Effect of calcium oxalate microcrystals on kidney proximal tubule epithelial cell gene expression in microgravity - npj microgravity Brief communication

Sep 30, 2026

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Evaluated spaceflight effects on a microphysiologic model of calcium oxalate kidney stone disease using confluent proximal tubule epithelial microtubules exposed to calcium oxalate (CaOx) crystals with or without potassium citrate as a countermeasure. Nine genes showed differential expression after CaOx crystal exposure during microgravity. The work leverages microgravity to study early stone-response biology and to interrogate mechanisms underlying potassium citrate efficacy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Background

Kidney stone disease risk in microgravity

Countermeasure: potassium citrate

Model and Experimental Rationale

Kidney microphysiological systems (MPS)

COM microcrystal challenge and biomarkers

Microgravity-Based Delivery Strategy

ISSNL dispersion for physiological exposure

Figure Overview

KC-02 experiment summary and characterization

npj | microgravity Brief communication | Published in cooperation with the Biodesign Institute at Arizona State University, with the support of NASA | | | | --- | --- | --- | | [https://doi.org/10.1038/s41526-025-00543-3](https://doi.org/10.1038/s41526-025-00543-3) | | | | Effect of calcium oxalate microcrystals on kidney proximal tubule epithelial cell gene expression in microgravity
Check for updates | | | | Kendan Jones-Isaac1,7, Catherine K. Yeung2,3 , Jacelyn Bain1, Kevin Lidberg1,8, Jade Yang1, Lu Wang4, James MacDonald4, Theo Bammler4, Kenneth E. Thummel1, Megan Corn1, Micaela Vela Ruiz1, Stefanie Countryman5, Paul Koenig5, Henning H. Mann6, Jonathan Himmelfarb3,9 & Edward J. Kelly1 | | | | We evaluated the impact of spaceﬂight on a microphysiologic model of calcium oxalate (CaOx) kidney stone disease. Proximal tubule epithelial cells cultured as conﬂuent microtubules were exposed to CaOx crystals with or without potassium citrate (a potential countermeasure) to determine the impact on gene expression. Nine genes were differentially expressed in response to CaOx crystal exposure during spaceﬂight. This project presents the use of microgravity as a unique environment to study kidney pathophysiology. | | | | Almost 12% of the global population is affected by kidney stone disease (KSD), with the experience being reported as painful and debilitating. Estimated recurrence rates for KSD have been reported as high as 67%—further compounding the considerable disease burden on the individual patient and economic strain on healthcare systems globally1. KSD poses an even greater threat in microgravity due to the inaccessibility of medical and surgical interventions readily available on Earth. Exposure to microgravity increases the risk ofKSD in humans2 due to a dehydration-like state caused by altered bodyﬂuid distribution, accelerated bone and muscle atrophy, and oxidative stress responses to elevated ROS generation during spaceﬂight2, increased inﬂammation and oxidative stress response3, and a diet enriched in protein and sodium2,4. A recent report conﬁrmed the potential for spaceﬂight-induced kidney dysfunction, highlighting renal transporterdephosphorylation, expansion ofthe distal convoluted tubule, loss oftubule density, and galactic cosmic radiation-caused kidney impairment inhuman datasets and spaceﬂight-exposed rodents5.
Citrate supplementation in the form of potassium citrate (KCit), an inexpensive and well-tolerated medication, has been used as a pharmacologic countermeasure to decrease the risk of kidney stone formation by reducing hypercalciuria in both spaceﬂight crew and the general public4. Prevention of symptomatic kidney stone formation is critical as larger stones require surgical intervention, including extracorporeal shock wave lithotripsy to pulverize stones or insertion of instrumentation percutaneously or via the urethra to mechanically extract stones from the kidney to prevent irreversible kidney damage6.
Flow-mediated 3D cultures of proximal tubule epithelium, referred to as kidney microphysiological systems (MPS), can be used to study kidney | function and biomarkers of developing pathologies7. Various stressors, including environmental toxins, medications, excess heat, and particulates, can be introduced into the system to elicit physiological responses in the human kidney8.
To study KSD pathophysiology, exposure to microcrystals (approximately 10 microns) of calcium oxalate monohydrate (COM), precursors of developing kidney stones, can be used to model early events underlying KSD progression. Biomarkers of kidney injury released into the efﬂuent in response to COM crystal exposure can indicate perturbed signaling/stress response pathways and may serve to guide disease treatment options. For example, interleukin 6 (IL-6), a cytokine marker of chronic inﬂammation, is elevated in vivo and in kidney proximal tubules after exposure to known nephrotoxins9, 10 and reactive oxygen spe

FAQs

How were proximal tubule epithelial cells exposed to calcium oxalate during microgravity?

Confluent proximal tubule epithelial cells in a kidney microphysiological system were exposed to calcium oxalate crystals, with microgravity in the ISSNL enabling even dispersion in treatment media for access to cells in the internal culture chamber.

What role does potassium citrate play in this study?

Potassium citrate is used as a pharmacologic countermeasure. The experiments assess how it influences gene expression changes triggered by CaOx crystal exposure during spaceflight.

Why is microgravity necessary for microcrystal challenge experiments in this model?

The document explains that ground-based MPS experiments cannot introduce calcium oxalate microcrystals at physiological flow and shear rates due to gravitational settling in media reservoirs, whereas microgravity prevents this problem and facilitates delivery.

Sep 30, 2026

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