The Nephrotic Syndrome is an immunoinflammatory disorder.
The Nephrotic Syndrome is still a therapeutic and physiopathological challenge. The clinical response to systemic immunosuppression shows that an immunoinflammatory disorder supports the nephrotic syndrome. Experimental (in vitro and in vivo) studies show that proteinuria may induce kidney secretion of proinflammatory and profibrotic cytokines and subsequent renal inflammation mediated by leukocyte recruitment. In turn,the infiltrating leukocytes contribute to renal damage by releasing proinflammatory and profibrotic cytokines (kidney acute remodelling). Chronic proteinuria maintains continuous local cytokine secretion and leukocyte influx into the glomerulus or the interstitial space (kidney chronic remodelling). In glomerular injury (podocyte injury), proteinuria itself, as well as glomerular secreted cyotokines, stimulates downstream tubular epithelial cells to secrete cytokines,as well. The mutual stimulation between proteinuria-cytokines-podocyte dysfunction-infiltrating leukocytes supports progressive tubular damage, renal fibrosis and glomerulosclerosis. Interfering with the cytokine network by inhibition/blockade of the cytokine receptor and its synthesis (via NFkB and the JAK/STAT intracellular signalling pathway) may represent a promising therapeutic option for systemic immunosuppression. Renal cytokine escape into systemic circulation may provide to hypercytokinemia stress syndrome,which could help to explain the increase in efferent renal sympathetic nerve activity (physiopathological sympathetic overactivity) observed during experimental nephrotic edema.
Camici
Marcello
M
Internal Medicine Department, Pisa University, Via Roma n. 67, 56126 Pisa, Italy. m.camici@med.unipi.it <m.camici@med.unipi.it>
D000418:Albumins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000473:pathology; D007154:Immune System Diseases / Q000175:diagnosis*; D007249:Inflammation / Q000175:diagnosis*; D007674:Kidney Diseases / Q000175:diagnosis*; D008954:Models, Biological; D008962:Models, Theoretical; D009404:Nephrotic Syndrome / Q000175:diagnosis*; D011507:Proteinuria / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism; D013312:Stress, Physiological
D000418:Albumins; D016207:Cytokines; D013256:Steroids