2.3.2. Changes in uNGAL and uKIM-1 after a Marathon

KIM-1 is a 38.7 kDa type 1 transmembrane glycoprotein member of the TIM family of immunoglobulin superfamily molecules. KIM-1 plays a role in kidney recovery and tubular regeneration because it acts as a phosphatidylserine receptor and thereby mediates the phagocytosis of apoptotic cells. KIM-1 protects kidney against ischemic-reperfusion injury [8]. KIM-1 was found to be expressed at low to undetectable levels in normal kidney tissue but is markedly expressed after ischemic or toxic injury in proximal tubule cells. KIM-1 can serve as a urine and blood AKI biomarker. KIM is elevated in early stages of AKI and its urinary concentration is closely related to the severity of renal damage [5,8,9].

The first study concerning changes in urinary NGAL and KIM-1 after a marathon was performed by McCullough and published in 2010 [23]. The authors showed a 5.7-fold increase in uNGAL and a minor rise in uKIM-1 after a marathon [23]. According to the authors, those were changes "supporting a pathobiologic case for AKI" [23]. Changes in uKIM-1 and uNGAL levels after a marathon were also studied by Mansour et al. [46] The results concerning uNGAL were very similar to these from McCullough's study (a 4.71-fold increase in uNGAL), but the increase in uKIM-1 was much higher. The decrease in uKIM-1 was slower than the other markers studied (uNGAL, uTNF-alfa [tumor necrosis factor α], uIL-18, uIL6, uIL8, uYKL-40, uMCP-1) and 24 h after a marathon, the level was still increased (Table 3) [46].


**Table 3.** Changes in uNGAL and uKIM-1 after a marathon.

**Abbreviations:** uNGAL—urinary neutrophil gelatinase-associated lipocalin, uKIM-1—urinary kidney injury molecule-1.

## 2.3.3. Changes in uNGAL after Exercises Shorter than a Marathon

No changes were found in the uNGAL level in Kanda's study on 9 untrained males during a one leg calf-rise exercise [37] and in the Wołyniec study of amateur runners after a submaximal test on a treadmill [47]. In contrast, in two other studies, uNGAL was increased after very short exercise. Junglee et al. noticed an increase in uNGAL and uNGAL/uCr immediately and 25 min after an 800 m run. The uNGAL level returned to the baseline levels after two hours [34]. Spada et al. also noticed an increase in uNGAL after 4 min of an high-intensity interval resistance training (HIIT) session (eight sets of squats performed with the fastest speed and the highest number of repetitions achievable in 20 s with 10 s of rest between sets). In this study, uNGAL was increased in women 2 after exercise and

returned to values similar to the baseline 24 h after exercise. In 5/29 females, uNGAL/uCr exceeded 100 ng/mgCr, the value of which is compatible with clinical AKI. In men, the increase in uNGAL and uNGAL/uCr was not statistically significant [48].

Junglee et al. found an 8-fold uNGAL increase after a 40-min heat stress run (65% VO2max, 33 ◦C): 80% of subjects from the muscle-damaging group and 30% from the flat-run group had uNGAL above the normal range after exercise [35]. Bongers, who studied uNGAL after 30 and 150 min of exercise, found that uncorrected uNGAL and uNGAL corrected to osmolality were increased, while there were no changes in uNGAL corrected to creatinine and cystatin-C [26]. After a 10-km run, both uNGAL and uNGAL/Cr increased significantly (3.9- and 2.9-fold, respectively) in the Wołyniec study [45]. Otherwise, in Semen et al.'s study, a 10 km run caused an increase in uNGAL only when combined with ibuprofen/naproxen use [49]. In the same study, a significant increase in uNGAL was observed in the half-marathon runners [49].

In another study, Semen et al. found that completion of a half marathon after use of a 400 mg single dose ibuprofen led to a 2-fold increase in uNGAL. However, this increase was smaller and not significant in the group supplemented with monomeric and oligomeric flavanols (MOF-VVPP) [50]. In the Wolyniec study, the increase in uNGAL was higher than in Semen's study, although the exercise was shorter. This difference could be partially explained by the higher intensity of a 10-km run but could also be related to the methodology. In the first study, urine samples were collected immediately after the run and in the second, urine samples were collected within 2 h after the run [45,50].
