Does Probiotic Supplementation Prevent Kidney Injury During Strenuous Physical Exercise?

Severe heat strain arising from intense physical work under climate conditions that does not allow sufficient heat dissipation may lead to heat stroke. This severe conditions is hypothesized to be secondary to increased gut permeability and leakage of bacterial toxins across the gut membrane, stimulating a systematic inflammatory response and associated organ injury. Repeated such sub-clinical increases in gut permeability has been suggested to contribute to the high burden of chronic kidney disease among heat-stressed workers. Many marathon runners experience a transient increase in kidney injury biomarkers while running. Probiotics have been studied as a way to decrease gut permeability and reduce systemic inflammation in many settings, including in athletes . However, no study has measured renal outcomes among workers or athletes performing strenuous activity. This is of interest as it could test the hypothesis that gut-induced inflammation is a driver of kidney injury during heat stress, and could point to a possible intervention to add on to efforts to relieve heat strain.

In the present study, recreational or professional runners will be randomized to take a probiotic supplement or placebo during a 4 week period preceding a strenuous physical exercise (minimum 21 km run). Urine samples will be taken before and after the run, and analyzed for markers of renal injury and inflammation.

Study Overview

• Status: Completed
• Conditions: Kidney Injury; Heat Stress
• Intervention / Treatment: Dietary supplement: Probiotic, Lactobacillus; Dietary supplement: Placebo

Detailed Description

Participants registered to run in organised half-marathons, marathons and ultramarathons in Southern Sweden will be recruited. They will be asked to abstain from probiotic supplementation (including functional foods with probiotics) for 2 weeks, and then commence a 4-week period of probiotic or placebo supplementation.

At the end of the 4 week treatment period, the participants run the race. Urine samples are taken before and after the race and analysed for kidney injury markers.

Stool samples are taken by participants at the initiation of the treatment period, last stool before the race, and first stool after the race.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, 40530
    • Occupational and Environmental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Planning to run one of the long-distance races included.

Exclusion Criteria:

• Not having run at least 21 km previously,
• smoking,
• living too far away from the study area,
• unwilling to abstain from probiotic supplementation during treatment period,
• unwilling to abstain from NSAIDs or gut-permeability lowering supplements before the run,
• regular use of prescribed drugs (including hormonal contraceptives).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; 10^10 colony-forming units of a Lactobacillus strain, packaged in a capsule, once daily	Dietary supplement: Probiotic, Lactobacillus; 10^10 colony-forming units of a Lactobacillus strain, packaged in a capsule, once daily
Placebo Comparator: Placebo; Inactive substance packaged to be identical to active treatment	Dietary supplement: Placebo; Inactive substance packaged to be identical to active treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine tubular kidney injury marker (Kidney Injury Molecule 1 (KIM-1), monocyte chemotactic protein 1 (MCP-1), Insulin Growth Factor Binding Protein 7 (IGFBP-7)) composite variable aggregated using structural equations modelling.	Tubular injury markers measured in urine (e.g. KIM-1, MCP-1, IGFBP-7) combined using structural equations modelling and then combined over the 24 hour post-run period by calculating the area under the curve of this composite outcome variable in the 24 hours after the run. Exact list of markers to be determined based on budget available after sample collection is completed.	From before the run to after the run (estimated run times 2-24 hours), morning urine after run, and 24 hours after the run finish. These time point are combined to one main outcome by calculating the area under the curve.

Collaborators and Investigators

• Sponsor: Göteborg University
• Investigators: Principal Investigator: Kristina Jakobsson, MD, PhD, Göteborg University

Publications and helpful links

General Publications

• Mansour SG, Verma G, Pata RW, Martin TG, Perazella MA, Parikh CR. Kidney Injury and Repair Biomarkers in Marathon Runners. Am J Kidney Dis. 2017 Aug;70(2):252-261. doi: 10.1053/j.ajkd.2017.01.045. Epub 2017 Mar 28. Erratum In: Am J Kidney Dis. 2017 Sep;70(3):452.
• Hansson E, Glaser J, Jakobsson K, Weiss I, Wesseling C, Lucas RAI, Wei JLK, Ekstrom U, Wijkstrom J, Bodin T, Johnson RJ, Wegman DH. Pathophysiological Mechanisms by which Heat Stress Potentially Induces Kidney Inflammation and Chronic Kidney Disease in Sugarcane Workers. Nutrients. 2020 Jun 2;12(6):1639. doi: 10.3390/nu12061639.
• Leon LR, Bouchama A. Heat stroke. Compr Physiol. 2015 Apr;5(2):611-47. doi: 10.1002/cphy.c140017.
• Vaisberg M, Paixao V, Almeida EB, Santos JMB, Foster R, Rossi M, Pithon-Curi TC, Gorjao R, Momesso CM, Andrade MS, Araujo JR, Garcia MC, Cohen M, Perez EC, Santos-Dias A, Vieira RP, Bachi ALL. Daily Intake of Fermented Milk Containing Lactobacillus casei Shirota (Lcs) Modulates Systemic and Upper Airways Immune/Inflammatory Responses in Marathon Runners. Nutrients. 2019 Jul 22;11(7):1678. doi: 10.3390/nu11071678.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Probiotic; Gut permeability; Kidney Injury; Heat stress
• Additional Relevant MeSH Terms: Wounds and Injuries; Heat Stress Disorders
• Other Study ID Numbers: 2021-01332

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: No information that could be used to identify individuals will be shared. Considering the small size of the study and that it will most likely be conducted over multiple small runs, it is unlikely that any information on age and sex of participants could be shared without a risk of revealing the identity of the individual. Data on treatment allocation, biological measurement and questionnaire data without such identifying individual participant information will however be shared.
• IPD Sharing Time Frame: After the researchers have reported on the pre-specified research questions or otherwise have decided to make the data publicly available before this. This may be in approximately 2023-2024. We will keep the records for five years.
• IPD Sharing Access Criteria: Scientifically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes