Ibrutinib-induced acute kidney injury via interstitial nephritis

Abstract

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 lmol/L to 125 lmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m 2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.

Rituximab treatment for refractory nephrotic syndrome in adults: a multicenter retrospective study

“…In our study, RTX appears to be effective in RNS across various clinical and pathological subtypes, exhibiting a low relapse rate and minimal significant side effects in the majority of patients. Indeed, the value of RTX is increasingly recognized for otherwise treatment-resistant renal vasculitis [ 34 ] or relatively novel, unusual considerations, such as checkpoint inhibitor-induced renal disease [ 35 ]. Moreover, RTX has shown a small incidence of adverse events and toxicity in many studies [ 36 ].…”

Untoward immune effects of modern medication

“…The underlying pathogenesis pathways involving immunoglobulin E (IgE), IgG, IgM, drug-antibody complexes, and T cells, have led to various types of allergic events, such as anaphylaxis and delayed hypersensitivity reactions in the clinic [ 1 , 6 ] . While the medical presentation of chemical drug allergy are highly heterogeneous from skin lesions to organ damages, the list of etiologic compounds has continuously been extending to involve viral and kinase inhibitors among other emerging agents in recent years [ 1 , 6 , 11 ] . For instance, ibrutinib and idelalisib were sometimes observed to induce immune pathology-associated interstitial nephritis and pneumonitis, respectively [ 11 – 12 ] .…”

“…While the medical presentation of chemical drug allergy are highly heterogeneous from skin lesions to organ damages, the list of etiologic compounds has continuously been extending to involve viral and kinase inhibitors among other emerging agents in recent years [ 1 , 6 , 11 ] . For instance, ibrutinib and idelalisib were sometimes observed to induce immune pathology-associated interstitial nephritis and pneumonitis, respectively [ 11 – 12 ] . Fresh insights into pathogenesis have revealed a link between specific human leukocyte antigen genes and differential chemical compounds.…”

Current Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features

“…Recently, renal toxicity due to Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been documented 37,38 . BTK plays an important role in the regulation of immune-system, including B-cell development, and production of inflammatory mediators and cytokines.…”