Therapeutic considerations for prevention and treatment of thrombotic events in COVID-19.

Thrombosis is a known complication of SARS-CoV-2 infection, particularly within a severely symptomatic subset of patients with COVID-19 disease, in whom an aggressive host immune response leads to cytokine storm syndrome (CSS). The incidence of thrombotic events coinciding with CSS may contribute to the severe morbidity and mortality observed in association with COVID-19. This review provides an overview of pharmacologic approaches based upon an emerging understanding of the mechanisms responsible for thrombosis across a spectrum of COVID-19 disease involving an interplay between immunologic and pro-thrombotic events, including endothelial injury, platelet activation, altered coagulation pathways, and impaired fibrinolysis.

The mechanistic basis linking cytokine storm to thrombosis in COVID-19.

It is now well established that infection with SARS-CoV-2 resulting in COVID-19 disease includes a severely symptomatic subset of patients in whom an aggressive and/or dysregulated host immune response leads to cytokine storm syndrome (CSS) that may be further complicated by thrombotic events, contributing to the severe morbidity and mortality observed in COVID-19. This review provides a brief overview of cytokine storm in COVID-19, and then presents a mechanistic discussion of how cytokine storm affects integrated pathways in thrombosis involving the endothelium, platelets, the coagulation cascade, eicosanoids, auto-antibody mediated thrombosis, and the fibrinolytic system.

Treatment of recurrent, post-kidney transplant membranoproliferative glomerulonephritis with plasmapheresis and rituximab: A case report and literature review
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Membranoproliferative glomerulonephritis is known to recur after kidney transplantation and may lead to allograft loss. Although an optimal treatment has not been determined, B-cell targeted therapies are now increasingly used as first-line agents, based on growing data showing antibodies as key players in the pathogenesis of membranoproliferative glomerulonephritis. Here, we report a case of recurrent immune complex-mediated membranoproliferative glomerulonephritis 3 years after a living-donor kidney transplant. Treatment with plasmapheresis and rituximab resulted in immediate and sustained improvement in allograft function.
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Routine ultrasonography surveillance of native kidneys for renal cell carcinoma in kidney transplant candidates.

Renal cell carcinoma (RCC) has a high incidence in the kidney transplant population and annual surveillance detects these tumors early in their natural history. Minimal guidelines exist regarding RCC surveillance in ESRD patients awaiting transplant. A retrospective review of our kidney transplant database examined the outcomes of annual ultrasonographic surveillance during initial kidney transplant evaluation and upon annual reassessment. Of 2642 patients listed for transplant, 145 patients were found to have masses during initial kidney transplant evaluation or annual imaging consistent with new complex cystic disease or RCC. A total of 71 patients had RCC identified, with 52 found on initial kidney transplant evaluation and 19 identified on annual surveillance. Male gender and African-American race were independently associated with RCC (P<.05). RCC was detected a median of 2.0 years after listing (two annual ultrasonography studies). Patients with complex cysts were more likely to undergo transplantation (48.7%) compared to patients with RCC (21.1%; P<.001). There was no significant difference in survival between RCC patients and those found to have complex cystic disease, suggesting incidental RCC can be diagnosed early in the natural history and at a curable stage through implementation of a biennial surveillance program.

West Nile virus infection in kidney and pancreas transplant recipients in the Dallas-Fort Worth Metroplex during the 2012 Texas epidemic.

BACKGROUND: In 2012, the United States experienced one of its worst West Nile virus (WNV) epidemics, reporting 5,387 human cases and final death toll of 243. Texas was at the epicenter of the outbreak, with 1,875 reported cases and 89 deaths that year. The Texas outbreak centered mainly in the Dallas-Fort Worth area where 30 deaths were reported. We report three cases of severe WNV infection complicated by meningoencephalitis in our organ transplant population. METHODS: Clinical data were collected from chart review. Therapy and outcomes on three identified patients were reviewed and compared with previously reported cases of WNV infection in kidney/pancreas transplant recipients and the general population. RESULTS: Two recipients of kidney and one recipient of a combined kidney and pancreas transplant were treated at our center for WNV infection. All three patients presented with a rapid decline in mental status within 24 hours of admission consistent with meningoencephalitis. Diagnosis was made based on detection of WNV IgM in the serum. All patients received intravenous immunoglobulin (IVIG) therapy at 400 mg/kg × 3 to 4 doses. As a result, two patients had a full recovery, and one patient died. CONCLUSION: Transplant recipients have a higher risk of neurologic complications from WNV infection. In areas where WNV is endemic, clinicians must have a high index of suspicion when treating patients presenting with fever, headache, and confusion. Full recovery in two of three patients suggests a potential role of IVIG therapy in controlling active WNV infection, particularly in immunosuppressed patients.

Use of an immune function assay to monitor immunosuppression for treatment of post-transplant lymphoproliferative disorder.

The first-line treatment for PTLD is reduction in immunosuppression, allowing partial reconstitution of cell-mediated immunity. However, there is a risk of inducing acute allograft rejection during clinical resolution of PTLD. A recently available assay, Immuknow, measures the cell-mediated immune response and could be used to monitor reduction of immunosuppression. We report a case of PTLD occurring in a pediatric kidney transplant recipient where the reduction in immunosuppression was serially followed using this assay and quantitative EBV-PCR. A rapid reduction to minimal immunosuppression was followed by resolution of PTLD. Later, when the cell-mediated immune response increased, with negative viral load, immunosuppression was gradually increased utilizing the assay to adjust dosing. Presently, there are no signs of PTLD and renal function remains normal.

Renal transplantation: older recipients and donors.

The majority of patients receiving a renal allograft, including a kidney from an older donor, do well. Renal transplantation from a living donor is associated with distinct advantages, including prolonged allograft survival. When live donors are not available, however, deceased donor kidneys provide suitable renal function that frequently lasts the lifetime of elderly recipients. Elderly patients who receive a kidney transplant enjoy improved survival, better quality of life, and lower medical costs than those who remain on dialysis.