“+1” Proteinuria in the Nondiabetic Hypertensive

The phrase “managing cardiovascular risk” has become synonymous with caring for the hypertensive patient. While guidelines proliferate, and blood pressure goals adapt to lower levels depending on comorbidities, an occasional hypertensive patient whose urinalysis shows “+1 protein” may not show up immediately on the radar screen (or the pocket algorithms) of busy practitioners coping with glucose, cholesterol, and numerous other data bits. How common is this finding, and how much cardiovascular risk is buried in low‐grade proteinuria?

The commonly used urine “dipstick” measures protein concentration through an indicator‐dye reaction (often mediated by a bromosulfophthalein derivative) that turns progressively darker green colors proportional to the level of protein. These dipsticks measure albumin well, globulin proteins less well, and light chains basically not at all. In many instances, a “trace” reading (<30 mg/dL) will return to normal on rechecking. When the sticks read +1, and especially +2 or more, the finding is likely to remain. In the Framingham study, in the absence of diabetes, proteinuria was relatively uncommon in the population using the dipstick method, the exception occurring in nondiabetic hypertensives who had 2–4 times the incidence of proteinuria. ¹ In general the incidence of proteinuria in the hypertensive population increases with age, and is in the general range of 5%–20%. ²

As to what they mean, the current popularity of microalbumin as a cardiovascular marker serves as something of a guide. If very small amounts of albumin (with a negative dipstick, i.e., microalbumin) are markers for future heart disease, much larger amounts of albumin (with a positive dipstick) are even more likely, and have been shown to reflect enhanced cardiovascular risk. ¹ , ² One of the most important things to remember about proteinuria is that it is not just a kidney disease. Damage to the renal circulation resulting in proteinuria is a proxy for understanding vascular jeopardy in the systemic circulation. Although the literature abounds with advice on managing all levels of proteinuria in hypertensive diabetics through interruption of the renin‐angiotensin system, less is known about the nondiabetics with non‐nephrotic proteinuria (the typical +1 or +2 urine dipsticks). In treating nondiabetic, non‐nephrotic patients many authorities espouse the use of an angiotensin‐converting enzyme inhibitor or an angiotensin receptor blocker. However, current experience has not proved that the degree of benefit in prevention of an outcome like progressive renal failure, when low‐grade (<500 mg/24 hours) compared with higher‐grade proteinuria is present, ³ is greater with these agents compared with conventional antihypertensive agents. Still, it does make sense if you are treating their hypertension anyway to use an agent from the antirenin system class (usually along with a diuretic to achieve goal blood pressure levels).

In some ways, finding +1 proteinuria is akin to receiving notice of an impending visit from an important but irritating in‐law. Although not the most welcome of visitors, it does prompt one to make sure the house is in order prior to their arrival. Low‐grade proteinuria may serve as a vehicle to reconsider the total cardiovascular picture in an individual, and tidy up some of the looser ends such as sedentary lifestyle, high‐salt diet, marginal cholesterol, etc. that are frequent accompaniments.