Proteinuria and growth factors in the development of tubulointerstitial injury and scarring in kidney disease.
OBJECTIVE
There are ongoing debates as to the role and mechanisms of proteinuria in tubulointerstitial fibrogenesis. Moreover, recent experimental findings have allowed for further insights into mediators and interactions between cells in the renal interstitium during fibrogenesis.


RESULTS
Proteinuria or albuminuria are likely just markers for the glomerular ultrafiltration and tubular actions of ultrafiltered, biologically active growth factors which 'activate' tubular cells causing basolateral secretion of chemokines and cytokines. Chemokines attract and activate macrophages. Tubular cell-derived platelet-derived growth factor (PDGF) and macrophage-derived transforming growth factor-beta cause fibroblast proliferation. Several growth factors contribute to their transition into extracellular matrix-producing myofibroblasts. This cascade of events provides targets for some currently available and several novel therapies.


CONCLUSIONS
Albuminuria or glomerular proteinuria appear to be markers but ultrafiltered, bioactive growth factors are culprits in proteinuria-associated interstitial fibrosis. Interactions of tubular cells with macrophages and fibroblasts in the interstitium via defined growth factor/cytokines provide opportunities for therapeutic interventions.
Hirschberg
Raimund
R
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. rhirschberg@labiomed.org
Wang
Shinong
S
D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000378:metabolism* / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta