Role of the kidney in plasma cytokine removal in sepsis syndrome: a pilot study.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Graziani
Giorgio
G
Nephrology and Dialysis Department, Istituto Clinico Humanitas, Rozzano, Milano, Italy. giorgio.graziani@humanitas.it
Bordone
Giovanni
G
Bellato
Valentina
V
Finazzi
Silvia
S
Angelini
Claudio
C
Badalamenti
Salvatore
S
D058186:Acute Kidney Injury / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000652:urine*; D000368:Aged; D016207:Cytokines / Q000097:blood* / Q000652:urine*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000652:urine*
D016207:Cytokines