“One out of every five healthcare dollars is spent caring for someone with diagnosed diabetes, while one in ten healthcare dollars is attributed to diabetes.”
[American Diabetes Association]

Molecular Basis of Diabetic Kidney Disease

Hyperglycemia is an established risk factor for diabetic complications According to the large-scale DCCT (and EDIC follow-up studies) and UKPDS trials of patients with type 1 and type 2 diabetes, the severity of these complications is linked to the degree of glucose control. Diabetic complications, such as nephropathy, retinopathy, and neuropathy arise in tissues that are not under direct insulin control, resulting in elevated levels of glucose during hyperglycemia excursions. This condition leads to a perturbation of many metabolic pathways and the emergence of nonenzymatic chemistries that form pathogenic compounds including:

At the glomerular level, elevated glucose and its related pathogenic oxidative chemistries have been shown to cause or contribute to:

These changes are contributing factors to the decline of glomerular function, as manifest by proteinuria and/or a decline in creatinine clearance that leads to elevated serum creatinine levels.

Diabetes-induced renal pathology also compromises tubular function and leads to more serious consequences. Tubular dysfunction has been linked to damage from exposure to circulating low-molecular-weight AGE-modified peptides that would normally be catabolized in the tubules but instead bind to so-called AGE receptors or become cross-linked to that tissue.

Ultimately, untreated nephropathy progresses to irreversible tubulointerstitial fibrosis resulting from the continuous overproduction of multiple growth factors and increased deposition of extracellular matrix, a process similar to what occurs earlier on the glomerular side with basement membrane thickening and mesangium expansion.