Acute Renal Injury During High Intensity Training
Condition: Acute Kidney Injury; Exercise
MeSH terms: Acute Kidney Injury; Wounds and Injuries
Study type: Interventional

Summary: 
      The proposed work is designed to be the first in a series of studies investigating the health
      benefits and risks related to high intensity training (HIT) exercise. Our specific aims are
      to determine, 1) if participation in a single bout of HIT induces hematological markers
      consistent with acute kidney injury (AKI), and 2) if risk is predicted by the pre-exercise
      concentration of plasma proenkephalin-A.

      This investigation is an observational case control study. In year one, data collection
      procedures will be refined with ~40 participants local to the University of Wyoming and
      training will occur for collaborators from Wyoming community and tribal colleges. In year
      two, data collection will expand to some of the 12 CrossFit® gyms in Wyoming with assistance
      from the community and tribal colleges. Blood and urine samples will be collected before and
      up to 48 h after a standardized bout of HIT exercise on ~100 participants. Baseline blood
      samples will be analyzed for proenkephalin-A. All blood samples will be analyzed for markers
      of muscle damage (e.g., creatine kinase and myoglobin), and markers of kidney function (e.g.,
      serum creatinine and blood urea nitrogen). Urine will be analyzed for markers of filtration
      function (e.g., albumin, creatinine, neutrophil gelatinase-associated lipocalin [NGAL], and
      kidney injury molecule 1 [KIM-1]). Lastly, the severity of kidney damage will be compared
      with the number of risk alleles and proenkephalin-A concentration.

      The investigators envision that the bout of HIT exercise will induce markers consistent with
      skeletal muscle damage in most participants and, based on literature from other styles of
      intense exercise, that acute kidney injury will be diagnosable in between 50-75% of
      participants. Secondarily, the investigators predict that the concentration of
      proenkephalin-A will be inversely related to the change in kidney function from before to
      after the HIT exercise bout.
    

Detailed description: 
      The HIT-KH investigation is proposed to take place over the course of two calendar years.
      During year one collaborations with gyms specializing in High Intensity Resistance and
      Functional Training style workouts (referred to from this point forward as satellite data
      collection sites) as well as community and tribal colleges (referred to from this point
      forward as partner institutions) local to these facilities will be solidified. Also, during
      the summer of year one data collection will occur on a small subset of individuals (~40) at a
      data collection site local to the University of Wyoming (Figure 1.). It is our plan to use
      this first data collection in Laramie, WY as a training session for all students from partner
      institutions so that the students are prepared when the data collection is expanded to the
      satellite data collection sites in year 2.

      In order to properly power this investigation the investigators have estimated that about 100
      participants will be needed. Given that the investigators can expect about 40 participants
      from the local Larmie data collection gym (CrossFit® 7220)this will require the investigators
      to partner with other high intensity resistance and functional training gyms around the state
      of Wyoming in year 2. The investigators have chosen to reach out to CrossFit® gyms
      specifically because it is common practice for most CrossFit® gyms to program the workout the
      investigators are interested in observing (Murph), at least once per year. Collection data on
      60 additional participants will require partnership with 3 additional gyms (i.e., 20
      participants / facility). At this point the investigators have been in contact with 3 gym
      owners all of whom have offered verbal agreement to assisting with data collection. Among
      these gyms is CrossFit® Leveler, located on the Wind River Reservation in Fort Washikie,
      Wyoming. This facility is a Native American owned business and it primarily caters to those
      Native American's living on the reservation. Because the state of Wyoming is ~2% Native
      American in population, the inclusion of this facility in our investigation is very important
      for proper sampling (see attached letter of support from owner Mike Ute). Additional gyms
      that have been contacted and are in the process of providing written approval are CrossFit®
      Frontier (Cheyenne), and, Cloud Peak CrossFit® (Sheridan).

      Because our data collection will be occurring throughout the state the investigators also
      plan to partner with local community and tribal colleges local to many of the above satellite
      data collection sites. Briefly, the investigators plan to incorporate up to three students
      and one faculty mentor from each of the following educational institutions; Laramie County
      Community College, Wind River Tribal College, and Sheridan Community College. Regarding the
      inclusion of Wind River Tribal College and the Wind River Indian Reservation, Investigator
      Johnson is under the guidance of Dr. Christine Porter who is also in the University of
      Wyoming Division of Kinesiology and Health. Dr. Porter has successfully implemented several
      research studies on the Wind River Reservation and is well versed in the intricacies and
      requirements necessary for the completion of data collection in this partnership. Lastly, the
      partner institutions are beneficial to the project because the data collection takes place
      over the course of 5 consecutive days, training and working with local researchers will
      enable this project to reduce the cost because a large research team from Laramie, Wyoming
      will not be required for each data collection.

      As mentioned above 1-3 students from each of the above institutions will be requested to
      assist with data collection for HIT-KH. Part of our grant funding is devoted to payment of
      fees for these student's training. This includes travel fees to travel and stay in Laramie,
      Wyoming during year 1 for observation and basic level assistance with the initial data
      collection. During the end of year 1 and/or beginning of year 2 additional funds have been
      allocated to provide phlebotomy training to interested students. These students will then be
      utilized during year two data collections to assist with blood draws. Finally, funds have
      been allocated for travel to and attendance of the Rocky Mountain Regional American College
      of Sports Medicine conference. It is our goal that at least one student will be able to use
      the preliminary data from the year 1 data collection to compile a research abstract that will
      be submitted for presentation. All other students will be offered the ability to attend and
      participate in the conference during the spring of 2019.

      Blood samples will be collected one day before participants take part in the workout, and 24
      and 48hrs after completion. Sampling will take place by single venipuncture to an antecubital
      vein by a trained investigator using sterile technique and universal precautions. Following
      any needle removal, firm pressure will be applied over the site of the blood draw with gauze
      to minimize the occurrence of a hematoma. Blood will be drawn into vacutainers specific for
      each of the analytes to be analyzed later. Tubes will be centrifuged as soon as possible,
      then the blood plasma, serum, or white blood cells will be removed and aliquoted into
      separate cryovials. These cryovials will be frozen in the -80C freezer as soon as possible.
      For satellite data collections, if -80C freezers are not available at the local partner
      institution, liquid nitrogen will be used to freeze and store samples until the samples can
      be transported back to the University of Wyoming for more permanent storage.

      Urine samples will be collected in 24 hr collection jugs for the period immediately prior to
      the workout and for two 24hr periods following. Each sample will be weighed for measurement
      of total volume, evaluated for urine color and urine specific gravity. Dipsticks will be used
      on fresh samples while three 2mL aliquots of each 24hr sample will be separated and stored at
      room temperature until the samples are returned to the University of Wyoming where the
      samples will be frozen at -80C for future analysis.

      Fresh 24hr urine samples will be analyzed using traditional dipsticks for the following
      variables: leukocytes, nitrite, urobilinogen, protein, pH, hemoglobin, ketone, bilirubin, and
      glucose. Additionally, fresh samples will be evaluated for urine color and specific gravity
      via handheld refractometer in order to establish hydration state. Further biochemical urinary
      analysis are reviewed below.

      Proenkephalin-A will be analyzed at the Clinical Research Center by the use of a
      chemiluminometric sandwich immunoassay. The laboratory group in Malmo has previously
      successfully measured this hormone (Schulz et al., 2017). All remaining blood and urine
      samples will be analyzed within the Human Integrated Physiology laboratory located at the
      University of Wyoming using colorimetric enzyme-linked immunosorbent assays (ELISA). These
      samples will be analyzed for the following variables; serum creatinine, blood urea nitrogen,
      urinary creatinine, neutrophil gelatinase-associated lipocalin [NGAL], and kidney injury
      molecule 1 [KIM-1]). All ELISA antibodies will be supplied by "Abcam", (Cambridge,
      Massachusetts, USA) and microplates will be read according the manufacturer's instructions on
      spectrophotometer (Epoch 2, Biotek, Winooski, Vermont, USA).
    

Intervention name(s): HIFRT Workout
Intervention type(s): Other
Intervention description(s): A single high intensity functional resistance training (HIFRT) exercise bout.
Intervention model: Single Group Assignment
Intervention model description: All participants will take part in the same, single bout, exercise intervention
Masking: None (Open Label)
Primary purpose: Screening
Keywords: High intensity exercise; Proenkephalin-A