2.2.1. Changes in Plasma NGAL (pNGAL) after Short Exercises

Changes in pNGAL after exercise were first investigated by Junglee et al. in 2012. In this study dedicated to AKI in exercise, after relatively short exercise (an 800 m run), pNGAL was decreased, which was interpreted by the authors as an effect of increased NGAL renal clearance [34].

In another study performed by Junglee, the pNGAL level increased after a 40-min heat stress run (running on a treadmill on a 1% gradient for 40 min at 65% VO2max (maximal oxygen consumption) in an environmental chamber maintained at a dry bulb temperature of 33 ◦C with 50% relative humidity (RH)). In this study, the heat stress run was preceded by a 60-min downhill muscle-damaging run (EIMD group) or a 60-min flat run (CON group) and a 30-min seated rest. pNGAL increased in both groups, but the increase was greater in the EIMD group [35].

There were also three studies dedicated to investigating a pNGAL as a marker of inflammation, neutrophil degranulation and organ damage, but not an AKI biomarker [36–38].

Bender et al. studied pNGAL as an inflammatory marker of hand osteoarthiritis (OA) after mechanical exercise of the OA hand. pNGLA increased during the first 15 min after exercising the index hand within the venous blood of the ipsilateral forearm [36]. Kanda et al. studied 9 untrained men during a one leg, calf-rise exercise. pNGAL was studied as a marker of organ damage, muscle disruption and neutrophil mobilization and migration. The authors did not find any changes in pNGAL [37]. Rullman et al., found no significant changes in pNGAL after 27 and 57 min of cycle exercise. During the first 20 min, the subjects exercised at 50% of VO2max and during the next 40 min, at 65% VO2max. In the Rullman study, pNGAL was investigated as a marker of neutrophil degranulation [38].

#### 2.2.2. Changes in pNGAL or Serum NGAL (sNGAL) Levels after Long Exercises

Chapman et al. studied the impact of soft drink consumption during long exercise in heat. Twelve healthy subjects drank two liters of a beverage (soft drink or water) during four hours of exercise in 35.1 ◦C heat. pNGAL increased post-exercise in both groups [18].

McDermott et al. found a 2-fold significant increase in sNGAL (from 68.51 to 139.12 ng/mL) after a 6-h endurance cycling event during heat (33.2 ± 5.0 ◦C, 38.4 ± 10.7% RH). Moderate ibuprofen ingestion of 600 mg ibuprofen had no influence on the sNGAL level [39]. Moreover, Lippi et al., found a significant 1.6-fold increase in sNGAL (from 105 to 196 ng/mL) after a 60-km run in a group of trained male athletes [40].

Furthermore, Andrezzoli et al. found only a mild increase in pNGAL in a group of professional cyclists after the mountain stages of two major European professional cycling competitions (Giro D'Italia and Tour de France). Post-competition NGAL values of all the variables investigated remained within the physiological range. The results suggest that even if NGAL values rose slightly and not significantly after competition, no kidney injury occurred in these highly trained athletes during the mountain stages of professional competitions [41].

NGAL, which is an acute phase protein and is upregulated in the lungs during inflammation, was also studied as a marker of inflammation and oxidative stress after long exercise. Mellor et al. found a non-significant NGAL rise after an ascent from sea level to 1085 m over 6 h [42]. In this study, two other cohorts were also studied. There were no changes in NGAL after 3 h exposure to normobaric hypoxia with a 5-min step test, but there was an increase in NGAL after trekking in Nepal [42].

#### 2.2.3. Changes in pNGAL after Work in Heat

Chapman et al. analyzed changes in pNGAL and other biomarkers in two interesting studies. In the first, the impact of different beverage consumption (soft drink or water) during exercise in heat was studied. Twelve healthy subjects drank two liters of fluid during four hours of exercise in 35.1 ◦C heat [18]. In the second study, thirteen healthy adults (3 women, 10 men, age 23 ± 2 years) exercised for 2 h in a 39.7 ± 0.6 ◦C, 32% ± 3% relative humidity environmental chamber. In four trials, the subjects received water to remain hydrated (*Water group*), were exposed to continuous upper-body cooling (*Cooling group*), a combination of both (*Water* + *Cooling group*), or no intervention (*Control group*) [43]. In the first study, in both groups, pNGAL was increased post-exercise and returned to pre-exercise levels after 24 h [18]. In the second study, an increase in pNGAL was also observed and was greater in the control group (without hydration and cooling) compared with the other conditions [43].
