Evidence map›Paper›PMID 42441134›Full record

ArticleFrontiers in physiology2026

Temporal dynamics of glomerular and microvascular remodeling in high-altitude renal injury: a structure-function analysis in rats.

Meng Jia, Quzhen Jimu, Suolang Deji, Yidan Guo, Huaying Wei, Zhihua Shi, Xiaoling Zhou, Ruiji Wang

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Article in Frontiers in physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

8 authors.

Meng JiaDepartment of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Quzhen JimuDepartment of Nephrology, Lhasa People's Hospital, Lhasa, China.
Suolang DejiDepartment of Nephrology, Lhasa People's Hospital, Lhasa, China.
Yidan GuoDepartment of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Huaying WeiDepartment of Respiratory and Critical Care Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Zhihua ShiDepartment of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Xiaoling ZhouDepartment of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Ruiji WangDepartment of Nephrology, Lhasa People's Hospital, Lhasa, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The temporal dynamics of renal acclimatization during the sub-acute transition to high altitude remain poorly defined. Specifically, the relationship between structural integrity and functional adaptation under sustained hypobaric hypoxia is unclear. This study aims to characterize the time-dependent trajectories of renal remodeling and identify the critical biological window for potential intervention. Methods: Male Sprague-Dawley (SD) rats were randomized to a normobaric normoxia control group or a simulated hypobaric hypoxia group (5,000 m, PO2: 11.3 kPa) for 3, 7, 14, and 28 days (n=6/group). Renal filtration function was assessed via serum creatinine (CRE) and cystatin C (CysC), while tubular injury and systemic inflammation were evaluated using neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18). Structural alterations were quantified through hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS) staining, with peritubular capillary (PTC) density assessed via immunohistochemistry. The temporal associations and exploratory biomarker discrimination were analyzed using restricted cubic spline (RCS) regression, Spearman correlation, and receiver operating characteristic (ROC) analyses. Results: Despite stable gross kidney weight and length throughout the exposure, histological analysis revealed progressive microscopic injury. PTC density exhibited a continuous, time-dependent decline that was significantly inversely correlated with tubular injury scores and medullary congestion. Notably, glomerular morphometry exhibited a distinct biphasic response: an initial significant reduction in glomerular diameter at Day 3, followed by subsequent enlargement peaking at Day 14. Temporally, serum biomarkers showed heterogeneous and exploratory trajectories, whereas histological injury remained more persistent. CysC and CRE showed overall temporal variation, but Tukey-adjusted Conclusion: Hypobaric hypoxia induces a distinct state of structure-function uncoupling, characterized by persistent microvascular rarefaction that antedates measurable systemic functional decline. The first week of exposure represents a biologically active phase of vascular remodeling and tubular stress. These findings suggest that relying solely on functional markers may underestimate the severity of sub-clinical renal injury in hypoxic environments, highlighting the potential value of integrating structural biomarkers for more accurate risk stratification.

Indexed as

high-altitudehypobaric hypoxiaKIM-1microvascular rarefactionperitubular capillariesrenal adaptationstructure-function uncoupling

Identifiers

PMID42441134
PMCPMC13334576

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