Kidney Injury Reported After Luspatercept Therapy: Case Study Raises Caution
France: A newly published case report in BMC Nephrology has highlighted a potential link between luspatercept therapy and a rare form of kidney injury, raising awareness about possible renal complications associated with the drug.
The report, authored by Dr. Stanislas Bataille of the Phocean Institute of Nephrology in Marseille, France, and colleagues, describes a 74-year-old woman who developed mesangial sclerosing glomerulopathy after receiving luspatercept for myelodysplastic syndrome with ring sideroblasts.
Luspatercept is a recombinant fusion protein designed to promote late-stage red blood cell production by blocking select ligands of the transforming growth factor beta (TGF-β) superfamily. It is approved for patients with transfusion-dependent β-thalassemia and certain forms of myelodysplastic syndrome.
Although animal studies have reported glomerular abnormalities associated with luspatercept, kidney toxicity has rarely been documented in humans. In this case, the patient was started on luspatercept to manage persistent anemia. During treatment, she developed acute kidney injury accompanied by heavy proteinuria in the glomerular range, microscopic hematuria, and leukocyturia.
A kidney biopsy was performed to determine the underlying cause. Histopathological examination revealed diffuse mesangial sclerosing glomerulopathy. The dominant feature was marked expansion of the mesangial matrix, with only minimal cellular proliferation. Importantly, immunofluorescence and electron microscopy did not detect immune complex deposits, suggesting a non-immune mechanism of injury.
Following the biopsy findings, luspatercept therapy was discontinued. The patient experienced partial recovery of kidney function; however, significant proteinuria persisted, indicating ongoing glomerular damage.
According to the authors, this appears to be only the second published case of biopsy-confirmed renal injury associated with luspatercept. The previously reported case involved immune complex–mediated membranoproliferative glomerulonephritis (MPGN), a distinct pathological process. In contrast, the current case describes a non-immune mesangial sclerosing lesion, expanding the spectrum of potential renal adverse effects linked to the drug.
The mechanism by which luspatercept may contribute to glomerular injury remains unclear. Given its action on TGF-β–related pathways—known to play a role in fibrosis and extracellular matrix regulation—there is biological plausibility for renal structural changes. However, more research is needed to establish causality and clarify the underlying pathways involved.
The authors emphasize that clinicians prescribing luspatercept should remain vigilant for signs of kidney involvement. They recommend routine monitoring of renal function and urinalysis in patients receiving the medication, particularly those who develop new urinary abnormalities or declining kidney function.
As the use of luspatercept expands in hematologic practice, further pharmacovigilance data and mechanistic studies will be essential to better define the incidence, patterns, and risk factors for renal complications. This case underscores the importance of early recognition and evaluation of kidney-related adverse events in patients undergoing novel targeted therapies.
Reference:
Bataille, S., Daniel, L., Torrents, J. et al. Mesangial sclerosing glomerulopathy following luspatercept treatment – a case report. BMC Nephrol (2026). https://doi.org/10.1186/s12882-026-04807-2
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