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Prevention of Chronic Rejection of Marginal Kidney Graft by Using a Hydrogen Gas-Containing Preservation Solution and Adequate Immunosuppression in a Miniature Pig Model

Nishi K, Iwai S, Tajima K, Okano S, Sano M, Kobayashi E. · Frontiers in Immunology. 2021;11:626295.

PreclinicalOther formsPublished 2021Source checked
Study record, not medical adviceThis record reports what the source states. It is not medical advice and does not establish that molecular hydrogen is effective, safe or appropriate for any person.
Quick summary

Study at a glance

Evidence type

Preclinical

Population or model

Four donor and eight recipient microminiature pigs; ischemic kidneys were transplanted across non-matched swine-leukocyte-antigen backgrounds with multidrug immunosuppression.

Intervention and dose

Donor kidneys were rinsed for ten minutes and stored for 60 or 240 minutes at 4°C in hydrogenated ETK preservation solution before transplantation. · Dissolved H₂ was maintained at at least 1 ppm for four hours. The preparation paragraph prints an internal container-pressure value of '0.06 ppm', which is dimensionally inconsistent and is preserved as a source issue rather than corrected by inference.

Duration

Ten-minute rinse, 60 or 240 minutes of cold storage, then follow-up to 100 days or humane endpoint.

Reported result

Three of four hydrogenated-solution recipients reached 100 days; the fourth had major ureteral obstruction/intervention. All three non-hydrogenated ischemic-kidney recipients were sacrificed on days 3–7 with anuria, thrombosis and worsening kidney function. Long-term H₂ grafts had absent or mild chronic rejection, but the comparison was extremely small and not balanced for all surgical details.

Main limitation

Only four treated and three ischemic controls, one living reference, unknown SLA haplotypes, surgical/ischemic heterogeneity, major ureteral complication, extensive immunosuppression and limited mechanistic tissue assays. Doctors Man funded the work and helped devise the H₂-infusion system; two authors were medical advisers to the company.

Evidence and classification

What kind of evidence is this?

Evidence type

Preclinical

Reported design

Controlled donor-after-cardiac-death kidney-transplant study in mature microminiature pigs

Research topic

Kidney and urinary health

Administration form

Other forms

Information not yet classified

Some editorial classification fields are still pending. The source-reported outcomes and result are shown below; Hydrogenology does not infer a positive or negative signal from prose automatically.

Reported in the source

Methods

Population or model

Four donor and eight recipient microminiature pigs; ischemic kidneys were transplanted across non-matched swine-leukocyte-antigen backgrounds with multidrug immunosuppression.

Sample

12 pigs overall. Recipient groups were hydrogenated preservation solution n=4, non-hydrogenated solution n=3 and one living-donor reference recipient n=1.

Duration

Ten-minute rinse, 60 or 240 minutes of cold storage, then follow-up to 100 days or humane endpoint.

Intervention

Donor kidneys were rinsed for ten minutes and stored for 60 or 240 minutes at 4°C in hydrogenated ETK preservation solution before transplantation.

Hydrogen form

H₂ dissolved in organ-preservation solution — H₂ only, not Brown's gas and not inhalation.

Dose or H₂ specification

Dissolved H₂ was maintained at at least 1 ppm for four hours. The preparation paragraph prints an internal container-pressure value of '0.06 ppm', which is dimensionally inconsistent and is preserved as a source issue rather than corrected by inference.

Comparator

Non-hydrogenated ETK after the same 20-minute donor ischemia, plus one living-donor reference kidney.

Reported, not endorsed

Outcomes and reported result

Outcomes measured

Survival, urine output, BUN/creatinine, renal blood flow and resistive index, CT perfusion, thrombosis, histopathology, chronic rejection/fibrosis and syndecan-1.

Reported result

Three of four hydrogenated-solution recipients reached 100 days; the fourth had major ureteral obstruction/intervention. All three non-hydrogenated ischemic-kidney recipients were sacrificed on days 3–7 with anuria, thrombosis and worsening kidney function. Long-term H₂ grafts had absent or mild chronic rejection, but the comparison was extremely small and not balanced for all surgical details.

Extraction completeness

The complete free PMC article, tables and supplement descriptions were checked for donor/recipient counts, preparation concentration, the printed unit inconsistency, storage schedules, survival and graft findings, complications, limitations, commercial funding and conflicts.

A reported association, difference or mechanism is not automatically a clinical benefit.

Interpretation limits

Limitations and applicability

Main methodological cautions

Only four treated and three ischemic controls, one living reference, unknown SLA haplotypes, surgical/ischemic heterogeneity, major ureteral complication, extensive immunosuppression and limited mechanistic tissue assays. Doctors Man funded the work and helped devise the H₂-infusion system; two authors were medical advisers to the company.

Applies directly to

Experimental marginal-kidney transplantation in mature miniature pigs; it does not establish human graft preservation or rejection prevention.

No single-study GRADE certainty rating is assigned. Read how records and evidence assessments are prepared.

Sources and status

Sources and record status

Identifiers

PMID: 33679720 · DOI: 10.3389/fimmu.2020.626295

Publisher access

Free full article in PubMed Central.

Extraction basis

Complete PMC article, supplementary descriptions and PubMed metadata; full-text extraction checked 9 August 2026.

Last reviewed

10 August 2026

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