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Lumbricus terrestris erythrocruorin (LtEc) as a red blood cell substitute in normothermic ex vivo kidney perfusion

Award Number: R21DK143430
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/11/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Lumbricus terrestris erythrocruorin (LtEc) as a red blood cell substitute in normothermic ex vivo kidney perfusion - PROJECT SUMMARY The ability to maintain the viability and function of organs outside the body (ex vivo) at body temperature (normothermia) is an emerging field of innovation. Normothermic ex vivo perfusion systems have been developed to maintain hearts, lungs, and livers in this fashion for up to several days and have been a valuable tool in transplantation medicine to extend the longevity of donor organs. The potential for these technologies to be utilized in other ways is now also being recognized. Normothermic ex vivo kidney perfusion (NEVKP), in comparison, has been more challenging to develop. The kidney is highly susceptible to damage from the products of red blood cell (RBC) degradation that are generated by machine perfusion. Because of this, existing NEVKP systems cannot reliably sustain the viability of kidneys beyond 24 hours. The goal of this project is to investigate whether this challenge can be overcome using a promising RBC alternative: the naturally acellular hemoglobin (erythrocruorin) of the earthworm Lumbricus terrestris. We aim to use this novel oxygen carrier to extend the duration of NEVKP, making it a more viable tool for kidney disease research. L. terrestris erythrocruorin (LtEc) has many properties suggesting it would be an ideal oxygen carrier for NEVKP. Having evolved to transport oxygen in an extracellular environment, LtEc is molecularly stable in a wide range of temperatures, has a low oxidation rate, and does not scavenge nitrous oxide (NO), an important vasodilator. Its size (30 nm) is favorable for perfusing the kidney as it would likely not get lost to glomerular filtration (6-8 nm cutoff) but remain able to perfuse vasoconstricted capillaries that are inaccessible to RBCs (8 µm). Together with preliminary results from our lab demonstrating that LtEc can sustain respiration in NEVKP, these properties strongly justify investigating the utility of LtEc in NEVKP. In this proposal, we will first evaluate LtEc by testing different LtEc concentrations in an NEVKP system against autologous porcine RBCs as a control. We will investigate the ability of LtEc to support kidney function and viability while monitoring adverse effects including oxidative stress, inflammation, and kidney injury. These experiments will help determine the concentration that best supports respiration and minimizes toxicity during NEVKP. LtEc will also be evaluated against other HBOCs to determine whether the advantageous molecular properties of LtEc confer an empirical benefit in NEVKP. We will then attempt to maintain NEVKP for up to 7 days using an LtEc-based perfusate. Optimizing the use of LtEc for NEVKP of porcine kidneys could result in two major breakthroughs: 1) the development of long-term NEVKP, a tool that would enable many avenues for novel discovery in kidney disease; and 2) the validation of LtEc as an effective and sustainable oxygen carrier in a mammalian organ, the impact of which could be relevant to numerous fields across medicine.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $423,017 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/10/2025	NEW	$423,017
														Subtotal = $423,017

Grand Total All Awards = $423,017

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Lumbricus terrestris erythrocruorin (LtEc) as a red blood cell substitute in normothermic ex vivo kidney perfusion

Award Number: R21DK143430

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/11/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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