What Should We Do About Proteinuria?

One of the most confusing issues primary care practitioners currently face is the appropriate medical management of proteinuria—an increasingly common condition. We used to think of proteinuria as something that related only to the kidneys. As such, only practitioners whose focus was on renal function (or dysfunction) paid much attention to proteinuria. In recent years, however, we have come to understand that the condition potentially has much larger implications. As a result, we are all obligated to pay more attention to proteinuria—but what exactly should we do about it?

Let’s first review what we know with reasonable certainty about proteinuria. We know that the presence of increased amounts of protein in the urine—either as microalbuminuria (best defined as a urinary albumin/creatinine ratio between 30 and 300 mg/g in a spot urine) or as frank proteinuria (an albumin/creatinine ratio of greater than 300 mg/g in a spot urine)—is an abnormal and un-desirable condition. The presence of proteinuria basically means that there are holes in the endothelial cells that are critical to maintaining the structural integrity of blood vessel walls. And vascular endothelial dysfunction is essentially a marker for systemic dysfunction of the entire endothelial infrastructure throughout the body. Proteinuria, therefore, becomes a “poor man’s” biopsy of the endothelial system, which is not otherwise amenable to sampling.

Given that major vascular events (such as myocardial infarction and stroke) are strongly associated with endothelial dysfunction, it comes as no surprise that proteinuria is a risk factor for these vascular catastrophes. And we know only too well that endothelial dysfunction can be accelerated by such cardiovascular risk factors as diabetes, dyslipidemia, smoking, obesity, and hypertension. But is proteinuria simply a marker (or consequence) of vascular disease or is it an actual cause or contributor? Answering this elusive question would have very important implications for the more practical issue of whether and when aggressive treatment of proteinuria—along with other established cardiovascular risk factors—is warranted.