Background: Kidney organ transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies directed against the virus are thought to offer protection, but a thorough characterization of anti-SARS-CoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. Methods: We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early (≤14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semi-quantitative Luminex-based multiplex assay, we determined IgM, IgG, IgG1-4 and IgA antibodies against 5 distinct viral epitopes. Results: Kidney transplant recipients showed lower levels of total IgG anti-trimeric spike (S), S1, S2, and receptor-binding domain (RBD), but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG anti-spike protein epitopes were also lower than in immunocompetent controls. Anti-SARS-CoV-2 antibodies were predominantly IgG1 and IgG3 with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG anti-Spike, S1, S2, RBD and NC were not significantly different between cohorts. There was no significant difference in the kinetics of either IgM or IgA anti-Spike, S1, RBD or S2 based on timing after diagnosis or transplant status. Conclusions: Kidney transplant recipients mount early anti-SARS-CoV-2 IgA and IgM responses while IgG responses are delayed compared to immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19.

Background and objectivesWomen with kidney failure have lower access to kidney transplantation compared with men, but the magnitude of this disparity may not be uniform across all kidney diseases. We hypothesized that the attributed cause of kidney failure may modify the magnitude of the disparities in transplant access by sex.Design, setting, participants, & measurementsWe performed a retrospective cohort study of adults who developed kidney failure between 2005 and 2017 according to the United States Renal Data System. We used adjusted Cox models to examine the association between sex and either access to waitlist registration or deceased-donor kidney transplantation, and tested for interaction between sex and the attributed cause of kidney failure using adjusted models.ResultsAmong a total of 1,478,037 patients, 271,111 were registered on the waitlist and 89,574 underwent deceased-donor transplantation. The rate of waitlisting was 6.5 per 100 person-years in women and 8.3 per 100 person-years for men. In adjusted analysis, women had lower access to the waitlist (hazard ratio, 0.89; 95% confidence interval, 0.89 to 0.90) and to deceased-donor transplantation after waitlisting (hazard ratio, 0.96; 95% confidence interval, 0.94 to 0.98). However, there was an interaction between sex and attributed cause of kidney disease in adjusted models (P<0.001). Women with kidney failure due to type 2 diabetes had 27% lower access to the kidney transplant waitlist (hazard ratio, 0.73; 95% confidence interval, 0.72 to 0.74) and 11% lower access to deceased-donor transplantation after waitlisting compared with men (hazard ratio, 0.89; 95% confidence interval, 0.86 to 0.92). In contrast, sex disparities in access to either the waitlist or transplantation were not observed in kidney failure secondary to cystic disease.ConclusionsThe disparity in transplant access by sex is not consistent across all causes of kidney failure. Lower deceased-donor transplantation rates in women compared with men are especially notable among patients with kidney failure attributed to diabetes.

Rationale & Objective: In the general population, girls have lower mortality risk compared to boys. However, few studies have focused on sex differences in survival and in access to kidney transplantation among children with end-stage renal disease (ESRD).

Key Points Question Has the risk of death from cardiovascular disease improved in children and young adults starting dialysis during the last 2 decades? Findings In this cohort study including 80 189 children and young adults initiating dialysis over a 20-year period, risk of cardiovascular-related mortality improved overall for both children and young adults over time. The risk of sudden cardiac death improved more for children than adults, while improvements in stroke-related mortality were slower to occur and less pronounced. Meaning Risk of cardiovascular-related mortality in a young population receiving dialysis improved overall, but further studies are needed to understand variations in changes to the risk of different cardiovascular-related causes of death.

Twenty-five to 30 per cent of hypotensive trauma patients require an emergent surgery, however, we have no reliable means to quickly determine that need. Our goal was to determine, via retrospective review, parameters available within minutes of arrival that predict the need for emergent surgery to control hemorrhage in hypotensive trauma patients. Inclusion criterion was initial systolic blood pressure (SBP) < 90 mm Hg in the emergency department (ED). Patients who were dead on arrival or underwent ED thoracotomy were excluded. Emergent surgery was defined as sternotomy, thoracotomy, laparotomy, or major neck vascular repair on day of admission. Potential clinical predictors were analyzed in a binary logistic regression model. Six hundred and thirty-nine hypotensive patients were identified and 193 excluded, leaving 446 with a mean age of 33 ± 19 years and Injury Severity Score of 22 ± 17. Thirty-two per cent suffered penetrating trauma, 30 per cent needed emergent surgery, and 19 per cent died. Independent predictors were: prolonged extrication (odds ratio (OR) 2.3), no loss of consciousness (OR 2.8), intubation (OR 1.7), central line placement (OR 1.7), and blood transfusion (OR 2.1, all P < 0.05). We concluded that hypotensive trauma patients without head injuries who require prolonged extrication, intubation, central venous access, and blood transfusion in the ED are more likely to need emergent surgery.

Original Clinical Science-General Background. Characterization of anti-HLA versus anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) immune globulin isotypes in organ transplant recipients after coronavirus disease 2019 (COVID-19) infection has not been reported. We aimed to determine changes in anti-HLA antibodies in renal transplant patients with COVID-19 and compare the immunoglobulin and epitope-binding pattern versus anti-SARS-CoV-2 antibodies. Methods. This is a crosssectional study of 46 kidney transplant recipients including 21 with longitudinal sampling. Using a semi-quantitative multiplex assay, we determined immunoglobulin (Ig) M, IgA, IgG, and IgG1-2-3-4 antibodies against Class I and Class II HLA, and 5 SARS-CoV-2 epitopes including the nucleocapsid protein and multiple regions of the spike protein.Results. Fourteen of 46 (30%) patients had donor-specific anti-HLA antibodies (donor-specific antibody [DSA]), 12 (26%) had non-DSA anti-HLA antibodies and 45 (98%) had anti-SARS-CoV-2 antibodies. Most DSAs targeted HLA-DQ (71%), with a dominant IgG isotype and IgG1 subtype prevalence (93%), and/or IgG3 (64%), followed by IgG2 (36%). Comparatively, there was a higher prevalence of IgA (85% versus 14%, P = 0.0001) and IgM (87%, versus 36%, P = 0.001) in the anti-SARS-CoV-2 antibody profile, when compared to DSAs, respectively. Anti-SARS-CoV-2 antibody profile was characterized by increased prevalence of IgM and IgA, when compared to DSAs. The median calculated panel reactive antibody before COVID-19 diagnosis (24%) tended to decrease after COVID-19 diagnosis (10%) but it was not statistically significant (P = 0.1). Conclusions. Anti-HLA antibody strength and calculated panel reactive antibody in kidney transplant recipients after COVID-19 do not significantly increase after infection. Although the IgG isotype was the dominant form in both HLA and SARS-CoV-2 antigens, the alloimmune response had a low IgA pattern, whereas anti-SARS-CoV-2 antibodies were high IgA/IgM.

Purpose Tacrolimus is a nephrotoxic immunosuppressant historically monitored via enzyme-based immunoassay (IA). After 2011, the 2 largest laboratory companies in the United States implemented tacrolimus quantification by liquid chromatography–mass spectrometry (LC-MS); this method excludes metabolites, potentially resulting in lower quantified drug concentrations. We sought to determine if tacrolimus therapeutic drug monitoring via LC-MS, as performed using trough targets originally derived from IA values, influences clinical outcomes. Methods In a single-center retrospective cohort study of lung transplant recipients, risks of acute kidney injury, acute renal failure, and new-onset diabetes after transplantation, as well as chronic lung allograft dysfunction–free survival, were compared in 82 subjects monitored by LC-MS and 102 subjects monitored by IA using Cox proportional hazard models adjusted for age, sex, baseline renal function, and race. Results LC-MS–based monitoring was associated with a greater risk of acute kidney injury (adjusted hazard ratio, 1.65; 95% confidence interval, 1.02–2.67). No statistically significant differences in risks of acute renal failure and new-onset diabetes after transplantation were observed. Conclusion Although LC-MS provides a more accurate representation of the blood concentration of the parent compound tacrolimus exclusive of metabolite, established cut points for tacrolimus dosing may need to be adjusted to account for the increased risk of renal injury.