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Acalabrutinib is a second generation Bruton’s tyrosine kinase (BTK) inhibitor used to treat various types of non-Hodgkin lymphoma, including mantle cell lymphoma and chronic lymphocytic leukaemia (CLL). It may be used both in relapsed as well as in treatment-naive settings. Acalabrutinib was approved for medical use in the United States in 2017 and in the European Union in November 2020. Common side effects of Acalabrutinib include headaches, tiredness, anaemia, thrombocytopenia. Acute Kidney Injury (AKI) is rarely reported with Acalabrutinib
We report a case report of severe tubulo-interstitial nephritis (TIN) due to Acalabrutinib in a patient with splenic marginal zone lymphoma
A 68-year-old lady with a history of hypertension for 18 years (well controlled on amlodipine 5mg) was diagnosed with splenic marginal zone lymphoma. Whole body FDG PET scan showed mild hepatosplenomegaly with diffuse metabolic activity in enlarged spleen and entire visualized bone marrow.
Patient was started on Acalabrutinib and after 2 months presented to our OPD with bilateral lower limb swelling and vomiting for 14 days. On evaluation, creatinine was elevated (8.82mg/dL) which was near normal before starting acalabrutinib (1.32mg/dL). Urine microscopy revealed occasional pus cells with trace proteinuria. 24-hour urinary protein excretion was 900mg. Antinuclear antibody, Anti neutrophil cytoplasmic antibodies, Anti Glomerular basement antibodies were negative and serum C3 and C4 level, serum protein electrophoresis and serum free light chains were within normal limits. Urine microscopy revealed few pus cells and WBC casts. Ultrasound of abdomen showed bilateral normal sized kidneys with altered cortico-medullary.
Renal Biopsy showed features of severe tubule-interstitial nephritis with acute tubular injury. Immunofluorescence microscopy revealed no significant immune deposits in the glomeruli, blood vessels, interstitium or tubules.
She was started on Prednisolone 50 mg (1mg/kg body weight) for one month which was tapered (5 mg per week) and stopped over three months. Acalabrutinib was withhold and she was started on Rituximab based regimen for splenic marginal zone lymphoma.
Her renal function improved with above measures. At one year of follow up she was normotensive with a serum Creatinine of 1.5 mg/dl, a estimated glomerular filtration rate of 38ml/min/1.73m2 and a urine protein-creatinine ratio of 0.4 mg/mg.
Acalabrutinib can be associated with cause severe AKI due to Tubulo-interstitial nephritis. Stopping the drug and institution of short course of steroid can treat the condition. The case report calls for awareness and monitoring of renal function while using this drug
