Focal segmental glomerulosclerosis lesion associated with inhibition of tyrosine kinases by lenvatinib: a case report.

BACKGROUND: Lenvatinib is a tyrosine kinase inhibitor with novel binding ability. It is considered the standard of care for metastatic thyroid cancer; moreover, whether it is indicated for other malignant tumors has been examined. Lenvatinib increases the risk of kidney injury in some patients. In comparison with sorafenib, which is a conventional tyrosine kinase inhibitor (TKI), lenvatinib results in more side effects, including hypertension and proteinuria. We describe a case of secondary focal segmental glomerulosclerosis (FSGS) that developed following treatment of metastatic thyroid cancer with lenvatinib and reviewed the mechanisms of renal impairment. CASE PRESENTATION: We describe a patient with metastatic thyroid cancer who developed hypertension, nephrotic syndrome, and acute kidney injury after 3 months of lenvatinib treatment. Renal biopsy results revealed that 7 of 16 glomeruli indicated complete hyalinization, and that the glomeruli with incomplete hyalinization showed FSGS due to a vascular endothelial disorder and podocyte damage, which seemed to have been induced by lenvatinib treatment. These findings were similar to those of renal impairment treated with conventional TKIs. Although lenvatinib treatment was discontinued, up to 15 months were required to achieve remission of proteinuria, thus leading to chronic kidney disease with hyalinized lesions. CONCLUSIONS: To the best of our knowledge, this is the first reported case of secondary FSGS by lenvatinib treatment. Renal impairment treated with TKIs is commonly associated with minimal change nephrotic syndrome/FSGS findings, and it is suggested that renal involvement with TKI is different from that with the vascular endothelial growth factor ligand. Overexpression of c-mip due to TKI causes disorders such as podocyte dysregulation and promotion of apoptosis, which cause FSGS. Lenvatinib may result in FSGS by a similar mechanism with another TKI and could cause irreversible renal impairment; therefore caution must be used. It is essential to monitor blood pressure, urinary findings, and the renal function.

Membranoproliferative glomerulonephritis-like findings for TAFRO syndrome, associated with an anterior mediastinal tumor: A case report.

RATIONALE: TAFRO syndrome is a systemic inflammatory disease proposed recently from Japan. The cause of TAFRO syndrome is unclear. Moreover, the disease characteristics and kidney pathology are yet unknown well and there are few cases. Herein, we report a patient with TAFRO syndrome and present the features of the renal histopathology. PATIENT CONCERNS: A 55-year-old woman presented to our hospital with the main complaint of subacute dyspnoea. DIAGNOSIS: Physical findings included a low-grade fever and generalised oedema. A blood test showed anaemia, coagulation abnormalities, hypoproteinaemia, impaired renal function, proteinuria, and elevated alkaline phosphatase (ALP), C-reactive protein (CRP), interleukin-6 (IL-6). Chest and abdominal computed tomography showed an anterior mediastinal mass and multiple enlarged lymph nodes. INTERVENTIONS: Nephrotic syndrome secondary to a malignant mediastinal tumour was suspected; therefore, the patient underwent resection of the anterior mediastinal mass. Histopathological examination of the resected specimen showed lymphocytic proliferation without signs of malignancy. These findings were compatible with hyaline vascular type Castleman disease (CD), and with the associated multiple lymph nodes enlargement, the patient was initially diagnosed with multicenteric CD. OUTCOMES: After resection of the whole tumour, all the clinical symptoms improved. However, after resection 6 months passed, the patient developed thrombocytopenia, anaemia, renal dysfunction, further enlargement of the residual lymph nodes, hepatosplenomegaly, and mild myelofibrosis. A diagnosis of TAFRO syndrome (TS) was eventually made. All symptoms improved with initial intravenous pulse steroid therapy followed by oral steroids. Histopathological examination of the renal biopsy samples showed findings resembling membranoproliferative glomerulonephritis (MPGN). LESSONS: In TS, all characteristic signs may not exist from the beginning. The association between TS and CD is not clear. When we compared our findings with previously published cases of TS and CD, we found that the renal pathology findings resembled MPGN in many cases of TS, while only a few cases showed amyloidosis. Recent results suggest that TS may be an independent disease from CD, and given the frequency of renal pathology findings, it may also have a different aetiology. To the best of our knowledge, this case report is rare to demonstrate the renal pathology in a patient with conventional TAFRO syndrome.