# Kidney involvement in VEXAS syndrome: insights from a rare case of secondary amyloidosis and systematic review of renal biopsy-confirmed reports

## TL;DR

This paper reports a rare case of kidney disease in a patient with VEXAS syndrome and reviews other similar cases to highlight the under-recognized kidney complications of this condition.

## Contribution

The study provides new insights into the renal manifestations of VEXAS syndrome through a case report and systematic review of biopsy-confirmed cases.

## Key findings

- Interstitial nephritis was the most common kidney pathology in VEXAS syndrome cases.
- Immunosuppressive therapies showed limited efficacy in treating renal involvement in VEXAS syndrome.
- Amyloidosis was identified as a complication of chronic inflammation in one VEXAS syndrome patient.

## Abstract

VEXAS syndrome is a recently identified autoinflammatory disorder caused by somatic mutations in the UBA1 gene, leading to systemic inflammation and hematologic abnormalities. While its renal involvement remains poorly understood, reported cases suggest a diverse spectrum of kidney pathology. We present a 69-year-old male with a history of systemic inflammation who developed nephrotic syndrome and worsening kidney function. His disease course included recurrent fevers, pulmonary infiltrates, cutaneous vasculitis, and hematologic abnormalities. A kidney biopsy revealed secondary amyloidosis, indicating chronic inflammation. Genetic testing confirmed a UBA1 mutation (c.121A > G, p.Met41Val), establishing the diagnosis of VEXAS syndrome. Despite treatment with corticosteroids, cyclosporine, and interleukin-1 blockade, the patient deteriorated and ultimately succumbed to septic shock. A systematic review of biopsy-confirmed renal involvement in VEXAS syndrome identified 23 cases, with interstitial nephritis as the most frequent histopathologic finding, followed by vasculitis, IgA nephropathy, minimal change disease, and amyloidosis. Treatment responses varied, with limited efficacy of immunosuppressive therapies. This case highlights the under-recognized renal manifestations of VEXAS syndrome, demonstrating its diagnostic challenges and the need for heightened clinical suspicion. Further research is required to define optimal management strategies and improve patient outcomes.

The online version contains supplementary material available at 10.1007/s10067-025-07506-9.