Lipotoxicity and immunometabolism in ischemic acute kidney injury: current perspectives and future directions.

Dysregulated lipid metabolism is implicated in the pathophysiology of a range of kidney diseases. The specific mechanisms through which lipotoxicity contributes to acute kidney injury (AKI) remain poorly understood. Herein we review the cardinal features of lipotoxic injury in ischemic kidney injury; lipid accumulation and mitochondrial lipotoxicity. We then explore a new mechanism of lipotoxicity, what we define as "immunometabolic" lipotoxicity, and discuss the potential therapeutic implications of targeting this lipotoxicity using lipid lowering medications.

HLA matching between donors and recipients improves clinical liver transplant graft survival.

BACKGROUND AND AIMS: The importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-centre database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status. METHODS: This retrospective observational analysis was performed using 22 702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs. 4-6 mismatches) and then subcategorized by indication and donor status. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. RESULTS: Allograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity, and congenital indications. Donor status also influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4-6 HLA mismatch group, whereas no significant difference was found in the 0-3 HLA mismatch group. CONCLUSION: HLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols, and transplant surveillance.

Symptomatic atherosclerotic vascular disease and graft survival in primary kidney transplant recipients - Observational analysis of the united network of organ sharing database.

OBJECTIVES: The aim of this study was to investigate whether symptomatic atherosclerotic vascular disease (SAVD) was associated with graft survival in primary kidney transplant recipients. SUMMARY BACKGROUND DATA: Recipient atherosclerotic vascular disease is associated with increased mortality rates amongst renal transplant patients. However, its relationship with graft survival has not been well studied. METHODS: This retrospective observational analysis was performed using data for adult kidney transplant recipients between 11/09/2000 and 28/02/2020 extracted from the UNOS national organ transplantation database. Patients were divided into two groups based on recipient history of symptomatic atherosclerotic disease (angina or peripheral vascular disease). Risk-adjusted outcomes were assessed by multivariate Cox regression analysis adjusting for both donor and recipient characteristics. RESULTS: 11,771 adult kidney transplant recipients from the UNOS database were eligible for analysis (1543 had a history of SAVD, 10,228 did not have a history of SAVD). After adjusting for confounders, positive SAVD status was associated with an adverse effect on graft survival at both 1 year (HR 1.35, p < 0.001) and 10 years (HR 1.15, p < 0.001). CONCLUSIONS: SAVD should be considered an independent risk factor for poor prognosis in patients undergoing kidney transplant.

Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: A Systematic Review of Reviews.

BACKGROUND: This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD). PURPOSE: To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality. DATA SOURCES: We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020. STUDY SELECTION: Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used. DATA EXTRACTION: One reviewer appraised and extracted data; data were checked by a second. DATA SYNTHESIS: Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection. LIMITATIONS: Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias. CONCLUSIONS: There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention.

Pilomatricoma on 18F-fluorodeoxyglucose positron emission tomography-computed tomography: Peripheral mimic of an aggressive soft-tissue malignancy.

Pilomatricoma, also known as calcifying epithelioma of Malherbe, is a rare skin tumor originating from the hair follicle matrix. We report a case of pilomatricoma in a 50-year-old woman, presenting as a rapidly growing pretibial mass. Malignant pilomatricoma is associated with potentially fatal metastases and are clinically and histologically indistinguishable from benign pilomatricoma. Thus, an 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scan was requested for staging, revealing marked FDG uptake restricted to the primary lesion and no evidence of separate disease. The purpose of this report is to demonstrate the importance of PET/CT in the staging of this FDG-avid tumor; the malignancy of which is often first revealed by metastases. Our case also demonstrates that pilomatricoma should be included in the differential diagnosis of a rapidly growing peripheral soft-tissue mass; conventionally, the domain of sarcoma.