title: Plasma gelsolin and circulating actin correlate with hemodialysis mortality.
abstract: Plasma gelsolin (pGSN) binds actin and bioactive mediators to localize inflammation. Low pGSN correlates with adverse outcomes in acute injury, whereas administration of recombinant pGSN reduces mortality in experimental sepsis. We found that mean pGSN levels of 150 patients randomly selected from 10,044 starting chronic hemodialysis were 140 +/- 42 mg/L, 30 to 50% lower than levels reported for healthy individuals. In a larger sample, we performed a case-control analysis to evaluate the relationship of pGSN and circulating actin with mortality; pGSN levels were significantly lower in 114 patients who died within 1 yr of dialysis initiation than in 109 survivors (117 +/- 38 mg/L versus 147 +/- 42 mg/L, P < 0.001). pGSN levels had a graded, inverse relationship with 1-yr mortality, such that patients with pGSN < 130 mg/L experienced a > 3-fold risk for mortality compared with those with pGSN > or = 150 mg/L. The 69% of patients with detectable circulating actin had lower pGSN levels than those without (127 +/- 45 mg/L versus 141 +/- 36 mg/L, P = 0.026). Compared with patients who had elevated pGSN and no detectable actin, those with low pGSN levels and detectable actin had markedly increased mortality (odds ratio 9.8, 95% confidence interval 2.9 to 33.5). Worsening renal function correlated with pGSN decline in 53 subjects with CKD not on dialysis. In summary, low pGSN and detectable circulating actin identify chronic hemodialysis patients at highest risk for 1-yr mortality.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Po-Shun
authors.initials: PS
authors.lastname: Lee
authors.forename: Kartik
authors.initials: K
authors.lastname: Sampath
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Hector
authors.initials: H
authors.lastname: Tamez
authors.forename: Ishir
authors.initials: I
authors.lastname: Bhan
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutierrez
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
authors.forename: Yuchiao
authors.initials: Y
authors.lastname: Chang
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Stossel
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
mesh_terms: D000199:Actins / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018260:Gelsolin / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D012016:Reference Values; D006435:Renal Dialysis / Q000401:mortality*; D016019:Survival Analysis; D017741:Survivors; D014481:United States
chemical_list: D000199:Actins; D015415:Biomarkers; D018260:Gelsolin