Glomerular injury and tubular loss in adriamycin nephrosis

Glomerular injury manifested by sustained proteinuria usually leads to tubu le injury and reduction of the GFR. The current study explored the link bet ween these processes in rats with adriamycin nephrosis. One group of nephro tic rats received a vasopressin V2 receptor blocker (V2X) from 4 to 16 wk a fter injection of adriamycin, whereas a second group received no treatment (NoRx). V2 receptor blockade increased urine volume without affecting prote in excretion. At 16 wk, both groups of nephrotic rats exhibited a marked re duction in GFR in comparison with normal controls (V2X, 0.22 +/- 0.19 ml/mi n; NoRx, 0.20 +/- 0.11 ml/min; control, 1.23 +/- 0.11 ml/min). Morphologic studies revealed that the majority of glomeruli in nephrotic rats were no l onger connected to normal tubule segments (V2X, 81 +/- 21%; NoRx, 85 +/- 18 %; control, 1 +/- 2%). Glomeruli without tubules were not, however, globall y sclerosed. Disruption of the glomerular tubular junction was associated w ith the presence of amorphous material separating damaged tubule cells from the basement membrane. Serial sections revealed that this material spread from extensive areas of adhesion between the glomerular tuft and capsule to invest the tubular neck. Reduction of the GFR was strongly correlated with the fraction of glomeruli not connected to normal tubules (r(2) = 0.82; P < 0.0001). V2 receptor blockade did not preserve renal function or structur e. These findings suggest that local extension of glomerular injury to dest roy the tubule neck is an important cause of loss of renal function in adri amycin nephrosis.