Angiotensin II (AII) plays a major role in the progression of chronic kidney diseases. Podocytes are essential components of the ultrafiltration apparatus, and are targets for AII signaling. AII has been shown to increase generation of reactive oxygen species (ROS) in podocytes. Canonical transient receptor potential-6 (TRPC6) channels stimulate Ca(2+) influx in podocytes, and have been implicated in glomerular disease. We observed that AII increased cationic currents in rat podocytes in an isolated glomerulus preparation in which podocytes are still attached to the underlying capillary. This effect was completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by endogenously expressed angiotensin II receptors in these cells. These responses were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor D-609, and by inhibition of G protein signaling. The pan-protein kinase C inhibitor chelerythrine had no effect. Importantly, pretreating podocytes with the ROS quencher manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) eliminated AII activation of TRPC6. Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). These data suggest that ROS production permits activation of TRPC6 channels by G protein and PLC-dependent cascades initiated by AII acting on AT1Rs in podocytes. This pathway also provides a basis whereby two forms of cellular stress-oxidative stress and Ca(2+) overload-converge on common pathways relevant to disease.

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Objectives Identification of racial differences in characteristics and comorbidities in patients hospitalized for COVID-19 and the impact on outcomes. Study design Retrospective observational study. Methods Data for all patients admitted to seven community hospitals in Michigan, United States with polymerase chain reaction confirmed diagnosis of COVID-19 from March 10 to April 15, 2020 was analyzed. The primary outcomes of racial disparity in inpatient mortality and intubation were analyzed using descriptive statistics and multivariate regression models. Results The study included 336 black and 408 white patients . Black patients were younger (62.9 +/- 15.0 years vs 71.8 +/- 16.4, P <.001), had a higher mean body mass index (32.4 +/- 8.6 vs 28.8 +/- 7.5, P <.001), had higher prevalence of diabetes (136/336 vs 130/408, P =.02) and presented later (6.6 +/-5.3 days after symptom onset vs. 5.4 +/- 5.4, P =.006) compared to white patients. Younger black patients had a higher prevalence of obesity (age< 65, 69.9%) than older black patients (age>65, 39.2%) and younger white patients (age<65, 55.1%). Intubation did not reach statistical significance for racial difference (black patients 61/335 vs. 54/406, P =.08). Mortality was not higher in black patients (65/335 vs. 142/406 in white patients, Odds ratio 0.61, 95% CI 0.37 to 0.99, 2 sided P =.05) in multivariate analysis, accounting for other risk factors associated with mortality. Conclusions Higher prevalence of obesity and diabetes in young black populations may be the critical factor driving disproportionate COVID-19 hospitalizations in black populations. Hospitalized black patients do not have worse outcomes compared to white patients.

Cytomegalovirus (CMV) infection is a common cause of morbidity and mortality in immunocompromised hosts. Tissue-invasive CMV disease causing ulcerative skin disease or esophageal necrosis is rare. We herein describe two cases: a 47-year-old renal and pancreas transplant recipient who presented with skin ulcerations on his elbow and a 50-year-old renal transplant recipient who presented with acute esophageal necrosis. In both, tissue biopsy revealed CMV inclusion bodies by immunohistochemical staining of infected endothelial and mucosal cells. Ganciclovir was given to both cases and full remission occurred. Due to the varying presentations of acute CMV infection in immunosuppressed hosts, high suspicion and early tissue biopsy are vital for proper diagnosis and treatment when any suspicious cutaneous or mucosal manifestations are present.

Antiphospholipid antibodies (aPLs) against Beta-2 glycoprotein-I (β 2 GPI) are considered to be the center of pathogenesis of antiphospholipid syndrome (APS). Autoimmune aPLs are pathogenic as patients are at increased risk of enhancing thrombin generation at a young age. There are only three aPLs considered as diagnostic laboratory markers for APS - IgM, IgG, and IgA isotypes. However, the association of the IgA isotypes with clinical thrombosis remains highly controversial. A 30-year-old male with a past medical history of childhood asthma initially presented to the hospital with acute left middle cerebral artery ischemic stroke, which did not get resolved with tissue plasminogen activator (tPA) but was successfully resolved with thromboembolectomy. It was speculated to be associated with a clot from mitral valve prolapse found subsequently on echocardiogram. Twenty-eight days later, the patient presented again with a high-grade luminal narrowing of his mid- and distal left internal carotid artery with 80% narrowing and an acute dissection of his left internal carotid artery. The recurrence of thrombosis was evaluated through hypercoagulable state workup, which demonstrated evidence of antiphospholipid syndrome with elevated beta-2 glycoprotein IgA antibody titers of more than 150 U/mL. This is one of the first cases reported nationwide as evidence of thrombogenesis recurrence induced by IgA antiphospholipid antibody β 2 glycoprotein I-dependent in early adulthood. IgA anti- β 2 GPI antibodies are found to have an association with many clinical manifestations of antiphospholipid syndrome and thrombotic events, particularly arterial thrombosis. To determine the link between the IgA-aβ 2 GPI antibodies and APS-events in asymptomatic individuals before recommending preventive treatments, there needs to be a broader intention to standardize IgA-aβ 2 GPI assays as a diagnostic criterion for APS.