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Kidney Injury Marker‐1: A Potential Point‐of‐Care Biomarker of Heat Stress
Author(s) -
Audet Gerald N,
Ward Jermaine A,
Dineen Shauna M,
Cheuvront Samuel N,
Leon Lisa R
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1243.3
Subject(s) - biomarker , medicine , kidney , acute kidney injury , heat stress , urine , heat illness , dehydration , zoology , chemistry , biology , biochemistry , physics , meteorology
Heat injury/stroke (HI/S) is a substantial threat to military operational readiness as well as athletic and occupational performance. There are currently no specific tests capable of delineating HI/S severity. The kidney has been implicated as one of the earliest sensors of heat stress. We hypothesized that kidney injury marker‐1 protein (KIM‐1) could be a novel biomarker in assessing heat stress severity during early stages of recovery. Both animal and human models were used in this study. 1) Conscious male mice (N=15) were heated passively until reaching a core temperature (T c ) of 42.7 °C. Mice were sacrificed at 3 time points‐ maximal core temperature (T c,Max ),and either ~3hrs (T3) or 24hrs post‐heating (24hr)‐ and kidneys were collected. 2) Conscious male rats (N=24) were passively heated to a T c,Max of 41.9 °C. Rats were segmented into 3 severities (mild;MILD, moderate; MOD, severe; SEV) based on T c , heart rate, and blood pressure during recovery and sacrificed at 24hrs for urine and kidney collection. 3) Human subjects (Male N= 9; Female N=3)were subjected to exercise (50% VO 2 , Max ) in the heat (T a 40°C) and either A) subjected to fluid restriction(dehydration, HS‐D) or B) or allowed to hydrate (euhydration, HS‐E). Urine samples were collected before heat stress and ~2 hours post heating. All rodent samples were analyzed for KIM‐1 using an ELISA assay or a KIM‐1 point of care (POC) test (Bio‐assay works). Humanurine was analyzed for KIM‐1 on a bio‐plex assay. In mouse kidney, KIM‐1 was unchanged at T c,Max , but increased at T3 (313% vs. Con m ) and 24hrs (>5000% vs. Con m ). In rat kidneys, KIM‐1 was increased in all groups and correlated with increasing severity (MILD 274%, MOD 352%, SEV 432% vs. Con r ). In rat urine, there was a ~200% increase in KIM‐1 vs Con r , however there was no difference between severities. The POC test was able to detect increased KIM‐1 content in the rat urine (10.9 μg/mL vs 0.0 μg/mL Con r ), but the test showed no differences between MILD(13.3 μg/mL) and MOD (9.0 μg/mL) (insufficient sample from SEV). In humans, HS‐D resulted in greater dehydration than HS‐E (HS‐D 3.8 ± 0.1 % vs HS‐E 0.9 ± 0.1%), with both groups showing elevated T c (T c,Max : HS‐D 39.1 ± 0.2 ° C , HS‐E 38.6 ± 0.1 °C). After heat stress, human urine showed an 80% and 275% increase in KIM‐1in HS‐E and HS‐D vs baseline, respectively. This suggests that KIM‐1 is sensitive to heat stress and the associated dehydration, and may also be able to predict the overall severity of heat stress. Further, the KIM‐1 POC test may serve as a simple and rapid tool for diagnosing heat stress. Author views not official US Army or DoD policy.