RESUMO
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. CONCLUSION: 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.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/fisiopatologia , Queimaduras/complicações , Proteinúria/etiologia , Sepse/complicações , Análise de Variância , Apoptose , Biomarcadores/sangue , Western Blotting , Queimaduras/fisiopatologia , Caspases/metabolismo , Proteína Ligante Fas/metabolismo , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Glomérulos Renais/metabolismo , Glomérulos Renais/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Podócitos/metabolismo , Estudos Prospectivos , Proteinúria/fisiopatologia , Fatores de Risco , Sepse/fisiopatologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue , Proteína X Associada a bcl-2/sangue , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To describe the clinical characteristics of postburn scars and determine the independent risk factors specific to these patients. While burns may generate widespread and disfiguring scars and have a dramatic influence on patient quality of life, the prevalence of postburn pathologic scarring is not well documented, and the impact of certain risk factors is poorly understood. METHODS: A retrospective analysis was conducted of the clinical records of 703 patients (2440 anatomic burn sites) treated at the Turin Burn Outpatient Clinic between January 1994 and May 15, 2006. Prevalence and evolution time of postburn pathologic scarring were analyzed with univariate and multivariate risk factor analysis by sex, age, burn surface and full-thickness area, cause of the burn, wound healing time, type of burn treatment, number of surgical procedures, type of surgery, type of skin graft, and excision and graft timing. RESULTS: Pathologic scarring was diagnosed in 540 patients (77%): 310 had hypertrophic scars (44%); 34, contractures (5%); and 196, hypertrophic-contracted scars (28%). The hypertrophic induction was assessed at a median of 23 days after reepithelialization and lasted 15 months (median). A nomogram, based on the multivariate regression model, showed that female sex, young age, burn sites on the neck and/or upper limbs, multiple surgical procedures, and meshed skin grafts were independent risk factors for postburn pathologic scarring (Dxy 0.30). CONCLUSION: The identification of the principal risk factors for postburn pathologic scarring not only would be a valuable aid in early risk stratification but also might help in assessing outcomes adjusted for patient risk.