**1. Introduction**

The analysis of human urine has been a part of medical practice for 6000 years. Uroscopy was "the mirror of medicine" or, in more ordinary terms, the first additional test in medicine, and was widely used to diagnose almost all medical conditions [1]. Now, urinalysis is one of the most common laboratory tests in medical practice.

Two-hundred years ago, the father of modern nephrology, Dr Richard Bright, discovered that patients with dropsy had albuminuria and structural changes in the kidneys. Dr Bright first described the classical nephrological triad and found a correlation between changes in urine (albuminuria) and diseased kidneys at autopsy [2]. Sixty-six years ago, Kenneth D. Gardner Jr. first described changes in urine after physical exercise. The proteinuria and hematuria were found in healthy subjects after relatively gentle exercise, therefore Gardner called these conditions "athletic pseudo-nephritis", assuming that it is a physiological, transient and benign condition [3]. Those two observations defined the limits of our understanding of the significance of proteinuria. On the one hand, albuminuria is one of the most important markers of severe and sometimes fatal kidney diseases with well-described structural changes. But on the other hand, the list of physiological conditions in which transient proteinuria is observed is quite long. Protein in urine is found after exercise, exposure to cold or heat and protein-rich food (alimentary proteinuria), and proteinuria can also occur in pregnancy, fever, heart failure and in a vertical position (orthostatic, postural proteinuria) [4].

In recent decades, new methods of urine examination have been proposed: tubular enzymes, novel biomarkers of acute kidney injury (AKI), metabolomics, proteomics, transcriptomics and genomics [5–7]. The very promising new AKI biomarkers were called "kidney troponins" and hinted at the possibility of early diagnosis of kidney diseases. Some of the markers showed high sensitivity in AKI diagnosis. Numerous studies concerned urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C (Cyst-C), liver-type fatty-acid-binding protein (L-FABP), interleukin 18, insulin-like growth factor binding protein 7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) [5,8,9]. Nevertheless, the only AKI biomarker test which is currently FDA (Food and Drug Administration)-approved for clinical use in the USA, and which is also used in some European countries, is NephroCheck, which combines TIMP-2 and IGFBP-7 [10].

The history of serum examination in kidney diseases is relatively short. In the last 100 years, creatinine established its position as the best marker of glomerular filtration rate (GFR) [11,12]. 22 years ago, Cyst-C was considered as an equal or even better marker of GFR than creatinine. Due to its higher price and lower availability, it is not widely used. Interestingly, although serum concentrations of both substances correlate strictly, they are eliminated by kidneys in two different ways. Both are freely filtered in the glomeruli, but creatinine is never reabsorbed and secreted, while cystatin C in healthy individuals is reabsorbed and metabolized in the proximal tubule. Therefore, in normal conditions, excretion of Cyst-C is very low [13]. Some other novel biomarkers of AKI, like NGAL and osteopontin, can be measured in serum [5].

The serum and urine markers of kidney injury were mainly studied in AKI. The aim of this review was to analyze changes of those markers after physiological condition—exercise. All but one of the studies analyzed were conducted in the last 10 years. The high number of proposed markers of AKI is sometimes confusing. Consequently, this review was ordered according to the classification suggested by Oh in a state-of-the-art review published this year (Table 1) [5]. The purpose of this review was to describe the newest markers of AKI, which is why conventional markers—creatinine, albuminuria, tubular enzymes—were not in the scope of the paper.


**Table 1.** Biomarkers of acute kidney injury (AKI) studied in exercise discussed in this review—classification according to Oh et al. [5].

**Abbreviations:** u—urinary, s—serum, p—plasma, Cyst-C—cystatin C, NGAL—neutrophil gelatinase-associated lipocalin, KIM-1—kidney injury molecule-1, L-FABP—liver-type fatty-acid-binding protein, IL—interleukin, TTF3—trefoil factor-3, TNFα—tumor necrosis factor α, YKL-40—chitinase 3-like protein 1, MCP-1—monocyte chemoattractant protein-1, IGFBP-7—insulin-like growth factor binding protein 7, TIMP-2—tissue inhibitor of metalloproteinases-2.

Repeated episodes of acute kidney failure may lead to chronic kidney disease (CKD); therefore, proper diagnosis of AKI is important [14]. There is no evidence that sport practicing can lead to chronic kidney problems; nevertheless, after marathon run and other endurance events, an acute renal failure requiring renal replacement therapy was observed [15]. The possible factors causing post-exercise AKI are dehydration, sub-clinical rhabdomyolysis, inflammation, increased energy demanding renal sodium uptake, reduced renal perfusion and nonsteroidal anti-inflammatory drugs (NSAIDs) frequently used by runners [16,17]. There is evidence that dehydration and soft drink intake during and following exercise may lead to acute kidney dysfunction [18] and that physical work in heat is leading to chronic kidney disease [19].
