Graziani Giorgio, Bordone Giovanni, Bellato Valentina, Finazzi Silvia, Angelini Claudio, Badalamenti Salvatore
Nephrology and Dialysis Department, Istituto Clinico Humanitas, Rozzano, Milano, Italy.
J Nephrol. 2006 Mar-Apr;19(2):176-82.
At the onset of sepsis, endotoxins or other components of the gram-negative capsular wall stimulate the synthesis of pro-inflammatory cytokines by activating the monocyte-macrophage system. In this context, interleukin-1 beta (IL-1), tumor necrosis factor-alpha (TNF) and IL-6 are considered co-responsible for the clinical picture of sepsis syndrome. Many organs can be involved, and kidney dysfunction occurs early with a picture of non-oliguric acute renal failure (NOARF) or oliguric acute renal failure (OARF). This study aimed to investigate the role of the kidney in plasma removal of some pro-inflammatory cytokines in the first 24 hr after the diagnosis of sepsis syndrome, when, according to the peak concentration hypothesis, their plasma concentration is maximal. 18 septic patients, six patients with normal renal function (NRF), six with NOARF and six with OARF were selected for the study. We measured the plasma levels and urinary excretion of IL-1, TNF and IL-6 at the moment of sepsis diagnosis (base-line) and 24 hr later. Moreover, urinary excretion of IL-1 and IL-6 was done in the same interval by measuring the percentage of fractional excretion (FE%) of these cytokines.
Multivariate analysis (ANOVA) showed no significant difference in plasma IL-1 levels at baseline in the NRF, NOARF and OARF patients (p=0.11), whereas a significant increase was found in OARF patients at 24 hr, p<0.023. OARF patients presented significantly higher IL-6 plasma levels compared with the other two groups, both at baseline (p<0.0002) and at 24 hr (p<0.0001). Plasma TNF levels were not significantly different at baseline (p=0.184), whereas the OARF group showed a significant increase at 24 hr, (p<0.05). The urinary FE of IL-1 was 1.2 +/- 0.6% in NRF, and 1.0 +/- 0.4% in NOARF (ns), the FE of IL-6 was 1.4 +/- 0.8% in NRF and 1.3 +/- 0.3% in NOARF (ns). A negative in-significant correlation was found between the plasma concentration and FE of IL-1 beta (r=-0.33, p<0.07). Urinary excretion of IL-6 was significantly related with urinary IL-1 beta, both expressed as pg/ml/mg of urinary creatinine (r=0.85, p<0.0001). No significant relation was found between IL-1 and IL-6 plasma concentrations or between plasma concentration and FE of IL-6.
These results suggest that at disease onset, the kidney removes some pro-inflammatory cytokines from the plasma of septic patients until diuresis is preserved. As it has been demonstrated that NOARF patients have a better prognosis than OARF patients and their survival in sepsis syndrome seems to be inversely related to the plasma pro-inflammatory cytokine levels, diuresis maintenance by diuretic infusion can be important to improve patient prognosis.
在脓毒症发作时，内毒素或革兰氏阴性菌荚膜壁的其他成分通过激活单核细胞 - 巨噬细胞系统刺激促炎细胞因子的合成。在这种情况下，白细胞介素 -1β（IL -1）、肿瘤坏死因子 -α（TNF）和IL -6被认为共同导致了脓毒症综合征的临床表现。许多器官都可能受累，肾功能障碍早期表现为非少尿型急性肾衰竭（NOARF）或少尿型急性肾衰竭（OARF）。本研究旨在调查脓毒症综合征诊断后的最初24小时内，肾脏在清除某些促炎细胞因子血浆中的作用，根据峰值浓度假说，此时它们的血浆浓度最高。选取了18例脓毒症患者，其中6例肾功能正常（NRF），6例为NOARF，6例为OARF进行研究。我们在脓毒症诊断时（基线）和24小时后测量了IL -1、TNF和IL -6的血浆水平及尿排泄量。此外，通过测量这些细胞因子的排泄分数百分比（FE%），在相同时间段内进行了IL -1和IL -6的尿排泄量测定。
多因素分析（方差分析）显示，NRF、NOARF和OARF患者基线时血浆IL -1水平无显著差异（p = 0.11），而OARF患者在24小时时显著升高，p < 0.023。与其他两组相比，OARF患者在基线时（p < 0.0002）和24小时时（p < 0.0001）的IL -6血浆水平均显著更高。基线时血浆TNF水平无显著差异（p = 0.184），而OARF组在24小时时显著升高（p < 0.05）。NRF组IL -1的尿排泄分数为1.2±0.6%，NOARF组为1.0±0.4%（无统计学意义），NRF组IL -6的尿排泄分数为1.4±0.8%，NOARF组为1.3±0.3%（无统计学意义）。IL -1β的血浆浓度与排泄分数之间存在负相关但无统计学意义（r = -0.33，p < 0.07）。IL -6的尿排泄量与尿IL -1β显著相关，两者均以每毫克尿肌酐中的pg/ml表示（r = 0.85，p < 0.0001）。IL -1和IL -6的血浆浓度之间或IL -6的血浆浓度与排泄分数之间未发现显著关系。
这些结果表明，在疾病发作时，肾脏可从脓毒症患者血浆中清除一些促炎细胞因子，直至维持利尿。由于已证明NOARF患者的预后优于OARF患者，且他们在脓毒症综合征中的生存似乎与血浆促炎细胞因子水平呈负相关，通过利尿剂输注维持利尿对于改善患者预后可能很重要。
