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Abstract: TH-PO719

Interstitial Inflammation and C3 Glomerulopathy Secondary to an Autoinflammatory Syndrome

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Saha, Manish K., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Rivenbark, Joshua, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Caceres-Nazario, Beatriz, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Buglioni, Alessia, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Rubinstein, Samuel M., The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Introduction

Dual presence of histiocytic interstitial inflammation and C3 glomerulopathy (C3GN) are uncommon. We report a rare case of non-Langerhans cell histicoytosis associated acute kidney injury (AKI).

Case Description

A 71-yr-old male was admitted to the hospital with anasarca and generalized weakness. Laboratory data were significant for anemia, AKI, hypercalcemia, and trace monoclonal IgA lambda. Autoimmune and infectious workup was unrevealing. PET scan revealed hypermetabolic extensive infiltration of kidneys, perirenal space, and mild bilateral hydronephrosis. Bone marrow biopsy demonstrated hypercellular marrow without evidence of neoplasm. Vacuolization was not demonstrated in neutrophils. Kidney biopsy showed C3GN. Interestingly, a cluster of interstitial CD68-positive and Langerin-negative histiocytes was present. C3GN was thought to be inactive in the absence of active urine sediment. Biopsy of the perinephric mass showed fibroconnective tissue primarily composed of histiocytes, without evidence of neoplasm. IgG4 and EBV staining were negative. Further evaluation led to the identification of a pathogenic variant in the UBA1 gene p.(M41) – a somatic variant which may result in promotion of pro-inflammatory gene expression, and implicated in the pathogenesis of VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic mutation) syndrome, a recently described autoinflammatory disease. The patient’s clinical presentation in the setting of a pathogenic UBA1 variant was consistent with VEXAS syndrome. Speculatively, the alternate complement pathway, could have been activated by the inflammatory mediators or IgA lambda protein, leading to C3GN (C3 Nef antibody was negative, normal C3/C4).
AKI was determined to be multifactorial and hypercalcemia was secondary to cytokine-mediated increased calcitriol synthesis by monocytes. This patient was treated with oral glucocorticoid and anti-IL-6 receptor monoclonal antibodies, with marked improvement in clinical status, inflammatory markers, kidney function, and metabolic uptake on follow-up PET scan.

Discussion

Acute interstitial inflammation with infiltration of non-Langerhans cell histiocytes due to VEXAS syndrome is a rare cause of AKI. A high degree of suspicion is required to diagnose VEXAS which carries significant mortality and morbidity without prompt treatment.