Short-term beneficial effects of methylene blue on kidney damage in septic shock patients.
OBJECTIVE
We previously demonstrated that upregulation of renal inducible nitric oxide synthase (iNOS) is associated with proximal tubule injury during systemic inflammation in humans. In this study we investigated the short-term effect of methylene blue (MB), an inhibitor of the NO pathway, on kidney damage and function in septic shock patients.


METHODS
A prospective clinical study conducted in an intensive care unit.


METHODS
Nine patients (four men, five women, mean age 71 +/- 3 years) with confirmed or suspected bacterial infection and with refractory septic shock defined as a mean arterial pressure < or = 70 mmHg despite norepinephrine infusion > or = 0.2 microg/kg per minute.


METHODS
A 4 h continuous intravenous infusion of 1 mg/kg MB per hour.


RESULTS
The urinary excretion of NO metabolites decreased with median 90% (range 75-95%) from baseline to 6 h after MB administration. The first 24 h creatinine clearance improved by 51% (18-173%) after MB treatment but was still strongly impaired. During the first 6 h after the start of MB treatment both the urinary excretion of cytosolic glutathione S-transferase A1-1 and P1-1, markers for proximal and distal tubule damage, respectively, decreased by 45% (10-70%) and 70% (40-85) vs. baseline. After termination of the MB infusion the NO metabolites and markers of tubular injury returned to pretreatment levels.


CONCLUSIONS
In septic patients with refractory shock short-term infusion of MB is associated with a decrease in NO production and an attenuation of the urinary excretion of renal tubular injury markers.
Heemskerk
Suzanne
S
Radboud University, Nijmegen Medical Centre, Department of Pharmacology and Toxicology, Nijmegen Center for Molecular Life Sciences, 6500 HB Nijmegen, The Netherlands.
van Haren
Frank M P
FM
Foudraine
Norbert A
NA
Peters
Wilbert H M
WH
van der Hoeven
Johannes G
JG
Russel
Frans G M
FG
Masereeuw
Rosalinde
R
Pickkers
Peter
P
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology*; D000368:Aged; D000704:Analysis of Variance; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008297:Male; D008751:Methylene Blue / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011446:Prospective Studies; D012772:Shock, Septic / Q000150:complications* / Q000201:enzymology; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D005982:Glutathione Transferase; D008751:Methylene Blue