Mesangial sclerosing glomerulopathy following luspatercept treatment - a case report

Luspatercept is a recombinant fusion protein that enhances late-stage erythropoiesis by inhibiting select transforming growth factor β (TGFβ) superfamily ligands. It is approved for transfusion-dependent β-thalassemia and myelodysplastic syndromes with ring sideroblasts. Kidney toxicity has been rarely reported in humans, although glomerular lesions have been described in preclinical studies. We report the case of a 74-year-old woman with myelodysplastic syndrome with ring sideroblasts treated with luspatercept for persistent anemia. She developed acute kidney injury, glomerular-range proteinuria, microscopic hematuria, and leukocyturia. Renal biopsy revealed a diffuse mesangial sclerosing glomerulopathy characterized by prominent mesangial matrix expansion with minimal proliferative changes, no immune complex deposits on immunofluorescence or electron microscopy. Luspatercept was discontinued, leading to a partial improvement in renal function but persistent proteinuria. This case documents a non-immune mesangial sclerosing glomerulopathy temporally associated with luspatercept therapy. Only one other case of biopsy-proven renal injury linked to luspatercept has previously been published, with an immune complex-mediated MPGN. Clinicians should be aware of possible renal involvement during luspatercept treatment and consider systematic monitoring of kidney function and urinalysis in treated patients. Further data are needed to clarify the spectrum and mechanisms of renal adverse events associated with this drug.