Albumin transport and processing by the proximal tubule: physiology and pathophysiology.
OBJECTIVE
Significant epidemiological and clinical trial evidence supports the association between increased urinary albumin excretion, cardiovascular events and renal failure. An increase in albumin excretion has traditionally been considered to reflect a 'glomerular' leak of protein; however, it is now recognized that significant tubular reabsorption of albumin occurs under physiological conditions that may be modified by genetic determinants, systemic disease and drug therapies.


RESULTS
The endocytosis of albumin by the proximal tubule is a highly regulated process depending on protein-protein interactions between several membrane proteins and scaffolding and regulatory molecules. The elucidation of these interactions is an ongoing research focus. There is also mounting evidence for a transcytotic pathway for retrieval of albumin from the tubular filtrate. The molecular basis for the role of albuminuria in both interstitial renal disease and cardiovascular pathology continues to be defined. The clinical implications of albuminuria due to a glomerular leak vs. reduced tubular reabsorption of albumin are, however, now under consideration. In particular, the prognostic implication of microalbuminuria induced by the more potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors is under study.


CONCLUSIONS
The currently defined mechanisms underpinning the tubular reabsorption of albumin, how these are modified by pathology and pharmacology, and the clinical implications are the subject of this review.
Pollock
Carol A
CA
Department of Medicine, University of Sydney, Kolling Institute, Royal North Shore Hospital, New South Wales, Australia. carpol@med.usyd.edu.au
Poronnik
Philip
P
D000418:Albumins / Q000009:adverse effects / Q000378:metabolism*; D000419:Albuminuria / Q000150:complications; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology; D004705:Endocytosis / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007674:Kidney Diseases / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000502:physiology* / Q000503:physiopathology*; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists; D010750:Phosphoproteins / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D000418:Albumins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D047495:PPAR gamma; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C029486:intrinsic factor-cobalamin receptor; C093376:sodium-hydrogen exchanger regulatory factor