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POS-906 TREATMENT WITH RECOMBINANT MUTATED HUMAN ANGIOPOIETIN-LIKE 4 AMELIORATES GLOMERULAR INJURY IN A MODEL OF THE COVID-19 CYTOKINE STORM
Kidney International Reports ; 7(2):S393-S394, 2022.
Article in English | EMBASE | ID: covidwho-1707796
ABSTRACT

Introduction:

Some patients with COVID-19 infection develop proteinuria or Acute Kidney Injury, and cases of COVID-19 related Collapsing Glomerulopathy have also been reported. Three published human kidney biopsy studies did not find viral particles in the glomeruli or tubules. This raises the possibility of glomerular and kidney injury induced by the extensive cytokine storm documented early on in the pandemic in hospitalized COVID-19 patients. Mutated forms of Human Angiopoietin-like 4 (protein 8520) were previously shown to reduce proteinuria in rat models of FSGS and diabetic nephropathy (Clement LC, Mace C et al. Nature Medicine 2014). Using different components or innate and adaptive immunity triggered during infection, we developed cytokine cocktails that mimic the COVID-19 cytokine storm, and tested the ability of protein 8520 to reduce glomerular injury in this model.

Methods:

After baseline urine and blood collections, two groups of BALB/c mice (mean n = 5 mice per group) were injected intravenously with dose 1.8 X of COVID Cocktail D. One hour later, they received 10 μg of His-Tag purified protein 8520 or control human albumin. Overall activity status was documented at 6 and 24 hours. At 24 hours after model induction, blood and urine samples were collected, and the mice euthanized, followed by harvesting of multiple organs including kidneys. Urine albumin was measured by ELISA (Bethyl Labs), and urine and serum creatinine by Mass Spectrometry.

Results:

Baseline urine albumin to creatinine ratio was similar between the two groups. At 24 hours, urine albumin to creatinine ratio was significantly lower in the 8520 treated compared to control treated group (P < 0.05). Serum creatinine on Day 1 was similar between both groups, and not significantly elevated compared to baseline. Kidney sections were processed for light and electron microscopy, and analysis of these studies is in progress.

Conclusions:

Treatment with recombinant mutated human Angiopoietin-like 4 reduces albuminuria in a mouse model of the COVID-19 cytokine storm. Further studies will be conducted to establish a potential therapeutic role in viral cytokine storms. No conflict of interest
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Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Kidney International Reports Year: 2022 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Kidney International Reports Year: 2022 Document Type: Article