Albuminuria: It is Not Just about Your Kidneys Anymore
For a long time, urinary albumin excretion—whether measured by the cumbersome 24-hour urine collection or the spot albumin/creatinine ratio (ACR)—was solely a reflection of kidney disease, especially in diabetic patients. We have since come a long way: This month’s Top Paper1 expands the intellectual horizons surrounding spot collections for urinary albumin.
While the Top Paper1 reviews myriad associations between albuminuria and renal injury, the data engaging albuminuria and risks for cardiovascular disease and death are worth discussing in detail.
Did you know?
• An ACR between 30 mg/g and 300 mg/g is independently associated with myocardial infarctions and coronary ischemia. In fact, albuminuria is associated with more than twice the risk of severe coronary artery disease than in controls with normal ACR excretion rates.
• Let's move on to other vascular beds, beginning with the carotid arteries. An elevated ACR is associated with increased carotid intimal thickening. Thickening of this nature in any arterial tree is a surrogate marker for arteriosclerosis.
• As ACRs increase, so do brachial-ankle pulse wave velocities. This is another measurement that reflects arterial disease. It is utilized as a noninvasive measure of peripheral vascular disease.
• If the risk for coronary disease is not enough, an ACR of 30 mg/g to 300 mg/g is predictive of left ventricular hypertrophy and diastolic dysfunction. We now know that albuminuria is associated with both varieties of heart failure—systolic and diastolic.
• One troublesome cohort is people who are frequently readmitted for heart failure. An ACR >30 mg/g is associated with a 41% greater risk of admission for heart failure and an ACR >300 mg/g is associated with an 88% higher risk. Increased urine albumin excretion is a valid marker for widespread vascular injury.
• A meta-analysis comprised of more than 1 million people demonstrated that an increasing ACR was also associated with an increase in deaths from all causes, not just cardiovascular causes. ACRs across the spectrum of 30 mg/g to 300 mg/g predicted a hazard ratio for all-cause deaths of 1.63 (ACR >30) to 2.22 (ACR >300).
The authors of the Top Paper1 offer therapeutic suggestions. First, control blood pressure to target in individuals with elevated ACR excretions. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are good choices. This recommendation is consistent with proven benefits of these classes of medications on renal and cardiac diseases (eg, decreasing proteinuria and progression of renal disease, improving blood pressure control, and decreasing afterloads on failing hearts). Note: Do not use both classes simultaneously. Refer those patients with higher ACR values and those with unexplained elevations of ACR to a nephrologist.
The "Take Home" Message: From now on when you obtain an ACR, think globally when it is elevated. There is more to ACR increases than kidney disease. An abnormal value is a reflection of vascular injury in multiple vascular beds. The approach after requires attention to every vascular risk factor, not just those that affect the kidneys. ■
Gregory W. Rutecki, MD, is a physician at the National Consult Service at the Cleveland Clinic. He is also a member of the editorial board of Consultant. Dr Rutecki reports that he has no relevant financial relationships to disclose.
1. Stephen R, Jolly SE, Nally JV Jr, Navaneethan SD. Albuminuria: when urine predicts kidney and cardiovascular disease. Cleve Clin J Med. 2014;81:41-50.