CD147/Basigin Deficiency Prevents the Development of Podocyte Injury through FAK Signaling.

Podocytes, which are susceptible to injury by various stimuli and stress, are critical regulators of proteinuric kidney diseases, regardless of the primary disease and pathogenesis. We further confirmed a significant correlation between urinary CD147/basigin (Bsg) levels and proteinuria in patients with focal segmental glomerulosclerosis. However, the molecular mechanism of podocyte injury involving Bsg is not fully understood. Here, the involvement of Bsg in the pathogenesis of podocyte injury was elucidated. Healthy podocytes rarely express Bsg protein. In two independent mouse models, including adriamycin-induced nephropathy and Nω-nitro-l-arginine methyl ester (l-name)-induced endothelial dysfunction, Bsg induction in injured podocytes caused podocyte effacement, which led to development of proteinuria. Bsg silencing in cultured podocytes exposed to transforming growth factor-ß suppressed focal adhesion rearrangement and cellular motility via the activation of ß1 integrin-focal adhesion kinase-matrix metallopeptidase signaling. In addition, induction of vascular endothelial growth factor and endothelin-1, which are implicated in podocyte-to-endothelial cross-communication, was lower in the supernatants of cultured Bsg-silenced podocytes stimulated with transforming growth factor-ß. In this setting, Bsg may be involved in a physiological positive feedback loop that accelerates podocyte cell motility and depolarization. The current study thus suggests that Bsg silencing via suppression of ß1 integrin-focal adhesion kinase-matrix metallopeptidase signaling may be an attractive therapeutic strategy for the maintenance of podocytes in patients with proteinuric kidney diseases.

The clinical relevance of plasma CD147/basigin in biopsy-proven kidney diseases.

BACKGROUND: Precise understanding of kidney disease activity is needed to design therapeutic strategies. CD147/basigin is involved in the pathogenesis of acute kidney injury and renal fibrosis through inflammatory cell infiltration. The present study examined the clinical relevance of CD147 in biopsy-proven kidney diseases that lead to the progression of chronic kidney disease. METHODS: Kidney biopsy specimens and plasma and urine samples were obtained from patients with kidney diseases, including IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), diabetic kidney disease (DKD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), who underwent renal biopsy between 2011 and 2014. Plasma and urinary CD147 levels were measured and evaluated for their ability to reflect histological features. Disease activity of IgAN tissues was evaluated according to the Oxford classification and the Japanese histological grading system. RESULTS: In biopsy tissues, CD147 induction was detected in injured lesions representing renal inflammation. Plasma CD147 values correlated with eGFR in patients with inflammation-related kidney diseases such as IgAN, HSPN, and DKD. Particularly in IgAN patients, plasma CD147 levels were correlated with injured regions comprising more than 50% of glomeruli or with tubular atrophy/interstitial injury in biopsy tissues. Proteinuria showed a closer correlation with urinary values of CD147 and L-FABP. Of note, plasma and urinary CD147 levels showed a strong correlation with eGFR or proteinuria, respectively, only in DKD patients. CONCLUSION: Evaluation of plasma and urinary CD147 levels might provide key insights for the understanding of the activity of various kidney diseases.

Anti-neutrophil cytoplasmic antibody-associated vasculitis associated with infectious mononucleosis due to primary Epstein-Barr virus infection: report of three cases.

Although the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis remains unclear, it is generally believed that environmental factors such as infections contribute to its development of ANCA-associated vasculitis. Prior Epstein-Barr virus (EBV) infection is reported to be a trigger of systemic vasculitis. We herein report three cases of ANCA-associated vasculitis presenting with infectious mononucleosis due to primary EBV infection. The causal link between the two pathologies could not be proved, but primary EBV infection may play a role in the initiation or exacerbation of ANCA-associated vasculitis. Future studies are necessary to determine the interaction between these diseases conditions.

[Granulomatous interstitial nephritis in a patient with Behçet's disease treated with infliximab].

The patient is a 41-year-old man diagnosed with uveitis in 2004. Although the patient was positive for HLA-B51, the primary disease could not be identified, and oral administration of prednisolone (PSL) was initiated. A subsequent gradual decrease in the PSL dose was accompanied by the development of recurrent spasmodic chorioretinopathy and hypopyon. In November 2007, the patient was diagnosed with Behçet's disease based on the findings of erythema nodosum, acneiform eruption, and oral aphtha. In order to control the ocular symptoms, infliximab was administered. However, the patient's renal function began to deteriorate in November 2011, and he was transferred to our department after 6 months. At that time, his creatinine level was 8.56 mg/dL. Renal biopsy examination revealed granulomatous interstitial nephritis. Moreover, only infliximab yielded a positive result in a drug-induced lymphocyte stimulation test (DLST). Following initiation of PSL administration at 60 mg/day, his renal function improved. His creatinine level remained constant at approximately 3 mg/dL. In the present case, Behçet's disease, sarcoidosis, and infection were excluded as the underlying disease causing granulomatous interstitial nephritis. Moreover, infliximab is reportedly involved in the development of granulomas. Recent reports have stated that administration of TNF-alpha inhibitors occasionally results in the development of granulomas in the lungs and skin, and sometimes, in the kidneys as well. When renal dysfunction occurs in patients receiving TNF-alpha inhibitors, we believe that it is essential to include adverse events associated with TNF-alpha inhibitors in the differential diagnoses.

Delayed diagnosis of traumatic diaphragmatic rupture.

We report a case of late presentation of traumatic rupture of the diaphragm discovered incidentally on chest radiography (CXR) during an annual medical checkup. A 60-year-old man suffered severe blunt trauma from heavy steel frames collapsing against his back, resulting in pelvic and femoral fractures as well as pulmonary contusions. The patient recovered, but 10 months later CXR performed for lung cancer surveillance during an annual medical checkup revealed a traumatic rupture of the diaphragm. Video-assisted thoracic surgery was performed with reduction of the intestine and primary closure of the diaphragmatic defect. The patient recovered uneventfully. This report serves as a useful reminder that a medical history of severe blunt trauma should provoke a high index of suspicion for diaphragmatic rupture during annual medical surveillance.

[Case of caffeine poisoning survived by percutaneous cardio-pulmonary support].

A 17-year-old woman presented to the Emergency Department of our hospital following a suicide attempt. She reported having ingested 340 tablets of caffeine, each of which contained 200mg of caffeine, about 3 hours earlier. Soon after arrival, her blood pressure dropped, and electrocardiography revealed sinus tachycardia and ventricular tachycardia (VT). Subsequently, she developed ventricular fibrillation (VF), and VF was resistant to pharmaceutical interventions and even to cardioversion. Therefore, we performed percutaneous cardiopulmonary support (PCPS). This resulted in disappearance of VF and tachycardia, symptoms of caffeine poisoning, and improvement was observed 16 hours after the start of PCPS. In our case, caffeine poisoning symptoms disappeared without blood purification, after PCPS had stabilized her circulation. Based on our observations in this case, stabilization of the circulation using PCPS in severe caffeine poisoning with VF, a potentially fatal arrhythmia, is a significantly beneficial strategy.