Renal and Genitourinary Problems

Overview: Etiologic factors can be categorized by location (kidney vs. bladder).

Nontraumatic renal: Decreased renal blood flow (700 mL per minute to 200 mL per minute, with decrease proportional to intensity) leads to ischemia in the nephron, increased permeability, and subsequent passage of RBCs. Also increased glomerular filtration pressure, secondary to efferent vasoconstriction, leads to passage of RBCs at the glomerulus. Clots are usually not renal in etiology; dysmorphic cells are suggestive of renal source.

Traumatic renal: Direct contact (helmet, ski pole, balance beam, etc.) vs. indirect trauma (“jarring” during running, jumping, etc.).

Bladder: Sports hematuria of bladder origin is almost always traumatic. This can be the result of single, large blunt trauma or multiple lesser forces. Repetitive contact of flaccid posterior bladder wall against anterior wall (trigone) is known as “bladder slap.” It can occur in athletes participating in intense physical activity such as long-distance running, track, swimming, lacrosse, and football. Cystoscopy shows damage of the superficial urothelium or contusion. Incidence can be decreased if bladder is partially filled and adequate hydration maintained.

Prostate/urethra: Usually traumatic, most often seen in cyclists because of repetitive jarring. May be the result of improper seat height and pitch.

Other causes of hematuria:

• Nephrolithiasis

• Urinary tract infection

• Sickle cell anemia or other blood disorder

• Malignancy

• Drug or medication use (including penicillin, cephalexin, thiazides, allopurinol, nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin, furosemide, and oral contraceptives)

• “Foot strike hemolysis”: possible phenomenon where trauma occurs to RBCs circulating in the feet during running, leading to hemolysis. As a result, haptoglobin binds free hemoglobin, and if haptoglobin binding becomes saturated, then hemoglobin is excreted in urine.

• Rhabdomyolysis (hematuria on urinalysis [UA] with absent RBCs on microscopy).

• Red-colored (without hematuria or RBCs on microscopy) urine attributed to beets, berries, food coloring, phenazopyridine, phenytoin, ibuprofen, nitrofurantoin, sulfamethoxazole, and rifampin.

Diagnosis made by urine dipstick and confirmed with microscopy

Timing of hematuria during urination is important to consider:

• Initial hematuria (beginning of urination) often urethral in origin

• Terminal hematuria (end of urination) may originate in bladder or prostate (men)

• Continuous hematuria suggests renal origin

Some have advocated using mean corpuscular volume (MCV) and RBC morphology to help establish the origin of hematuria:

• MCV less than 72 fL considered to be of glomerular origin

• MCV more than 72 fL considered to be of nonglomerular origin

• Casts or dysmorphic appearance of cells consistent with glomerular origin

If no concerning history, physical examination, or diagnosis, stop exercise and/or suspected medications and repeat UA after 24–72 hours.

• If urine clears after 24–72 hours and the patient is under 40 years old, can diagnose exercise-induced hematuria (benign)

• If gross or microscopic hematuria persists or patient is over 40 years old, consider further workup:

• Urine: culture, cytology

• Blood: creatinine, prothrombin time/partial thromboplastin time (PT/PTT), blood urea nitrogen (BUN), complete blood count (CBC), sickle cell (in high-risk populations)

• Imaging: renal ultrasound, computed tomography (CT) urography, and/or direct visualization with cystoscopy

If testing remains normal and hematuria persists, must consider intrinsic renal disease:

• Creatinine clearance and protein excretion should be measured

• Renal ultrasound, retrograde pyelography, and CT scan may be useful

• Indications for renal angiography and renal biopsy are controversial

Athletes with benign hematuria secondary to exercise may return to activity once hematuria resolves

Return to play for other causes of hematuria is diagnosis-dependent

Athletes, especially those with prior episodes of hematuria, should be encouraged to drink fluids before and during exercise to avoid dehydration

Keeping a slightly distended bladder during exercise can help prevent “bladder slap”

Root cause unknown, but renin–angiotensin system (RAS) and prostaglandins play a major role:

• Plasma concentration of angiotensin II increases during exercise, resulting in increased protein filtration through the glomerular membrane

• Strenuous exercise also activates the sympathetic nervous system, which releases catecholamines, also increasing glomerular membrane permeability

Creatine supplements do not increase proteinuria

In patients with underlying chronic kidney disease (CKD), low-intensity exercise does not increase proteinuria or lead to rapid progression of CKD

Urine dipstick is generally a good tool for initial evaluation

• Screening for proteinuria at sports preparticipation examinations is not recommended, as the diagnostic utility is low

• If a routine UA shows protein and was collected within 24 hours of intense exercise, repeat testing in absence of prior exercise to determine transient vs. persistent proteinuria

Other causes for false-positive proteinuria on UA:

• Highly concentrated urine (specific gravity >1.030)

• Contamination with antiseptics

• Pyridium (phenazopyridine HCl) use

• Highly alkaline urine (pH >8)

Thorough history should be taken, including personal and family history of:

• Renal disease

• Anemia

• Hypertension—make sure to get accurate, manual blood pressure reading

• Diabetes

• Medication use (e.g., NSAIDs, antibiotics)

Further workup may include:

• Serum tests for renal function (BUN, creatinine)

• Twenty-four-hour urine for total protein, creatinine, and creatinine clearance

• Fasting blood glucose or hemoglobin A1c

• CBC or other tests as medically indicated

• Imaging: renal ultrasound, CT

• Renal biopsy

If proteinuria is transient and exercise-induced, no treatment is indicated

If proteinuria is persistent and medically related, treatment depends on underlying cause

If proteinuria clears within 24–72 hours, OK for return to play

If proteinuria persists, further workup is needed before clearance

As exercise-induced proteinuria is likely a normal physiologic process during exercise, there are no known prevention strategies

Exercise-induced proteinuria does not decrease with regular physical training, even in high-level athletes

Adequate hydration with exercise can help avoid overly concentrated urine and subsequent false-positive proteinuria on urinalysis

Combined effects of exercise to exhaustion, dehydration, hyperpyrexia, and rhabdomyolysis culminate in renal dysfunction by release of muscle enzymes and myoglobin that precipitates in renal tubules ( Fig. 32.4 )

• Over 25% of participants in ultraendurance races have evidence of AKI (at least 1.5–2× normal creatinine)

Underlying renal disease, dehydration, heat stress, genetic predisposition (i.e., sickle cell trait), and NSAID use are risk factors

AKI defined as an increase in serum creatinine by ≥0.3 mg/dL or an increase to ≥1.5 times the baseline value

Creatine kinase (CK) levels correlate well with myoglobin concentrations in the blood and can be associated with AKI in rhabdomyolysis

Although CK levels of 20,000 IU per liter is the typical threshold for treatment and hospitalization, levels over 100,000 have been reported in asymptomatic individuals during and after exercise

AKI with rhabdomyolysis may also be associated with:

• Disseminated intravascular coagulation (DIC)

• Hyponatremia, hyperkalemia, hyperphosphatemia, hyperuricemia

• Hypocalcemia—caused by precipitation of calcium phosphate in muscle from hyperphosphatemia

An athlete with AKI should be treated according to standard treatment guidelines—crystalloid solution, electrolyte replacement, etc.

Hypertonic saline should be used in the case of acute neurologic deterioration with concurrent exercise-associated hyponatremia

Serum creatinine, CK, and electrolyte levels should return to baseline before return to play initiated

There is only theoretical risk, but no proven evidence, that repetitive AKI in athletes leads to development of CKD

Prevention is primarily related to proper hydration before and during exercise

Adequate training, heat acclimatization, and avoidance of NSAIDs may help as well

NSAIDs may have deleterious effects because of their ability to inhibit cyclooxygenase within the kidney ( Fig. 32.5 )

Cyclooxygenase is the rate-limiting enzyme for synthesis of prostaglandins (PGs)

Vasodilatory PGE ₂ and PGI ₂ play a protective role in the kidney by modulating renal vasoconstriction caused by:

• Increased renal sympathetic activity

• Renin-angiotensin II

• Circulating catecholamines

Under stress conditions (salt restriction, dehydration, and heat), ibuprofen decreases GFR after 45 minutes of exercise at 65% $\dot{\text{V}}{\text{O}}_2$ max, compared with placebo or acetaminophen

Both indomethacin and celecoxib showed decreases in free water clearance, which in certain environments or conditions can predispose to hyponatremia

Creatine monohydrate is widely used as an ergogenic aid for muscle performance

Increases muscle stores of creatine, leading to greater adenosine triphosphate (ATP) synthesis

In healthy individuals, there is no known link between creatine ingestion and renal dysfunction if used over the short term in typical doses (loading dose 20 g/day × 5 days and then 3–5 g/day maintenance dose)

There have been case reports of acute renal failure in individuals who were long-term, high-dose users

Those with established renal disease should avoid supplementation

End product of creatine is creatinine, which is filtered in the glomeruli and excreted; this can be a false indicator of renal dysfunction

In those using creatine, renal function can be evaluating by measuring, under resting conditions, the albumin excretion rate (normal: <20 mcg/min)