Kidney Week

Abstract: TH-PO067

A Clinicopathological Description of Kidney Features in VEXAS Syndrome

Session Information

• AKI: Clinical, Outcomes, and Trials - Epidemiology and Pathophysiology
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Mathurin, Martin, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Martin Mathurin, MD

• Hirsch, Pierre, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Pierre Hirsch, MD, PhD

• Buob, David, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

David Buob, MD

• El Karoui, Khalil, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France

Khalil El Karoui, MD, PhD

Group or Team Name

• FRENVEX Group.

Background

VEXAS (Vacuoles, enzyme E3, X linked, Autoinflammatory, Somatic) is a recently reported autoinflammatory syndrome characterized by myeloid lineage-restricted acquired variants in the ubiquitin-activating E1 (UBA1) gene. Renal lesions of VEXAS patients are poorly characterized.

Methods

We searched for patients with kidney biopsy (KB) among 303 VEXAS cases from the french nationalVEXAS cohort. We extracted data from medical records, and performed a centralized review of renal biopsies. We investigated the presence of UBA1 mutated clones within the kidney by sequencing DNA extracted from whole kidney tissue.

Results

We identified 11 patients with KB. All were male, mean age was 70 years old. Renal presentation included progressive chronic kidney disease in 5 patients and acute kidney injury (AKI) in 6 (including two needing renal replacement therapy). AKI episodes were chronologically linked with VEXAS flares in 3 patients. Mean sCreatinine was 363 µmol/l. All patients presented with extra renal manifestations. Renal function evolution was usually favorable after treatment with corticosteroids and various immunosuppressors. Histopathological findings were heterogenous, including acute interstitial nephritis (n=4), ANCA negative pauci-immune vasculitis (n=1), IgA nephropathy superimposed with minimal change disease (n=1), IgA nephropathy (n=1), diabetic nephropathy with extensive fibrosis (n=1), acute tubular necrosis (n=2), and AA amyloidosis (n=1). Interstitial inflammatory infiltration was noticed in 8/11 cases, whatever the primary diagnosis. Immunohistochemical characterization of interstitial inflammatory cells demonstrated the presence of lymphocytes and plasma cells, admixed with macrophages and neutrophil cells. MPO and CD68 immunostaining was positive in all cases, with a variable degree of expression. We performed molecular analysis of DNA extracted from 8 available frozen samples by next generation sequencing. UBA1 variation was detected in 7/8 samples, with VAF ranging from 2% to 17% of total kidney DNA.

Conclusion

This series highlights the heterogeneous clinical and histological presentation of VEXAS-associated kidney disease. The molecular analysis of kidney tissue along with the frequent histological finding of interstitial infiltration may suggest the existence of a specific involvement of clonal cells directly targeting the kidney during VEXAS.