Normal urine color varies from clear (dilute) to yellow to deep golden and cloudy. Many substances can cause urine color to appear abnormal (Table 40-1). Cloudy urine may be caused by infection (pyuria), but the most common cause is phosphaturia, in which phosphate crystals precipitate in alkaline urine. Microscopic analysis can differentiate these two entities. A strong or foul-smelling sample does not necessarily indicate infection. Urine odor may change because of dietary intake (e.g., asparagus), medications, illness, or concentration. Fecal odor suggests gastrointestinal-vesical fistula.

Table 40-1 Factors Affecting Urine Color

Color	Causative Factor
Colorless	Very dilute urine; overhydration
Cloudy, milky	Phosphaturia; pyuria; chyluria
Red	Hematuria; hemoglobinuria, myoglobinuria; anthocyanin in beets and blackberries; chronic lead and mercury poisoning; phenolphthalein (in bowel evacuants); phenothiazines (e.g., prochlorperazine [Compazine]); rifampin
Orange	Dehydration; phenazopyridine (Pyridium); sulfasalazine (Azulfidine)
Green-blue	Biliverdin; indicanuria (tryptophan indole metabolites); amitriptyline (Elavil); indigo carmine; methylene blue; phenols (e.g., IV cimetidine [Tagamet]; IV promethazine [Phenergan]); resorcinol; triamterene (Dyrenium)
Brown	Urobilinogen; porphyria; aloe, fava beans, rhubarb; chloroquine, primaquine; furazolidone (Furoxone); metronidazole (Flagyl); nitrofurantoin (Furadantin)
Brown-black	Alkaptonuria (homogentisic acid); hemorrhage; melanin; tyrosinosis (hydroxyphenylpyruvic acid); cascara, senna (laxatives); methocarbamol (Robaxin); methyldopa (Aldomet); sorbitol

From Hanno PM, Wein AJ. A Clinical Manual of Urology. Norwalk, Conn, Appleton-Century-Crofts, 1987, p 67.

Dipstick Urinalysis

Protein

Urine dipsticks are very sensitive and specific for albuminuria. The reagent color change roughly corresponds to the protein concentration in the sample (Table 40-2). Very dilute, alkaline, or nonalbumin proteinuria may cause false-negative results. Microalbuminuria screening usually requires a separate dipstick designed specifically for this purpose. A urine protein electrophoresis is needed to evaluate nonalbumin proteinuria, such as globulinuria or Bence Jones protein.

Table 40-2 Dipstick Protein Findings

Dipstick Color	Estimated Corresponding Protein Level (mg/dL)
Yellow	Negative (no protein)
Yellow-green	Trace (10-20)
Green	1+ (30)
Dark green	2+ (100)
Green-blue	3+ (300)
Blue	4+ (>1000)

From Simerville JA, Maxted WC, Pahira JJ. Urinalysis: a comprehensive review. Am Fam Physician 2005;71:1153-1162.

Urobilinogen

Urobilinogen is a breakdown product of conjugated bilirubin. There is normally a small amount present, but elevations indicate possible hemolysis or liver disease. Conjugated bilirubinuria is abnormal and signifies hepatic disease or biliary obstruction. Unconjugated bilirubin is not filtered by the glomerulus.

Urine Microscopy

To prepare a urine sample for microscopic analysis, centrifuge 10 mL of urine for 5 minutes at 2000 rpm. After centrifugation, pour off the supernatant and resuspend the remaining sample (0.5-1.0 mL). Place a drop of this sample on the slide and focus up to high power. Samples showing probable skin or vaginal contamination should be retested or a catheterized specimen obtained (Grossfeld et al., 2001a). Sediment counts should be estimated as the average number of elements viewed per high-power field (hpf).

Red Blood Cells

Urine specific gravity may affect findings, because red cells may lyse at values lower than 1.007 (Vaughan and Wyker, 1971). Normal-appearing red blood cells (RBCs) suggest a lesion in the urinary tract, whereas dysmorphic RBCs are probably of glomerular origin (Fig. 40-1). Red cell casts are typically found at the edges of the glass coverslip and are highly suspicious for renal parenchymal disease.

Figure 40-1 Urinalysis: dysmorphic red blood cells.

(From Gerber GS, Brendler CB. Evaluation of the urologic patient. In Wein AJ [ed]. Campbell-Walsh Urology, 9th ed, vol 1. Philadelphia, Saunders-Elsevier, 2007, p 106.)

White Blood Cells

Normal urine samples may show some white blood cells (WBCs) on high-power examination (Fig. 40-2). For women, fewer than 5 WBCs/hpf is normal, and for men fewer than 2 WBCs/hpf is normal (Simerville et al., 2005). Values in excess of these limits constitute microscopic pyuria. Purulent, cloudy urine with WBCs too numerous to count describes gross pyuria.

Figure 40-2 Urinalysis: white blood cells.

(From Gerber GS, Brendler CB. Evaluation of the urologic patient. In Wein AJ [ed]. Campbell-Walsh Urology, 9th ed, vol 1. Philadelphia, Saunders-Elsevier, 2007, p 107.)

White cells are inflammatory markers, so infection cannot be confirmed by their presence or ruled out by their absence. Common causes of sterile pyuria include STIs, kidney stones, prostatitis, and urinary tract neoplasms. In children, pyuria may occur during a febrile illness, even if a UTI is not present (Graham and Galloway, 2001).

Casts

RBC casts signify a nephritic or vasculitic process. WBC casts are often considered pathognomonic for pyelonephritis, but may be found in other types of nephritis. Granular and waxy casts signify renal parenchymal disease. Hyaline casts may be normal in concentrated specimens or a marker of renal infection or disease.

Crystals

Various crystal morphologies may be seen in urine samples (Fig. 40-3).

Figure 40-3 Crystal types found in urine samples. A, Cystine. B, Calcium oxalate. C, Uric acid stones are found in acidic urine. D, Triple-phosphate crystals are found in alkaline specimens.

(From Gerber GS, Brendler CB. Evaluation of the urologic patient. In Wein AJ [ed]. Campbell-Walsh Urology, 9th ed, vol 1. Philadelphia, Saunders-Elsevier, 2007, p 108.)

Urinary Epithelial (Urothelial) Cells

Transitional epithelial cells are normally found in microscopic specimens. They are uniform in shape and have a large, central nucleus. In contrast, squamous cells have irregular borders and a small nucleus. Squamous cells indicate skin contamination.

Bacteria

Bacteria may signify bacteruria, although in women vaginal contamination is also likely. A urine Gram stain is also helpful for identifying bacterial characteristics in urine samples in which infection is suspected.

Fungi

Yeast seen in urine specimens most likely indicates contamination from the skin or vagina. However, it may signify systemic Candida infection if found in a catheterized specimen (Graham and Galloway, 2001).

Trichomonads

These motile organisms signify a common STI and may be seen in urine samples. Treatment with metronidazole (2 g as a single dose or 500 mg twice daily for 7 days) is effective. Patients should be evaluated for other STIs.

Urine Culture

Urine culture is the “gold standard” test for diagnosing UTIs. Many sources have emphasized the midstream clean-catch technique as necessary for preventing contamination, although the value of this practice is uncertain (Lifshitz and Kramer, 2000). Bladder aspiration and catheterization are invasive sampling techniques. Urine from a catheter bag should not be used for culture, because bacterial contamination is typical.

More than one bacterial isolate on culture suggests contamination. Controversy exists regarding the threshold colony counts that define bacteruria consistent with infection. Although more than 10⁵ colony-forming units per milliliter (CFU/mL) is a well-known cutoff, lower values are meaningful in certain patients. In patients with typical UTI symptoms, counts as low as 10² CFU/mL signify infection if Escherichia coli or other enterobacteriaceae are isolated. A cutoff of 10³ CFU/mL is appropriate in men with symptoms (Graham and Galloway, 2001).

Other Diagnostic Tests

Postvoid Residual Measurement

Postvoid residual measurement assesses the volume of urine in the bladder after voiding and can be performed in the office. One method is to have the patient void and then measure any residual urine by catheterization. Less than 50 mL of residual urine is normal, and 200 mL or greater is abnormal (Nitti and Blaivas, 2007). Portable ultrasound units can also estimate postvoid residual urine. Urodynamics refers to a battery of tests examining micturition, which may include postvoid residual measurement as well as various tests of bladder and sphincter pressures.

Endoscopy

Urinary endoscopy (cystoscopy) provides visual diagnosis and the opportunity for intervention. Rigid or flexible endoscopic procedures are available. Common interventional techniques include stone retrieval, stent placement, tumor biopsy and resection, and laser treatment. Risks include infection, bleeding, urethral damage, and bladder perforation.

Imaging Studies

Key Points

• Ultrasound studies are ideal for evaluating renal parenchymal disease and testicular disorders.

• Computed tomography is a better choice for evaluating solid renal masses, renal infections, perirenal masses, and renal calculi.

Intravenous Urography

The standard method of upper urinary tract imaging is intravenous urography (IVU), also known as intravenous pyelography (IVP). It is widely available, has a low cost, and can detect upper tract urothelial tumors and renal calculi. However, it cannot distinguish solid from cystic masses. Thus, ultrasound studies are often required to evaluate abnormal findings. Ultrasound and IVU are limited in their ability to detect small renal masses, particularly those smaller than 3 cm. Further, IVU is only 52% to 59% sensitive for detecting renal calculi (Grossfeld et al., 2001b). IVU also requires administering radiographic contrast.

Ultrasound

Ultrasound has many applications for evaluating urinary tract disease. It is the method of choice for imaging renal cysts and the renal parenchyma as part of a renal disease workup. Ultrasound is also the test of choice for evaluating scrotal and testicular disorders. It can usually differentiate masses such as hydrocele, inguinal hernia, and varicocele. Furthermore, regular and color Doppler ultrasound are essential parts of evaluating acute scrotal pathology, such as epididymitis, orchitis, and testicular torsion.

Ultrasound is almost 100% sensitive for testicular tumors (Dogra et al., 2003). However, it does not provide tissue diagnosis. Rather, ultrasonography helps define the nature of the suspected lesion, differentiating it from the many other conditions that might mimic an intratesticular tumor.

Computed Tomography

Computed tomography (CT) is a better choice for evaluating solid renal masses, perirenal masses, and renal infections (Grossfeld et al., 2001b). CT is the test of choice for renal calculi (Lindbloom and Meadows, 2001). Other uses include CT angiography, trauma imaging, and cancer staging.

Other Techniques

Magnetic resonance imaging (MRI) is an option comparable with CT for detecting renal masses. MR urography is also available. MRI studies are more expensive than CT, however, and availability varies (Brehmer, 2002). Thus, this modality is often used when CT examination is equivocal or contraindicated. MRI is used for staging prostate cancers (Harisinghani et al., 2003).

Voiding cystourethrography (VCUG) uses contrast imaging of the bladder and urethra during urination. Contrast material is delivered via catheter, and the images are obtained while the patient voids. It is most often used to diagnose suspected vesicoureteral reflux. Nuclear medicine studies may also be used to examine possible vesicoureteral reflux, as well as renal function or suspected testicular torsion.

Common Urinary Tract Concerns

Key Points

• Dysuria most often indicates UTI, vaginitis, or STI.

• Gross hematuria requires aggressive evaluation.

• Urine microscopy is required to diagnose hematuria. In adults, risk factors for malignancy should be assessed; isolated hematuria is most common in children.

• Hematuria of renal origin often has dysmorphic red cells. Hematuria of bladder origin should show normal red cells.

• Nocturia is common in both genders and increases the risk of falling in older adults.

• The urine protein/creatinine (Upr/UCr) ratio correlates well with a 24-hour urine and is much easier to obtain.

• Proteinuria in children is most often orthostatic.

Dysuria

Urinary burning or pain most often represents UTI or vaginitis. It is common in middle-aged and/or sexually active women. In men, it is more likely to occur as they grow older (Bremnor and Sadovsky, 2002). Both voiding history and sexual history are essential. Questions regarding vaginal symptoms are important in women. Also, use of medications and personal hygiene products should be reviewed.

Dysuria significantly increases the chance that a patient has a UTI. However, there are many potential causes of dysuria (Box 40-1), and empiric treatment based on this symptom alone leads to unnecessary antibiotic use. Incorporating other symptoms increases the likelihood that a UTI is the cause (see Urinary Tract Infection) (Bent et al., 2002; McIsaac et al., 2002).

Flank Pain

Flank pain may be a presenting complaint indicating urinary tract disorder. It is typically not relieved by position changes and is colicky in nature. Nausea and vomiting may coincide. Obstruction (e.g., kidney stones) and inflammation (e.g., pyelonephritis) are the two most common causes. The location may help localize the underlying cause (Fig. 40-4). Tumors are less likely, because they are usually only symptomatic if they distend the renal capsule or obstruct the ureter.

Figure 40-4 Localization of flank pain.

(From Anderson JK, Kabalin JN, Cadeddu. Surgical anatomy of the retroperitoneum, adrenals, kidneys, and ureters. In Wein AJ [ed]. Campbell-Walsh Urology, 9th ed, vol 1. Philadelphia, Saunders-Elsevier, 2007, p 37.)

Urinary Frequency

As a complaint, urinary frequency implies a deviation from a patient’s normal urination pattern. Thus, it may either be truly abnormal or simply more than the patient’s custom (but still normal). It may exist alone or in concert with other symptoms. For example, UTI often causes urinary frequency, urgency, and dysuria.

Adults typically urinate five to six times a day (Gerber and Brendler, 2007). Frequency usually represents an increased number of episodes with small volumes of urine as opposed to increased urine volumes, such as in polyuria. These factors help narrow the differential diagnosis (Box 40-2).

Hematuria

Hematuria is often an incidental finding on urinalysis, and evaluation depends on whether it is gross or microscopic and whether it occurs in adults, children, or adolescents. Most patients with hematuria do not have significant pathology, but this depends on the type of hematuria and underlying risk factors. One prospective study found that 61% of patients with hematuria had no finding after evaluation (Khadra et al., 2000).

Gross hematuria is blood in the urine visible to the patient or physician. Microscopic hematuria is the more common entity. Various cutoff points exist; for adults, the American Urological Association (AUA) Best Practice Policy has defined microscopic hematuria as 3 or more (RBCs/hpf (Grossfeld et al., 2001a). In children, clear consensus is lacking, although more than 5 RBCs/hpf found in at least two weekly urine samples is considered abnormal (Dodge et al., 1976; Vehaskari et al., 1979). The reasons for the different definitions may reflect a lower evaluation threshold in adults because of the larger spectrum of potential causes.

Dipstick urinalysis alone is insufficient for diagnosing hematuria, because certain substances (e.g., myoglobin) and test characteristics (e.g., specificity) can cause false-positive results. Thus, microscopic analysis is necessary and inherent in the definition.

Hematuria in Adults

Gross Hematuria

Gross hematuria is a common presenting symptom for patients with bladder or renal cancer (Yun et al., 2004). The sensitivity of gross hematuria for bladder cancer is 83%, and the positive predictive value (PPV) is 22% (Buntinx and Wauters, 1997). However, the studies generating these values were of low quality and based on referral populations. No studies are available on the likelihood that family medicine patients with this finding will have serious pathology. Pending this research, the approach to gross hematuria should remain aggressive (Khadra et al., 2000).

Confirmation of blood in the urine with dipstick and microscopy is needed in cases of red-tinted urine, because certain substances can discolor the urine (see Table 40-1). However, visible clots are unlikely to have a mimic. History should focus on signs and symptoms of infection, trauma, as well as risk factors for urinary tract malignancy (see Bladder Cancer). Physical examination should assess the external genitalia and include a pelvic examination in women and a prostate examination in men. Urology consultation is appropriate, except when an obviously benign (e.g., menses) or treatable cause is found. Even when a treatable cause is identified (e.g., renal calculi), close follow-up with repeat urinalysis is needed because gross hematuria is frequently a harbinger of serious urinary tract pathology (Khadra et al., 2000).

Microscopic Hematuria

Asymptomatic hematuria potentially signals serious urinary tract disease, although there are many causes, often benign. Hematuria may occur in 9% to 18% of normal subjects (Grossfeld et al., 2001a). Most studies evaluating and defining this problem were not performed in typical family medicine populations or are of lower quality, or both. No prospective studies demonstrate an improved outcome from routine screening. For the general population, finding asymptomatic microscopic hematuria carries a predictive value of only 0.5% (Brehmer, 2002). Thus, benefit from routine microhematuria screening is unlikely (Kryszczuk et al., 2004).

Because routine screening is unhelpful, family physicians encountering microhematuria should consider patient risk characteristics and systematic laboratory testing and imaging (Fig. 40-5). The first step in approaching asymptomatic microscopic hematuria is to verify it is a consistent finding. Patients should have repeat urinalysis, and if two separate follow-up samples are normal, no further evaluation is needed. Transient hematuria is not unusual, and serious urinary tract pathology is unlikely in patients younger than 40 years. Furthermore, history or examination may reveal a benign cause—menses, sexual activity, vigorous exercise, viral illness, or trauma. If repeat examination is normal after these considerations, no further examination is needed. A caveat would be the patient at risk for bladder cancer, because intermittent hematuria can precede this finding, and more extensive follow-up may be warranted (Grossfeld et al., 2001b). Family physicians should be cautious not to misattribute certain causes as benign. For example, warfarin (Coumadin) may cause hematuria if the patient is excessively anticoagulated, but it should not cause hematuria within its goal international normalized ratio (INR) range. Hematuria in this setting is often a sign of urologic disease (Culclasure et al., 1994).

Figure 40-5 Evaluation and follow-up of asymptomatic microscopic hematuria. BP, Blood pressure; HTN, hypertension; RBCs, red blood cells; UA, urinalysis.

If hematuria is consistently found, the next step is to risk-stratify the patient based on history, physical, and baseline laboratory findings. Initial laboratory testing should include urinalysis, urine culture (if indicated), and serum creatinine level. If UTI is present, a repeat examination 6 weeks after treatment is appropriate. High-risk patients are those at increased risk for urologic malignancy—older than 40 years, tobacco history, analgesic abuse, pelvic irradiation, occupational exposures (see Bladder Cancer), prior urologic disease, irritative voiding symptoms, history of UTIs, and cyclophosphamide use (Grossfeld et al., 2001b). These patients should undergo a more thorough evaluation for the cause of their hematuria, whereas lower-risk patients can have a more limited testing battery (Grossfeld et al., 2001a). Hematuria of renal origin may be associated with microscopic red cell casts or dysmorphic RBCs. Other findings may include proteinuria, elevated serum creatinine, or a physical finding such as hypertension or edema. These patients need evaluation for renal disease, including urine protein quantification. Some patients will have risk factors and findings for both renal and urologic disease or may already have a history of chronic kidney disease (CKD), so simultaneous evaluations for both causes may be necessary.

Patients whose initial evaluation does not suggest primary renal disease should undergo urologic evaluation based on their risk category. This includes upper urinary tract imaging, urine cytology, and cystoscopy. There are no prospective outcome data on the impact of imaging on asymptomatic microscopic hematuria. Thus, patient-oriented recommendations are unavailable, and family physicians should consider the advantages and disadvantages of the different techniques (see earlier Imaging Studies) when deciding on the appropriate method. IVU is widely available and less costly, and has a low chance of missing pathology when appropriate follow-up studies are used. CT is a good choice for a broad range of urinary tract disorders. Non-contrast-enhanced scans can be performed initially. If these show calculi in a low-risk patient, no further imaging is needed. Contrast studies can follow in all other cases (Grossfeld et al., 2001b). CT is the modality of choice when other techniques fail to reveal a cause (Lang et al., 2002). Deciding between IVU and CT is challenging because the lower cost of IVU may be offset by the eventual need for CT (McDonald et al., 2006). Radiation exposure must be considered as well. Kidney, ureter, and bladder (KUB) studies with ultrasound or MRI are alternatives for patients unable to receive radiographic contrast. However, in the case of CKD patients, the risk of nephrogenic systemic sclerosis from gadolinium contrast may also limit use of MRI.

Cystoscopy is necessary to rule out bladder cancer confidently because no imaging study is adequate for evaluation. Urine cytology is often performed with cystoscopy and has a sensitivity of 40% to 76% for bladder cancer. A positive finding is diagnostic, but a negative finding does not rule out disease. Thus, in high-risk patients, cytology is used adjunctively and in follow-up. Cystoscopy is optional in low-risk patients because it is unlikely to yield a definitive finding. These patients should undergo urine cytology. Furthermore, if they develop any high-risk characteristics, they should undergo cystoscopy (Grossfeld et al., 2001b). Urine tumor markers are available but not yet validated for routine use (Cohen and Brown, 2003).

A cause for hematuria is often not found even after a complete evaluation. Isolated hematuria is asymptomatic microscopic hematuria with a normal urologic evaluation and no signs of systemic disease or microscopic evidence of intrinsic renal disease (the definition slightly differs for children). The prognosis is good, although some studies indicate a high proportion of renal abnormalities (e.g., IgA nephropathy). Thus, surveillance for signs of renal disease is appropriate (Grossfeld et al., 2001b). Also, up to 3% of patients with initially negative workups are later found to have a urinary tract malignancy. High-risk patients should have periodic follow-up with focused history, blood pressure, urinalysis, and urine cytology for up to 3 years. This regimen can also be considered for low-risk patients (see Fig. 40-5). Evaluation and treatment of symptomatic microscopic hematuria is directed at the condition. However, family physicians should consider the underlying risk of urinary tract abnormalities when deciding on follow-up. For example, a patient with a symptomatic kidney stone may have microhematuria. Although this provides the most likely explanation for the bleeding, if the patient has a background risk for malignancy (e.g., smoking) or renal disease, repeat urinalysis is needed to ensure resolution.

Hematuria in Children and Adolescents

Hematuria is a relatively common finding in children, with an estimated prevalence of 0.5% to 2% of asymptomatic school-age children (Dodge et al., 1976). Those with hematuria and proteinuria, particularly when associated with hypertension, edema, or urinary casts, need aggressive evaluation for underlying glomerular disease or uropathy. The vast majority of children with hematuria, however, present with isolated hematuria. This is typically detected on a random urine sample obtained in the context of a routine physical examination but may also present as asymptomatic gross hematuria. In children, the term isolated refers to the complete absence of symptoms, significant past medical or family history, physical examination findings, or other abnormalities on urinalysis. This distinction often separates those children with benign processes from those with underlying pathology.

Once the diagnosis of hematuria has been confirmed and a complete history obtained and physical examination performed, a staged evaluation should ensue (Fig. 40-6). Significant underlying renal or urologic disease is highly unlikely in children with isolated microscopic hematuria (Bergstein et al., 2005). A more thorough evaluation is indicated for asymptomatic macroscopic hematuria.

Figure 40-6 Approach to the child with hematuria. ANA, Antinuclear antibody; BUN, blood urea nitrogen; CBC, complete blood cell count; Cr, creatinine; RBCs/hpf, red blood cells per high-power field.

The most common glomerular diseases associated with isolated hematuria are subclinical postinfectious glomerulonephritis, IgA nephropathy, and Alport’s syndrome. In the absence of proteinuria or more advanced disease, there is no treatment given for these conditions. Yearly follow-up with blood pressure and urinalysis is indicated for all forms of persistent hematuria.

Hypercalciuria may or may not be associated with pain. The exact mechanism by which hypercalciuria causes hematuria is unproven but probably secondary to crystalluria (Stapleton, 1994). Hypercalciuria is generally defined by a urinary calcium excretion higher than 4 mg/kg/day or a random urine calcium/creatinine ratio higher than 0.2. Higher excretion rates are expected in infants and toddlers. Patients with documented hypercalciuria should undergo a renal ultrasound to rule out nephrocalcinosis or significant stone disease. The treatment is to increase fluid intake and restrict dietary sodium (<3 g/day) while maintaining the recommended daily allowance of calcium (Srivastava and Alon, 2005). This dietary intervention may lower the urine calcium concentration and ultimately result in resolution of the hematuria. A thiazide diuretic should be considered if there is evidence of nephrocalcinosis or nephrolithiasis.

Lower Urinary Tract Symptoms

Lower urinary tract symptoms (LUTS) are the symptoms traditionally associated with benign prostatic hyperplasia (BPH). Many subcategories of LUTS exist, but the two most prominent are storage and voiding symptoms (Box 40-3). Voiding symptoms imply obstruction, but physical obstruction may not be responsible. In men with BPH, for example, detrusor overactivity, neurologic disorders, or age-related smooth muscle dysfunction may be the cause. Thus, LUTS should shift attention toward a larger symptom complex with many potential causes. This is particularly important when dealing with urinary tract disorders such as BPH, incontinence, and overactive bladder.

Nocturia

Nocturia describes waking at night to urinate. It is more common in older adults, but no population data define a normal range for any group; therefore the complaint implies a deviation from a perceived norm. Furthermore, the primary complaint often centers on the sleep disturbance rather than on urination. It may represent frequent nocturnal urination or excessive nocturnal urine production (nocturnal polyuria). Although often thought of as a prostatic symptom, it is common in both men and women. The many secondary causes in addition to local causes include prostatic hyperplasia and bladder dysfunction (Box 40-4). In patients with prominent lower urinary tract symptoms, the problem is compounded by urination difficulty. Furthermore, studies in older adults indicate that nocturia/LUTS increases risk of falling (Parsons, et al., 2009). Age-related variations in arginine vasopressin secretion may play a role in nocturnal polyuria (Weiss and Blaivas, 2000).

Treatment centers on the underlying cause, and a voiding diary may aid clinical decisions. Prostate hyperplasia or bladder dysfunction often receives first attention. Treating BPH may help, although BPH often does not result in true physical obstruction, and epidemiologic data have indicated that nocturia is common in men without prostatic obstruction. Thus, family physicians should consider the contribution of nocturnal polyuria. For example, patients with chronic heart failure and leg edema may benefit from fluid restriction and napping with leg elevation during the day. Treating obstructive sleep apnea helps alleviate the increased urine production resulting from increased atrial natriuretic peptide production. Behavioral interventions include avoiding excess nighttime alcohol or fluid intake and afternoon napping. Adjusting diuretic doses so they are given earlier in the evening should negate medication effects during sleep (Weiss and Blaivas, 2000).

Proteinuria

The kidneys normally excrete a small amount of protein daily, usually glycoproteins. Only very small amounts of globulins, light-chain proteins, or albumin are released. Functional proteinuria may result from physiologic changes in glomerular filtration, as occurs with exercise (Venkat, 2004). However, consistent albuminuria implies glomerular or tubular dysfunction.

The urine dipstick is the most convenient measurement, but a more accurate test is the Upr/UCr ratio, obtained by dividing the random urine sample protein level by the urine creatinine level (both in mg/dL). This ratio has proven correlation with 24-hour excretion rates (Ginsberg et al., 1983). Thus, random urine samples are the best way to identify and follow proteinuria, and 24-hour collections are usually not needed (Levey et al., 2003) (Table 40-3). However, results from those with low or high levels of muscle mass may not correlate as well with 24-hour measurements (Venkat, 2004).

Table 40-3 Proteinuria Values

Test	Protein Value
Dipstick	≥1+ if urine specific gravity ≤1.015 or ≥2+ if urine specific gravity >1.015
UPr/UCr^∗	Children >0.5 (age 6 mo to 2 yr) >0.25 (>2 yr) Adults: >0.2
24-hour urine assay	Children >4 mg/m²/hr >100 mg/m²/day Adults 30-300 mg/24 hr—microalbuminuria >300 mg/24 hr—albuminuria >3.5 g/24 hr—nephritic-range proteinuria

∗ Urine protein/creatinine ratio.

Proteinuria in Adults

Proteinuria is a marker of kidney disease in adults and may actually contribute to renal impairment. Patients with diabetes should be periodically tested for microalbuminuria. Others at risk for kidney disease, such as patients with hypertension, should also be tested.

Adults with proteinuria need their UPr/Ucr determined. Those with values outside the normal range should undergo an evaluation for CKD (see later). Patients with dipstick proteinuria but normal-range UPr/UCr values should be rechecked at periodic follow-up (Fig. 40-7).

Figure 40-7 Approach to proteinuria in adults.

(Modified from Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139:137-147, E148-E149. Redrawn from National Kidney Foundation/Kidney Disease Quality Initiative. See Web Resources.)

Proteinuria in Children and Adolescents

Most proteinuria in children is transient when followed up with weekly urine sample testing. Persistent proteinuria found in at least two of three weekly urine samples warrants further evaluation to identify those children who may have chronic renal disease.

Proteinuria in children may be classified as functional, isolated, or symptomatic. Functional proteinuria may occur with fever or exercise. Isolated proteinuria is defined by the absence of abnormal history, physical examination findings, symptoms, or other urinary abnormalities. The most common cause of this form is benign orthostatic proteinuria, defined by normal protein excretion overnight or in the supine position. The initial evaluation for isolated proteinuria involves obtaining a first-morning urine sample for protein and creatinine as well as a formal urinalysis for microscopy review (Hogg et al., 2000). The absence of morning proteinuria, as evidenced by normal UPr/UCr, supports the diagnosis of benign orthostatic proteinuria. A more accurate assessment is a split 24-hour urine collection for protein. Benign orthostatic proteinuria may be transient or fixed and in either case has an excellent prognosis (Springberg et al., 1982). In contrast, nonorthostatic isolated proteinuria with a duration of 1 year or longer may represent significant renal pathology (Trachtman et al., 1994). Thus, these patients need yearly or twice-yearly clinical follow-up with assessment of blood pressure, renal function, serum albumin, urine microscopy, and urine protein.

Pathologic proteinuria, whether isolated or symptomatic, occurs in the setting of a variety of glomerular and tubulointerstitial diseases (Box 40-5). Some children may present with the nephrotic syndrome (proteinuria, hypoalbuminemia, edema). Depending on the degree of proteinuria and the results of the initial laboratory evaluation, a renal biopsy may be indicated (Fig. 40-8).

Figure 40-8 Approach to the child with proteinuria. ANA, Antinuclear antibody; BUN, blood urea nitrogen; U/A, urinalysis; UPr:UCr, urine protein/urine creatinine.

Anatomic Disorders

Key Points

• Prenatally identified hydronephrosis may be caused by underlying urinary tract obstruction. These infants need close follow-up with ultrasound in the first week of life.

• Hydroceles in infants often resolve by age 2 years. Hydroceles in adults may have a secondary cause.

• Reassure patients with Peyronie’s disease that it is usually self-limited.

• Testicular torsion is a medical emergency. Torsion of the appendix testis is less severe and can be managed with supportive care.

• Undescended testes increase the risk for testicular cancer in the undescended as well as contralateral testicle.

Anatomic urinary tract disorders involve various congenital and acquired abnormalities, most notably of the external genitalia. Testicular disorders are seen more often than abnormalities of the penis, particularly undescended testes. Anatomic derangements of the bladder, ureter, and kidney are often only discovered incidentally or during an evaluation for UTIs, voiding problems, CKD, or pain possibly related to the urinary tract. For example, posterior urethral valves cause vesicoureteral reflux and may contribute to recurrent UTIs (see Urinary Tract Infections in Children).

Scrotal masses are frequently encountered in family medicine. Anatomic causes of scrotal masses are not limited to the urinary tract, and neoplastic and infectious causes are also in the differential diagnosis (Table 40-4). Scrotal or testicular pain, the so-called acute scrotum, implies a more urgent or emergent cause (e.g., testicular torsion). Because the history and physical examination may not be adequate to differentiate certain conditions (e.g., epididymo-orchitis from testicular torsion), adjunctive imaging such as ultrasound is often used.

Table 40-4 Selected Differential Diagnosis of Scrotal Masses with Physical Findings

Abnormality	Physical Finding
Epididymitis, orchitis	Tender mass
Hydrocele	Transilluminates
Inguinal hernia	Does not transilluminate
Testicular torsion	Pain and loss of cremasteric reflex
Torsion of the appendix testis	Blue dot sign
Trauma	Tender scrotum, edema, trauma history
Tumor	Solid mass
Spermatocele	Nontender cystic mass
Varicocele	Bag of worms appearance

Fetal Hydronephrosis

With the pervasive use of fetal ultrasound, hydronephrosis is more often diagnosed prenatally. A dilated renal collecting system is often the only indication of a number of congenital uropathies (Ismaili et al., 2004). Two processes cause hydronephrosis, reverse urine flow (vesicoureteral reflux, VUR) and impaired forward urine flow (obstruction). VUR occurs as an isolated entity or can be associated with a more complicated uropathy, such as bladder outlet obstruction with VUR. Obstructive uropathy may occur at different sites along the urinary tract, most often the ureteropelvic junction (UPJ).

Infants with fetal hydronephrosis need an ultrasound in the first week of life. If normal, a repeat ultrasound should be done in 2 to 4 weeks because of the possibility of a false-negative study in the low urine flow state characteristic of the newborn (Becker and Avner, 1995). Once the diagnosis is confirmed, evaluation includes a urinalysis, urine culture, basic metabolic panel (if bilateral), and a VCUG. If the VCUG is normal, a furosemide renogram is needed to determine the presence and degree of obstruction.

Hydrocele

Hydroceles are fluid accumulations in the tunica vaginalis and can be primary, resulting from a failure of the processus vaginalis to close during development, or secondary to epididymitis, orchitis, testicular torsion, trauma, or tumors (Brenner and Ojo, 2004). Hydroceles typically transilluminate, whereas inguinal hernias do not. In young children, management is supportive, with the hydrocele often resolving by age 2 years. Hydroceles presenting beyond 2 years or those associated with inguinal hernias require surgical consultation. Also, some hydroceles are communicating; that is, fluid can pass from the peritoneal cavity into the hydrocele. These may change in size with activity or during the day and need surgical evaluation (Schneck and Bellinger, 2007). Hydroceles arising de novo in adults often have a secondary cause and require evaluation (Dogra et al., 2003).

Hypospadias

Hypospadias, in which the urethra opens on the underside of the penis, is infrequently seen (Fig. 40-9). However, it is important that hypospadias is recognized early, preferably at the initial newborn examination. It can occur with or without chordee (curvature). Circumcision should be withheld and a urology consultation obtained. Hypospadias must be differentiated from ambiguous genitalia, which implies an intersex disorder. Epispadias, in which the meatus is located on the dorsal surface of the penis, is uncommon and is usually associated with extrophy of the bladder.

Figure 40-9 Hypospadias.

(From Borer JG, Retik AB. Hypospadias. In Wein AJ [ed]. Campbell-Walsh Urology, 9th ed, vol IV, Philadelphia, Elsevier, 2007.)

Labial Adhesions

Labial adhesions may be seen in young girls and may be partial or complete (fusion) and asymptomatic. However, labial adhesions can be associated with difficult or abnormal urination and may contribute to the development of UTIs. It is important to perform an external genital examination in the female with her first UTI (Fig. 40-10). Retrospective data and case series support topical estrogen cream to the affected areas, with gentle traction until the adhesions have separated (Bacon, 2002). In a recent study, however, labial separation occurred more quickly and with less recurrence in patients treated with betamethasone than in those treated with estrogen cream (Mayoglou et al., 2009).

Figure 40-10 Techniques for pediatric female genital examination.

(From Canning DA, Nguyen MT. Evaluation of the pediatric urologic patient. In Wein AJ [ed]. Campbell-Walsh Urology, 9th ed, vol 1. Philadelphia, Saunders, 2007.)

Peyronie’s Disease

Peyronie’s disease is characterized by formation of fibrosis in the tunica albuginea, with resulting penile deformity and pain. Symptoms include painful erection, physical penile deformity (often curvature), palpable penile plaque (fibrosis), and erectile dysfunction. Pain is typically transient, and most cases do not result in a deformity so severe that it impairs intercourse. Sexual history, counseling, and partner involvement are important, because Peyronie’s disease can be disruptive to a relationship. Most patients do not require any treatment beyond reassurance and counseling. Nonsurgical treatments are available (e.g., colchicine, intralesional verapamil), but supporting evidence is limited, and urologic consultation should be considered before exploring treatment. Steroid injection is best avoided. Surgery is an option in severe cases (Lewis and Munarriz, 2007).

Phimosis and Paraphimosis

Phimosis (inability to retract foreskin over glans) and paraphimosis (inability to return retracted foreskin over glans) are possible complications seen in the uncircumcised male (Fig. 40-11). About 50% of boys typically are able to retract their foreskin by 1 year of age and 80% by age 3 (Anderson and Anderson, 1999). Topical estrogen therapy has been reported as successful, but no randomized trials support its use (Yanagisawa et al., 2000). However, low-potency topical corticosteroid therapy combined with daily prepuce retraction appears effective for phimosis (Zampieri et al., 2005).