Imaging of Nephrolithiasis, Urinary Tract Infections, and Their Complications 29

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29

Imaging of Nephrolithiasis, Urinary Tract Infections,

and Their Complications

Julia R. Fielding and Raj S. Pruthi

Issues of Imaging of Nephrolithiasis

I. What is the appropriate test for suspicion of obstructing ureteral stone?

II. How should stones be followed after treatment?

III. Special case: the pregnant patient

Issues of Imaging of Urinary Tract Infections

IV. When is imaging required in the adult female with a urinary tract infection?

V. When is imaging required in the adult male with a urinary tract infection?

VI. When is imaging required in the child with a urinary tract infection?

VII. Special case: the neurogenic bladder

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Nephrolithiasis

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Non–contrast-enhanced helical computed tomography (CT) with 5-mm slice thickness is the test of choice for the patient with a sus- pected obstructing ureteral stone. In the absence of an available CT scanner, intravenous urography (IVU) or a combination of plain ﬁlm and ultrasonography (US) should be performed (moderate evidence).

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Plain ﬁlm should be used to follow the descent of stones along the ureter (moderate evidence).

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For the pregnant patient with a suspected renal stone, there is insuf- ﬁcient evidence to determine whether IVU or CT is the appropriate test when US is not diagnostic (insufﬁcient evidence).

Issues

Key Points

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Urinary Tract Infection

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Uncomplicated urinary tract infections (UTIs) in women, those without systemic signs or symptoms, do not require imaging (moderate evidence).

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Complicated UTIs in women, those that occur in combination with pregnancy or with symptoms that extend beyond 10 days and evolve to include fever, chills, and flank pain may require imaging to exclude renal abscess. It is unclear what clinical finding should prompt imaging and whether CT or US should be performed (insufficient evidence).

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Uncomplicated, isolated UTIs in men are uncommon. It is unclear when US or cystoscopy should be performed to exclude associated infection of the testis or epididymis and bladder cancer, respectively (insufﬁcient evidence).

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Because of the high likelihood of vesicoureteral reflux in children with UTIs, US and voiding cystourethrogram (VCUG) should be per- formed in children with a UTI (moderate evidence). At most acade- mic institutions in the United States, both US and VCUG are performed in boys and girls to exclude hydronephrosis, significant renal scars, and vesicoureteral reflux. Nuclear medicine cystogram may be substituted for VCUG; however, the currently used low-dose fluoroscopy units and higher spatial resolution make VCUG the more commonly used test.

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Patients with neurogenic bladders often have colonized the urine with pathogens. They may demonstrate few signs and symptoms when developing a complicated infection. It is unclear when and what type of imaging should be performed (insufﬁcient evidence).

Deﬁnition and Pathophysiology

Urolithiasis is the presence of stones within the urinary tract. Some patients with stones in the kidney live out their lives without incident. Many patients suffer from hematuria as the stones grow and move within the renal pelves and experience severe ﬂank pain when the stone(s) become lodged in the ureter. The most common renal stones in the United States are calcium based and are formed at the tip of the papilla when excess calcium is excreted into the urine. Less common stone varieties include those made of uric acid, struvite (ammonium/magnesium/phosphate), cystine, and xanthine.

Urinary tract infection occurs when urine stasis or an altered local resis- tance allows a bacterial pathogen to grow in the bladder. Patients complain of pain and usually have a urinalysis positive for the presence of white blood cells ( >100,000 organisms/1mL of urine) and bacterial organisms.

On occasion, the infectious process will ascend the ureter to involve the

intrarenal collecting system and renal cortex leading to pyelonephritis and

renal abscess. With certain organisms, such as tuberculosis, the bacteria

may be hematogenously seeded into the renal cortex and the infectious

process descends into the bladder.

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Epidemiology

Nephrolithiasis is a common problem of people living in temperate cli- mates. It is estimated that at least 5% of female and 12% of the male pop- ulation will have at least one episode of renal colic due to stone disease by the age of 70 years (1). In the U.S., the majority of stone disease cases are seen in the southeastern part of the country where diet, genetic predispo- sition, and certain occupations all may predispose to stone formation.

Nephrolithiasis is three times more common in males. The peak age for onset of renal stone disease is age 20 to 30, but stone formation is often a lifelong problem. Stone disease is rare in children.

Because of the short female urethra, it is much easier for bacteria to ascend into the bladder and therefore the vast preponderance of infections occur in females, particularly in children and women of childbearing age. During any given year, 11% of women report having had a UTI and more than half of all women has at least one such infection during their lifetime (2). After the age of 50, the number of infections in males and females is nearly equal, likely because the bladder outlet obstruction due to enlargement of the prostate in males leads to urine stasis.

Overall Cost to Society

Nephrolithiasis

Because nephrolithiasis is such a common process, the cumulative expense of imaging and clinical evaluations is quite high. In 1995 Clark et al. (3) estimated the annual cost of nephrolithiasis in the U.S. to be $1.23 billion, with the cost of outpatient evaluation at $278 million.

Again, because UTIs are extremely common, the cost of diagnosis and treatment is very high. Each year in the U.S., uncomplicated acute cystitis is responsible for 3.6 million ofﬁce visits, accounting for direct costs of $1.6 billion (4,5). The majority of patients are treated based on symptomatology and the results of a urine dipstick detecting the presence of nitrite of leuko- cyte esterase. Only a small percentage of these patients will undergo imaging as part of the workup, usually when structural abnormalities of the urinary tract are suspected or the patient fails treatment and develops signs of an upper tract infection.

Goals

The goal of imaging in the case of nephrolithiasis is twofold: ﬁrst, to deter-

mine the presence or absence of an obstructing ureteral stone; and second,

to contribute to treatment planning. In a patient who chronically forms

stones, imaging can also be used to follow renal stone burden. Imaging of

UTIs is undertaken to identify complications, speciﬁcally renal abscess. In

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children with UTIs, imaging is undertaken to exclude vesicoureteral reﬂux or renal scarring.

Methodology

A Medline search was performed using PubMed (National Library of Medicine, Bethesda, Maryland) for original research publications relating the diagnostic performance and accuracy for imaging of nephrolithiasis and UTIs. Clinical indicators of urinary tract disease including hematuria and ﬂank pain were also included. The search covered the period 1966 to March 2004. The search strategy employed different combinations of the following terms: (1) nephrolithiasis, (2) renal abscess, (3) UTI, and (4) radiog- raphy or imaging or computed tomography or intravenous urography or ultra- sound. This search was limited to the English language and human studies.

Using the Limits feature of PubMed and the above terms, the database was also searched speciﬁcally for clinical trials and meta-analyses. After review of the abstracts of the search results, we reviewed the entire text of rele- vant articles. In addition, additional pertinent publications were gleaned from a review of the reference lists.

I. What Is the Appropriate Test for Suspicion of Obstructing Ureteral Stone?

Summary of Evidence: Patients with clinical signs and symptoms of renal obstruction should undergo unenhanced helical CT of the abdomen and pelvis. The accuracy of this test has been shown to be higher than that of IVU and a combination of US and plain ﬁlm in level II (moderate evidence) studies. In addition, CT is quick to perform and interpret and does not require the administration of intravenous contrast medium. Findings on the CT scan can be used by the referring physician to determine treatment.

The drawbacks of the technique include cost and a relatively high dose of ionizing radiation (30–40 mSv). When CT is not available either IVU or a combination of plain ﬁlm and sonography may be used.

Supporting Evidence: For many years, IVU served as the test of choice for identification of obstructing ureteral stones. Following administration of intravenous contrast medium, delayed renal enhancement and excretion and a filling defect within the ureter were diagnostic findings. Because this test dates to the beginning of modern radiology, no prospective studies were performed to determine its accuracy. It was one of the few imaging tests available. In recent years, level II and III (moderate and limited evidence) studies have revealed an accuracy between 85% and 90% (6,7).

Unfortunately, the IVU, while accurate, often requires several hours to perform. In addition, the excretion of contrast into the dilated ureter tends to increase the patient’s already severe pain.

An alternative imaging scenario used commonly in Europe and the Far East combines a plain ﬁlm with an ultrasound examination. In a level II (moderate evidence) study comparing IVU and US in the identiﬁcation of ureteral stones, both modalities revealed 44 stones for a sensitivity of 64%

(8). More recently, unenhanced helical CT has become the preeminent test

for the diagnosis of renal colic in the U.S. In one of the largest published

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series, 210 patients with a confirmed diagnosis for flank pain underwent helical CT (9); 100 stones were recovered and 30 patients were found to have a source for pain beyond the urinary tract. There were three false neg- atives and four false positives for stone disease. These data yield a sensi- tivity of 97%, specificity of 96%, and accuracy of 97% for the diagnosis of obstructing ureteral stone. Of note, all stones are radiodense on CT with the exception of the urinary concretions formed by HIV patients taking protease inhibitors (10,11). Similar level II (moderate evidence) clinical studies have been performed by multiple groups with reported diagnostic accuracies ranging from 0.90 to 0.97, high interobserver reliability, and accurate depiction of stone size (12–15). Level II (moderate evidence) and level III (limited evidence) studies have also shown that stone size, shape, and location can be used to determine whether the stone will pass spon- taneously or is likely to require intervention (12,14). Stones that are 5 mm or less in size, of regular shape, are located in the distal two thirds of the ureter, and are present on one or two consecutive CT images 5 mm in thick- ness are most likely to pass spontaneously. These same studies also demon- strate an alternative source for flank pain in 15% of cases, including ovarian masses, appendicitis, and diverticulitis.

In a level II (moderate evidence) study comparing the combination of plain film and sonography with unenhanced CT in 181 patients with flank pain, CT was found to have a greater sensitivity (92% vs. 77%), negative predictive value (87% vs. 68%), and overall accuracy (94% vs. 83%) for identification of flank pain (16). Sourtzis et al. (6) reported similar results in a level III (limited evidence) study. When CT was compared with both IVU and sonography in 64 patients with recovered ureteral stones, sensi- tivities were 94%, 52%, and 19%, respectively (7).

II. How Should Stones Be Followed After Treatment?

Summary of Evidence: Because plain ﬁlm has the highest spatial resolution of any imaging modality, has good contrast sensitivity, is inexpensive, and delivers minimal radiation dose, it is at present the best way to follow the passage of a stone down the ureter over time.

Supporting Evidence: Level II and III (moderate and limited evidence) studies report that 60% of ureteral stones are visible on plain radiography (17,18). The low detection rate is likely due to overlying fecal material and the presence of some radiolucent stones, such as those composed of uric acid. Despite the relatively low detection rate, the use of repeat CT studies is likely not justiﬁed because of the cumulative radiation dose. An excep- tion may be made when following the results of lithotripsy and the detec- tion of small intrarenal stone fragments is of importance.

III. Special Case: The Pregnant Patient

Summary of Evidence: There is no compelling published evidence that IVU,

plain ﬁlm, and sonography or helical CT is the preferred test. In dealing

with the pregnant patient, fetal age and estimated radiation dose is of para-

mount importance. Pregnant patients routinely have right hydronephrosis

as the enlarging uterus turns slightly to the right, compressing the ureter.

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Computed tomography, the most accurate test, delivers approximately 16 mSv to the fetus. Two plain films obtained prior to and after administra- tion of intravenous contrast material deliver significantly less radiation but may be more difficult to interpret because of the overlying bony fetal parts and lateral deviation of the ureters. Dilation of the left ureter is thought to be less common, and the presence of left hydronephrosis with flank pain or hematuria is often enough clinical evidence for clinicians to begin treat- ment for stone disease.

IV. When Is Imaging Required in the Adult Female with a Urinary Tract Infection?

Summary of Evidence: Level II (moderate evidence) studies have revealed that IVU and US are of little value in males or females in the diagnosis of uncomplicated UTIs in which symptoms are conﬁned to the pelvis. In eval- uating recurrent UTIs, IVU may be of some use, particularly when a struc- tural abnormality of the urinary tract is suspected. There is no compelling evidence to determine when and how imaging of complicated UTIs should be performed. Complicated infections include those in which symptoms exceed 10 days, there is coexisting pregnancy, or symptoms evolve to include fever, chills, and ﬂank pain.

Supporting Evidence: In a study of 328 patients referred for imaging of the urinary tract performed by Lewis-Jones et al. (19) in the United Kingdom, the small subset with a positive urine culture and UTI (n = 33) had no abnormalities detected using either IVU or US. In a similar study per- formed by Little et al. (20), 200 consecutive patients were evaluated for a variety of complaints using IVU. In the subset of patients with recurrent UTI (n = 60) ﬁve patients (8%) had abnormalities including at least one case of carcinoma.

Urinary tract infection is the most common medical complication of pregnancy. Although pregnant women are at no greater risk for develop- ing an uncomplicated UTI, the compression of the bladder and uterus on the ureters is thought to lead to a higher incidence of reﬂux and pyelonephritis. For asymptomatic patients, treatment is usually antibiotics on an outpatient basis. The exception would be group B streptococcus, which usually requires inpatient intravenous antibiotic treatment because of its association with neonatal sepsis (21).

There is no compelling evidence to suggest when CT or US should be performed when a renal abscess is suspected. Opinion articles, level IV (insufﬁcient evidence), suggest that development of the appropriate clini- cal symptomatology despite treatment with antibiotics for 10 days should prompt imaging (22,23).

V. When Is Imaging Required in the Adult Male with a Urinary Tract Infection?

Summary of Evidence: There is no compelling evidence to indicate the role

of imaging in men with UTIs. Isolated UTIs are uncommon. Associated dis-

orders such as orchitis, epididymitis, and prostate enlargement can be

detected using US. It is possible that IVU and other contrast studies may

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be of use when stones or strictures of the ureter are suspected; however, there is no compelling evidence to support this (20).

VI. When is Imaging Required in the Child with a Urinary Tract Infection?

Summary of Evidence: During the ﬁrst 6 years of life, 8% of all girls and 2%

of all boys will have a symptomatic UTI (24). The diagnosis is conﬁrmed by the presence of bacterial organisms and white blood cells in the urine.

Diagnosis of pyelonephritis in small children who cannot communicate the location of pain remains a challenge. In a study of 919 girls undergoing a first imaging evaluation for UTI, Gelfand et al. (25) found that vesi- coureteral reflux was extremely uncommon in girls with a fever less than 38.5°C and greater than 10 years of age. Because UTIs can be associated with vesicoureteral reflux, the standard imaging algorithm consists of a voiding fluoroscopic or nuclear cystourethrogram and a renal US.

Supporting Evidence: Level II (moderate evidence) suggests that the current model of VCUG and US is appropriate. Kass et al. (26) examined 453 chil- dren with UTI using ultrasound and VCUG; 152 had normal renal US, of whom 101 also had normal VCUG. Vesicoureteral reflux was identified on VCUG in 23 (23%) of patients with normal sonography. Similar results were obtained by Goldman et al. (27), who studied 45 male neonates pre- senting with a first UTI. Both investigators suggested that US and VCUG should be routinely performed. Power Doppler may improve the sensitiv- ity of US. In a level II (moderate evidence) study of 19 children with pyelonephritis as diagnosed by clinical symptomatology and contrast- enhanced CT, power Doppler US identified 89% of cases (28). For patient convenience and because of the high loss to follow-up, most institutions perform a US and VCUG on the same day. Despite its lower radiation dose, nuclear cystogram has fallen out of favor in many areas of the U.S. because referring urologists require a clear assessment of ureteral anatomy and because new fluoroscopic equipment allows acquisition of 7 frames/sec, decreasing the amount of radiation received by the child by 75% compared with standard adult fluoroscopic technique.

Nuclear cystogram using technetium-99m (Tc-99m)-labeled dimercapto- succinic acid (DMSA) may be of particular value in girls, for whom ure- thral obstruction is not an issue or for follow-up of well-documented vesicoureteral reflux. Level II, moderate evidence, studies have shown an increase in the incidence (25–45%) of vesicoureteral reflux in siblings afflicted with the disease (29,30). For this reason, siblings under 10 years of age are often tested for reflux. Laboratory studies have shown that sen- sitivity of Tc-99m DMSA for diagnosis of pyelonephritis in a piglet model is approximately 90% (31,32). In a large retrospective level II (moderate evidence) study of inpatients and outpatients, Desphande and Jones (33) found renal scarring present on DMSA scans in 2% of the outpatients and 33% of inpatients, indicating that clinical findings of severe disease may be important in deciding on this imaging algorithm. There is no compelling evidence describing the imaging findings of CT or magnetic resonance imaging (MRI) in the diagnosis of pyelonephritis in adults or children.

Case series of CT scans often describe a striated nephrogram or diminished

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regions of uptake in the affected kidney. Magnetic resonance imaging, while avoiding patient radiation exposure, also lacks speciﬁc ﬁndings to indicate renal infection.

In a recent laboratory study, Majd et al. (34) compared Tc-99m single photon emission computed tomography (SPECT), helical CT, MRI, and power Doppler US for diagnosis of pyelonephritis in a piglet model. They found that Tc-99m SPECT, CT, and MRI were equally sensitive (87–92%) and specific (88–94%) for the diagnosis of pyelonephritis in 38 kidneys with 102 zones of disease. Power Doppler US performed at a lower level, with sensitivity of 57% and specificity of 82%. A level III (limited evidence) study performed on 37 children with fever-producing UTIs by Lonergan et al. (35) showed abnormality consisting of diminished perfusion in 38 kidneys using MRI. Determination of whether CT or MRI, with their respective drawbacks of radiation exposure and sedation, should be added to the routine diagnostic imaging algorithm of pyelonephritis awaits further scientific work.

VII. Special Case: The Neurogenic Bladder

Summary of Evidence: The neurogenic bladder fails to ﬁll and empty on a regular basis due to neuropathy. This may be due to a congenital anomaly such as myelomeningocele, trauma to the spinal cord or pelvic nerves, or ischemic neuropathy such as occurs in diabetes mellitus. Because of stasis, the urine of many of these patients is colonized by bacterial pathogens.

Asymptomatic UTIs are rarely treated. The difﬁculty arises when a com- plicated infection occurs. Because of the neuropathy, affected patients may not feel pain or distention of the bladder, and the immune system may not respond adequately leading to minimal symptoms.

Supporting Evidence: There is no compelling evidence to determine when such patients require imaging. Expert opinion (level IV, insufﬁcient evi- dence) suggests that patients who develop fevers undergo a urologic workup including Gram stain and culture of the urine to determine correct antibiotic usage. Failure to respond to antibiotics within a short period of time should prompt the use of US or CT (36,37).

Take-Home Table

Table 29.1. Diagnostic performance for CT, US, and IVU in detection of ureteral stones Lead author Year of publication N Stones+ Test Sensitivity Speciﬁcity

Catalano 2002 181 82 CT 0.92 0.96

US/plain 0.77 0.96

radiography

Boulay 1999 51 49 CT 1.0 0.96

Sheley 1999 180 87 CT 0.86 0.91

Sourtzis 1999 36 36 CT 1.0 1.0

IVU 0.66 1.0

Yilmaz 1998 97 64 CT 0.94 0.97

US 0.19 0.97

IVU 0.52 0.94

Smith 1996 210 100 CT 0.97 0.96

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Future Research

• Clinical prediction rules for development of pyelonephritis in pregnant women and those patients with a neurogenic bladder.

• Imaging diagnosis of pyelonephritis and its sequelae in children, par- ticularly using sonographic and MRI contrast agents.

Imaging Case Studies

Figure 29.1. Imaging case study for nephrolithiasis. Woman with right ﬂank pain underwent non–contrast-enhanced helical computed tomography (CT) that revealed a solitary right kidney with hydronephrosis (A) and an obstructing ureteral stone at the level of the mid-ureter (B) (arrow).

A

B

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Suggested Computed Tomography Imaging Protocols

Suspected obstructing ureteral stone: non–contrast-enhanced helical CT performed with 120 kV and the milliamperes (mA) approximately equal to the patient’s weight in pounds (to minimize radiation dose). Data acquisition thickness and table speed vary with scanner type; recon- structed images should be 5 mm in thickness. Viewing the images using cine mode facilitates stone detection.

Figure 29.2. Imaging case study for urinary tract infection (UTI). Woman with UTI unresponsive to antibiotics for days and with interval development of ﬂank pain and fever. An ovoid right renal mass is hypodense to the adjacent renal parenchyma on a contrast-enhanced CT scan (A) (arrow). There is rim enhancement of the developing renal abscess and stranding of the adjacent fat (B) (arrow).

A

B

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Suspected renal abscess: CT following administration of intravenous con- trast agent, 120 kV and mA approximately equal to the patient’s weight in pounds (to minimize radiation dose). Data acquisition thickness and table speed vary with scanner type; reconstructed images should be 5 to 10 mm in thickness.

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