KITAMOTO, Y., YIDE, C., TOMITA, M, and SATO, T. The Mechanism of Glomerular Dysmorphic Red Cell Formation in the Kidney. Tohoku J. Exp. Med., 1992, 167 (2), 93-105- The mechanism of glomerular dysmorphic cell formation was studied in a in vitro system simulating the process of concentrated acidic urine formation along the nephron. Red cells suspended in phosphate buffer were exposed to three sequential pH gradients, (1) pH 7.4-6.6, (2) pH 6.6-6.5, and (3) pH 6.5-5.2, accompanying osmolality gradients, (1) 280-1200mOsm/kg H₂O, (2) 1, 200-140mOsm/kg H₂O, and (3) 140-1, 100mOsm/kg H₂O, respectively, for 15 to 60min, and red cell shapes were observed by differential interference microscopy. The appearance rate of glomerular dysmorphic cells was 37.7 to 47.1% after finishing all the gradients. The last gradient, simulating the work of the collecting duct, was essential for the dysmorphic cell formation; maximal formation was at the final pH of 5.0 and osmolality of 1, 000mOsm/kg H₂O. No dysmorphic cells were observed in gradients simulating alkaline or diluted urine formation. In 10 glomerulonephritic patients, glomerular dysmorphic cells appeared over five times as frequently in concentrated acidic urine as in alkaline or diluted urine. Results of in vitro and patient studies coincided well with each other, suggesting that in glomerulonephritic patients, dysmorphic cells might be produced while red cells are passing through the tubules, where concentrated acidic urine is formed.