The following is the summary of a book chapter written by Sandra Sabatini and me in Advances in Pathogensis of Diabetic Nephropathy published by Nova. The chapter details the current state of our knowledge about globular hyperfiltration as a causal event in the glomerulosclerosis that characterizes diabetic nephropathy. The entire chapter is appended below as a pdf file.
The pathogenesis of diabetic nephropathy is doubtless multifactorial. Hyperfiltration secondary to a rise in glomerular capillary pressure is key in increasing SNGFR in early disease. It appears that physical factors, (i.e., stretch or sheer stress) lead to events at the cellular level which increase certain growth factors including epidermal growth factor, TGF-β1, AngII, and VEGF. All of these stimulate an increase in mesangial matrix either by stimulating collagenous or non-collagenous protein synthesis or both. This enlargement of the mesangium affects the glomerular podocytes and their negative charge on the glomerular basement membrane, thus allowing proteins to be excreted in the urine. The cascade for diabetic nephropathy is now set in motion. Identifying patients early so that regression of the renal abnormalities, not progression, is key.