Microalbuminuria: causes and implications

Abstract

Management strategies are increasingly focused on tackling the increasing burden of cardiovascular disease worldwide. Microalbuminuria is a powerful predictor of cardiovascular disease and mortality in adults. This holds true in the general adult population but is particularly recognized in those with diabetes, where it identifies those likely to develop progressive atherosclerotic vascular disease and renal impairment. The atherosclerotic process begins in childhood with likely consequences in later life. In-depth understanding of the mechanisms through which microalbuminuria occurs holds promise for designing therapies to arrest its development in the future. Microalbuminuria arises from increased leakage of albumin through the complex glomerular sieve known as the glomerular filtration barrier. This requires changes in the physio-chemical properties of components of this barrier. However, the increased glomerular permeability confirmed in disease does not necessarily correlate with recognized histological changes in the glomerulus, suggesting that perhaps more subtle ultrastructural changes may be relevant. The epidemiology of microalbuminuria reveals a close association between systemic endothelial dysfunction and vascular disease, also implicating glomerular endothelial dysfunction in microalbuminuria. This review discusses the mechanisms of microalbuminuria in disease, particularly the emerging role of the glomerular endothelium and its glycocalyx, and examines its implications for cardiovascular disease in the pediatric population.

Fig. 1

Schematic drawing of components of the glomerular filtration barrier (GFB). Fenestrated glomerular endothelial cells (GEnC) form the luminal side of the sieve and facilitate the high flux of water and small molecules (blue arrows); glomerular basement membrane (GBM) in the middle, and the podocyte foot processes and slit diaphragms on the urinary side. The GEnC (including the fenestrae) are covered by a mesh-like, anionic layer of glycocalyx composed of sialic acid-rich glycoproteins and proteoglycans consisting of core proteins and attached branching glycosaminoglycan chains (mainly heparan sulphate and chondroitin sulphate). The glycosaminoglycan hyaluronan is non-covalently bound to the cell surface and other glycocalyx components. Adsorbed plasma proteins including albumin (yellow dots) and orosomucoid (purple dots) contribute to the high negative charge of the glycocalyx layer. In the healthy, all the three components of the GFB work together and conserve 99.9% of proteins in the capillary lumen