[Role of proteinuria in clinical research: for each old-answer, a new key-question.]

The presence of proteinuria, i.e. an abnormal amount of proteins in the urine is a well documented cardiovascular (CV) and renal risk factor either in the general population or in high-risk populations such as patients with type 2 diabetes, previous CV disease and patients under regular nephrology care. Indeed, the increase in proteinuria levels, even if of small entity, is associated to a faster decline in renal function over time, increased risk of End-Stage-Kidney-Disease and CV mortality. The deleterious effect of proteinuria on the kidney is attributable to the primitive glomerular damage as well as to the direct toxicity the proteinuria exerts on the tubule-interstitium. In addition, the more general association with the increased CV risk can be explained by the evidence that proteinuria can be considered a marker of systemic and renal endothelial damage. A reduction in proteinuria over time (a 30% decrease after 6 months of treatment in proteinuria is considered acceptable) as response to antihypertensive or antiproteinuric drugs protects against the development of all mentioned endpoints. Further studies are needed to better clarify: what is the normal value of proteinuria excretion, how many measures should be done during follow-up to truely assess the risk of future outcomes, what is the exact prognostic role of proteinuria.