Proteinuria is now accepted to be not just a sign of renal disease but also a contributory factor to the development of progressive tubulointerstitial fibrosis. Excellent correlations between the degree of proteinuria and rate of decline of glomerular filtration rate have been demonstrated. What has been investigated less is whether the type of protein found in the urine is important. Using transformed and primary human proximal tubular epithelial cells, we have investigated the binding of albumin and retinol binding protein to plasma membrane preparations and studied the response of the intact cells to increasing concentrations of these same proteins. We have preliminary evidence for differences in the pattern of binding of these two proteins to the plasma membrane receptors and also for differential release of pro-inflammatory cytokines from intact cells. These in vitro results, along with those of other groups, and some recent clinical findings suggest that the quality of proteinuria may play a role in the early development of interstitial fibrosis. Furthermore, the use of such in vitro model systems based on human proximal epithelial cell culture can provide a means of evaluating the potential significance of different markers of tubular damage.