Trace element supplementation preserves metabolic resilience in chronic kidney disease
- 1Yanbian University Hospital
Abstract
BackgroundChronic kidney disease (CKD) imposes persistent metabolic stress, yet whether metabolic organization can be preserved under sustained renal stress remains unclear. Essential trace elements support redox defense, mitochondrial function, and intermediary metabolism, and their homeostasis is disturbed in CKD; however, single-element supplementation has yielded heterogeneous results. We examined whether a defined multi-element formulation preserves metabolic resilience in CKD.
MethodsIn a randomized, double-blind, placebo-controlled trial, 80 maintenance dialysis patients received standard care alone (n = 40) or plus a trace element cocktail (TEX, 20 mL/day; n = 40). Longitudinal trajectories were analyzed with linear mixed-effects models; endpoint plasma metabolomics and fecal metagenomics were profiled in subsets. A 5/6 nephrectomy mouse model was used to quantify plasma tryptophan-pathway branches and renal spatial metabolism by MALDI imaging mass spectrometry.
ResultsTEX was well tolerated, with no treatment-related safety signal, and was associated with modestly more favorable creatinine and eGFR trajectories. Supplementation constrained, rather than erased, CKD-associated metabolic displacement (median |Cohens d|, 0.25 versus 2.09 for disease effects), selectively realigning circulating metabolism toward the healthy state. The host kynurenine branch responded most strongly, whereas microbial indole metabolism and gut community structure changed little. Renal metabolic remodeling was region-specific, with preservation of selected tubular and antioxidant features.
ConclusionsTrace element supplementation preserved metabolic resilience in CKD, limiting metabolic displacement without complete restoration. Preservation of metabolic organization may represent a complementary dimension of therapeutic response in CKD.
Trial registrationInternational Traditional Medicine Clinical Trial Registry, ITMCTR2026000263 (registered 3 February 2026).
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BibTeX
@misc{piao2026trace,
title = {{Trace element supplementation preserves metabolic resilience in chronic kidney disease}},
author = {J. Piao and M. Jin and F. Yin and Z. Quan and Z. Gao and Z. Cui},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.26365915},
url = {https://www.medrxiv.org/content/10.64898/2026.10.19.26365915v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Trace element supplementation preserves metabolic resilience in chronic kidney disease
AU - J. Piao
AU - M. Jin
AU - F. Yin
AU - Z. Quan
AU - Z. Gao
AU - Z. Cui
PY - 2026
DA - 2026/10/19
PB - medRxiv
DO - 10.64898/2026.10.19.26365915
UR - https://www.medrxiv.org/content/10.64898/2026.10.19.26365915v1
AB - BackgroundChronic kidney disease (CKD) imposes persistent metabolic stress, yet whether metabolic organization can be preserved under sustained renal stress remains unclear. Essential trace elements support redox defense, mitochondrial function, and intermediary metabolism, and their homeostasis is disturbed in CKD; however, single-element supplementation has yielded heterogeneous results. We examined whether a defined multi-element formulation preserves metabolic resilience in CKD. MethodsIn a randomized, double-blind, placebo-controlled trial, 80 maintenance dialysis patients received standard care alone (n = 40) or plus a trace element cocktail (TEX, 20 mL/day; n = 40). Longitudinal trajectories were analyzed with linear mixed-effects models; endpoint plasma metabolomics and fecal metagenomics were profiled in subsets. A 5/6 nephrectomy mouse model was used to quantify plasma tryptophan-pathway branches and renal spatial metabolism by MALDI imaging mass spectrometry. ResultsTEX was well tolerated, with no treatment-related safety signal, and was associated with modestly more favorable creatinine and eGFR trajectories. Supplementation constrained, rather than erased, CKD-associated metabolic displacement (median |Cohens d|, 0.25 versus 2.09 for disease effects), selectively realigning circulating metabolism toward the healthy state. The host kynurenine branch responded most strongly, whereas microbial indole metabolism and gut community structure changed little. Renal metabolic remodeling was region-specific, with preservation of selected tubular and antioxidant features. ConclusionsTrace element supplementation preserved metabolic resilience in CKD, limiting metabolic displacement without complete restoration. Preservation of metabolic organization may represent a complementary dimension of therapeutic response in CKD. Trial registrationInternational Traditional Medicine Clinical Trial Registry, ITMCTR2026000263 (registered 3 February 2026).
ER -