Glomerular Structure in Diabetes - Can It Predict the Future?

stage is too late as the lesions are advanced and cannot be reversed without pancreas transplantation. Similarly, it has been argued that the widely used clinical predictor of progression – MA – is imprecise and occurs when damage has already been done. If it was possible to identify patients who were likely to progress much earlier – even at the NA stage – then it could be possible to target such patients with the aim of preventing the development of advanced lesions and maintaining glomerular function. The largest longitudinal study of NA type 1 patients is from a group in Minneapolis [7]; this study has been exploring the natural history of DN in these patients and analysing several structural parameters in order to determine which parameters identify those patients who are most likely to progress to P or ESRD. The first structural change seen in the glomeruli of diabetic patients is the thickening of the glomerular basement membrane (GBM) [1], and increased GBM width has been shown to predict progression of DN in NA type 1 diabetic patients [7] . Interestingly, the increased GBM width predicts progression not only from NA to MA but also from NA to P and ESRD so is a strong independent predictor of DN risk. In recent years, interest in glomerular structure has moved from the GBM and mesangium to the podocyte. In DN there is podocyte foot process widening or ‘effacement’ with loss of filtration slits. Foot process effacement should be reversible as long as the podocytes themselves Researchers have been performing in-depth quantitative analysis of glomerular structural parameters for several decades [1] and have long ago established the link between structural abnormalities and renal function [2] . However, it is still unclear whether changes in glomerular structure are a cause or effect of diabetic nephropathy (DN). It is certainly likely that even if initially the lesions are a result of the diabetic milieu, they are themselves going to contribute to the progression. The study of glomerular structure using both light and electron microscopy can provide insight into the natural history of DN and can also be used to assess the effectiveness of treatment with, for instance, renin-angiotensin system blocking agents. It has been shown that the diabetic lesions can be reversed after 10 years in type 1 patients receiving pancreas transplants [3] . But will detailed quantification of structural parameters predict which patients are likely to progress from normoalbuminuria (NA) to microalbuminuria (MA) and on to proteinuria (P) and end-stage renal disease (ESRD)? In order to predict progression, a study must, of course, be longitudinal. Many of the reported studies using biopsy data are cross-sectional, but there have been some longitudinal studies providing information on disease progression. For patients at later stages of DN, studies have shown that glomerular podocyte parameters at baseline correlate with function at follow-up [4–6] . However, it could be argued that identifying progressors at this Published online: May 22, 2015 Nephrology American Journal of