Urinary Podocyte Loss Is a More Specific Marker of Ongoing Glomerular Damage than Proteinuria

<jats:sec> <jats:title /> <jats:p> <jats:bold>Podocyte loss contributes to the development of glomerulosclerosis. Although podocyte detachment has been recognized as a new mechanism of podocyte loss in glomerular diseases, its time course and relationship to disease activity are not known. Urinary excretion of viable podocytes was quantified in two models of transient glomerular injury,</jats:bold> <jats:bold> i.e. </jats:bold> <jats:bold>, rats with puromycin aminonucleoside-induced nephrosis (PAN) and mesangioproliferative nephropathy (anti-Thy 1.1 nephritis model), as well as in a model of continuous glomerular injury,</jats:bold> <jats:bold> i.e. </jats:bold> <jats:bold>, hypertensive nephropathy (5/6-nephrectomy model), and in aging rats. The number of glomerular Wilm's tumor (WT)-1-positive podocytes and the glomerular expression of cell-cycle proteins</jats:bold> <jats:bold> in vivo </jats:bold> <jats:bold>were assessed. Urinary podocyte loss occurred in both primary (PAN) and secondary (anti-Thy 1.1 nephritis) in parallel to the onset of proteinuria. However, subsequently proteinuria persisted despite remission of podocyturia. In continuous glomerular injury,</jats:bold> <jats:bold> i.e. </jats:bold> <jats:bold>, after 5/6-nephrectomy, podocyturia paralleled the course of proteinuria and of systemic hypertension, whereas no podocyturia became detectable during normal aging (up to 12 mo). Despite podocyte detachment of varying degrees, no decrease in glomerular podocyte counts (</jats:bold> <jats:bold> i.e. </jats:bold> <jats:bold>, WT-1 positive nuclei) was noted in either disease model. Podocyturia in the PAN and anti-Thy 1.1 nephritis model was preceded by entry of glomerular podocytes into the cell cycle,</jats:bold> <jats:bold> i.e. </jats:bold> <jats:bold>, cyclin D1, cdc2, and/or proliferating cell nuclear antigen (PCNA) expression. Podocyturia is a widespread phenomenon in glomerular disease and not simply a reflection of proteinuria because it is limited to phases of ongoing glomerular injury. The data suggest that podocyturia may become a more sensitive means to assess the activity of glomerular damage than proteinuria.</jats:bold> </jats:p> </jats:sec>