Proteinuria in diabetes: bystander or pathway to cardiorenal disease?

The development of albuminuria in diabetics is closely associated with an enhanced risk of renal and cardiovascular disease. However, the role of albuminuria in the pathogenesis of these clinical conditions remains controversial. Whether albuminuria is simply a biomarker or qualifies as a surrogate endpoint for cardiorenal disease has wide-ranging implications from the monitoring and treatment of patients to the design of clinical trials and drug development. We critically review available data to determine whether the association between albuminuria and cardiorenal disease is causative. Current evidence suggests the significance of albuminuria depends on its severity (degree or level) and on the specific clinical outcome under consideration. For diabetic kidney disease, there is convincing epidemiologic and experimental evidence to assign clinical albuminuria status as a surrogate endpoint, but for lower levels of albuminuria (microalbuminuria and normoalbuminuria), the evidence is inconclusive or not available. Albuminuria of any degree is unlikely to be causally related to diabetic cardiovascular disease, but its onset might be useful to identify those subjects at cardiovascular risk and to detect and treat other modifiable risk factors.