Renal Manifestations in VEXAS Syndrome: A Systematic Review of Clinical Features, Pathology, and Outcomes

This review aimed to synthesise current literature on the clinical presentation, renal pathology, treatment, and outcomes of kidney involvement in VEXAS syndrome.

We conducted a systematic review in accordance with PRISMA guidelines, including all original English-language publications from 2020 to May 14, 2025, that described any form of renal involvement in VEXAS syndrome. Data extracted included patient demographics, clinical presentation, renal biopsy findings, treatment strategies (including dialysis), clinical outcomes, and cause of death.

We included nine studies (five case series, three case reports, and one retrospective cohort), providing a total of 39 individual patient records. The reported frequency of renal involvement in VEXAS syndrome ranged from 3.6% to as high as 39% at 10-year follow-up. All documented cases involved male patients. The most common clinical presentations included acute kidney injury (AKI), chronic kidney disease (CKD), proteinuria, and haematuria. Among biopsy findings, interstitial nephritis was most frequently reported, followed by glomerulonephritis, minimal change disease, acute tubular injury, and IgA nephropathy. Less frequently, membranous nephropathy, peritubular capillaritis, glomerulosclerosis, and light chain cast nephropathy were also observed. Treatment primarily involved glucocorticoids, with steroid-sparing agents added based on the presence of coexisting non-renal manifestations. Renal outcomes were generally favourable, with most patients achieving recovery and only rare instances of dialysis dependence. The contribution of renal involvement to overall mortality remains unclear.

Renal manifestations in VEXAS syndrome are varied but remain underexplored due to the rarity of the disease. Focused studies on kidney involvement are crucial to improve our understanding of the underlying pathophysiology and its clinical implications.