title: Circulating plasma factors induce tubular and glomerular alterations in septic burns patients.
abstract: BACKGROUND
  Severe burn is a systemic illness often complicated by sepsis. Kidney is one of the organs invariably affected, and proteinuria is a constant clinical finding. We studied the relationships between proteinuria and patient outcome, severity of renal dysfunction and systemic inflammatory state in burns patients who developed sepsis-associated acute renal failure (ARF). We then tested the hypothesis that plasma in these patients induces apoptosis and functional alterations that could account for proteinuria and severity of renal dysfunction in tubular cells and podocytes.
  
  
  METHODS
  We studied the correlation between proteinuria and indexes of systemic inflammation or renal function prospectively in 19 severe burns patients with septic shock and ARF, and we evaluated the effect of plasma on apoptosis, polarity and functional alterations in cultured human tubular cells and podocytes. As controls, we collected plasma from 10 burns patients with septic shock but without ARF, 10 burns patients with septic shock and ARF, 10 non-burns patients with septic shock without ARF, 10 chronic uremic patients and 10 healthy volunteers.
  
  
  RESULTS
  Septic burns patients with ARF presented a severe proteinuria that correlated to outcome, glomerular (creatinine/urea clearance) and tubular (fractional excretion of sodium and potassium) functional impairment and systemic inflammation (white blood cell (WBC) and platelet counts). Plasma from these patients induced a pro-apoptotic effect in tubular cells and podocytes that correlated with the extent of proteinuria. Plasma-induced apoptosis was significantly higher in septic severe burns patients with ARF with respect to those without ARF or with septic shock without burns. Moreover, plasma from septic burns patients induced an alteration of polarity in tubular cells, as well as reduced expression of the tight junction protein ZO-1 and of the endocytic receptor megalin. In podocytes, plasma from septic burns patients increased permeability to albumin and decreased the expression of the slit diaphragm protein nephrin.
  
  
  CONCLUSIONS
  Plasma from burns patients with sepsis-associated ARF contains factors that affect the function and survival of tubular cells and podocytes. These factors are likely to be involved in the pathogenesis of acute tubular injury and proteinuria, which is a negative prognostic factor and an index of renal involvement in the systemic inflammatory reaction.
authors: Dipartimento di Area Medica, Unita' di Nefrologia e Dialisi, Ospedale CTO, Via G, Zuretti 29, Torino, 10126, Italy. filippo.mariano@cto.to.it
authors: Filippo
authors: F
authors: Mariano
authors: Vincenzo
authors: V
authors: Cantaluppi
authors: Maurizio
authors: M
authors: Stella
authors: Giuseppe Mauriello
authors: GM
authors: Romanazzi
authors: Barbara
authors: B
authors: Assenzio
authors: Monica
authors: M
authors: Cairo
authors: Luigi
authors: L
authors: Biancone
authors: Giorgio
authors: G
authors: Triolo
authors: V Marco
authors: VM
authors: Ranieri
authors: Giovanni
authors: G
authors: Camussi
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000503:physiopathology*; D000704:Analysis of Variance; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002056:Burns / Q000150:complications* / Q000503:physiopathology; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism; D011446:Prospective Studies; D011507:Proteinuria / Q000209:etiology* / Q000503:physiopathology; D012307:Risk Factors; D018805:Sepsis / Q000150:complications* / Q000503:physiopathology; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000097:blood / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053222:Fas Ligand Protein; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D020169:Caspases