Basigin is released in extracellular vesicles derived from the renal tubular epithelium in response to albuminuria.

AIM: Irrespective of the cause, albumin/proteinuria induces tubulointerstitial damage and accelerates the progression of kidney diseases. Our series of studies demonstrated that proteinuria, an independent prognostic factor for chronic kidney disease (CKD), is correlated with urinary basigin/CD147 (Bsg) levels. We examined the morphology and origin of Bsg in the tubular lumen through the effects of filtered glucose and protein solutes on the tubules. METHODS: Diabetic kidney disease (DKD) patients (N = 50) were treated with spironolactone 25 mg for 4 weeks or by conservative treatment. The associations between urinary Bsg values and clinical indicators were examined. Primary-cultured proximal tubular epithelial cells (PTECs) from human adult kidneys were exposed to high glucose or bovine serum albumin (BSA). RESULTS: In patients with early phase DKD, urinary Bsg levels were closely correlated with proteinuria but not HbA1c. Full-length Bsg on extracellular vesicles (EVs) was investigated primarily in urine collected from DKD patients. EVs obtained from the urine of DKD patients included Bsg and SGLT2 proteins. Notably, spironolactone treatment concomitantly suppressed the release of Bsg-bearing EVs in correlation with decreased albuminuria. Exposure of PTECs to BSA (but not high glucose) enhanced the storage of supernatant Bsg in EVs despite the absence of exposure-specific changes in Bsg transcription. CONCLUSION: Proteinuria induces the release of Bsg-bearing EVs derived from PTECs into the tubular lumen.

IgA nephropathy diagnosed as a result of acute exacerbation due to G-CSF administration.

Granulocyte colony-stimulating factor (G-CSF) is commonly used to stimulate bone marrow production. G-CSF is usually safe but sometimes causes serious adverse effects and, in rare cases, exacerbates glomerulonephritis. We report a case of immunoglobulin A (IgA) nephropathy that was aggravated by G-CSF. A 56-year-old Japanese man with no relevant medical history was admitted to our hospital as a donor of peripheral blood stem cells (PBSCs) for transplantation. To mobilize PBSCs, he received subcutaneous G-CSF (lenograstim), 500 µg for 4 days. Three days after the first dose of lenograstim, gross hematuria appeared, and after administration on the fourth day, renal dysfunction and nephrotic-range proteinuria were observed. Renal biopsy and light microscopic study revealed mild mesangial proliferation with expansion in association with the presence of cellular segmental crescents. Immunofluorescence study revealed diffuse, granular staining in the mesangium for IgA, complement component 3 (C3), and lambda light chains. We diagnosed highly active IgA nephropathy and initiated treatment with prednisolone and azathioprine. Three months later, renal function returned to normal. Screening for hidden chronic glomerulonephritis should be performed when G-CSF is administered, as in PBSC donors. Immunosuppressant therapy, such as prednisolone or azathioprine, is considered for exacerbations of highly active glomerulonephritis.

Rapidly Progressive Kidney Failure Associated with Perirenal Capsular Lesion Due to IgG4-Related Disease.

A 71-year-old Japanese man with progressive kidney failure was referred to our hospital. Laboratory tests showed elevated IgG4 levels. Contrast-enhanced computed tomography (CT) revealed soft tissue surrounding the left kidney and right atrophic kidney. A histopathological examination revealed inflammation and fibrosis with rich IgG4-positive cells in the thickened kidney capsule, but not in the kidney parenchyma. Poor enhancement in the left kidney on contrast-enhanced CT and wrinkling of glomerular capillaries in pathological tissues were also observed. These findings indicated IgG4-related perirenal lesions leading to low renal perfusion and kidney failure. The perirenal lesions and kidney failure were improved by corticosteroid therapy.

Gene expression of neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex components in the olfactory organ and brain during seaward and homeward migration by pink salmon (Oncorhynchus gorbuscha).

The expression of synaptic vesicle exocytosis-regulator SNARE complex component genes (snap25, stx1 and vamp2) was examined in the olfactory nervous system during seaward and homeward migration by pink salmon (Oncorhynchus gorbuscha). The expression levels of snares in the olfactory organ were higher in seaward fry than in feeding and homeward adults, reflecting the development of the olfactory nervous system. The expression of snap25a, b and stx1a was upregulated or stable in the adult olfactory bulb and telencephalon. This upregulated expression suggested alterations in olfactory neuronal plasticity that may be related to the discrimination of natal rivers. The expression of stx1b was downregulated in the adult olfactory bulb, but remained stable in the adult telencephalon. The expression of vamp2 was initially strong in seaward fry, but was downregulated in adults in both the olfactory bulb and telencephalon. Pink salmon has the lowest diversity of maturation age, the largest population, and the most evolutional position in Pacific salmon (genus Oncorhynchus). The expression of snares in the olfactory center of pink salmon reflected the timing of sexual maturation and homeward migration. The present results and our previous studies indicate that snares show distinct expression patterns between two salmon species that depend on physiological and ecological features of migration.

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.

Massive ascites caused by intra-pancreatic arterioportal fistula: a rare complication of chronic pancreatitis.

An 86-year-old man with a long-term habit of ethanol consumption was admitted due to massive transudate ascites and leg edema. Abdominal computed tomography revealed a dilated main pancreatic duct and atrophied pancreatic parenchyma, leading to the diagnosis of chronic pancreatitis. Moreover, the portal vein was enhanced in the early arterial phase, which indicated the presence of an arterioportal fistula. The fistula was located between the posterior superior pancreaticoduodenal artery and the portal vein near a pancreatic retention cyst. Transarterial coil embolization dramatically improved the ascites. Arterioportal fistula and ensuing ascites should be recognized as a complication of chronic pancreatitis.

Spatio-temporal spread of neuronal death after focal photolysis of caged glutamate in neuron/astrocyte co-cultures.

Glutamate-mediated excitotoxicity is now accepted as a major mechanism of ischemic neuronal damage. In the infarct core region, massive neuronal death is observed, but neurons in the surroundings of the core (ischemic penumbra) seem viable at the time of stroke. Several hours or days after a stroke, however, many neurons in the penumbra will undergo delayed neuronal death (DND). The mechanisms responsible for such DND are not fully understood. In this study, we investigated whether and how glutamate-mediated localized excitotoxic neuronal death affects surrounding neurons and astrocytes. To induce spatially-restricted excitotoxic neuronal death, a caged glutamate was focally photolyzed by a UV flash in neuron/astrocyte co-cultures. Uncaging of the glutamate resulted in acute neuronal death in the flashed area. After that, DND was observed in the surroundings of the flashed area late after the uncaging. In contrast, DND was not observed in neuron-enriched cultures, suggesting that functional changes in astrocytes, not neurons, after focal acute neuronal death were involved in the induction of DND. The present in vitro study showed that the spatially-restricted excitotoxic neuronal death resulted in DND in the surroundings of the flashed area, and suggested that the nitric oxide (NO)-induced reduction in the expression of astrocytic GLT-1 was responsible for the occurrence of the DND.

Infraorbital nerve swelling associated with autoimmune pancreatitis.

PURPOSE: The aim of our study was to examine the relation between autoimmune pancreatitis (AIP) and infraorbital nerve swelling. MATERIALS AND METHODS: A total of 11 AIP patients underwent magnetic resonance imaging (MRI) examination of the head and neck region. The infraorbital nerve thicknesses were measured on coronal images and compared with those of a control group. We also examined whether the infraorbital nerve thicknesses were altered from before to after steroid therapy in nine patients who underwent MRI examination after such therapy. RESULTS: The mean thicknesses were 3.8 ± 2.0 mm in the AIP group and 2.6 ± 0.5 mm in the control group (P < 0.05). The nerve thicknesses were >5 mm in 5 of 11 patients (45%) in the AIP group, and <5 mm in all of the control group. Among the nine patients who underwent MRI examination after steroid therapy, three had shown nerve swelling before steroid therapy; the therapy diminished the swelling in all three patients. CONCLUSION: Infraorbital nerve swelling was observed more frequently in AIP patients than in patients without a history of AIP. Therefore, such swelling seems to be an extrapancreatic lesion of AIP.

Cold-induced sweating syndrome with neonatal features of Crisponi syndrome: longitudinal observation of a patient homozygous for a CRLF1 mutation.

Cold-induced sweating syndrome (CISS) is a rare autosomal recessive disorder caused by mutations in CRLF1 (cytokine receptor-like factor 1), characterized by profuse sweating in cold environmental temperature and craniofacial and skeletal features. Mutations in CRLF1 also cause Crisponi syndrome (CS), characterized by neonatal-onset paroxysmal muscular contractions as well as craniofacial and skeletal manifestations and abnormal functions of the autonomic nerve system. To date, it is an unresolved problem whether the two conditions are distinct clinical entities or a single clinical entity with variable expressions or with different presentations depending on the patients' age at diagnosis. We report on a 30-year-old Japanese woman with CISS and homozygous out-of-frame 23-base deletion of CRLF1. In infancy, she did not show paroxysmal muscular contractions, but showed feeding difficulty, hyperthermia, and facial characteristics including thick and arched eyebrows, a short nose with anteverted nostrils, full cheeks, an inverted upper lip, and a small mouth, resembling those observed in CS. Profuse sweating was noticed at 3 years of age. Cold-induced sweating was recognized in her elementary school days. In adolescence to adulthood, she showed a Marfanoid habitus with progressive kyphoscoliosis and craniofacial characteristics including dolichocephaly, a slender face with poor expression, a distinctive nose with hypoplastic nares, malar hypoplasia, prognathism, and a small mouth. This is the first report of detailed longitudinal observation of a patient with CRLF1 abnormalities, compatible with the notion that CISS and CS may be a single clinical entity.