# Protective pathways in sepsis-induced renal injury

> **NIH VA I01** · RLR VA MEDICAL CENTER · 2022 · —

## Abstract

Project Summary/Abstract
Sepsis-induced acute kidney injury is a major life-threatening condition with no effective therapy to date. The
host responses to sepsis are wide-ranging, cell-type dependent, and importantly, temporally distinct. These
cellular and molecular responses to sepsis can favorably or negatively affect host fitness. However, the
distinction between adaptive and maladaptive responses is often not apparent a priori, and the same response
may have opposite implications depending on where the patient is in the timeline of sepsis. Our current studies
using a range of omics approaches have identified that altered polyamine metabolism is a prominent feature of
sepsis-induced acute kidney injury. Polyamines, namely putrescine, spermidine and spermine, are involved in
a multitude of fundamental biological processes such as protein synthesis and redox regulation both in host
and pathogens. Our data demonstrate that modulation of polyamine metabolism can significantly influence the
outcome of kidney injury in a highly complex manner, highlighting the need for better understanding the
principles of polyamine metabolism in time and space during sepsis. Accordingly, in Specific Aim 1 of this
proposal, we will examine the effects of modulating polyamines on kidney function across the timeline of
sepsis. We will test the hypothesis that therapeutic effects of polyamine modulation are temporally distinct and
have opposing effects between early and late phase sepsis. Furthermore, to enable a transition to clinical
therapeutic applications, we will seek to define the stages of sepsis using a novel time-sensitive molecular
fingerprint that is linked to the status of polyamine metabolism. In Specific Aim 2, we will determine the
genome-wide molecular effects of polyamine modulation in the kidney with a primary focus on their impact on
protein synthesis. Global mapping of polyamine-dependent translational changes could bridge our knowledge
gap between large scale phenomena such as altered kidney function as investigated in Aim 1 and the
molecular regulation afforded by polyamines at codon-level resolution.

## Key facts

- **NIH application ID:** 10398885
- **Project number:** 5I01BX002901-06
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** Takashi Hato
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398885

## Citation

> US National Institutes of Health, RePORTER application 10398885, Protective pathways in sepsis-induced renal injury (5I01BX002901-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10398885. Licensed CC0.

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