Background/Aims: We previously reported that patients with chronic kidney disease (CKD) receiving warfarin therapy and whose international normalized ratio increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this condition warfarin-related nephropathy (WRN). We also previously reported that acute excessive anticoagulation with brodifacoum (superwarfarin) induces AKI in 5/6 nephrectomy (5/6NE) rats. Limitations of the brodifacoum model precluded a careful assessment of dose-response relationships. Methods: Warfarin treatment was used in 5/6NE. Results: Herein we report that warfarin treatment of 5/6NE rats resulted in a dose-dependent increase in serum creatinine (SC). The increase in SC following warfarin treatment was greater at 3 and 19 weeks after the ablative surgery, than that observed 8 weeks after the ablative surgery. The SC increase was correlated with the prothrombin time increase. Morphologically, 5/6NE, but not control rats, had acute tubular injury with RBC and RBC casts in the tubules. Treatment with vitamin K prevented SC increase and morphologic changes in the kidney associated with warfarin treatment. A single episode of WRN did not affect the progression of CKD in 5/6NE. Conclusion: (1) The 5/6NE model of CKD is an appropriate animal model to study the pathogenesis of WRN. (2) The pharmacokinetics of warfarin is better suited to the study of WRN than that of brodifacoum. (3) The more advanced stages of 5/6NE are more susceptible to WRN than the earlier stages. (4) Vitamin K treatment prevents WRN.

Protocol-driven management decreased glucose levels 7 of 14 days after admission without outcome change. One or more glucose levels > or =150 mg/dL were associated with worse outcome.

Solid organ transplant (SOT) recipients are at high risk for severe coronavirus disease 2019 (COVID‐19). Studies suggest that early intervention with monoclonal antibody (MAB) treatment directed against the SARS‐CoV‐2 spike protein may reduce the risk of emergency department visits or hospitalization for COVID‐19, especially in high‐risk patients. Herein we describe our single‐center experience of 93 SOT (50 kidney, 17 liver, 11 lung, 9 heart and 6 dual‐organ) recipients with mild to moderate COVID‐19 who were treated with bamlanivimab or casirivimab‐imdevimab per Emergency Use Authorization guidelines. Median age of recipients was 55 (IQR 44–63) years and 41% were diabetic. Median time from transplant to MAB was 64 (IQR 24–122) months and median time from onset of COVID‐19 symptoms to the infusion was 6 (IQR 4–7) days. All patients had a minimum 30 days of study follow up. The 30‐day hospitalization rate for COVID‐19 directed therapy was 8.7%. Infusion‐related adverse events were rare and generally mild. Biopsy‐proven organ rejection occurred in 2 patients and there were no graft losses or deaths. A comparator group of 72 SOT recipients diagnosed with COVID‐19 who were eligible but did not receive MAB treatment had a higher 30‐day hospitalization rate for COVID‐19 directed therapy (15.3%), although this difference was not statistically significant, after adjustment for age [OR 0.49 (95% CI 0.18‐1.32), p = 0.16]. Our experience suggests that MAB treatment, with respect to the available MAB formulations and circulating viral variants present during our study period, may provide favorable outcomes for mild to moderate COVID‐19 in SOT recipients. This article is protected by copyright. All rights reserved

Background: Transplant practices related to use of organs from Hepatitis C virus infected donors (DHCV+) is evolving rapidly. Methods: We surveyed U.S. kidney transplant programs by email and professional society listserv postings between 7/19-1/20 to assess attitudes, management strategies, and barriers related to use of viremic (nucleic acid testing (NAT)+) donor organs in HCV uninfected recipients. Results: Staff at 112 unique programs responded, representing 54% of U.S. adult kidney transplant programs and 69% of adult deceased donor kidney transplant volume in 2019. Most survey respondents were transplant nephrologists (46%) or surgeons (43%). Among responding programs, 67% currently transplant DHCV antibody+/NAT-organs under a clinical protocol or as standard of care. By comparison, only 58% offer DHCV NAT+ kidney transplant to HCV-recipients, including 35% under clinical protocols, 14% as standard of care, and 9% under research protocols. Following transplant of DHCV NAT+ organs to uninfected recipients, 53% start direct acting antiviral agent (DAA) therapy after discharge and documented viremia. Viral monitoring protocols after DHCV NAT+ to HCV uninfected recipient kidney transplantation varied substantially. 56% of programs performing these transplants report having an institutional plan to provide DAA treatment if declined by the recipient's insurance. Respondents felt a mean decrease in waiting time of >18 months (range 0-60) justifies the practice. Program concerns related to use of DHCV NAT+ kidneys include insurance coverage concerns (72%), cost (60%), and perceived risk of transmitting resistant infection (44%). Conclusions: Addressing knowledge about safety and logistical/financial barriers related to use of DHCV NAT+ kidney transplantation for HCV uninfected recipients may help reduced discards and expand the organ supply.

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