From Bone-centric to Kidney-centric: Environment-Dependent Shift of Spaceflight Renal Stone Pathways
- 1Soochow University
Abstract
Human deep-space missions face bone-kidney risks that cannot be extrapolated from six-month ISS data. We built a 12-state Ca-bone-urine-stone mechanistic ODE model and jointly calibrated its 11 physiological parameters on eight ISS targets by Bayesian identification (M base = 19-D; M extension adds a GCR-bone coupling term for parsimony testing only), then propagated the M posterior to four environments (ISS, Lunar subsurface, Lunar surface, Mars). Lumbar-lower BMD loss increases with mission duration and partial-gravity unloading (ISS 180 d -4.83% [->] Mars 730 d -12.15%; 23 factorial: duration 82.9%, gravity 12.5%, GCR main effect {approx} 0), whereas stone rate follows the opposite gradient (ISS 16.1 vs Mars 13.1 per 1000 person-years), reflecting weakened partial-gravity bone resorption alongside residual urinary chemistry changes. The dominant pathway thus shifts from bone-centric on the ISS to kidney-centric on Mars, where residual urinary-chemistry changes--not bone resorption--drive stone risk. The direct GCR-bone coupling term is unidentifiable at current ISS doses ({Delta}WAIC = +0.0076 {+/-} 0.126 SE), so M is retained as the main inference model. Bisphosphonates provide [≥]84% BMD protection but leave a urinary-chemistry residual, so bisphosphonate monotherapy would underestimate Mars stone risk; potassium-magnesium-citrate combinations (RRR_RSS 51%) should therefore be added to deep-space countermeasures. A Lunar-surface 365-day mission is the earliest environment on the NASA roadmap to cross a composite RED threshold. That profile differs from the regolith-shielded 180-day case in both cumulative GCR ([~]69x) and duration (2x), so a shielding-specific effect cannot be isolated here; forcing the GCR coupling terms to zero leaves all four composite tiers unchanged (0/4, Supp [§]S24), and the shielded 180-day profile is YELLOW rather than GREEN. Independent hold-out validation (Culliton 2025 60-day HDT-bedrest RCT, n=8 control arm of n=24 total) supports the M posterior predictive distribution on the lumbar-BMD sub-scope.
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BibTeX
@misc{shi2026from,
title = {{From Bone-centric to Kidney-centric: Environment-Dependent Shift of Spaceflight Renal Stone Pathways}},
author = {J. Shi and Q. Gu and J. Pan and A. Yang and M. Fan},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.27.26360881},
url = {https://www.medrxiv.org/content/10.64898/2026.08.27.26360881v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - From Bone-centric to Kidney-centric: Environment-Dependent Shift of Spaceflight Renal Stone Pathways
AU - J. Shi
AU - Q. Gu
AU - J. Pan
AU - A. Yang
AU - M. Fan
PY - 2026
DA - 2026/08/27
PB - medRxiv
DO - 10.64898/2026.08.27.26360881
UR - https://www.medrxiv.org/content/10.64898/2026.08.27.26360881v1
AB - Human deep-space missions face bone-kidney risks that cannot be extrapolated from six-month ISS data. We built a 12-state Ca-bone-urine-stone mechanistic ODE model and jointly calibrated its 11 physiological parameters on eight ISS targets by Bayesian identification (M base = 19-D; M extension adds a GCR-bone coupling term for parsimony testing only), then propagated the M posterior to four environments (ISS, Lunar subsurface, Lunar surface, Mars). Lumbar-lower BMD loss increases with mission duration and partial-gravity unloading (ISS 180 d -4.83% [->] Mars 730 d -12.15%; 23 factorial: duration 82.9%, gravity 12.5%, GCR main effect {approx} 0), whereas stone rate follows the opposite gradient (ISS 16.1 vs Mars 13.1 per 1000 person-years), reflecting weakened partial-gravity bone resorption alongside residual urinary chemistry changes. The dominant pathway thus shifts from bone-centric on the ISS to kidney-centric on Mars, where residual urinary-chemistry changes--not bone resorption--drive stone risk. The direct GCR-bone coupling term is unidentifiable at current ISS doses ({Delta}WAIC = +0.0076 {+/-} 0.126 SE), so M is retained as the main inference model. Bisphosphonates provide [≥]84% BMD protection but leave a urinary-chemistry residual, so bisphosphonate monotherapy would underestimate Mars stone risk; potassium-magnesium-citrate combinations (RRR_RSS 51%) should therefore be added to deep-space countermeasures. A Lunar-surface 365-day mission is the earliest environment on the NASA roadmap to cross a composite RED threshold. That profile differs from the regolith-shielded 180-day case in both cumulative GCR ([~]69x) and duration (2x), so a shielding-specific effect cannot be isolated here; forcing the GCR coupling terms to zero leaves all four composite tiers unchanged (0/4, Supp [§]S24), and the shielded 180-day profile is YELLOW rather than GREEN. Independent hold-out validation (Culliton 2025 60-day HDT-bedrest RCT, n=8 control arm of n=24 total) supports the M posterior predictive distribution on the lumbar-BMD sub-scope.
ER -