Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies

Background. Nephrotic syndromes result from increased glomerular permeability to proteins and are structurally believed to be associated with podocyte foot process effacement. Despite increasing knowledge of the molecular composition of the glomerular filtration barrier, the relationship between proteinuria and foot process effacement is unclear. Methods. We conducted a morphologic study on the relationship between podocyte foot process effacement and proteinuria. Electron microscope pictures of glomerular capillaries were randomly taken from 27 cases in various stages of minimal change nephrotic syndrome (MCNS), from six cases of IgA nephropathy (IgAN) with high proteinuria and from seven control kidneys. From each picture, the mean width of the foot processes (FPW) was quantitated. Results. In normal kidney the mean FPW was 580 +/- 40 nm. In biopsies from patients with MCNS without treatment, foot processes were diffusely effaced, reflected by a FPW of 1600 +/- 440 nm. In biopsies from patients with MCNS relapsing under prednisolone treatment, foot processes were significantly less effaced than in untreated MCNS (FPW 920 +/- 200 nm). In biopsies displaying IgAN, effacement was significantly more segmental than in untreated MCNS (FPW 800 +/- 170 nm). Proteinuria did not differ significantly among the groups. Neither in MCNS nor in IgAN was the extent of foot process effacement correlated with the level of proteinuria. Conclusion. Podocyte foot process effacement is not correlated with proteinuria. The differences in podocyte effacement between MCNS, MCNS relapsing under prednisolone treatment, and IgAN may point to different mechanisms of podocyte injury in these diseases.