The Evaluation of Exercise-Induced Hematuria in Endurance Athletes

Authors:
Gregory Marshall, RN, BSN, MSN-S
Devinder Jarial, RN, BSN, MSN-S
Dr. Jessica L. Durbin, DNP, FNP-BC

Corresponding Author:
Devinder Jarial, RN, BSN, MSN-S
8942 Bryant Lane Apartment 1A
Indianapolis, IN 46250
dsjarial@gmail.com
317-213-7904

Gregory Marshall and Devinder Jarial are graduate students at Indiana State University completing their Master of Science in Nursing degrees with a family nurse practitioner concentration. Dr. Jessica Durbin is an Assistant Professor in the Department of Advanced Nursing Practice at Indiana State University.

The Evaluation of Exercise-Induced Hematuria in Endurance Athletes

ABSTRACT
Microscopic hematuria can be defined as the presence of greater (>) than 3 red blood cells per milliliter (mL) detected on a high-powered microscopic field, or > 50 red blood cells per mL of urine present on a urine dipstick (14). Exercise-induced hematuria in healthy young adults is not usually associated with significant morbidity or mortality (15). Moderate exercise-induced hematuria is seen habitually, both in athletes and in the general public (14). However, hematuria can be a signal of more serious diseases (15). In endurance athletes, the microscopic hematuria is often self-limiting and resolves within 48-72 hours (1). The abnormal presence of red blood cells in urine may indicate kidney inflammation, infection or trauma in the urinary tract, or neoplastic diseases in the urogenital tract (6). If hematuria doesn’t resolve within 48-72 hours, providers should consider further evaluation. Diagnostics and interventions should be adapted to the individual based on the history of present illness, age, and past medical history. Future research on this topic could be adapted to evaluating and treating microscopic hematuria in multiple sports and activities.

Keywords: Exercise-induced, hematuria, endurance, athlete.

INTRODUCTION
For primary care providers, this condition often presents during routine urine dipstick tests. These results often require further testing such as urine cultures, creatinine lab tests, and formal microscopic urinalysis (10). This type of screening would include a large portion of endurance athletes who do not have an underlying renal pathology. Microscopic hematuria in a family practice setting that does not resolve within 48-72 hours, or when there are excessive red blood cells present, may require a referral to a specialist in urology or nephrology for an expert opinion and further evaluation (15).

The population (P) being studied covers endurance athletes. In today’s day and age, endurance athletes could cover a wide range of sports and activities including basketball, hockey, football, mountain climbing, and certain Olympic activities. The intervention (I) focuses on education regarding the need for urological work-up for microscopic hematuria. The comparison (C), or main alternative to compare with the intervention, involves benign versus pathological hematuria percentages. The outcome (O) we would like to achieve would be to assess when hematuria of any kind necessitates a urological work up when a patient presents gross or microscopic hematuria.

EVIDENCE SUPPORTING EVALUATION
There are well-supported evidence-based guidelines for providers for the treatment of microscopic hematuria. There is substantial research over endurance running and subsequent effects on the renal system. In contrast, the research involving endurance athletes as a whole is not as conclusive. Microscopic hematuria is common even in the adult population, with a prevalence of 38% in asymptomatic military personnel and of 13% in adults aged >35 years (14). The prevalence rates in endurance athletes are difficult to calculate, as large-scale data has not been collected. However, it is estimated that microscopic hematuria was present in 18% of athletes immediately after and three days post event (1). The diagnostic approach to microscopic hematuria is to rule out malignancy in the renal system (7). This paper will provide the provider data to help evaluate and treat exercise-induced hematuria.

PURPOSE OF REVIEW
The purpose of this review is to help establish standards for evaluation of microscopic hematuria in primary care settings, and determine a need for further evaluation by a specialist. Health care providers already have standards in place for detecting hematuria through urine dipstick evaluations. When hematuria does not resolve within 48-72 hours, providers need to consider the need for further work up, a formal microscopic urinalysis, or referral. In these cases, additional focus should be placed on possible causes of injury, duration of activity prior to onset of symptoms, previous instances of the presenting problem, familial history, diet, and possible use of performance enhancing drugs. A thorough history can provide clues to primary care providers or specialists towards possible causes.

Exercise-induced hematuria can be attributed to various mechanisms that include increased body temperature, lactic acidosis, hemolysis, free radicals, or renal ischemia (11). The use of anabolic steroids in endurance athletes is another variable that warrants consideration because anabolic steroid use has been associated with renal dysfunction and elevated serum creatinine values (13). In extreme cases, these variables could possibly lead to renal carcinoma, renal failure, or sudden death.

Exercise can be delineated into a variety of activities. Competition in amateur and professional sports is as intense as it has ever been. Participating in a sport or activity safely should be a primary consideration when participating in a sport or activity in general. This type of reasoning and analysis should give health care providers an idea of the advantages of testing, monitoring, and further evaluation of an endurance athlete who presents with hematuria. This concept should also be relevant to athletes, trainers, coaches, or managers because this condition could manifest through different activities and sports.

SEARCH CRITERIA FOR RELEVANT LITERATURE
A challenge for this topic is what defines an “endurance athlete.” There is limited research in the area, and even less data for what this definition could include. Prior research has focused on endurance running. Exercise-induced hematuria has also been shown in rowing, swimming, lacrosse, track, and football in similar percentages as marathon running (2). Hematuria is dependent on variables such as intensity or exertion, and prolonged exercise may lead to more prominent hematuria (6). Further discussion and research is needed to help determine and categorize definitions of endurance athletics and endurance activities.

In this review, the search for published literature consisted of the use of the online databases MEDLINE, and Pubmed from 1970-2017. Search terms included “hematuria,” “endurance athlete,” “kidney sports injury,” and “athlete.” These database searches found 77 studies, and six were selected for further investigation. A search using Google Scholar was also conducted, and two studies were selected. One study was found through a general Internet search. Duplicate studies were then discarded from our source data pool. Studies included case reports, nonrandomized control trials, quasi-experimental studies, and systematic reviews. A Cochrane review was completed without a subject review on the topic. Most included studies were from 2013-2017.

SUMMARY OF LITERATURE
Laboratory evaluation is an important component to evaluate microscopic hematuria. Many organizations recommend no screening for asymptomatic microscopic hematuria, so investigations can be done if researchers intentionally are searching for exercise microscopic hematuria (1). Patients with persistent hematuria of longer than 48 hours should undergo cystoscopy of the urinary bladder, and gross or microscopic cytological evaluation of exfoliated cells in the urine sample (1). A repeat urinalysis should occur two days after activity if the cause behind hematuria is thought to be physiological in nature due to menstruation, sexual activity, strenuous exercise, and trauma (1).

Performance, distance, and intensity are relevant to endurance and the development of acute renal injuries. In a study of 25 male 100-kilometer (km) ultra-endurance runners, 17 tested positive for hematuria post-race (3). When the runners were re-checked 24 hours post-event, six tested positive for hematuria (3). Prolonged activity modifies hematological parameters and promotes anemia, leading to decreases in hemoglobin and hematocrit levels (3). Oxidative stress responses, hemolysis, and gastrointestinal bleeding were thought to contribute to the development of hematuria (3).

The presence of hematuria can be a benign clinical problem, or a malignant process, that may indicate altered function of the kidney (5). However, hematuria is one of the most common urine abnormalities found after physical activity (5). Countermovement jumping on a force platform performed post-race, and increased exercise intensity is thought to have been a contributing factor to urological changes, in addition to muscle fatigue and muscle breakdown (5). These variables suggest rapid changes in body mass due to prolonged exercise could be a contributing factor to the development of hematuria.

The diagnostic approach to microscopic hematuria is to rule out renal injury and urethral, ureteral, bladder, or renal malignancy (8). The American Urological Association recommends computed tomography (CT) scans, urography and cystoscopy as interventions (7). Risks of these tests include infection, radiation exposure, and contrast-induced nephropathy (7). In 2012, the diagnosis of hematuria was associated with 2.7 percent of all urological visits (7). While no major organization supports routine genitourinary cancer screening, routine urinalysis can detect hematuria (7). The combination of ultrasound and cystoscopy are cost-effective strategies for diagnosing, or ruling out malignancy (7).

Iron is a critical mineral that helps optimize athletic performance due to the role it plays in energy metabolism, oxygen transports, and balancing acid-base levels (8). Common reasons for elevated urinary blood losses are damage to the kidney because of hypoxia, increased renal blood pressure, increased body temperature, exercise-associated acidosis, renal or bladder trauma, and dehydration (8). Increasing iron intake through diet modification or supplementation can decrease the risk of exercise-induced inflammation due to changes in hepcidin levels (8).

Another study found that, among 26 subjects who participated in a 100 km ultra-marathon, three subjects were observed to have hematuria immediately after the race (9). Plasma levels of potassium ions, sodium, creatinine, creatine kinase, renin, and aldosterone were significantly elevated immediately after the race, and were then significantly reduced one day after the race (9). The development of hematuria in this situation, in addition to the rapid changes in lab values, demonstrates acute kidney injury due to prolonged exercise (9).

Pretesting is an important variable to consider when evaluating hematuria or urological changes in addition to testing after the event. Another study involved 38 adolescent soccer players, in which 25 were found to have hematuria after the match (16). These athletes had a urinalysis and blood pressure screening before the start to the soccer season (16). Urinary proteins, osmolality, and cytology were also examined before and after matches used for evaluation (16).

Transient hematuria can be considered benign after intense physical activity; however, there is still a need to establish underlying causes and understand reasons for progression to chronic renal damage (14). Microscopic hematuria is common even in the adult population, with a prevalence of 38% in asymptomatic military personnel, and 13% in adults ages > 35 years (14). The loss of red blood cells following exercise can be up to two to three percent of the total red blood cell count, and the body quickly compensates within two to three days (14).

Hematuria can also develop due to sports-related blunt trauma (12). High-grade renal injuries can develop from a solitary blow to the flank (12). Hematuria could be detected through urinalysis or visualization. CT scanning is the imaging modality of choice to evaluate and grade renal injuries due to trauma (12). While these types of injuries might be isolated, they can occur during a prolonged sports event that falls under the category of an endurance activity.

DISCUSSION
This topic examines the causes, evaluation, follow-up, and potential treatment for the analysis of exercise-induced hematuria in endurance athletes. It is important to define what an endurance athlete is or could be. Physical endurance is tied to activities involving conditioning, execution, skill, and technique. Endurance can be conceptualized as the ability to withstand hardship, adversity, or stress. Athletes are trained or skilled in exercises, sports, or games requiring physical strength, agility, or stamina. For the purposes of this review, endurance athletes will be defined as persons who participate in a wide range of sports and activities that could include marathon running, sprinting, soccer, swimming, basketball, hockey, football, gymnastics, wrestling, mountain climbing, or tennis.

Microscopic hematuria is a problem in endurance athletes that often creates a dilemma for a provider. It is important to not dismiss the results, as malignancy is still a possibility for adults. Having the patient avoid physical activity, then complete another urinalysis in 48-72 hours is suggested if hematuria is thought to be from exercise. If the urinalysis is negative for hematuria, it can be categorized as benign hematuria; if positive the sample should be tested under microscopic examination to confirm or refute the results (4). In instances of a positive microscopic sample, the patient should then be referred to a nephrologist or urologist for further evaluation. The exact mechanism of injury of microscopic hematuria is unknown, but often reverses with cessation of insulting action. It is imperative that the provider consider exercise-induced hematuria in a patient who reports large amounts of physical activity, as repeat testing will hopefully avoid further advanced testing and expert consultation.

CONCLUSION
Follow up is a final consideration when exercise-induced hematuria is identified. According to the American Urological Association, the clinician has discretion as to when to re-test the patient (4). A standard time could provide better outcomes and research opportunities in the future. In general, the medical field focuses less on prevention and more on treatment. There are considerations providers and athletes should take into account to prevent microscopic hematuria. Performance and intensity are relevant to endurance and the development of acute renal injuries. The systemic oxidative stress response that occurs during exercise is a major factor that contributes to the development of hematuria (3). Dehydration can contribute to the development of acute kidney injury (9). We would recommend that athletes stay hydrated prior to, during, and after intense events or training. Simply drinking more fluids could prevent the problem from occurring in the first place.

IMPLICATIONS FOR APPLICATION IN SPORTS
One implication for practice is to evaluate for known causes of benign hematuria in patients who have a positive urine dipstick. Identifiable causes of hematuria include vigorous exercise, presence of pre-existing medical renal disease, presence of infection or viral illness, present or recent menstruation, exposure to trauma, or recent urological procedures (4). If this symptom is associated with vigorous exercise, the patient should withhold exercise prior to the next urological evaluation. It is thought that microscopic hematuria is present immediately after and three days post event in 18% of endurance athletes (1). Recognizing these causes can reduce anxiety associated with testing for more severe illnesses, and possibly decrease overall medical costs.

Another implication is that a full urological workup must be completed if the patient has a positive dipstick test for hemoglobin and has red blood cells present on microscopic analysis. The patient then should be evaluated to rule out malignancy (4). For a family nurse practitioner, this often involves a referral to an urologist for further evaluation (15). Specialist interventions could include cystoscopy of the bladder, and cytological evaluation of exfoliated cells in the urine sample (1). Even with rates of malignancy in asymptomatic patients around 4%, interventions should improve patients’ overall health (4).

Prior data and research regarding exercised-induced hematuria is limited. If further research is conducted on this topic, there are variables to consider such as a lack of large studies and diversity in different types of endurance activities. Many of the publications reviewed in this manuscript had a small sample size with a lack of control of variables. Several publications were based only on marathon or ultra-endurance running. None of research reviewed had considerations toward how to define an endurance athlete. Further research to evaluate if exercise-induced hematuria predisposes the patient to permanent kidney damage should be conducted. Studies that control for intensity, duration, and types of activities could further evaluate microscopic hematuria in endurance athletes.

ACKNOWLEDGEMENTS
No funding sources were used in the creation of this manuscript. The authors declare that there are no financial or non-financial conflicts of interest. There will be no monetary reimbursements in any companies or organizations who would receive financial gains from the publication of this manuscript. There are no patents or pending patents related to the topic that is being reviewed in this publication.

REFERENCES
1. Alhazmi, H. (2015). Microscopic hematuria in athletes: A review of the literature. Saudi Journal of Sports Medicine, 15(2), 131-136. doi:10.4103/1319-6308.156343

2. Chase, R. T., Lowenthal, D. T. (1984). Exercise-induced changes in laboratory chemistries. Journal of Medical Technology, 1(7), 541-545.

3. Chiu, Y., Lai, J., Wang, S., How, C., Li, L., Kao, W., Chen, R. (2015). Early changes of the anemia phenomenon in male 100-km ultramarathoners. Journal of the Chinese Medical Association, 78(2), 108-113. doi:10.1016/j.jcma.2014.09.004

4. Davis, R., Jones, J. S., Barocas, D. A., Castle, E. P., Lang, E. K., Leveillee, R. J., …Weitzel, W. (2012). Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. Journal of Urology, 188(6), 2473-2481. doi:10.1016/j.juro.2012.09.078

5. Del Coso, J., Salinero, J. J., Abian-Vicen, J., Gonzalez-Millan, C., Garde, S., Vega, P., & Perez Gonzalez, B. (2013). Influence of body mass loss and myoglobinuria on the development of muscle fatigue after a marathon in a warm environment. Applied Physiology, Nutrition, and Metabolism, 38(3), 286-291. doi:10.1139/apnm-2012-0241

6. Gonçalves, L. G. C., Aquino, R. L. Q. T., & Puggina, E. F. (2015). Long distance run induced hydration and kidney function changes in marathoners. Motriz: Revista De Educação Física, 21(3), 299-304. doi:10.1590/S1980-65742015000300011

7. Halpern, .J.A., Chughtai, B., Ghomrawi, H. (2017). Cost-effectiveness of common diagnostic approaches for evaluation of asymptomatic microscopic hematuria. JAMA Internal Medicine, 177(6), 800-807. doi: 10.1001/jamainternmed.2017.0739

8. Hinton, P. S. (2014). Iron and the endurance athlete. Applied Physiology, Nutrition, and Metabolism, 39(9), 1012-1018. doi:10.1139/apnm-2014-0147
9. Kao, W., Hou, S., Chiu, Y., Chou, S., Kuo, F., Wang, S., & Chen, J. (2015). Effects of 100-km ultramarathon on acute kidney injury. Clinical Journal of Sport Medicine, 25(1), 49-54. doi:10.1097/JSM.0000000000000116

10. Loo, R., Whittaker, J., & Rabrenivich, V. (2009). National practice recommendations for hematuria: How to evaluate in the absence of strong evidence? The Permanente Journal, 13(1), 37–46.

11. Mousavi, M., Sanavi, S., & Afshar, R. (2011). Effects of continuous and intermittent trainings on exercise-induced hematuria and proteinuria in untrained adult females. NDT Plus, 4(3), 217-218.

12. Patel, D. P., Redshaw, J. D., Breyer, B. N., Smith, T. G., Erickson, B. A., Majercik, S. D., … Myers, J. B. (2015). High-grade renal injuries are often isolated in sports-related trauma. Injury, 46(7), 1245–1249. http://doi.org/10.1016/j.injury.2015.02.00

13. Robles-Diaz, M., Gonzalez-Jimenez, A., Medina-Caliz, I., Stephens, C., García-Cortes, M., García-Muñoz, B., & … Andrade, R. J. (2015). Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Alimentary Pharmacology & Therapeutics, 41(1), 116-125. doi:10.1111/apt.13023

14. Shephard, R. J. (2016). Exercise proteinuria and hematuria: Current knowledge and future directions. The Journal of Sports Medicine and Physical Fitness, 56(9), 1060-1076.

15. Uphold, C. R. & Graham, M. V. (2013). Clinical guidelines in family practice (5th ed.). Gainesville, FL: Barmarrae Books, Inc.

16. Van Biervliet, S., Van Biervliet, J. P., Watteyne, K., Langlois, M., Bernard, D., Vande Walle, J. (2013). Psuedonephritis is associated with high urinary osmolality and high specific gravity in adolescent soccer players. Pediatr Exercise Science, 25(3), 360-369.

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