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Human Acute Kidney Injury (AKI) is Associated with a Pro-inflammatory Phenotype
M Varrier, N Gauge, D Boardman, M Hernandez-Fuentes, M Ostermann
Guy’s and St Thomas’ Hospital and King’s College London
Introduction: Patients with AKI have markedly worse outcomes than otherwise matched controls.
There is increasing evidence from animal models that leukocytes play a central role in the
pathophysiology of AKI resulting in an inflammatory response (1, 2). We conducted a pilot study
aiming to describe the immune phenotype in human AKI using flow cytometry.
Methods: We enrolled three groups of patients: 1) AKI stage II/III (defined by KDIGO criteria) and
systemic inflammatory response syndrome (SIRS) without sepsis; 2) SIRS without AKI; and 3) AKI
stage II/III without SIRS. A healthy control population was used for baseline comparison. Serial
blood samples were taken on day 0, 2 and 7. Cells were separated from whole blood using percoll
gradients and stained using panels of antibodies specific for lymphocyte, monocyte or neutrophil
markers. Cells were acquired by flow cytometry using BD LSR Fortessa and analysed using FlowJo
(Tree Star, USA). We compared the median values on day 0 between all groups.
Results: Results from 24 day 0 samples identified statistically significant differences in the
proportion of cytotoxic CD8+ T Cells, CD45-CD25+++ regulatory T cells and CD45-CD25++
cytokine secreting non T regulatory cells between SIRS, AKI, AKI + SIRS and healthy controls
(Table 1). The percentage of CD69 positive neutrophils was significantly increased across all 3
groups relative to controls, with little variation between AKI, SIRS and AKI+SIRS patients.
Table 1- Group column values are percentages
Cell type day 0
CD8+ Cytotoxic T cells
Fr. II CD45-CD25+++ T cell regs
Fr. III CD45-CD25+ Cytokine Secreting
non T regs
CD69+ Neutrophils
23.3
4.1
AKI
alone
16.7
2.7
SIRS
alone
11.6
1.6
11.5
21.2
83.9
69.7
AKI+SIRS
Controls
p value
31.1
1.2
0.039
0.002
13.9
8.0
0.008
65.5
7.35
0.023
Conclusions: Our results indicate that AKI is associated with an inflammatory phenotype similar to
patients meeting SIRS criteria. The combination of AKI and SIRS is associated with increased CD8+
cytotoxic T cells. In addition cytokine secreting non-regulatory T cells (Fr. III) appear particularly
elevated in patients with AKI alone. We aim to complete recruitment of 20 patients in each group,
analyse day 2 and 7 results and perform cytokine profiling on saved serum samples to conclude this
study. More research is needed to fully characterise the inflammatory response in human AKI and any
resultant systemic effects in order to develop targeted treatment to improve clinical outcomes.
References
1.
2.
Kinsey GR, Okusa MD. Role of leukocytes in the pathogenesis of acute kidney injury. Crit
Care. 2012;16(2):214.
Kinsey GR, Okusa MD. Expanding role of T cells in acute kidney injury. Curr Opin Nephrol
Hypertens. 2014;23(1):9-16.