scholarly journals Nintedanib-Induced Renal Thrombotic Microangiopathy

2021 ◽  
pp. 227-232
Author(s):  
Takeshi Fujita ◽  
Hideyuki Nakagawa ◽  
Takashi Yokota ◽  
Jun Umetani ◽  
Daiki Nagawa ◽  
...  
Keyword(s):  
Thrombotic Microangiopathy ◽  
Kinase Inhibitor ◽  
Enzyme Level ◽  
Kidney Injury ◽  
Basement Membranes ◽  
Lung Function Decline ◽  
Multiple Processes ◽  
Level Elevation ◽  
Reduced Kidney Function ◽  
Endothelial Growth Factor

Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent’s targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient’s nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.

scholarly journals Thrombotic microangiopathy in dasatinib-treated patients with chronic myeloid leukemia

2019 ◽  
Vol 4 (1-2) ◽  
pp. 41-45 ◽  
Author(s):  
Takeo Koshida ◽  
Sylvia Wu ◽  
Hitoshi Suzuki ◽  
Rimda Wanchoo ◽  
Vanesa Bijol ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Thrombotic Microangiopathy ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kidney Biopsy ◽  
Kinase Inhibitor ◽  
Target Effect

Dasatinib is the second-generation tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia. Proteinuria has been reported with this agent. We describe two kidney biopsy–proven cases of dasatinib-induced thrombotic microangiopathy that responded to stoppage of dasatinib and using an alternate tyrosine kinase inhibitor. Certain specific tyrosine kinase inhibitors lead to endothelial injury and renal-limited thrombotic microangiopathy. Hematologists and nephrologists need to be familiar with this off-target effect of dasatinib.

scholarly journals Brain Complete Response to Cabozantinib prior to Radiation Therapy in Metastatic Renal Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
An Uche ◽  
Chad Sila ◽  
Tad Tanoura ◽  
James Yeh ◽  
Neil Bhowmick ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Complete Response ◽  
Heavily Pretreated ◽  
Treatment Paradigm ◽  
Endothelial Growth Factor

Cabozantinib represents an established vascular endothelial growth factor- (VEGF-) tyrosine kinase inhibitor (TKI) in the treatment paradigm of metastatic renal cell carcinoma (mRCC). Its activity in mRCC patients with brain metastases (BMs) has been largely underreported in prospective clinical trials. We present the unique case of a heavily pretreated mRCC patient with BMs who achieved a brain complete response to cabozantinib prior to receiving radiation therapy. We end with a literature review and discussion of the biologic rationale and growing evidence supporting the intracranial activity of cabozantinib.

Bleeding with vascular endothelial growth factor tyrosine kinase inhibitor: A network meta-analysis

2021 ◽  
Vol 157 ◽  
pp. 103186
Author(s):  
Avash Das ◽  
Somnath Mahapatra ◽  
Dhrubajyoti Bandyopadhyay ◽  
Santanu Samanta ◽  
Sandipan Chakraborty ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals SARS-CoV-2 infection and recurrence of anti-glomerular basement disease: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Alexander Winkler ◽  
Emanuel Zitt ◽  
Hannelore Sprenger-Mähr ◽  
Afschin Soleiman ◽  
Manfred Cejna ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Plasma Cells ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Pulmonary Involvement ◽  
Pulmonary Haemorrhage ◽  
Basement Membranes ◽  
High Avidity ◽  
History Of

Abstract Background Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection. Case presentation The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome. Conclusion Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.

DNA damage repair (DDR) pathway alteration in advanced renal cell carcinoma (RCC) is association with good progression-free survival with tyrosine kinase inhibitor (TKI) therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 346-346
Author(s):  
Wei Zhai ◽  
Junyun Wang ◽  
Ning He ◽  
Jiale Zhou ◽  
Jianfei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Damage Repair ◽  
Endothelial Growth Factor

346 Background: Alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may be as potential biomarkers for vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy in renal cell carcinoma. However, biologic significance and relevance to TKI targeted therapy in metastatic RCC are unknown. Methods: Genomic data and treatment outcomes were retrospectively collected for patients with metastatic RCC. Tumor and germline DNA were subject to targeted next generation sequencing across 642 genes of interest, including 60 DDR genes. Patients were dichotomized according to underlying DDR gene alteration into (1) DDR gene alterations present (Mut DDR); (2) wildtype (WT) DDR gene alterations present (WT DDR). Association between DDR status and therapeutic benefit was investigated separately for and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy. Results: Mut DDR were detected in 17/40 patients (42.5%). The most frequently DDR altered genes were TP53. For patients with TKI treatment, Mut DDR status was associated with superior progression free survival (log-rank p = 0.048), but not with superior overall survival (log-rank p = 0.39); after adjusting for International Metastatic Renal Cell Carcinoma Database Consortium risks and extent of prior therapy, the HR for Mut DDR was 2.68 (95% CI: 0.96–7.46; p = 0.059). Conclusions: DDR alterations are recurrent genomic events in patients with advanced RCC and were mostly clonal in this cohort. Dysfunction events in these genes may affect outcome with TKI therapy in adanced RCC, and these hypothesis-generating results deserve further study.

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