Hypohydration augments the acute increase in urinary biomarkers of kidney injury following the 100-mile Western States Endurance Run

J Appl Physiol (1985). 2025 Nov 1;139(5):1379-1391. doi: 10.1152/japplphysiol.00289.2025. Epub 2025 Oct 20.

Abstract

Ultraendurance races may transiently increase acute kidney injury (AKI) risk, yet data on contributing factors are sparse. Therefore, we examined the acute effects of the Western States Endurance Run [WSER (100 miles; 161 km)] on urinary AKI biomarkers and kidney blood flow, while also assessing the influence of race pace and hydration status. Blood and urine samples were collected to assess urine specific gravity (USG), creatinine, and AKI risk [nephrin, neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP2), and IGFBP-7·TIMP-2]. Renal blood velocity and conductance were measured via Doppler ultrasonography. Pre and post measures were obtained from 36 runners (29 males/7 females, age: 44 ± 9 yr, mean finish time: 25:45:55). Urinary AKI biomarkers increased postrace, with nephrin, IGFBP7, and IGFBP7·TIMP-2 remaining elevated after indexing to creatinine (Ps < 0.008). Hydration status declined, with only 8 of 35 runners remaining euhydrated postrace. Finishing euhydrated attenuated increases in urinary creatinine and creatinine-indexed IGFBP-7·TIMP-2 (Ps ≤ 0.006). Faster race pace correlated with increases in USG (rho, ρ = 0.338, P = 0.048) and urinary creatinine (rho, ρ = 0.443, P = 0.010), but not with creatinine-indexed AKI biomarkers (Ps ≥ 0.382). Kidney blood velocity and conductance were unchanged (Ps ≥ 0.186). Finishing hydrated appears to help mitigate the transient increase in kidney injury following an ultraendurance race.NEW & NOTEWORTHY Urinary concentrations of several acute kidney injury (AKI) biomarkers increased after completing the 2023 Western States Endurance Run; however, there were no changes in renal blood flow in a subset of runners. When normalized to creatinine, several AKI biomarkers, including IGFBP7·TIMP2 (an FDA-approved biomarker of AKI), remained elevated. Notably, finishing the race euhydrated appeared to have a protective effect, mitigating increases in IGFBP7·TIMP2.

Keywords: acute kidney injury; hydration; performance; renal blood flow; ultramarathon.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / physiopathology
  • Acute Kidney Injury* / urine
  • Adult
  • Biomarkers / urine
  • Creatinine / urine
  • Dehydration* / physiopathology
  • Dehydration* / urine
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / urine
  • Kidney / blood supply
  • Kidney / metabolism
  • Male
  • Middle Aged
  • Physical Endurance* / physiology
  • Running* / physiology
  • Tissue Inhibitor of Metalloproteinase-2 / urine

Substances

  • Biomarkers
  • Tissue Inhibitor of Metalloproteinase-2
  • Insulin-Like Growth Factor Binding Proteins
  • insulin-like growth factor binding protein-related protein 1
  • TIMP2 protein, human
  • Creatinine