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

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Diabetic kidney disease (DKD) patients (<jats:italic>N</jats:italic> = 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).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Proteinuria induces the release of Bsg‐bearing EVs derived from PTECs into the tubular lumen.</jats:p></jats:sec>