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HIV and Urology: Benign Prostatic Hypertrophy, Erectile Dysfunction, Epididymitis, Nephrolithiasis

for Health Care Providers

Urology

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Key Points

Benign Prostatic Hypertrophy (BPH)

  • Approximately 19% of men aged >38 have symptoms related to BPH; the proportion increases with age.
  • Treat mild to moderate BPH with alpha-adrenergic antagonist monotherapy. Treat moderate to severe BPH with combination alpha-adrenergic antagonist and 5-alpha-reductase inhibitor therapy.

Erectile Dysfunction (ED)

  • HIV-infected men are more likely than age-matched HIV-uninfected men to have ED. Some studies have found the prevalence of ED among HIV-infected men to be as high as 70%.
  • First-line therapy: Phosphodiesterase 5 (PDE5) inhibitors. Note: serum levels of PDE5 inhibitors are increased significantly in the presence of CYP 3A4 inhibitors such as PIs. PDE5 inhibitors are contraindicated for use with patients receiving nitrates.

Epididymitis

  • Among sexually active men aged <35, acute epididymitis is most frequently caused by Chlamydia trachomatis and Neisseria gonorrhoeae. Escherichia coli, and other enteric organisms are common causes among men who practice insertive anal intercourse.
  • Among HIV-infected men, especially those with advanced immunosuppression, fungi and mycobacteria can cause acute epididymitis and should be considered in the differential diagnosis when symptoms do not respond to first-line treatment.

Nephrolithiasis

  • Formation of renal stones is influenced by diet, metabolism, comorbid conditions, and drugs.
  • Some PIs can cause renal stones: IDV can precipitate within the urinary tract to form stones. ATV and NFV also have been reported to form stones.
  • Diagnosis relies on imaging, although IDV-containing stones may be radiolucent on both plain X rays and CT.
  • The majority of patients can be managed with hydration and analgesics. The underlying cause should be defined in order to determine therapy to prevent recurrences.

Benign Prostatic Hypertrophy

Background

BPH is a nonmalignant overgrowth of prostate tissue (stromal components > epithelial cells), usually originating in the central/transitional zone of the prostate.

  • BPH may cause symptoms of urinary obstruction, which vary widely in degree of severity.
  • Symptoms typically appear slowly and progress gradually over the course of several years.
  • Overall prevalence of BPH symptoms in men aged >38 is 19%; the prevalence increases with age.
  • Approximately 40% of men will have pathologic evidence of BPH by age 60, increasing to 90% by age 90.
  • Men with symptomatic BPH who are not treated have a 2.5% per-year risk of developing acute urinary retention.

Veterans with HIV*

BPH: 8%

*Veterans in the VA HIV Clinical Case Registry in care in 2007 who had an ICD-9 code corresponding to this condition

Evaluation

  • There are no consensus diagnostic criteria for BPH. Generally, diagnosis is made clinically on the basis of lower urinary tract symptoms (LUTS). The American Urological Association (AUA) has created the International Prostate Symptoms Score (IPSS) to evaluate LUTS. See AUA IPSS chart, below.
History
  • Symptoms:
    • Increased frequency of urination
    • Nocturia
    • Hesitancy
    • Urgency
    • Weak urinary stream
  • Family history of BPH or prostate cancer
  • Medications that can impair bladder function, especially:
    • Anticholinergics and antihistamines
  • Medications that can increase outflow resistance:
    • Sympathomimetics
  • Type 2 diabetes, which increases risk of BPH
  • Sexual dysfunction, which occurs in about 62% of men with LUTS
  • Gross hematuria, which may signify calculi or bladder tumor
  • History of urethral trauma, urethritis, or urethral instrumentation, which can lead to a urethral stricture
  • Use the AUA IPSS chart, below, to score symptoms
Differential diagnosis (partial)
  • Urinary tract infection (UTI), prostatitis
  • Neurogenic bladder
  • Prostate cancer
  • Bladder calculi
  • Bladder cancer
  • Urethral stricture
  • Bladder neck contracture
  • Medication adverse effects
Physical examination, laboratory tests, imaging
  • Digital rectal examination to assess prostate size and detect nodules
  • Urinalysis: white blood cells (WBCs) (suggest infection), and red blood cells (suggest calculi or tumor)
  • To screen for prostate cancer: digital rectal examination and serum prostate-specific antigen (PSA) (Note: elevated PSA is not specific for cancer; may indicate prostate inflammation or large prostate resulting from BPH)
  • Optional: postvoid residual urine volume (>50 mL is abnormal, measured by straight catheter or bladder scanner); maximal urinary flow rate, measured in Urology Clinic (<15 mL/sec is abnormal)
  • If signs of significant obstruction, check serum creatinine; if creatinine level is high, obtain ultrasound of the bladder, ureters, and kidneys to check for hydronephrosis
  • Suspected bladder calculi or tumor: refer to Urology Clinic for urethrocystoscopy

IPSS: AUA Symptom Index + Quality-of-Life Question

The International Prostate Symptom Score uses the 7 questions of the AUA Symptom Index (presented below) plus a disease-specific quality-of-life question (bother score).

Reprinted from the Journal of Urology (1992), 148(5), Barry, M. J., Fowler Jr, F. J., O'Leary, M. P., Bruskewitz, R. C., Holtgrewe, H. L., Mebust, W. K. and Cockett, A. T. (The Measurement Committee of the American Urological Association), 'The American Urological Association Symptom Index for Benign Prostatic Hyperplasia', pp. 1549-1557. (c) American Urological Association, 1992. Reproduced with permission.
Patient name: _____________ DOB: __________ ID: _________ Date of assessment: ___________
Initial Assessment ( ) Monitor during: ________ Therapy ( ) after: __________ Therapy/surgery ( ) ________
AUA BPH Symptom Score
Not at allLess than 1 time in 5Less than half the timeAbout half the timeMore than half the timeAlmost always
1. Over the past month, how often have you had a sensation of not emptying your bladder completely after you finished urinating?012345
2. Over the past month, how often have you had to urinate again less than 2 hours after you finished urinating?012345
3. Over the past month, how often have you found you stopped and started again several times when you urinated?012345
4. Over the past month, how often have you found it difficult to postpone urination?012345
5. Over the past month, how often have you had a weak urinary stream?012345
6. Over the past month, how often have you had to push or strain to begin urination?012345
None1 time2 times3 times4 times5 or more times
7. Over the past month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?012345
Total Symptom Score:

IPSS Score:

0-7: Mild symptoms

8-19: Moderate symptoms

20-35: Severe symptoms

The Disease-Specific Quality-of-Life Question (bother score):

"If you were to spend the rest of your life with your urinary condition just the way it is now, how would you feel about that?"

Delighted (0); Pleased (1); Mostly satisfied (2); Mixed (3); Mostly disappointed (4); Unhappy (5); Terrible (6)

Treatment Decisions:

IPSS ≤7, or no bothersome symptoms: watchful waiting

IPSS ≥8: discuss treatment options; consider referral to Urology for further testing

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Management

  • Behavior modifications:
    • Avoid drinking fluids before bedtime and before going out.
    • Avoid or reduce diuretics, including caffeine and alcohol.
    • Void twice in order to empty the bladder more completely.
  • Avoid use of antihistamine, anticholinergic, and sympathomimetic agents.
  • Medical treatment (for patients who have symptoms that are significant enough to create desire for therapy).
    • Mild to moderate BPH by AUA IPSS score: alpha-adrenergic antagonist monotherapy
      • Terazosin: 1 mg QHS; if tolerated, titrate upward every 5-7 days to effect (eg, increase to 2 mg, then 5 mg, 10 mg, 20 mg [maximum]). Usual dose is 5-10 mg; patient should experience clinical effect within 4-6 weeks.
      • Doxazosin: 1 mg QHS; if tolerated, titrate upward every 5-7 days to effect (eg, increase to 2 mg, then 4 mg, 8 mg, 16 mg [maximum]). Usual dose is 4-8 mg; patient should experience clinical effect within 4-6 weeks.
      • Prazosin: Not recommended by the AUA.
      • Common adverse effects: orthostatic hypotension and dizziness, asthenia, and nasal congestion
        • Terazosin and doxazosin may lower blood pressure more significantly than other alpha-adrenergic antagonists and therefore should be taken at bedtime; caution for additive hypotension if used concurrently with antihypertensives or sildenafil or vardenafil (for more details, see PBM Criteria for Use).
      • Uroselective alpha-adrenergic antagonists:
        • Not currently listed on the VHA National Formulary, but may be considered for patients who have significant orthostatic or postural hypotension on a nonselective alpha-adrenergic antagonist (see PBM Criteria for Use for these agents); tamsulosin is the preferred nonformulary uroselective agent:
        • Tamsulosin: 0.4 mg QD, can increase to 0.8 mg QD after 2-4 weeks, if indicated
        • Alfuzosin: 10 mg QD
        • Silodosin: 8 mg QD
        • Note: ↑ risk of hypotension if used with PDE5 inhibitors
  • Patients with hypertension should not, in general, be treated with an alpha-adrenergic antagonist as monotherapy for hypertension (see Hypertension, as well as table of blood pressure changes expected with these agents.
Table 1. Potential ARV and Other Drug Interactions (BPH)

(Print table)

  • Tamsulosin: Levels may ↑ sharply in patients who are taking P450 inhibitors, including PIs.
  • Alfuzosin: Avoid use with patients who are taking P450 inhibitors.
    • PIs such as RTV, SQV, IDV, and NFV ↑ serum alfuzosin concentrations.
    • Other P450 inhibitors including azole antifungals (eg, ketoconazole, voriconazole, posaconazole, and itraconazole) can ↑ alfuzosin concentrations to toxic volumes. Concurrent use of alfuzosin and azoles can ↑ sthe risk of QTc prolongation.
    • Other P450 inhibitors including azole antifungals (eg, ketoconazole, voriconazole, posaconazole, and itraconazole) can ↑ alfuzosin concentrations to toxic levels. Concurrent use of alfuzosin and azoles can increase the risk of QTc prolongation.
  • Silodosin: Contraindicated in patients on RTV-boosted PIs or other strong P450 inhibitors.
  • Moderate to severe BPH by AUA score, or BPH not controlled by an alpha-adrenergic antagonist alone: Combination therapy with 5-alpha-reductase inhibitor and maximum tolerated dosage of an alpha-adrenergic antagonist may be of benefit.
    • Combination therapy can reduce the size of the prostate gland over a 6- to 12-month period. Used alone, 5-alpha-reductase inhibitors have not shown efficacy for BPH treatment. Consider for patients who are on a maintenance dosage of an alpha-adrenergic antagonist (eg, terazosin 10 mg QD), or on the highest tolerated dosage if a maintenance dosage was not achieved; who have a large prostate (>40 mL, the size of a golf ball), and who show clinical progression of BPH symptoms as suggested by:
      • An increase in the AUA score ≥4 points from baseline, or
      • A history of acute urinary retention, or
      • Persistently bothersome symptoms despite adequate alpha-adrenergic antagonist therapy, as above
    • Consider for patients who have not tried alpha-adrenergic antagonist therapy but who have an AUA score >12 and are at high risk of urinary retention or require an intervention.
    • See PBM Criteria for Use.
  • 5-alpha-reductase inhibitors
    • Finasteride: 5 mg QD.
    • Dutasteride: 0.5 mg QD (may be more potent than finasteride).
    • Possible adverse effects: decreased libido, ejaculatory dysfunction, ED. Both finasteride and dutasteride have been associated with development of higher-grade prostate cancer in patients diagnosed with prostate cancer while on this agent.
    • Note: These medications can cause PSA levels to decrease by 50%. This should be taken into account if PSA levels are being followed to track other diseases.
When to Refer

Refer to Urology for evaluation or possible surgical interventions for patients who develop:

  • Hydronephrosis
  • Urinary retention
  • Bladder stones
  • Renal dysfunction
  • Recurrent infection
  • Severe symptoms that do not respond well to medical therapy
  • Elevated serum PSA or microscopic or gross hematuria

Erectile Dysfunction

Background

  • ED is the inability to achieve or maintain penile erection sufficient for satisfactory sexual performance (National Institutes of Health Consensus Panel definition).
  • HIV-infected men have a higher prevalence of ED than age-matched HIV-uninfected men.
  • In some outpatient studies of HIV-infected men, the prevalence of ED is as high as 70%.
  • Sexual dysfunction also occurs in women, but is less well studied.
  • Sexual dysfunction often is multifactorial in etiology; causes can include:
    • Medication effects (see below)
    • Psychological: depression, stress
    • Endocrine: androgen deficiency, thyroid disease, diabetes mellitus
    • Neurologic: stroke, spinal cord or back injury, prostate surgery, pelvic trauma, multiple sclerosis, or dementia
    • Vascular: cardiovascular disease, hypertension
    • Metabolic and diet-related: obesity, dyslipidemia
    • Substance use: alcohol, tobacco; methamphetamine, cocaine, and heroin can initially increase libido but over time can cause inability to sustain an erection
  • Among HIV-infected men, ED has been associated with:
    • Age >40
    • Depression, anxiety, posttraumatic stress disorder
    • Use of antidepressants (although the effect of these medications is difficult to separate from the effect of underlying depression)
    • Use of psychotropic medications (although the effect is difficult to separate from that of underlying psychiatric disease)
    • Duration of ART (higher prevalence of ED with longer duration of ART, regardless of regimen)
    • Presence of peripheral neuropathy
    • Hypogonadism
    • Heterosexual orientation
    • Nonuse of alcohol

Veterans with HIV*

Erectile dysfunction: 18% (filled prescriptions for ED drugs)

*Veterans in the VA HIV Clinical Case Registry in care in 2007 who had an ICD-9 code corresponding to this condition

Medications Commonly Associated with ED

  • Antidepressants (particularly SSRI, serotonin-norepinephrine reuptake inhibitor [SNRI] classes)
    • Bupropion, mirtazapine, and nefazodone confer lower risk of ED
  • Spironolactone
  • Thiazide diuretics
  • Beta-blockers (not clearly associated; mixed data)
  • Clonidine
  • Methyldopa
  • Ketoconazole
  • Cimetidine

Evaluation

  • The abridged International Index of Erectile Function (IIEF-5) is a validated question set used to diagnose the presence and severity of ED.
  • The sensitivity of the IIEF-5 is 98% and the specificity is 88%, using a cutoff score of 21.
The International Index of Erectile Function (IIEF-5) Questionnaire
Reprinted by permission from Macmillan Publishers Ltd: Rosen RC, Cappelleri JC, Smith MD, et al. Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999 Dec;11(6):319-26. © 1999
Over the past 6 months:
1. How do you rate your confidence that you could get and keep an erection?Very low 1Low 2Moderate 3High 4Very high 5
2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration?Almost never/never 1A few times (much less than half the time) 2Sometimes (about half the time) 3Most times (much more than half the time) 4Almost always/always 5
3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner?Almost never/never 1A few times (much less than half the time) 2Sometimes (about half the time) 3Most times (much more than half the time)4Almost always/always 5
4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse?Extremely difficult 1Very difficult 2Difficult 3Slightly difficult 4Not difficult 5
5. When you attempted sexual intercourse, how often was it satisfactory for you?Almost never/never 1A few times (much less than half the time) 2Sometimes (about half the time) 3Most times (much more than half the time) 4Almost always/always 5

IIEF-5 scoring:

The IIEF-5 score is the sum of the ordinal responses to the 5 items.

22-25: No erectile dysfunction

17-21: Mild erectile dysfunction

12-16: Mild to moderate erectile dysfunction

8-11: Moderate erectile dysfunction

5-7: Severe erectile dysfunction

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History
  • Rapidity of onset: sudden onset points to psychogenic causes
  • Presence or absence of spontaneous erections: absence suggests vascular or neurogenic causes
  • Screen for depression, anxiety, and posttraumatic stress disorder (including rape, sexual assault, and military sexual trauma)
  • Screen for interpersonal conflict with sex partner(s)
Physical examination
  • Penis: corporal plaques associated with Peyronie disease (buildup of scar tissue in erectile tissues can cause pain or bending with erections)
  • Testes: size, symmetry, consistency, masses
  • Epididymis and vas deferens: swelling or varicoceles
  • If patient is aged >50, consider digital rectal examination and PSA for prostate cancer screening
  • Cardiovascular system (heart, femoral, and peripheral pulses): vascular health
  • Secondary sexual characteristics, gynecomastia: endocrine health
  • Neurologic screen: sensorimotor examination of S2-S4. Rapid screen:
    • Anal wink test: anal sphincter contracts when perianal skin is stroked
    • Bulbocavernosus reflex test: anal sphincter contracts when the glans penis is squeezed
    • Anal sphincter tone: digital rectal examination; ask patient to contract the sphincter during the examination
Laboratory evaluations and other studies
  • Testosterone: to evaluate for hypogonadism (for greatest accuracy, check in the morning) (see Androgen Deficiency)
  • Fasting glucose, HbA1c: screen for diabetes
  • Fasting lipid panel: screen for hyperlipidemia and underlying vascular disease
  • TSH to evaluate for hypothyroidism
  • Consider referral to Urology for nocturnal penile tumescence (NPT) testing, which is a home test of number of nocturnal erections and level of penile rigidity a man experiences during sleep; a normal NPT measurement suggests psychogenic ED

Management

  • It is critical that management of ED be accompanied by discussions regarding sexual health and practice of safer sex (see Prevention for Positives).
  • Obese patients: Weight loss and increased physical activity are associated with improvement in erectile function in one third of patients.
  • Psychotherapy with or without psychoactive medications is indicated for men with depression or anxiety (avoid antidepressant medications that may cause ED, if possible; see Medications Commonly Associated with ED, above).
  • Men with hypogonadism: androgen replacement (testosterone); see Androgen Deficiency.
    Note: Testosterone preparations are classified as Schedule III controlled substances.
    • Intramuscular testosterone(eg, cypionate): 200 mg IM every 2 weeks
    • Gel: 1% gel, 5-10 mg QD
    • Transdermal patch: 5 mg QD
    • Buccal: 30 mg BID
    • Possible adverse effects (particularly with IM testosterone) include mood swings, gynecomastia, testicular atrophy, acne, erythrocytosis, dyslipidemia, and elevation of serum transaminase levels. Also, pain and irritation at injection or application sites, local pruritus and erythema with patches (which can be relieved by topical steroids); bitter taste with the buccal delivery method.
    • Contraindications: prostate cancer.
    • Monitoring (particularly important with IM testosterone): testosterone levels 1-2 months after initiation. (Note: For patients on IM testosterone, check testosterone level at nadir, just before scheduled injection.); PSA every 6-12 months; hemoglobin and liver function tests every 3-6 months.
  • PDE5 inhibitors
    • See VA PBM for a summary of information on PDE5 inhibitors.
    • PDE5 inhibitors interact with PIs and often require dosage adjustment; see below.
    • All are equally effective.
    • Vardenafil is currently the PDE5 inhibitor on the VHA National Formulary. For information on obtaining another PDE5 inhibitor for a patient in whom vardenafil has been ineffective, see VA PBM.
    • Tadalafil has a longer duration of action than sildenafil or vardenafil, up to 36 hours.
    • If tolerated, titrate to effect.
Table 2. Potential ARV Interactions (ED)
Recommended Dosing of PDE5 Inhibitors

Serum levels of all PDE5 inhibitors are significantly increased in the presence of CYP 3A4 inhibitors such as PIs. See Recommended Dosing below.

PDE5 InhibitorDosing InstructionsPatients on PIs and Other Strong CYP 3A4 InhibitorsPatients Not on Interacting Drugs
Vardenafil (Levitra)Take on empty stomach 1 hour before sexual activity
  • Start: 2.5 mg per 72 hours
  • Maximum: 5 mg per 72 hrs
  • Start: 2.5-10 mg per day (≤5 mg if age >65)
  • Maximum: 20 mg every 24 hours
Sildenafil (Viagra)Take on empty stomach 0.5-4 hours before sexual activity
  • Start: 25 mg per day
  • Maximum: 25 mg every 48 hours
  • Start: 25-50 mg per day (25 mg if age >65)
  • Maximum: 100 mg every 24 hours
Tadalafil (Cialis)Take with or without food, before sexual activity
  • 5 mg per day
  • Maximum: 10 mg every 72 hours
  • Start: 5-10 mg per day
  • Maximum: 10 mg every 72 hours

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  • Use low dosages or avoid for patients with significant liver disease.
  • Possible adverse effects: (common) headache, flushing, dizziness, nasal congestion; (<2% but serious) hypotension, cardiac arrest, cerebrovascular hemorrhage, ischemic optic neuropathy, vision loss, priapism.
  • All PDE5 inhibitors are contraindicated for use by patients who take nitrate drugs.
  • Exercise caution if using PDE5 inhibitors concurrently with alpha-adrenergic antagonists (eg, terazosin) because of risk of hypotension, although tamsulosin 0.4 mg QD seems to be safe with tadalafil use (for more details, see Critera for Use).
  • Patients on a stable alpha-adrenergic antagonist regimen should start the PDE5 inhibitor at the lowest possible dosage.
  • Other agents: Consider for patients in whom PDE5 inhibitors are contraindicated (eg, patients on nitrate drugs), not tolerated, or not effective.
    • Yohimbine hydrochloride, an alpha2-adrenergic antagonist. Starting dosage is 5.4 mg (may be increased to 10.8 mg) PO TID. Side effects include nausea, dizziness, and nervousness. No data on ARV interactions are available.
      The following require referral to a urologist and instruction on proper use:
    • Penile self-injectable drugs (eg, intracavernous alprostadil, papaverine, phentolamine)
      • Override sympathetic inhibition and encourage relaxation of the penile smooth muscle.
      • Require injection with an insulin syringe through the shaft of the penis into a corporeal body a few minutes before sexual activity.
    • Intraurethral alprostadil
      • Alprostadil is instilled into the urethra, followed by penile massage for 1 minute to distribute the medication into the corpora cavernosae.
    • Vacuum devices
      • Mechanical devices increase arterial inflow, and occlusive rings decrease venous outflow from the corpora cavernosae.
  • Refractory ED: For patients who are refractory to or unable to use PDE5 inhibitors, injectables, intraurethrals, or vacuum devices, options include:
    • Referral for surgical implantation of penile prosthesis, including malleable rods and inflatable prostheses

Epididymitis

Background

  • Acute epididymitis is a syndrome consisting of pain, swelling, and inflammation of the epididymis lasting <6 weeks.
  • Chronic epididymitis lasts ≥6 weeks and consists of pain in the scrotum, testicle, or epididymis, localized on physical examination.
  • Testicular pain and swelling (orchitis) also may be present.
  • It is often accompanied by dysuria, urinary frequency, and urgency.
  • Among sexually active men aged <35, acute epididymitis is most frequently caused by infection, particularly by C trachomatis and N gonorrhoeae. E coli and other enteric organisms are common causes among men who practice insertive anal sex.
  • Among HIV-infected men, especially those with advanced immunosuppression, fungi and mycobacteria cause acute epididymitis more frequently than they do among HIV-uninfected men. These should be considered in the differential diagnosis when symptoms do not respond to first-line treatment.
  • Other causes include lower urinary tract obstruction (eg, BPH, occlusive sexual enhancement aids), surgical instrumentation.

Evaluation

Symptoms
  • Unilateral testicular pain, with or without swelling
Differential diagnosis
  • Urethritis without epididymitis
  • UTI
  • Testicular abscess
  • Testicular tumor
  • Infarction
  • Testicular torsion
Note: Testicular torsion is a surgical emergency, because testicular viability is at risk:
It is important to differentiate torsion and epididymitis. Torsion involves sudden and severe onset of pain, generally without evidence of inflammation or infection. Obtain urgent testicular ultrasound, urologic consultation, or both if torsion is suspected.
Physical examination
  • Examine testes and epididymis: exquisite tenderness and palpable swelling of the epididymis (usually begins at the tail and spreads to the rest of the epididymis and testicle), hydrocele, mass.
  • Spermatic cord: usually tender and swollen.
Laboratory evaluation and imaging
  • If urethritis: Gram stain of urethral secretions; ≥5 WBC per oil immersion field indicates infection. Presence of gram-negative diplococci (intracellular or closely associated with WBCs) is diagnostic for gonococcal infection.
  • First-void urine: ≥10 WBC per high-powered field on microscopy indicates infection. Send urine for nucleic acid amplification tests (NAAT) for C trachomatis and N gonorrhoeae. Send urine culture if infection with other organisms (eg, E coli) is suspected.
  • Testicular/scrotal ultrasound: Radiologic evaluation is not routinely necessary, but is important if other testicular conditions such as torsion, mass, and abscess are suspected. Doppler ultrasonography is 70% sensitive and 88% specific in diagnosing acute epididymitis.

Management

  • Consider hospitalization for patients who are febrile and for those with severe pain that suggests other diagnoses (eg, torsion, testicular infarction, and abscess) that require more complicated evaluation.
  • Acute epididymitis:
    • Begin empiric antibiotic treatment based on suspected cause.
    • C trachomatis or N gonorrhoeae confirmed or suspected:
      • Ceftriaxone 250 mg IM in a single dose
        Plus
      • Doxycycline 100 mg BID for 10 days
    • Note: Fluoroquinolones are not recommended for treatment of confirmed or suspected N gonorrhoeae because of high rates of resistance. N gonorrhoeae resistance to cephalosporins is also possible. In a patient with gonococcal infection and suspected treatment failure, perform culture and susceptibility testing on relevant clinical specimens; consider ID consultation. Enteric organisms confirmed or suspected; or, patient is allergic to cephalosporins or tetracyclines:
      • Levofloxacin 500 mg QD for 10 days, OR
      • Ofloxacin 300 mg BID for 10 days
  • Management of sex partners:
    • Refer sex partners for evaluation and treatment if the patient has confirmed or suspected C trachomatis or N gonorrhoeae epididymitis and sexual contact has occurred within 60 days from onset of symptoms.
    • At the current time, VA facilities are not authorized to evaluate or treat nonveteran sex partners.
    • VA facilities are strongly encouraged to report notifiable STDs to the local public health department, in accordance with established VA policies and procedures.
    • Patients should avoid sexual contact until they and their sex partners have completed therapy and no longer have symptoms.
  • Follow-up: Symptoms should improve within 3 days of initiating therapy. If there is no improvement or if the symptoms persist after completion of antibiotics, reevaluate for the following:
    • Other causes of epididymitis (eg, fungi, mycobacteria)
    • Testicular abscess
    • Testicular infarction
    • Testicular tumor

Nephrolithiasis

Background

  • Renal calculi are common in the general population, affecting 12% of men and 5% of women.
  • Stones result from supersaturation of urine with a normally soluble compound, with subsequent nucleation, crystal aggregation, and stone formation.
  • Stones typically result from a combination of dietary, metabolic, genetic, and medical factors.
  • Calculi most often are composed of calcium, but may form from uric acid or cystine.
  • Stones also may be composed of drugs; IDV in particular may cause nephrolithiasis. Among HIV-infected patients who receive IDV, 5-15% develop stones. Other PIs (NFV,ATV) also have been reported as causes of stones.
  • 50% of patients will have a recurrence within 10 years. It is important to define the underlying cause in order to determine preventive therapy.

Evaluation

History Symptoms

  • Flank pain, frequently severe, radiating to groin
  • Undulating cramps
  • Gross hematuria
  • Nausea, vomiting
Ask about:

  • Duration, characteristics, location of pain
  • History of renal stones
  • UTIs
  • Family history of renal stones
  • Solitary or transplanted kidney
  • Medications: IDV, sulfa drugs, penicillins, quinolones
  • Presence of metabolic syndrome, diabetes mellitus
Differential diagnosis (partial)
  • Appendicitis
  • Biliary colic
  • Diverticulitis
  • Pancreatitis
  • Lumbar disc disease
  • UTI
  • Ectopic pregnancy
  • Abdominal abscess
  • Aortic aneurysm
  • Bowel ischemia
Physical examination, laboratory evaluation, imaging On physical examination, look for:

  • Costovertebral tenderness
  • Absence of peritoneal signs
Laboratory studies

  • Urinalysis (85% of patients will have hematuria)
  • CBC, electrolytes, creatinine, calcium, uric acid, phosphorus, parathyroid hormone levels (if serum calcium is elevated)
  • 24-hour urine collection for patients <30 years of age, multiple calculi, renal failure, renal transplant, family history of calculi, recurrent calculi; analyze for pH, calcium, oxalate, uric acid, sodium, phosphorus, citrate, magnesium, creatinine, total volume
  • Stone analysis (size, morphology, composition); if IDV or ATV suspected, may need to order specific testing
Imaging studies:

  • Abdominal X ray (calcium-containing stones are radiopaque; IDV stones are radiolucent)
  • Renal ultrasound
  • Intravenous urography (may be the only way to detect IDV-containing stones)
  • Helical CT without contrast (will not demonstrate IDV stones)

Management

Acute

  • In the absence of infection, most (80%) patients can be managed medically.
    • Stones <5 mm in diameter typically pass spontaneously.
    • Hydration and analgesia (see Pain Medications) should be instituted promptly.
    • Consider use of medications that relax ureteral smooth muscle (eg, terazosin; nifedipine [use caution regarding interactions with PIs; see Hypertension]).
    • For patients suspected of having an IDV stone, it is reasonable to discontinue IDV temporarily to lower urinary concentrations and allow dissolution. (To avoid the development of virologic failure and HIV resistance, IDV should be replaced by another appropriate ARV, or all ARVs should be stopped temporarily.) Urine acidification may promote IDV stone dissolution.
    • Indications for hospitalization include infection with concurrent obstruction, patients with a solitary or transplanted kidney, uncontrolled pain, intractable emesis, or comorbidities (eg, coronary artery disease) that may complicate management.
    • If infection is suspected, consult a urologist regarding drainage via nephrostomy tube placement.
    • Passed stones should be analyzed to determine their composition in order to design a preventive therapy regimen.
  • Larger (>10 mm) stones and those located more proximally are less likely to pass spontaneously and frequently require surgical therapy; consult a urologist for percutaneous nephrostolithotomy, ureterorenoscopy, or shock wave lithotripsy.
    • IDV stones typically are gelatinous and thus not amenable to lithotripsy; endoscopic stent placement is the procedure of choice for patients who do not respond to medical therapy alone.

Prevention

  • All patients with a history of nephrolithiasis should maintain a daily fluid intake >2 L and restrict sodium intake.
  • Targeted preventive therapy depends on identified metabolic abnormalities and stone analysis:
    • If hyperparathyroidism has been excluded, patients with hypercalciuria should restrict dietary calcium to 600-800 mg/day; consider use of a thiazide diuretic to decrease urinary calcium excretion.
    • Patients with hyperoxaluria should increase daily intake of calcium to 1-4 g (calcium citrate is the preferred agent) and avoid foods high in oxalate (chocolate, spinach, rhubarb, beets).
    • Patients with hyperuricosuria should be treated with potassium citrate (60-80 mEq/day), along with allopurinol 100-300 mg/day to decrease uric acid excretion.
    • Patients with recurrent UTI resulting from struvite stones should undergo stone removal.
    • Patients with IDV stones should maintain an adequate fluid intake (>1.5 L/day) if continued on IDV.

References