[Effect of proteinuria on tubulointerstitial damage].
BACKGROUND
Glomerular basal membrane represents a mechanical and electric barrier for plasma proteins. In physiological conditions only plasma proteins of low molecular weight are completely filtered through basal membrane. Due to damages of glomerular basal membrane there is an increase in filtration of plasma proteins of moderate and high molecular weight.
In regard to its etiology proteinuria can be prerenal, renal and postrenal. By analyzing albumin, 1-microglobulin, immunoglobulin G and 2-macroglobulin, together with total protein in urine, it is possible to detect and differentiate causes of prerenal, glomerular, tubular and postrenal proteinuria. Abnormal glomerular permeability to macromolecules results in excessive protein delivery and reabsorption in proximal tubules. Excessive reabsorption in turn may cause congetion of intracellular endocytic and biosynthetic compartments leading to NFkB-dependent and -independent gene upregulation. Among those genes, monocyte chemoattractant protein-1 (MCP-1), cytokines, osteopontin and endothelin stimulate processes of interstitial inflammation and fibroblast proliferation and are ultimately responsible for enhanced extracellular matrix deposition and renal scarring. Human tubular cells exposed to albumin and HDL increase production of endothelin-1. Endothelin-1 affects microcirculation and fibroblasts and is a monocyte chemoattractant. Specific proteins that are cytotoxic are transferrin/iron, low-density lipoprotein, and complement components, all of which appear in urine in proteinuric states. Adequate and early diagnosis and differentiation of proteinuria are of immense therapeutic importance.
Stojimirović
Biljana
B
Klinika za nefrologiju, Institut za urologiju i nefrologiju, Klinicki centar Srbije, Beograd. bistoj@ptt.yu
Petrović
Dejan
D
D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology* / Q000652:urine; D007684:Kidney Tubules / Q000503:physiopathology*; D009395:Nephritis, Interstitial / Q000503:physiopathology / Q000652:urine; D011507:Proteinuria / Q000503:physiopathology*