ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2019 and some content may be unavailable. To unlock all content for 2019, please visit the archives.

Abstract: FR-PO105

CpG C Dinucleotide Is a TL9 Agonist That Increases IgM Levels and Attenuates AKI in Mice

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Skrypnyk, Nataliya, University of Virginia, Charlottesville, Virginia, United States
  • Lobo, Peter I., University of Virginia, Charlottesville, Virginia, United States
  • Okusa, Mark D., University of Virginia, Charlottesville, Virginia, United States
Background

Acute kidney injury (AKI) is a common complication in hospitalized patients with high mortality rates and no FDA approved therapies available except dialysis and kidney transplant.CpG oligodinucleotides (ODNs) are short synthetic single-stranded DNA molecules containing unmethylated CpG dinucleotides in particular sequence contexts (CpG motifs).CpG class B has been approved by FDA in vaccine therapy as it strongly activates B-cells and IL-6 secretion but weakly stimulates interferon (IFN)-alpha secretion. CpG class C equally activates B-cells and IFN-alfa secretion but mild IL-6 secretion. It is known that CpG has protective effect on ischemic brain and heart injury. We hypothesize that CpG can have protective effect on the AKI.

Methods

C57BL/6 mice were anesthetized and subjected kidneys to ischemia-reperfusion (IR: 26 min of ischemia and 24 hrs of reperfusion). 50µg of CpG B or CpG C were administered i.v. 5 days before IR. Serum creatinine and BUN were measured and survival rates were recorded. In in vitro assays, freshly isolated murine splenocytes were activated with CpG C and intracytoplasmic IgM levels in B cells were evaluated by flow cytometry on day 5 (Figure 1).

Results

As depicted in Table 1, following IR the increase in plasma creatinine as well as mortality was significantly reduced by CpG C. In vitro studies CpG significantly increased intracytoplasmic IgM (Figure 1).

Conclusion

CpG C is more effective in ameliorating ischemia induced AKI than CpG B and also reduces post injury mortality rates. Potential mechanisms include increasing natural IgM levels (see Figure 1) and inducing regulatory activity in B cells and antigen presenting cells (Lobo PI, Frontiers in Immunology, 2017). CpG C has a broad range of applications that could be useful for preventive treatment of patients with AKI.

Table 1
 Day1 (creatinine)Day3 (creatinine)Survival
Control1.8±0.11.5±0.345% on Day 12
CpG B1.5±0.21.0±0.245% on Day 12
CpG C1.1±0.1#0.8±0.1#100% on Day 30*

*p≤0.05, #p≤0.01

Funding

  • NIDDK Support