Mariano Filippo, Cantaluppi Vincenzo, Stella Maurizio, Romanazzi Giuseppe Mauriello, Assenzio Barbara, Cairo Monica, Biancone Luigi, Triolo Giorgio, Ranieri V Marco, Camussi Giovanni
Dipartimento di Area Medica, Unita' di Nefrologia e Dialisi, Ospedale CTO, Via G, Zuretti 29, Torino, 10126, Italy.
Crit Care. 2008;12(2):R42. doi: 10.1186/cc6848. Epub 2008 Mar 25.
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.
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.
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.
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.
严重烧伤是一种常并发脓毒症的全身性疾病。肾脏是常受影响的器官之一，蛋白尿是常见的临床发现。我们研究了发生脓毒症相关急性肾衰竭（ARF）的烧伤患者中蛋白尿与患者预后、肾功能障碍严重程度及全身炎症状态之间的关系。然后我们检验了这样一个假设，即这些患者的血浆会诱导细胞凋亡和功能改变，从而导致肾小管细胞和足细胞出现蛋白尿及肾功能障碍的严重程度。
我们前瞻性地研究了19例伴有脓毒性休克和ARF的严重烧伤患者中蛋白尿与全身炎症指标或肾功能之间的相关性，并评估了血浆对培养的人肾小管细胞和足细胞凋亡、极性及功能改变的影响。作为对照，我们收集了10例伴有脓毒性休克但无ARF的烧伤患者、10例伴有脓毒性休克和ARF的烧伤患者、10例伴有脓毒性休克但无ARF的非烧伤患者、10例慢性尿毒症患者及10例健康志愿者的血浆。
伴有ARF的脓毒症烧伤患者出现严重蛋白尿，其与预后、肾小球（肌酐/尿素清除率）和肾小管（钠和钾分数排泄率）功能损害及全身炎症（白细胞（WBC）和血小板计数）相关。这些患者的血浆在肾小管细胞和足细胞中诱导了促凋亡效应，且与蛋白尿程度相关。伴有ARF的脓毒症严重烧伤患者的血浆诱导的细胞凋亡显著高于无ARF或伴有脓毒性休克但无烧伤的患者。此外，脓毒症烧伤患者的血浆诱导肾小管细胞极性改变，以及紧密连接蛋白ZO-1和内吞受体巨膜蛋白的表达降低。在足细胞中，脓毒症烧伤患者的血浆增加了对白蛋白的通透性，并降低了裂孔隔膜蛋白nephrin的表达。
伴有脓毒症相关ARF的烧伤患者的血浆含有影响肾小管细胞和足细胞功能及存活的因子。这些因子可能参与急性肾小管损伤和蛋白尿的发病机制，蛋白尿是一个不良预后因素及全身炎症反应中肾脏受累的指标。
