Acute Renal Injury During High Intensity Training
| Status: | Recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease, Hospital |
| Therapuetic Areas: | Nephrology / Urology, Other |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 9/21/2018 |
| Start Date: | October 1, 2018 |
| End Date: | June 30, 2019 |
| Contact: | Evan C Johnson, PhD |
| Email: | evan.johnson@uwyo.edu |
| Phone: | 307-766-5282 |
Hematological Risk Factors Related to Acute Renal Injury During High Intensity Training
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.
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.
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).
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).
Inclusion Criteria:
1. Healthy individual who has completed this specific workout on at least one prior
occasion
Exclusion Criteria:
1. Score of "0" on the Functional Movement Screening (FMS) test as evaluated by two
investigators * indicating pain during any of the seven functional movements
2. Self- reported Kidney (chronic kidney disease, polycystic kidney disease,
glomerulonephritis, diabetic nephropathy, interstitial nephritis, Goodpasture
syndrome) or other medical condition contraindicating participation in HIFRT
(Hypertension, dyslipidemia, type II diabetes mellitus, BMI >30)
3. Pregnancy, suspected pregnancy, or breastfeeding
4. Blood donations within the last eight weeks leading up to testing day
5. Any musculoskeletal injuries which have resulted in > 1 week of absence from HIFRT
within the last six months
6. Not passing the physical activity readiness questionnaire (PAR-Q)
7. Allergy to ibuprofen or non-steroidal anti-inflammatory medication
8. Surgical operation on digestive tract or kidneys, except appendectomy
9. Inability to participate in the entire study
10. Recurrent urinary tract infections or kidney stones
11. History of protein or blood in urine
12. Moving from a location of low altitude (< 3,000') to Laramie within the past 3 months
13. Inability to understand and write English
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