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Immobilized ion receptors for maintaining electrolyte homeostasis with acellular wearable artificial kidneys

Award Number: R01DK124333
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: 09/20/2020
PERIOD OF PERFORMANCE END DATE: 12/31/2029

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Immobilized ion receptors for maintaining electrolyte homeostasis with acellular wearable artificial kidneys - One in seven Americans suffer from chronic kidney disease, of which 519,000 rely on thrice-weekly dialysis for survival while awaiting kidney transplant. Dialysis, however, is a flawed technique, with patient outcome and life expectancy remaining very poor. Even in the US, patients on dialysis have a 50% mortality rate within the first three years of treatment. It has long been recognized that patient quality of life and life expectancy could both be significantly increased with continuous renal replacement therapy. Current wearable artificial kidneys (WAKs) rely on miniaturization of dialysis machines with constant regeneration of dialysate. They have failed to advance to the clinic, in part because they are heavy and cumbersome, and in part because this approach does not enable safe and effective homeostasis of electrolytes with a lightweight and simple instrument. The overarching goal of this project is to develop safe, scalable and effective acellular wearable artificial kidneys that replicate renal function. The overall objective of this application is to develop a scalable module for efficient homeostasis of electrolytes, addressing the primary challenge faced by current WAKs. Our central hypothesis is that we can achieve our goal using highly selective supramolecular receptors whose affinity for each cation and anion can be fine-tuned to match the healthy concentration of electrolytes in the blood, thereby maintaining the concentration of each ion within healthy range. We further hypothesize that immobilizing these receptors on polymeric nanoparticles will enable the design of simpler, lighter, and more compact WAK that do not require dialysates and pumps. The rationale for the proposed research is that highly selective receptors for each electrolyte will maintain normal levels over a period of a day by removing just the right amount of each ion. Based on strong preliminary results and the success of our prior R01 project on the treatment of hyperphosphatemia, we plan to accomplish the specific objectives identified by the Kidney Health Initiative regarding electrolyte homeostasis by pursuing the following Specific Aims: 1) Develop second-generation receptors for bicarbonate and chloride. 2) Develop tunable polypeptide-supported receptors to augment selective electrolyte removal. Our research is significant because it aims to develop a new scalable technology to efficiently and safely maintain electrolyte balance in patients undergoing near-continuous treatment with a WAK. This will improve both the outcome and the quality of life of patients with CKD. Our research is innovative because, unlike current acellular WAKs, it employs tunable and selective supramolecular receptors and does not necessitate dialysate nor bulky and heavy devices.


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: 2026 ( Subtotal = $573,410 )
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	2/17/2026	COMPETING CONTINUATION	$573,410
2026	2026	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	7	2/23/2026	COMPETING CONTINUATION	$0
2026	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	2/9/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $573,410

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	4/16/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$385,454
2025	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/15/2025	NON-COMPETING CONTINUATION	-$385,454
2025	2024	UNIVERSITY OF UTAH	201 PRESIDENTS CIR	SALT LAKE CITY	UT	84112	SALT LAKE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	6	8/13/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	7/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $385,454 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	8/16/2024	NON-COMPETING CONTINUATION	$385,454
														Subtotal = $385,454

Issue Date FY: 2023 ( Subtotal = $401,514 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	8/24/2023	NON-COMPETING CONTINUATION	$401,514
														Subtotal = $401,514

Issue Date FY: 2022 ( Subtotal = $330,492 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/10/2022	NON-COMPETING CONTINUATION	$330,492
														Subtotal = $330,492

Issue Date FY: 2021 ( Subtotal = $330,492 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/11/2021	NON-COMPETING CONTINUATION	$330,492
														Subtotal = $330,492

Issue Date FY: 2020 ( Subtotal = $343,902 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/14/2020	NEW	$343,902
														Subtotal = $343,902

Grand Total All Awards = $2,365,264

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Immobilized ion receptors for maintaining electrolyte homeostasis with acellular wearable artificial kidneys

Award Number: R01DK124333

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: 09/20/2020

PERIOD OF PERFORMANCE END DATE: 12/31/2029

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