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Subclinical kidney and cardiovascular indicators of transplant-associated thrombotic microangiopathy (TMA)

Award Number: R01HL185049
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/05/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Subclinical kidney and cardiovascular indicators of transplant-associated thrombotic microangiopathy (TMA) - PROJECT SUMMARY/ABSTRACT Transplant-associated thrombotic microangiopathy (TMA) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT) that occurs within the first 100 days of transplant. Over the last decade, our research team has advanced understanding of the diagnosis and management of TMA. Standardized diagnostic and risk stratification criteria for TMA, developed by our group, were recently adopted by international consensus. High-risk (severe) TMA is analogous to an uncontrolled fire, leading to multi-organ injury and very high mortality. Accordingly, established diagnostic criteria and targeted complement blockade have focused on improving outcomes in patients with the highest risk TMA. Despite this past and ongoing work, knowledge gaps remain in our understanding of the clinical significance of different TMA risk phenotypes. While using complement blockade in patients meeting high-risk criteria is associated with increased survival, we need to determine the earliest time to initiate therapy for TMA, as our long-standing experience and clinical data indicates that patients with less than severe TMA also suffer from TMA-associated organ injury and have reduced post-transplant survival. Identifying subclinical indicators of impending TMA or identifying patients at high-risk to develop TMA will inform new diagnostic approaches to improve outcomes in patients with TMA before the fire burns out of control. We hypothesize that sensitive or subclinical markers of kidney and cardiovascular injury are early indicators of impending TMA after allogeneic HSCT. The objective of the current proposal is to identify early indicators of impending TMA in an established cohort of children and young adults (N=300) undergoing HSCT. We are focusing on the kidney and the cardiovascular system because this hypothesis is supported by our published and preliminary data and because early TMA-associated kidney and cardiac injury can be identified by sensitive biomarker monitoring. Specifically, our preliminary data support that soluble urokinase plasminogen activator receptor (suPAR), a marker of kidney injury, measured in baseline plasma before HSCT, predicts TMA. Furthermore, elevations of serum cystatin C and protein in the urine were also associated with a higher risk of TMA. These biomarkers will be examined in Aim 1 focusing on subclinical kidney injury. Aim 2 will evaluate cardiovascular injury biomarkers, such as ST2, CXCL8 and CXCL3 and also include comprehensive assessments of blood pressure and echocardiograms. Our preliminary data supports that endothelial injury presenting as systemic hypertension or pulmonary hypertension are also early indicators of impending TMA. Finally, the knowledge gained from Aim 1 and Aim 2 will be applied to a new prospectively enrolled validation cohort (N=100). The prospective cohort will test, during clinical care, how the identified biomarkers identify impending TMA and its severity after HSCT. Our approach will inform the optimal timing to initiate therapy in the most appropriate patients. This will aid in the design of future interventional trials to prevent, treat, or decrease the severity of TMA after HSCT and improve patient survival for this high-risk population.


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 = $638,652 )
2026	2026	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Cardiovascular Diseases Research	000	1	9/4/2026	NEW	$638,652
														Subtotal = $638,652

Grand Total All Awards = $638,652

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Subclinical kidney and cardiovascular indicators of transplant-associated thrombotic microangiopathy (TMA)

Award Number: R01HL185049

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/05/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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