Nintedanib-Induced Renal Thrombotic Microangiopathy.

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.

PolyIC Induces Retinoic Acid-inducible Gene-I and Melanoma Differentiation-associated Gene 5 and Modulates Inflammation in Podocytes.

BACKGROUND/AIM: Viral infection often exacerbates proteinuria, which has been suggested to be due to antiviral responses of podocytes. We examined the effect of polyinosinic-polycytidylic acid (polyIC) on the expression of retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in differentiated human podocytes in culture. MATERIALS AND METHODS: The podocytes were treated with 2 ng/ml to 500 µg/ml of polyIC for 3 to 36 h, and also transfected with siRNA against RIG-I and MDA5. F-actin staining was performed to assess actin reorganization. RESULTS: PolyIC induced the expression of RIG-I and MDA5 in dose- and time-dependent manner, accompanied with interferon-ß (IFN-ß) and interleukin-6 (IL-6) up-regulation and actin reorganization. Temporal knockdown of RIG-I by siRNA decreased IFN-ß expression, while MDA5 siRNA inhibited IFN-ß and IL-6 expression. Actin reorganization was attenuated by RIG-I and MDA5 knockdown. CONCLUSION: RIG-I and MDA5 may play a role in the antiviral responses of podocytes.

Clinical Outcomes of Acute Myocardial Infarction Patients With a History of Malignant Tumor.

BACKGROUND: Little is known about the clinical outcomes of acute myocardial infarction (AMI) in patients with a history of malignant tumor (MT). PATIENTS AND METHODS: We retrospectively studied 1,295 consecutive patients with AMI who underwent primary percutaneous coronary intervention within 24 hours of onset. The patients were divided into two groups: those with a history of MT (MT group, n=50) and those without (non-MT group, n=1,245). RESULTS: The MT group was older, and had lower hemoglobin, total protein, and albumin levels. All-cause mortality and re-admission rates due to acute decompensated heart failure (ADHF) were significantly higher in the MT group. Multivariate analysis showed that a history of MT was an independent predictor for all-cause mortality and re-admission due to ADHF. CONCLUSION: The clinical outcomes of patients with AMI with a history of MT are poor, and a history of MT is an independent predictor for all-cause mortality and re-admission due to ADHF. These patients may need careful risk management for heart failure to avoid re-admissions due to ADHF.