Profile:
Brandi Reeves, MD
University of North Caroline at Chapel Hill
Hematologist discovers the kidneys: One researcher’s quest to explain an overlooked MPN complication
It all started with a series of patients who couldn’t qualify for a clinical trial.
Not for lack of interest — one after another, patients with myeloproliferative neoplasms (MPNs) couldn’t meet enrollment criteria. For Dr. Brandi Reeves, a hematologist and researcher at the University of North Carolina, it was the beginning of an unexpected journey.
Her experience led her to a bold hypothesis: that a clot-promoting protein called tissue factor, when on the surface of certain immune cells, might silently damage the kidneys of MPN patients — and no one had noticed.
The spark: A clinical challenge turns into a research pursuit
Dr. Reeves had been treating MPN patients for years when her study’s exclusion criteria stopped her progress in its tracks. “The biggest reason I was having a hard time recruiting was that the kidney function was not adequate for the study,” Reeves recalls.
Reeves turned to the literature and colleagues — and quickly found a paper that would become foundational: a 2021 analysis by Dr. Steffen Koschmieder in Germany. Surprisingly, studies suggested that 80% of MPN patients had chronic kidney disease (CKD), and that kidney dysfunction correlated strongly with thrombosis, hypertension, and inflammation.
“I thought, why in the heck would kidney disease have the same risk factors as thrombosis in these patients? There’s probably some link here…” Since then, Dr. Reeve’s laboratory has been digging into that link to discover new cellular connections.
The knowledge gap: What we know — and don’t — about MPNs and kidneys
Despite its prevalence, kidney disease in MPNs is largely unstudied and didn’t warrant a mention in the new 2025 NCCN Clinical Guidelines. This is in part because most MPN-related kidney dysfunction is subtle — typically stage 1 or 2 CKD — and easy to miss without careful biochemical testing.
“The descriptions that do exist aren’t based on direct measurements of kidney function,” Reeves notes. “They’re based on inferred kidney function from blood tests. We don’t even know about protein in the urine of our patients.”
That silence in the literature also means that, until recently, no one had proposed a biological mechanism to explain how a rare blood cancer could affect the blood’s primary waste filtration system.
Enter tissue factor: The hypothesis guiding her work
Tissue factor is the body’s “super glue,” as Reeves puts it — the protein that initiates clotting when blood vessels are injured. Normally, it stays hidden beneath the cells lining blood vessels. When injury exposes it to the blood stream, a cascade of coagulation propels the creation of a clot. But in certain diseases, it’s hypothesized that immune cells begin expressing tissue factor where it doesn’t belong — in the bloodstream.
Her laboratory reported that in MPN patients, neutrophil cells — the immune system’s first responders — aberrantly express tissue factor on their surfaces. This finding was validated at every level: RNA, protein, and clotting activity.
Her theory: this misplaced tissue factor sparks tiny clots in the kidney’s smallest blood vessels. These microscopic vascular events could quietly damage the kidney’s filtering structures — especially the glomeruli, which are intricate tangles of capillaries no wider than a human hair.
Each glomerulus functions like a molecular sieve, filtering waste from over a liter of blood every minute. Damage to this system disrupts blood pressure and waste removal long before traditional blood tests register a problem.
The MPN Challenge™ study: Testing the tissue factor — kidney link
With funding from the 2024 MPN Challenge™, Reeves is now testing her hypothesis in a powerful set of experiments:
- Transgenic mice that lack tissue factor specifically in neutrophils
- Mapping gene expression in kidney tissue at high resolution called spatial transcriptomics
- A close partnership with nephrologists and pathologists to compare mouse and human findings
Already, the results are eye-opening. “The PhD nephropathologist that we work closely with says that she’s never seen kidneys like this before… the mesangial cells in MPN mice will actually break apart and lyse, and so you’ll see these little holes in the glomeruli.”
If confirmed in humans, this pattern of damage could become a hallmark of MPN-related kidney disease and a new target for intervention.
Broader implications: Rethinking how we monitor and treat MPN
For patients, the work opens new possibilities. Most notably, it suggests that serum creatinine — the standard kidney test — may miss early signs of damage. “It takes half of your kidney function being gone before it’s reflected in the bloodwork…We’re hoping that by using other assays we can actually detect earlier kidney dysfunction,” Reeves says.
Partnering with Dr. Koschmieder, Reeve’s international team is also exploring whether kidney function could serve as a meaningful endpoint in MPN clinical trials. Kidneys might be useful as a clinical study end organ — a major organ that is particularly susceptible to damage or dysfunction because of a disease. “You could use kidney function as a readout,” she says — perhaps allowing trials to measure end-organ protection sooner, instead of waiting years for events like thrombosis or fibrosis to occur.
The project could also lead to new treatment strategies — especially for therapies that target inflammation or clotting, which might also protect the kidneys.
Looking ahead: A foundation for future trials
Reeve’s frustrating clinical experience sparked a research question — and potentially, a breakthrough in how scientists understand the intersection between hematology and nephrology.
In collaboration with the German Study Group for MPN and their bioregistry, Reeves’ team is now collecting longitudinal urine and plasma samples to track kidney health over time and search for early biomarkers.
The vision? To move kidney dysfunction from a footnote to a focus — not only to better understand MPN biology, but to improve the lives of patients.
Sources:
Christensen, A. S., Møller, J. B., & Hasselbalch, H. C. (2014). Chronic kidney disease in patients with the Philadelphia-negative chronic myeloproliferative neoplasms. Leukemia Research, 38(4), 490–495. https://doi.org/10.1016/j.leukres.2014.01.014
Gecht, J., Tsoukakis, I., Kricheldorf, K., Stegelmann, F., Klausmann, M., Griesshammer, M., Schulz, H., Hollburg, W., Göthert, J. R., Sockel, K., Heidel, F. H., Gattermann, N., Maintz, C., Al-Ali, H. K., Platzbecker, U., Hansen, R., Hänel, M., Parmentier, S., Bommer, M., … Koschmieder, S. (2021). Kidney Dysfunction Is Associated with Thrombosis and Disease Severity in Myeloproliferative Neoplasms: Implications from the German Study Group for MPN Bioregistry. Cancers, 13(16), Article 16. https://doi.org/10.3390/cancers13164086
Kalejaiye, T. D., Holmes, J. A., Bhattacharya, R., & Musah, S. (2022). Chapter 24—Reconstitution of the kidney glomerular capillary wall. In M. S. Goligorsky (Ed.), Regenerative Nephrology (Second Edition) (pp. 331–351). Academic Press. https://doi.org/10.1016/B978-0-12-823318-4.00007-X
