Kidney Disease, Proteinuria: Implications for Cardiovascular Risk

Kidney Disease, Proteinuria: Implications for Cardiovascular Risk

Hillel Sternlicht, MD

George L. Bakris, MD


Albumin is a protein produced by the liver with a half-life of 28 days and reflects our nutritional status. It is also responsible for maintaining our plasma oncotic pressure to prevent peripheral edema. In healthy people, the filtering head of the nephron, the glomerulus, is impermeable to albumin (molecular weight: 65,000 Da) and therefore, only present in minute quantities. Hence, high levels of albumin in the urine, ie, albuminuria, signify some underlying pathophysiologic problem associated with an inflammatory process in almost all cases.

Although the terms proteinuria and albuminuria are often employed interchangeably, this is not correct. Albumin is but one of several proteins that may be found in the urine. The most frequently encountered and largest is uromodulin (Tamm-Horsfall proteins), a mucinous, glycosylated urinary protein. Because uromodulin weighs 80,000 Da and the glomerulus only allows proteins less than 40,000 Da in mass to traverse the basement membrane, it does not enter the urine by filtration but rather is secreted by the distal tubule (ie, tubular proteinuria).1 “Low-molecular-weight” proteins (<25,000 Da) such as immunoglobulins, beta-2 microglobulin, and light chains are freely filtered but subsequently reabsorbed by the proximal tubule.2

Levels of albuminuria between 30 and 300 mg/d are defined as high albuminuria (formerly microalbuminuria) and levels above 300 mg/d designated as very high albuminuria (previously macroalbuminuria).3 Levels at 30 mg/d or higher signify underlying inflammation that can be from a variety of causes (Figure 31.1). Albuminuria levels above 300 mg/d signify the presence of kidney disease and an even higher inflammatory burden. Because albuminuria has been extensively investigated concerning cardiovascular and renal outcomes, albuminuria and its integration into cardiorenal risk stratification is the focus of this chapter.3