{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Soochow University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "J. Shi"
    },
    {
      "name": "Q. Gu"
    },
    {
      "name": "J. Pan"
    },
    {
      "name": "A. Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Fan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/85xdpnnc1ej44.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.27.26360881",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26360881v1.full",
  "id": "85xdpnnc1ej44",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26360881v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "urology"
    ],
    [
      "openalex",
      "2737|Spaceflight effects on biology"
    ]
  ],
  "openalex": "W7204753003",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26360881v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/85xdpnnc1ej44.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:26Z",
      "native_id": "10.64898/2026.08.27.26360881",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26360881v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Spaceflight effects on biology",
      "subfield": "physiology"
    }
  ],
  "title": "From Bone-centric to Kidney-centric: Environment-Dependent Shift of Spaceflight Renal Stone Pathways",
  "title_text": "From Bone-centric to Kidney-centric: Environment-Dependent Shift of Spaceflight Renal Stone Pathways",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:26Z",
  "url": "https://research.draconitic.com/paper/85xdpnnc1ej44",
  "venue": "medRxiv",
  "versions": []
}