Robert C. Gambrell
Bloody or discolored urine after exercise can have various etiologies. Exercise-induced hematuria is a common, benign cause of discolored urine following strenuous exercise. Evaluation of patients with this complaint begins with a thorough history, a focused physical examination and a microscopic examination of the urine. Using a systematic approach, the physician can detect serious, treatable problems, and testing can be limited. Patients with exercise-induced hematuria can be reassured that the condition is benign and that they can return to full activity.
Bloody or discolored urine is a common presenting complaint in athletes. Although this complaint is frequently caused by exercise-induced hematuria, it must be differentiated from other causes of discolored urine.
Exercise-induced hematuria is extremely common, with a reported incidence ranging from 11 to 100 percent among various populations of athletes, depending on the type and amount of exercise and the athlete’s state of hydration.(1) (2) (3) (4) When blood in the urine is found in an athlete, the physician may be asked the following questions: Does this blood represent a serious problem? How should it be evaluated? Will there be any permanent damage? When can normal activity be resumed?
Hematuria in athletes has been known by several other names, including “sports hematuria,” “stress hematuria,” “bongo drum hematuria,” “athletic pseudonephritis” and “10,000-meter hematuria.”(2) The condition was first reported in 1700, although it may have been recognized as early as the first century A.D.(5)
The first formal description of exercise-induced hematuria was provided in 1910, when red blood cells were detected in the urine of 18 marathon runners after a 40-kilometer race.(6) Similar findings were noted in track and baseball athletes, with the urinary abnormalities resolving promptly after the cessation of daily exercise. To date, exercise-induced hematuria has been described in association with a variety of different sports, including swimming, lacrosse, track, football, rowing, boxing, hockey and soccer.(2), (7) (8) (9) (10)
Exercise-induced hematuria may be defined as hematuria, either gross or microscopic, that occurs following strenuous exercise and resolves with rest in individuals with no underlying urinary tract abnormality. Because the early reports of this condition were almost exclusively in men, some investigators thought that the condition only occurred in male athletes.(9) However, recent evidence in a population of male and female runners suggests a 15 to 30 percent incidence without a sex bias.(2) Fortunately, the incidence of serious disease in patients with exercise-induced hematuria is very low in both men(11) and women,(12) especially in athletes younger than 40 years.(11) (12) (13) (14)
The etiology of exercise-induced hematuria is not completely understood, but it appears to be multifactorial. The various etiologies have been subdivided according to the anatomic sites of injury and the nature of the sport activity in which the injury occurs.(1), (15) These categories include a traumatic renal source, a nontraumatic renal source, the bladder and the prostate or urethra.(1)
A traumatic renal source of exercise-induced hematuria is thought to originate from the renal vasculature. The trauma may be from either a direct blow (e.g., in boxing or football) or from shaking and jostling (e.g., in running or jumping).
Nontraumatic renal injury during exercise is thought to result from hypoxic damage to the nephron as a consequence of decreased renal blood flow.(1), (15) During exercise, blood is preferentially shifted to the skeletal muscles, heart and lungs, with a concomitant decrease in renal blood flow.(16) The decrease in renal blood flow is proportional to the intensity of exercise. This results in hypoxic damage to the nephron and increased glomerular permeability, the-oretically allowing excretion of red blood cells into the urine.
Renal vasoconstriction, also thought to play a role, can result in increased filtration pressure and stasis in glomerular capillaries, facilitating the excretion of red blood cells into the urine. This theory is supported by the fact that in athletes, proteinuria is more common than hematuria, suggesting that the protein leak signifies early changes in glomerular permeability. With progressive stress, the membrane leak increases, possibly allowing the passage of red blood cells into the urine.(2)
Both traumatic and nontraumatic renal mechanisms may be involved concurrently in exercise-induced hematuria. The incidence of exercise-induced hematuria is related to the duration and intensity of the activity performed. One study(7) showed that swimmers in distance events (440 yards and 1,500 meters) had a significantly higher incidence of hematuria than swimmers in the short events (50 to 100 yards). The same was true of runners, with those who competed in longer events (400 yards to 2 miles) having a considerably higher incidence of urine abnormalities than those who competed in sprints (100 and 220 yards).
These findings can support both traumatic and nontraumatic etiologies for exercise-induced hematuria. In the previously discussed study,(7) 80 percent of the swimmers had hematuria, compared with 50 percent of the football players, which seemingly supports a nontraumatic renal etiology for the hematuria. However, the football players had a greater amount of blood in their urine than did the athletes in other sports. Considering the direct blows football players may be subjected to and the amount of time football players spend exerting themselves, it is reasonable to guess that trauma to the kidney may play a role in the hematuria found in these athletes. Nonetheless, it is virtually impossible to precisely determine the relative contribution of traumatic and nontraumatic renal mechanisms in these cases.
One study(8) implicated the bladder as a source of exercise-induced hematuria. In this study, cystoscopy was performed in eight long-distance runners who had hematuria within 48 hours after they had completed a race. Contusions of the bladder wall that were found on the initial cystoscopic examination were shown to rapidly resolve on subsequent examinations. The findings suggested that the flaccid posterior wall of the bladder was slapping against its fixed base at the trigone, causing “mirror-image” lesions on the posterior wall and the trigone.
PROSTATIC OR URETHRAL SOURCE
Other sources of exercise-induced hematuria to consider are the prostate and the urethra. Hematuria has been reported in cyclists and in children riding bicycles with banana-style seats.(17) (18) (19) The hematuria resolved after the front of the bicycle seat was lowered.[ILLUSTRATION OMITTED]
An algorithm for the evaluation of hematuria is shown in Figure 1.(20) Evaluation begins with a thorough medical history (Table 1)(21) and a physical examination that emphasizes the vital signs, abdomen, flank, back, rectum, scrotum and genitalia.
Issues to Consider in the Medical History of Patients with Hematuria or Discolored Urine
Pseudohematuria due to drugs, vegetable dyes, pigments (see Table 3)
Factitious disorders: Munchausen syndrome, narcotic-seeking behavior
Gross hematuria: relation to exercise or infection
Relation of gross hematuria to urinary stream: initial (urethra distal to urogenital diaphragm), total (bladder proper or upper urinary tract), terminal (bladder neck or prostatic urethra)
Clots, which indicate nonglomerular bleeding: large thick clots (bladder), small, stringy clots (upper tract)
Painful hematuria: urinary tract infection or calculus, papillary necrosis, passage of clots, obstruction, loin-pain hematuria syndrome, glomerulonephritis
Genitourinary history: flank trauma or pain, frequency, nocturia, dysuria, prior stones, tissue passage, infections, vaginal or penile discharge, sexual activity, presence of urinary catheter
Relation to menstruation: endometriosis
Sickle cell disease or trait
Medications (see Table 4)
Connective tissue disease: fever, rash, joint pain, weight loss
Malignancy: weight loss, fatigue, anorexia
Infectious etiology: night sweats, sore throat, impetigo, tooth extraction or other invasive procedures, diarrhea, travel to area endemic for Schistosoma haematobium
Risk factors for urologic cancer: age greater than 40 years, tobacco use, analgesic abuse, pelvic irradiation, cyclophosphamide (Cytoxan), S. haematobium, occupational exposure to dyes or rubber compounds
Family history: benign familial hematuria, renal disease, sickle cell disease, deafness (Alport’s syndrome), bleeding diathesis
Prior testing: blood pressure, urinalysis, serum chemistries, intravenous pyelography
Pregnancies: proteinuria, hypertension (and month of onset)
Factors indicating diagnosis is not exercise-induced hematuria: hematuria does not clear in 24 to 72 hours, gross hematuria, male age greater than 40 years, recurrent episodes of hematuria, hematuria not related to prolonged or intense exercise
Adapted from Sutton JM. Evaluation of hematuria in adults. JAMA 1990; 263:2475-80. Used with permission.
Common Causes of Hematuria
Drug (see Table 4)
Hematologic disorders (e.g., sickle cell disease or trait, coagulopathies)
Infection or inflammation
Polycystic kidney disease
Adapted from Elliot DL, Goldberg L, Eichner ER. Hematuria in a young recreational runner. Med Sci Sports Exerc 1991;23:892-4. Used with permission.
The patient’s symptoms often point to a cause for the hematuria (Table 2).(22) In women, dysuria, urgency and frequency are symptoms of cystitis. Vaginal bleeding or menstruation may confuse the clinical picture when the urine sample is contaminated with blood. Colicky flank pain may be caused by a kidney stone or, if associated with a fever, an infection. In men, urethral discharge, perineal pain and dysuria suggest urethritis or prostatitis. In both men and women, glomerulonephritis is suspected when new-onset hematuria, edema and hypertension are preceded by a sore throat or a skin infection. Gross painless hematuria in an adult should be considered secondary to bladder cancer until proven otherwise.(23)
Many medications are known to cause hematuria or to discolor the urine (Tables 3 and 4).(23) Discolored urine may be due to pseudohematuria following the ingestion of a variety of medications, vegetable dyes and food colorings, or it may be caused by concentrated urate excretion.
The initial laboratory studies include a urine dipstick test and microscopic examination of the urine. Further testing is guided by the results of these studies and by the findings of the history and the physical examination.
With pseudohematuria, the urine dipstick test is negative for blood and no red blood cells are found in the urine on microscopic examination. A urine dipstick test that is positive for blood is caused by hematuria, hemoglobinuria or myoglobinuria. The microscopic urine examination differentiates hematuria (three or more red blood cells per high-power field)(21) from other causes of discolored urine, such as hemoglobinuria, hematospermia, myoglobinuria or ingested substances.(23)
Hemoglobinuria and myoglobinuria may be further differentiated using specific immunoassays. “Active” urinary sediment with red blood cell casts, marked proteinuria or dysmorphic urinary red blood cells suggests a glomerular source.(21)
The algorithm in Figure 1 is based on the demographic association of hematuria etiologies.(20) It facilitates the identification of serious, treatable problems while limiting unnecessary testing. As the algorithm indicates, prompt evaluation is required for any patient with unstable vital signs or with the recent onset of hypertension, edema, oliguria, red cell casts in the urine or significant proteinuria suggesting glomerular disease. In patients with gross hematuria, there is an increased risk of a urologic neoplasm.(21) A patient with gross painless hematuria should be evaluated with cystoscopy. Minimum follow-up requirements include microscopic urinalysis and blood pressure checks annually.
Two tests that also can be considered are spot urine calcium-to-creatinine ratio and phase-contrast microscopy of red cell morphology. A spot urine calcium-to-creatinine ratio of greater than 0.2 indicates the need for a 24-hour urine calcium measurement to look for benign hypercalcinuria. Hypercalcinuria may be the most common definable cause of hematuria in children who do not have a urinary infection or proteinuria.(24) Phase-contrast microscopy of the urine can aid in identifying the source of the hematuria.(1), (21) Dysmorphic urinary red blood cells of various sizes, shapes and hemoglobin content indicate a glomerular process, and those of uniform configuration indicate a nonglomerular process. However, the precise use of phase-contrast microscopy is not yet clear.
Ingested Substances That May Cause Nonbloody Red Urine
Ibuprofen (Motrin, Nuprin, etc.)
Phenazopyridine (Azo Standard, Pyridiate, Pyridium, etc., and in combination drugs such as Azo Gantrisin)
Rifampin (Rifadin, Rimactane)
Sulfamethoxazole (in Bactrim, Septra, etc.)
Adapted from Restrepo NC, Curey PO. Evaluating hematuria in adults. Am Fam Physician 1989;40(2):149-56.
Commonly Used Drugs That May Cause Hematuria
(7) Alyea EP, Parish HH. Renal response to exercise–urinary findings. JAMA 1958;167:807-13.
(8) Blacklock NJ. Bladder trauma in the long-distance runner: “10,000 metres hematuria.” Br J Urol 1977;49:129-32.
(9) Fred HL, Natelson EA. Grossly bloody urine of runners. South Med J 1977;70:1394-6.
(10) Gardner KD Jr. “Athletic pseudonephritis”–alteration of urine sediment by athletic competition. JAMA 1956;161:1613-7.
(11) Froom P, Gross M, Froom J, Caine Y, Margaliot S, Benbassat J. Factors associated with microhematuria in asymptomatic young men. Clin Chem 1986;32:2013-5.
(12) Bard RH. The significance of asymptomatic microhematuria in women and its economic implications. A ten-year study. Arch Intern Med 1988;148:2629-32.
(13) Murakami M, Yamamoto H, Ueda Y, Murakami K, Yamauchi K. Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo. Pediatr Nephrol 1991;5:50-3.
(14) Turi S, Visy M, Vissy A, Jaszai V, Czirbesz Z, Haszon I, et. al. Outcome of isolated haematuria in children. Contrib Nephrol 1988;67:219-25.
(15) Cianflocco AJ, Renal complications of exercise. Clin Sports Med 1992;11:437-51.
(16) Poortmans JR, Exercise and renal function. Sports Med 1984;1:25-53.
(17) LeRoy JB. Banana-seat hematuria. N Engl J Med 1972;287:311.
(18) Nichols TW Jr. Bicycle-seat hematuria [Letter]. N Engl J Med 1984;311:1128.
(19) Salcedo JR, Huffy-bike hematuria [Letter]. N Engl J Med 1986;315:768.
(20) Benson GS, Brewer ED. Hematuria: algorithms for diagnosis. II. Hematuria in the adult and hematuria secondary to trauma. JAMA 1981;246:993-5.
(21) Sutton JM. Evaluation of hematuria in adults. JAMA 1990;263:2475-80.
(22) Elliot DL, Goldberg L, Eichner ER. Hematuria in a young recreational runner. Med Sci Sports Exerc 1991;23:892-4.
(23) Restrepo NC, Carey PO. Evaluating hematuria in adults. Am Fam Physician 1989;40(2):149-56.
(24) Lieu TA, Grasmeder HM 3d, Kaplan BS. An approach to the evaluation and treatment of microscopic hematuria. Pediatr Clin North Am 1991;38:579-92.
(25) Thompson IM. The evaluation of microscopic hematuria: a population-based study. J Urol 1987;138:1189-90.
(26) Mariani AJ, Mariani MC, Macchioni C, Stams UK, Hariharan A, Moriera A. The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effective analysis. J Urol 1989;141:350-5.
(27) Boone AW, Haltiwanger E, Chambers RL. Football hematuria. JAMA 1955;158:1516-7.
(28) Amelar RD, Solomon C. Acute renal trauma in boxers. J Urol 1954;72:145.
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