Increase in tubular flow directly induces hypertrophy of proximal tubular cells

Glomerular hyperfiltration, as seen for instance in diabetic nephropathy or in response to loss of kidney tissue, induces hypertrophy of proximal tubular cells. In our study we tested whether the increase in proximal tubular flow which results from glomerular hyperfiltration can directly induce hypertrophy of proximal tubular cells. Unilateral nephrectomy in mice resulted in an increase in the GFR (130% of control) and in an increase in the cell area of proximal tubular cells in kidney sections (117% of sham controls) within 3 days, indicating functional and structural adaptation to loss of kidney tissue is a rapid process. The flow velocity in proximal tubules of living mice was around 400 µm/s as determined by intravital microscopy. Accordingly, murine primary proximal tubular cells (PPTC) or LLCPK1 cells were superfused for 20 hours in closed perfusion chambers with serum- and hormone-free medium at flow velocities between 0 and 1mm/s resulting in physiological shear stress rates. In fact, higher flow ...