# Red blood cell congestion in AKI to CKD transition

> **NIH NIH F31** · AUGUSTA UNIVERSITY · 2021 · $38,110

## Abstract

lschemic acute kidney injury (AKI} results in both tubular injury and red blood cell (RBC) congestion in the renal
medulla. RBC congestion of medullary capillaries leads to prolonged hypoxia and long-term ischemia in the renal
medulla. Much evidence suggests that medullary ischemia and vascular rarefaction promotes the development
of hypertension. Further, hypertension may drive glomerular injury and chronic kidney disease (CKD) following
nephron loss. Our goal is to better understand the mechanisms by which renal medullary RBC congestion can
be experimentally prevented and whether RBC congestion drives the long-term sequelae of ischemic AKI. As
such, Aim 1 will test whether prevention of renal medullary RBC congestion prevents development of
hypertension and CKD following ischemic AKI utilizing gold-standard techniques to assess renal function and
microvascular rarefaction, including telemetry, microphil infusion, and small animal micro CT. The results from
this aim will help to better delineate the contribution of the initial tubular injury resulting from ischemia-reperfusion
{IR} within 24h of ischemia, versus the contribution of RBC congestion and prolonged medullary ischemia {days),
to the development of hypertension and CKD. Our novel preliminary data indicate that pre-treatment with low
doses of lipopolysaccharide (LPS) completely prevents RBC congestion in the peritubular capillaries following
IR, independent of the initial level of tubular injury. lmmunohistological analysis of the first 24 hours following
reperfusion revels that RBC congestion originates in the ascending vasa recta (VR) during the ischemic period.
Further, rapid-reperfusion of the VR which drain the renal medulla upon reperfusion, occurs only in LPS treated
rats, which then prevents peritubular congestion. VR are densely surrounded by contractile pericytes, and NO
has been shown to limit pericyte constriction. Upregulation of iNOS in VR may protect the kidney from
subsequent ischemia by reducing VR resistance, promoting rapid reperfusion of these important vessels, and
thereby preventing peritubular congestion. Aim 2 will test whether low dose LPS promotes increases in iNOS-mediated
nitric oxide production in medullary VR. These aims test our central hypothesis that preconditioning
with low dose LPS results in rapid reperfusion of the medullary VR due to increased VR iNOS activity and nitric
oxide production and that this will prevent peritubular capillary congestion, greatly improve recovery of renal
function, and prevent the subsequent development of hypertension and CKD following IR. The proposed study
will establish the significance of RBC congestion in the medulla to drive long-term ischemic injury and
complications, with hope that understanding the mechanisms by which we prevent congestion, may provide
much needed novel therapeutic approaches. My strong preliminary data, experienced mentor team, and rigorous
training plan ensure this proposal has a high likelihood...

## Key facts

- **NIH application ID:** 10233153
- **Project number:** 1F31DK127683-01A1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Sarah Ray McLarnon
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,110
- **Award type:** 1
- **Project period:** 2021-04-01 → 2021-12-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233153

## Citation

> US National Institutes of Health, RePORTER application 10233153, Red blood cell congestion in AKI to CKD transition (1F31DK127683-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10233153. Licensed CC0.

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