to longer-term glucose control and serious clinical events. RESEARCH DESIGN AND METHODSA retrospective observational cohort study within the Veterans Affairs Health Care System was used to compare glucose control and hypoglycemia- or hyperglycemia-related admission to an emergency room or hospital and all-cause hospitalization between propensity score overlap weighted initiators of CGM and nonusers over 12 months. RESULTSCGM users receiving insulin (n = 5,015 with T1D and n = 15,706 with T2D) and similar numbers of nonusers were identified from 1 January 2015 to 31 December 2020. Declines in HbA1c were significantly greater in CGM users with T1D (−0.26%; 95% CI −0.33, −0.19%) and T2D (−0.35%; 95% CI −0.40, −0.31%) than in nonusers at 12 months. Percentages of patients achieving HbA1c <8 and <9% after 12 months were greater in CGM users. In T1D, CGM initiation was associated with significantly reduced risk of hypoglycemia (hazard ratio [HR] 0.69; 95% CI 0.48, 0.98) and all-cause hospitalization (HR 0.75; 95% CI 0.63, 0.90). In patients with T2D, there was a reduction in risk of hyperglycemia in CGM users (HR 0.87; 95% CI 0.77, 0.99) and all-cause hospitalization (HR 0.89; 95% CI 0.83, 0.97). Several subgroups (based on baseline age, HbA1c, hypoglycemic risk, or follow-up CGM use) had even greater responses. CONCLUSIONSIn a large national cohort, initiation of CGM was associated with sustained improvement in HbA1c in patients with later-onset T1D and patients with T2D using insulin. This was accompanied by a clear pattern of reduced risk of admission to an emergency room or hospital for hypoglycemia or hyperglycemia and of all-cause hospitalization. 

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4. The Houston Methodist lung transplant risk model – a validated tool for pre-transplant risk assessment

   https://doi.org/10.1016/j.athoracsur.2019.03.108  

   Chan EY, Nguyen DT (October 2019, The annals of thoracic surgery)

   BACKGROUND: Lung transplantation is the gold standard for a carefully selected patient population with end-stage lung disease. We sought to create a unique risk stratification model using only preoperative recipient data to predict one-year postoperative mortality during our pre-transplant assessment. METHODS: Data of lung transplant recipients at Houston Methodist Hospital (HMH) from 1/2009 to 12/2014 were extracted from the United Network for Organ Sharing (UNOS) database. Patients were randomly divided into development and validation cohorts. Cox proportional-hazards models were conducted. Variables associated with 1-year mortality post-transplant were assigned weights based on the beta coefficients, and risk scores were derived. Patients were stratified into low-, medium- and high-risk categories. Our model was validated using the validation dataset and data from other US transplant centers in the UNOS database RESULTS: We randomized 633 lung recipients from HMH into the development (n=317 patients) and validation cohort (n=316). One-year survival after transplant was significantly different among risk groups: 95% (low-risk), 84% (medium-risk), and 72% (high-risk) (p<0.001) with a C-statistic of 0.74. Patient survival in the validation cohort was also significantly different among risk groups (85%, 77% and 65%, respectively, p<0.001). Validation of the model with the UNOS dataset included 9,920 patients and found 1-year survival to be 91%, 86% and 82%, respectively (p < 0.001). CONCLUSIONS: Using only recipient data collected at the time of pre-listing evaluation, our simple scoring system has good discrimination power and can be a practical tool in the assessment and selection of potential lung transplant recipients. 

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5. Hospital antimicrobial stewardship: profiling the oral microbiome after exposure to COVID-19 and antibiotics

   https://doi.org/10.3389/fmicb.2024.1346762  

   Buendia, Patricia; Fernandez, Krystal; Raley, Castle; Rahnavard, Ali; Crandall, Keith A; Castro, Jose Guillermo (February 2024, Frontiers in Microbiology)

   IntroductionDuring the COVID-19 Delta variant surge, the CLAIRE cross-sectional study sampled saliva from 120 hospitalized patients, 116 of whom had a positive COVID-19 PCR test. Patients received antibiotics upon admission due to possible secondary bacterial infections, with patients at risk of sepsis receiving broad-spectrum antibiotics (BSA). MethodsThe saliva samples were analyzed with shotgun DNA metagenomics and respiratory RNA virome sequencing. Medical records for the period of hospitalization were obtained for all patients. Once hospitalization outcomes were known, patients were classified based on their COVID-19 disease severity and the antibiotics they received. ResultsOur study reveals that BSA regimens differentially impacted the human salivary microbiome and disease progression. 12 patients died and all of them received BSA. Significant associations were found between the composition of the COVID-19 saliva microbiome and BSA use, between SARS-CoV-2 genome coverage and severity of disease. We also found significant associations between the non-bacterial microbiome and severity of disease, withCandida albicansdetected most frequently in critical patients. For patients who did not receive BSA before saliva sampling, our study suggestsStaphylococcus aureusas a potential risk factor for sepsis. DiscussionOur results indicate that the course of the infection may be explained by both monitoring antibiotic treatment and profiling a patient’s salivary microbiome, establishing a compelling link between microbiome and the specific antibiotic type and timing of treatment. This approach can aid with emergency room triage and inpatient management but also requires a better understanding of and access to narrow-spectrum agents that target pathogenic bacteria. 

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