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Renal and Urologic Disorders in Antiretroviral-Treated Patients with HIV Infection or AIDS: Spectrum of Cross-Sectional Imaging Findings
Renal and Urologic Disorders in AntiretroviralTreated Patients with HIV Infection or AIDS: Spectrum of Cross-Sectional Imaging Findings Massimo Tonolini, MD, Federica Villa, MD, Chiara Villa, MD, Sonia Ippolito, MD, and Roberto Bianco, MD
In the aging human immunodeficiency virus (HIV)-infected population with improved immune function under antiretroviral treatment, many different opportunistic disorders may be encountered, along with rare presentations or complicated forms of common diseases. Renal and urologic abnormalities observed in the setting of HIV infection or acquired immunodeficiency syndrome are reviewed with their imaging appearances, including renal dysfunction, urolithiasis, urinary tract infections and related complications, genitourinary tuberculosis, vascular lesions, urogenital tumors, and bladder abnormalities, with emphasis on characterization. In HIV-positive patients, early crosssectional imaging is warranted to detect uncommon disorders and complications, with the aim to preserve renal function.
Introduction Owing to the growing prevalence of human immunodeficiency virus (HIV) infection worldwide, and to the improved survival following the introduction of highly active antiretroviral therapy (HAART), clinicians and radiologists are increasingly confronted with aging HIV populations with complaints and abnormalities involving many organ systems, particularly the genitourinary tract.1-3 In HIV-positive patients, cross-sectional imaging is frequently crucial to investigate nonspecific symptoms and physical findings, because different or coexisting From the Department of Radiology, “Luigi Sacco” University Hospital, Milan, Italy. Reprint requests: Massimo Tonolini, MD, Department of Radiology, “Luigi Sacco” University Hospital, Via G.B. Grassi 74, 20157 Milan, Italy. E-mail: [email protected]. Curr Probl Diagn Radiol 2013;42:266–278. & 2013 Mosby, Inc. All rights reserved. 0363-0188/$36.00 + 0 http://dx.doi.org/10.1067/j.cpradiol.2013.04.001
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infectious and neoplastic opportunistic urogenital diseases may be encountered, along with severe complications of urinary tract infection (UTI), and with disorders resulting from side effects of HAART drugs.1,2,4,5 In this pictorial article, we present our experience, at a large teaching hospital specializing in infectious diseases, about multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) appearances of common and unusual renal and urologic disorders observed in patients with HIV infection or acquired immunodeficiency syndrome (AIDS) in the antiretroviral era, including causes of renal dysfunction, urolithiasis, UTI and related complications, hemorrhages, tumors, and urinary bladder lesions. Emphasis is placed on those findings that may be useful for differential diagnosis, together with pertinent clinical information.3
Renal Function Impairment Among HIV-positive patients, renal impairment ranging from minor or transient serum creatinine (S-Cr) level increase to end-stage renal failure is increasingly recognized as an important comorbidity. Renal dysfunction is common in untreated patients and patients with AIDS, and can be sometimes encountered even in the primary stages of HIV infection. Decreased (o60 mL/min) glomerular filtration rate (GFR) is reported in 3%-10% of HIV cohorts; however, subclinical renal damage suggested by excessive proteinuria is probably much more common.3,6,7 Mostly reported among African Americans rather than among Europeans because of a peculiar genetic susceptibility, HIV-associated nephropathy (HIVAN) is a progressive form of chronic kidney disease, histologically characterized by collapsing focal segmental
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glomerulosclerosis with microcystic tubular dilatation, podocyte proliferation, interstitial inflammation, and fibrosis, which results from direct viral infection of renal epithelial cells. Clinically, HIVAN manifests as proteinuria and rapid kidney function deterioration with increased S-Cr level, without edema and hypertension. Although in the past HIVAN represented the leading cause (nearly 50% of cases) of renal failure in HIV patients, its occurrence has been dramatically reduced by HAART and is almost limited to HAART-naïve patients.3,8,9 Definitive diagnosis of HIVAN requires renal biopsy. In HIVAN, ultrasound... ultrasound may show normal-sized or moderately enlarged kidneys with increased cortical echogenicity (which is superior that of the liver), pelvicalyceal urothelial thickening, and sometimes loss of the normal sinus fat (Fig 1 A and B). Despite MDCT and MRI findings are scarcely reported and unspecific, in our experience loss of corticomedullary differentiation may represent a useful
sign (Fig 1 C and D). In the appropriate clinical context, these bilateral appearances may support a clinical and laboratory diagnosis of HIVAN.3,8 Currently, renal dysfunction among HIV-infected patients is usually due to comorbidities (particularly diabetes), infections, drug toxicity, and noninfectious illnesses such as infiltrating tumors (mostly lymphoma). Tenofovir treatment is an independent risk factor for renal function damage, because GFR reduction related to treatment duration is observed in 50% of patients.3,10,11 Although the incidence of kidney failure is decreasing compared to the pre-HAART era, radiologists should be aware of the nonnegligible occurrence of renal impairment in relatively young patients with HIV or AIDS. Therefore, recent S-Cr measurement and GFR estimation using the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration formulas are strongly recommended prior to contrast-enhanced CT and MRI studies.6,12
FIG 1. HIV-associated nephropathy in 2 different patients. Ultrasound (A and B) in a 34-year-old female shows enlarged kidneys (15-cm craniocaudal diameter) with increased parenchymal echogenicity and urothelial thickening of the renal pelvis (arrowheads in B). In a 46-year-old female with markedly reduced renal function (25 mL/min estimated glomerular filtration rate), unenhanced T1- (C) and T2-weighted (D) MRI images show symmetric kidneys with size at upper normal limits, normal parenchymal thickness, and loss of the normal corticomedullary differentiation.
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Urolithiasis Since the early years of HAART, indinavir was recognized to cause nephrolithiasis in up to 20% of treated HIV patients. Indinavir stones, primarily composed of crystallized protease inhibitor drug, are hypoechoic, nonradiopaque on plain abdominal radiographs, and hypoattenuating at CT, so that their presence was suggested by hydronephrosis, or detected as filling defects in the opacified collecting systems during excretory urography.3 Currently, the prevalence of urolithiasis reported in HIV populations (11%) is not significantly different from that in control groups. Furthermore, indinavir lithiasis is becoming less prevalent compared with other types of stones, which result from metabolic abnormalities including decreased urinary excretion of citrate and magnesium, plus increased urinary concentrations of oxalate, calcium, and uric acid.2,13,14 Although ultrasound remains useful as a screening modality, low-dose unenhanced MDCT currently represents a well-established modality to investigate patients with suspected urolithiasis, providing quick, accurate localization of calculi and detection of secondary signs consistent with acute renal colic such as calyceal, pyelic, or ureteral dilatation, renal enlargement, and perinephric fat stranding (Fig 2).15,16
Urinary Tract Infections In the general population, most uncomplicated UTIs are confidently diagnosed on the basis of history, physical examination, and laboratory tests and do not require radiologic investigation, so that imaging is
reserved for patients that do not respond to treatment, with atypical clinical presentation, recurrent or unusually severe symptoms. Conversely, UTI represents a major source of morbidity and mortality in immunosuppressed patients, in whom rare opportunistic pathogens, such as Candida, Aspergillus, and Pneumocystis jirovecii, may be encountered. Furthermore, severe clinical presentation with signs and symptoms of sepsis and abscess collections are not unusual. Therefore, in high-risk patients such as those with HIV infection, early imaging is beneficial to define the extent of disease and identify complications.3,17 Acute pyelonephritis (APN) is a bacterial or fungal infection of the kidney parenchyma and collecting system, which is usually diagnosed clinically and confirmed by characteristic laboratory findings and urine cultures. In the general population, APN invariably results from ascending gram-negative UTI causing bacterial invasion of the kidney. Conversely, in HIV-positive patients, urine cultures revealing gram-negative organisms indicate an ascending infection, whereas gram-positive bacteria suggest a hematogenous route particularly in association with sepsis, endocarditis, or intravenous drug abuse.2,17-19 In APN, ultrasound may show renal enlargement, diffuse hyperechoic changes with decreased corticomedullary differentiation and focal, poorly marginated hypoechoic regions from interstitial edema (Fig 3A). However, sonography is relatively insensitive with abnormal findings in only 25% of patients, as it easily misses subtle changes of mild APN and provides limited assessment of perinephric fat and structures.16-20
FIG 2. Left-sided flank pain in a 45-year-old female investigated with urgent unenhanced MDCT. Axial (A) and coronal (B) images show mild pyelocalyceal dilatation (arrowhead), perinephric fat stranding, and Gerota fascia thickening (thin arrow) consistent with acute renal colic. An 8-mm calcific calculus is detected in the ipsilateral pelvic ureter (arrow in B).
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FIG 3. Acute bacterial pyelonephritis in a 28-year-old male. Ultrasound (A) shows increased cortical echogenicity of the right kidney and minimal perinephric fluid (arrowhead). After 48 hours, contrast-enhanced MDCT (B) shows characteristic “striated nephrogram” appearance (thin arrows), which becomes inconspicuous in the excretory phase (C).
Although MDCT has the disadvantages of radiation exposure and use of iodinated contrast, it currently represents the preferred imaging modality to investigate most urologic disorders and the most consistent modality to image APN. The nephrographic phase (acquired 60-100 seconds after contrast administration) provides the maximum detection and visualization of both infectious and solid renal abnormalities in their full extent. The MDCT hallmark of uncomplicated APN is represented by the “striated nephrogram” appearance (Fig 3B), including sharply defined wedge-shaped areas, linear bands, or streaky zones of reduced enhancement radiating from the papilla toward and perpendicularly to the cortical surface. These alternating bands of hypoattenuation represent areas of nonfunctioning parenchyma due to tubular obstruction by inflammatory debris, interstitial edema,
and vasospasm, with intervening normal tubules (Fig 3B).17-20 Untreated or progressive APN causes lesions to coalesce, with appearance of peripheral round or extensive hypoattenuating areas (Figs 4 and 5). The preliminary acquisition of unenhanced images may be helpful to detect coexisting lithiasis and secondary signs, such as unilateral focal or global enlargement of the kidney, subtle decreased parenchymal attenuation (best identified with narrow window settings), perinephric fat stranding, and thickening of Gerota fascia (Fig 4). Additionally, an excretory phase MDCT acquisition may be performed when urinary obstruction, delayed nephrogram, or filling defects in the collecting systems or hypoattenuation areas are observed in nephrographic images. In pyelographic phase images, the striated nephrogram is less
FIG 4. Acute bacterial pyelonephritis in a 45-year-old woman. Unenhanced acquisition (A) detects mildly increased attenuation of perinephric fat and Gerota fascia thickening (thin arrow) on the left side, without hydronephrosis and urolithiasis. In the nephrographic phase (detailed image in B), the ipsilateral kidney shows poor, inhomogeneous contrast enhancement with a “striated” appearance and some tiny nonenhancing fluid-like foci suggesting microabscesses (arrowheads).
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FIG 5. Renal abscesses in 2 different patients. In a 37-year-old female (A), the left kidney shows a large wedge-shaped perfusion defect, in which tiny subcapsular fluid-like foci are identified (arrows), allowing diagnosis of lobar pyelonephritis with microabscesses and differentiation from infarction and lymphoma. In a 67-year-old male with acute urinary infection (B), a larger mesorenal collection (n) with enhancing peripheral rim and perinephric extension (thin arrows) is seen.
conspicuous (Fig 3C); however, delayed enhancement of hypoattenuating areas may differentiate functional from damaged parenchyma.17-19,21,22 APN changes should be reported as unilateral or bilateral, focal or diffuse, with or without focal swelling, and renal enlargement. Multiple small, nonenhancing fluid-like collections within the affected areas indicate the development of microabscesses (Figs 4B and 5), which may suggest an underlying fungal infection caused by Candida or Aspergillus species, reflecting the presence of fungal spores, hyphae, and pseudohyphae.3 Furthermore, microabscesses represent a useful feature to differentiate APN from neoplastic renal lesions, together with a poorly defined interface between the affected area and surrounding parenchyma, associated perinephric stranding and fascial thickening, and appropriate clinical and laboratory data. The differential diagnosis of focal APN mostly includes renal infarction particularly during sepsis or endocarditis, tuberculosis (TB), and tumors such as lymphoma.19,22 Extrarenal accessory signs of APN include lung base effusions, periportal tracking, and gallbladder edema (Fig 6A), which should not be confused with cholecystitis. Mild-to-moderate pelvicalyceal or ureteral thickening with increased urothelial enhancement suggesting pyeloureteritis (Fig 6 A-C) is commonly observed, most conspicuous in the nephrographic phase, and sometimes the only perceptible feature of acute UTI. Extensive and circumferential involvement is helpful to differentiate from transitional cell carcinoma. Importantly, these changes resolve after treatment (Fig 6D).19,20,23
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Although with increased cost and limited availability, MRI represents an attractive, effective modality to diagnose and follow-up APN, particularly in pregnant or young patients for whom obviating radiation exposure is recommended. Furthermore, in patients with contraindications to intravenous contrast because of allergy or renal impairment, an unenhanced MRI acquisition is usually sufficient to confirm the diagnosis and stage APN. On MRI, the affected area shows low T1- and increased T2-signal intensity, decreased corticomedullary differentiation, sometimes enlarged global edematous renal, and associated perinephric fluid. Contrast enhancement patterns closely reflect those observed using MDCT. Abscess collections have variable and inhomogeneous, mostly T1-hypointense and T2-hyperintense signal intensity depending on the amount of protein, fluid, and cellular debris. Pitfalls of MRI include limited detection of lithiasis and gas-forming infections.17,19,24
Complications of Urinary Tract Infections Owing to immune suppression, HIV-infected patients are among those at high risk for complicated UTI. In untreated APN, tiny suppurative foci can coalesce, leading to the formation of variable-sized abscess collections, which may be sometimes identified sonographically as hypoanechoic cavities without internal color flow signals. By far superior for the assessment of APN complications, MDCT consistently depicts intrarenal or perirenal abscesses as round or geographic hypoattenuating collections, often surrounded by decreased parenchymal enhancement reflecting
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FIG 6. Accessory signs of acute pyelonephritis in 2 different patients. In a 32-year-old female (A), gallbladder edema (n) is seen in association with left kidney enlargement with inhomogeneous perfusion, Gerota fascia thickening (thin arrow), and enhancing pyelourothelial thickening (arrowhead). In a 42-year-old female with clinical presentation suggesting sepsis, bilaterally preserved, symmetric renal perfusion, right-sided pelvicalyceal (B), and ureteral (C) enhancing mural thickening are seen as the only feature suggesting urinary tract infection, which resolved after antibiotic treatment (D).
nonnecrotic infected kidney. A peripheral, thickened enhancing capsule is the hallmark of the mature abscess (Fig 5B).17-19,22 In the context of UTI, untreated hydronephrosis results in persistent infection and permanent renal impairment. Pyonephrosis, defined by an infected and obstructed collecting system, represents a urologic emergency requiring intervention to prevent life-threatening sepsis and rapid, permanent loss of function.17,18 However, pyonephrosis is difficult to distinguish from noninfected dilatation by imaging. Although ultrasound readily detects hydronephrosis, echogenic intraluminal debris or a urine-debris level is exceptionally recognized. A high level of suspicion should be maintained when nonspecific MDCT signs, including renal enlargement, striated or poorly functioning nephrogram, perinephric fat inflammatory changes, and pyeloureteral thickening, are observed together with collecting system dilatation (Fig 7). Sometimes, the obstructed cavities show higher-than-water (10-50 Hounsfield
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Units, HU) attenuation due to purulent urine.15,17,18 Additionally, MR urography sequences may be performed to visualize the obstructed collecting systems and may reveal fluid-fluid levels suggesting pyonephrosis.17,19,24 In chronic, long-standing or recurrent UTI, parenchymal destruction leads to renal “scarring” with cortical thinning and decrease in size, and pyelocalyceal and ureteral distortion, resulting in permanent functional impairment (Fig 8).17 The currently exceptional nephrocutaneous fistula (NCF) involves spontaneous development of an abnormal communication between the kidney and the skin, crossing through the retroperitoneum and abdominal wall structures along the lowest resistance points represented by the Petit triangle and the Grynfeld quadrilateral. Invariably associated with chronic UTI and long-standing nephrolithiasis, NCF is clinically suggested by local tenderness and swelling near the flank or lumbar region plus urine 271
FIG 7. Pyonephrosis in a 72-year-old male with septic shock. Initial postcontrast MDCT acquisition (A) shows hypoperfused left kidney with parenchymal thinning, perinephric fat stranding (n), and Gerota fascia thickening (thin arrow). The collecting system is overdistended despite ureteral stent, with enhancing thickened urothelium (arrowheads). After stent repositioning and infected urine drainage, follow-up MDCT (B) shows resolved pyonephrosis and improved renal thickness and enhancement.
leakage from a cutaneous orifice, and usually requires nephrectomy and fistulectomy to eradicate infection.25-27
In the past, most NCFs were investigated with retrograde pyelogram or fistulography or both, directly opacifying the abnormal track and the urinary
FIG 8. Chronic urinary infection in a 44-year-old male with permanent Foley catheter. Initially, MDCT shows severe urothelial thickening with moderate contrast enhancement in the right pelvicalyceal system and left ureter (arrowheads in A), and the urinary bladder including a focal wall calcification (B). Excretory urography (C) shows diffuse caliber and contour irregularities in the left ureter and bladder. Follow-up MDCT (D) shows absent hydronephrosis and appearance of severe “scarred” parenchymal thinning in the upper third of the left kidney.
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collecting system, but without cross-sectional information concerning the surrounding anatomical structures. Currently, MDCT provides additional information about size, parenchymal thickness, and function of the kidney involved, comprehensive characterization of the underlying lithiasis or infection or both, and visualization of the fistulous track (Fig 9).26,28
Genitourinary Tuberculosis In developed countries, TB is increasingly encountered, particularly in immigrants and immunosuppressed individuals such as HIV-positive patients. Resulting from hematogenous spread and subsequent reactivation of Mycobacterium tuberculosis, genitourinary TB is one of the commonest sites of extrapulmonary involvement, not unusually without active lung infection. Recognition of genitourinary TB is important because if untreated it leads to shrunken, nonfunctioning kidneys. However, it is usually a challenging clinical diagnosis because of subtle, unspecific symptoms and time-consuming, difficult cultures.29,30 Early renal involvement mimics APN with or without abscesses on MDCT, including poor nephrographic enhancement, unspecific hypoattenuating parenchymal regions, and sometimes abscess collections (Fig 10). Focal dilatation or distortion of the pelvicalyceal structures or both should suggest the possibility of kidney TB. Late renal TB changes are well known and more specific, including amorphous calcifications (present in almost 50% of patients), focal or diffuse cortical scars, parenchymal
FIG 10. Genitourinary involvement from disseminated tuberculosis in a 48-year-old female African immigrant. Panoramic body MDCT images show supraclavicular and mediastinal necrotic adenopathies (arrows in A), small hypovascular lesions in the liver and spleen (thin arrows), hypoperfused kidneys with a “striated nephrogram” appearance, and fluid-like collection (n) consistent with left-sided salpingitis (detailed image in B).
destruction, and cavities communicating with the collecting systems.21,29,30 Other intra-abdominal manifestations may be variably associated, particularly in the peritoneum, lymph nodes, liver, and spleen. Furthermore, the ureter, urinary bladder, adnexa (Fig 10), prostate, seminal vesicles, and epididymis are often involved.21,29,30
FIG 9. Nephrocutaneous fistulization in a 45-year-old female with long-standing history of nephrolithiasis. MDCT shows left-sided hydronephrosis with enhancing thickened urothelium (arrowheads) and calcific stones in the lumbar ureter, plus an enlarged lymph node (arrow in A). Additionally, the nephrocutaneous fistula (thin arrows in B) is identified as a fluid-like track with enhancing margins, which crosses posteroinferiorly from the kidney through the posterior pararenal space, quadratus lumborum muscle, and subcutaneous fat to the cutaneous orifice draining greenish pus.
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Vascular and Bleeding Lesions In the aging HAART-treated HIV population, accelerated atherosclerosis results from an increased prevalence of dyslipidemia, insulin resistance, fat redistribution, and hypertension, sometimes causing renal artery stenosis.3 Alternatively, a necrotizing vasculitis involving small-caliber vessels may be encountered in the setting of HIV. Sharing most clinical and arteriographic features with polyarteritis nodosa, HIV-related renal vasculitis may be occasionally complicated by spontaneous hemorrhage, clinically manifesting with abdominal or flank pain and tenderness, and variable signs of hemodynamic compromise.31-34 Prompt investigation with MDCT reliably assesses presence, size, topography (subcapsular, perirenal, or pararenal), mass effect, and sometimes the cause of renal hematoma. Attenuation values vary according to clot age, with acute hematomas being typically hyperattenuating (40-70 HU) (Fig 11). Furthermore, MDCT identifies important findings suggesting the need for endovascular or surgical treatment, such as contrast medium extravasation indicating active bleeding and capsule laceration.31-34
Neoplasms In the HAART era, long-standing HIV infection is increasingly associated with the development of tumors. Among these, non-Hodgkin lymphoma (NHL) is currently the most common cancer in HIV populations and represents an AIDS-defining malignancy. Histologically, NHL is usually high-grade,
poorly differentiated with disseminated or extranodal involvement.35,36 Because of its panoramic body exploration, MDCT is optimally suited for staging and follow-up of systemic diseases such as NHL. In the genitourinary tract, the kidney is the most commonly involved organ. Often involving both kidneys, NHL most usually appears as solitary (10%-20%) or multiple (60% of cases) circumscribed masses that may sometimes diffusely replace most of the renal parenchyma. Isoattenuating to slightly hyperattenuating on unenhanced MDCT images, NHL characteristically shows minimal contrast enhancement and is best depicted in the nephrographic phase as hypovascular compared with the renal parenchyma (Fig 12 A-D). The absence of clinical and imaging signs suggesting infection and the association of lymphadenopathies or other involved organs help in the differentiation of NHL from APN. Conversely, lesion heterogeneity and hypervascularization indicate a different diagnosis, such as renal cell carcinoma (Fig 12 E and F), or metastases (Fig 12G).36-38 Alternatively, in 25% of cases, the kidneys may get involved by direct extension of bulky soft-tissue lymphomatous retroperitoneal masses to the perinephric space, causing displacement or encasement of blood vessels (Fig 12H). Hydronephrosis may result from ureteral obstruction or compression by enlarged retroperitoneal lymph nodes.36 Currently, tumors such as NHL represent a not unusual cause underlying renal impairment in HIV patients.2,3,11,37 Heralded by firm, painless scrotal enlargement, NHL may involve the testis or epididymis or both,
FIG 11. Spontaneous perinephric hematoma in a 43-year-old male presenting with abdominal pain and hypotension. At admission, unenhanced MDCT due to renal failure (A) detects fairly large hyperattenuating (60-65 HU) blood collection (n) compressing the right kidney. Days later, with improved renal function, follow-up contrast-enhanced MDCT (B) shows stable subcapsular hematoma without enhancing tissue nor contrast extravasation indicating ongoing bleeding.
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FIG 12. Different renal neoplasms in HIV-positive patients. In a 45-year-old male with history of treated mediastinal non-Hodgkin lymphoma, axial (A) and coronal (B) nephrographic phase MDCT images show a hypovascular lobulated mass at the upper right renal pole, consistent with lymphoma relapse. In a 52-year-old woman (C and D), a large isoattenuating, poorly enhancing lymphomatous mass with tiny calcifications replaces most of the left kidney. In a 42-year-old woman, T2-(E) and contrast-enhanced T1-weighted (F) MRI images show a 3.5-cm left-sided intrarenal mass with inhomogeneous intensity with a moderate, eccentric enhancement. Surgical resection demonstrated papillary renal cell carcinoma. In a 49-year-old male (G) with known hepatocellular carcinoma (n), follow-up MDCT detects appearance of a vascularized, inhomogeneous left kidney mass with necrosis and calcification consistent with metastasis. Retroperitoneal soft-tissue lymphoma tissue encasing the left renal vessels is seen in a 68-year-old male (H).
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FIG 13. Non-Hodgkin lymphoma in a 35-year-old male presenting with firm, nontender right scrotal enlargement. Ultrasound shows roundish 2-cm hypoechoic intratesticular lesion on the right (A) and 2 tiny similar lesions on the left side (B). MRI (C) confirms lesion bilaterality with hypointense T2signal (thin arrow). Body CT staging (D) detects innumerable small-sized hypovascular foci in both kidneys.
mostly in association with nodal or other visceral sites.36,37 Ultrasound with high-frequency linear transducers depicts either homogeneously hypoechoic
enlarged testes in cases of diffuse infiltration or variable-sized hypoechoic focal lesions (Fig 13), sometimes with intralesional flow signals at color or power
FIG 14. Nephrogenic adenoma (NA) of the urinary bladder in a 36-year-old male with chronic urinary infections. Ultrasound (A) shows broadbased endoluminal vegetation along the right bladder wall. Unenhanced (B) and postcontrast (C) MDCT images depict diffuse mural thickening of the anterior and right bladder wall with solid density and moderate enhancement suggesting carcinoma, without involvement of the perivesical fat planes and adenopathies. Cystoscopy confirmed multiple vegetations with irregular mucosal surfaces. Histology on extensive transurethral endoscopic resection diagnosed NA. Follow-up MDCT urography 3 months later (D) visualized well-distended opacified bladder with disappeared abnormalities.
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Doppler. Although an intratesticular topography and bilaterality suggest malignancy, sometimes NHL may invade the epididymis, which then appears enlarged and hypoechoic, causing diagnostic uncertainty with epididymo-orchitis.38 As MRI is increasingly used as an ideal second-line modality for scrotal disorders, NHL may be appreciated as focal masses or diffusely infiltrating tissue, T2hypointense relative to normal testicular tissue (Fig 13).39,40
Urinary Bladder Abnormalities HIV infection is an independent risk factor for lower urinary tract complaints.41 In the setting of HIV, bladder urothelial and prostate cancers are increasingly encountered often at a younger age than that in noninfected people, with similar behavior and imaging features. Therefore, hematuria in HIV warrants a thorough evaluation, including urinary cytology, cystoscopy, and MDCT urography.42 The male HIV population is considered a high-risk group to receive strict clinical and prostate-specific antigen screening.43,44 In our experience, male HIV-infected patients may sometimes develop urinary bladder nephrogenic adenoma (NA), which closely mimics transitional cell carcinoma clinically, endoscopically, and at imaging. Despite its name, NA is a rare, nonmalignant urinary tract lesion, which is believed to represent a reactive metaplastic process of the urothelium following chronic mucosal irritation by recurrent infection, lithiasis, intravesical instrumentation, or surgery. By far most frequent in the bladder, NA is histologically characterized by proliferation of tubules, cysts, and papillae lined by low cuboidal to columnar epithelium. Although NA is not premalignant, surveillance is needed as a result of the high (63%) recurrence rate.45-47 Sonographically detected as endoluminal vegetations or sessile masses, NA lesions at MDCT appear as polypoid or plaque-like mural bladder lesions that moderately enhance in the nephrographic phase, and are seen as endoluminal vegetations against opacified urine in the excretory phase (Fig 14). Circumferential wall thickening may be observed with widespread lesions.45-47 Most usually diagnosed on endoscopic biopsy and resection specimens, NA may be suggested considering the younger age of most patients compared to that of urothelial cancer, the presence of typical risk factors such as immunosuppression and
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chronic urinary infection, history of previous endoscopic or surgical procedures, the absence of calcifications, and invasion of the perivesical fat planes.45,48
Conclusion In the aging HIV-infected population with improved immune function and survival under HAART, symptoms and signs related to the genitourinary tract involve a wide differential diagnosis. Therefore, cross-sectional imaging, most usually with MDCT, is required to provide a quick and reliable diagnosis, with the aim to reduce morbidity and preserve renal function. State-of-the-art MDCT and MRI technology, knowledge of pertinent clinical information, and familiarity with common and unusual infectious, neoplastic diseases allow radiologists to confidently detect and characterize renal and urologic abnormalities on abdominopelvic studies performed in HIV-infected patients.
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12. ESUR. European Society of Urogenital Radiology Guidelines on Contrast Media. 2012. Freely available at: http://www.esur. org/esur-guidelines/. 13. Raheem OA, Mirheydar HS, Palazzi K, et al. Prevalence of nephrolithiasis in human immunodeficiency virus infected patients on the highly active antiretroviral therapy. J Endourol 2012;26(8):1095-8. 14. Nadler RB, Rubenstein JN, Eggener SE, et al. The etiology of urolithiasis in HIV infected patients. J Urol 2003;169 (2):475-7. 15. Coppenrath EM, Mueller-Lisse UG. Multidetector CT of the kidney. Eur Radiol 2006;16(11):2603-11. 16. Rickards D. Non-traumatic abdominal emergencies: Imaging and intervention in acute urinary conditions. Eur Radiol 2002;12(10):2435-42. 17. Browne RF, Zwirewich C, Torreggiani WC. Imaging of urinary tract infection in the adult. Eur Radiol 2004;14 (suppl 3):E168-83. 18. Craig WD, Wagner BJ, Travis MD. Pyelonephritis: Radiologic-pathologic review. Radiographics 2008;28(1): 255-77 [quiz 327-8]. 19. Stunell H, Buckley O, Feeney J, et al. Imaging of acute pyelonephritis in the adult. Eur Radiol 2007;17(7):1820-8. 20. Zissin R, Osadchy A, Gayer G, et al. Extrarenal manifestations of severe acute pyelonephritis: CT findings in 21 cases. Emerg Radiol 2006;13(2):73-7. 21. Zissin R, Gayer G, Chowers M, et al. Computerized tomography findings of abdominal tuberculosis: Report of 19 cases. Isr Med Assoc J 2001;3(6):414-8. 22. Demertzis J, Menias CO. State of the art: Imaging of renal infections. Emerg Radiol 2007;14(1):13-22. 23. Wasnik AP, Elsayes KM, Kaza RK, et al. Multimodality imaging in ureteric and periureteric pathologic abnormalities. Am J Roentgenol 2011;197(6):W1083-92. 24. Martina MC, Campanino PP, Caraffo F, et al. Dynamic magnetic resonance imaging in acute pyelonephritis. Radiol Med 2010;115(2):287-300. 25. Antunes AA, Calado AA, Falcao E. Spontaneous nephrocutaneous fistula. Int Braz J Urol 2004;30(4):316-8. 26. Yu NC, Raman SS, Patel M, et al. Fistulas of the genitourinary tract: A radiologic review. Radiographics 2004;24 (5):1331-52. 27. Ansari MS, Singh I, Dogra PN. Spontaneous nephrocutaneous fistula—2 unusual case reports with review of literature. Int Urol Nephrol 2004;36(2):239-43. 28. Cooper SG, Richman AH, Tager MG. Nephrocutaneous fistula diagnosed by computed tomography. Urol Radiol 1989;11 (1):33-6. 29. Engin G, Acunas B, Acunas G, et al. Imaging of extrapulmonary tusberculosis. Radiographics 2000;20(2):471-88 [quiz 529-30, 32]. 30. Jung YY, Kim JK, Cho KS. Genitourinary tuberculosis: Comprehensive cross-sectional imaging. Am J Roentgenol 2005;184(1):143-50.
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31. Sanchez-Chapado M, Angulo Cuesta J, Guil Cid M, et al. Spontaneous perinephric hematoma in a case of AIDS. Arch Esp Urol 1995;48(10):1050-2. 32. Sagcan A, Tunc E, Keser G, et al. Spontaneous bilateral perirenal hematoma as a complication of polyarteritis nodosa in a patient with human immunodeficiency virus infection. Rheumatol Int 2002;21(6):239-42. 33. Ruiz Cerda JL, Osca Garcia JM, La Cruz Rodrigo J, et al. Spontaneous bilateral perirenal hematoma as a complication of nodose panarteritis in a patient with human immunodeficiency virus (HIV) infection. Actas Urol Esp 1993;17 (3):196-8. 34. Garcia Panos JM, Jimenez Leiro JF, Sampietro Crespo A, et al. Perirenal spontaneous hematoma in HIV(þ)-patient in pelvic kidney. Arch Esp Urol 2000;53(2):161-3. 35. Spencer SP, Power N, Reznek RH. Multidetector computed tomography of the acute abdomen in the immunocompromised host: A pictorial review. Curr Probl Diagn Radiol 2009;38(4):145-55. 36. Leite NP, Kased N, Hanna RF, et al. Cross-sectional imaging of extranodal involvement in abdominopelvic lymphoproliferative malignancies. Radiographics 2007;27(6):1613-34. 37. Lee WK, Lau EW, Duddalwar VA, et al. Abdominal manifestations of extranodal lymphoma: Spectrum of imaging findings. Am J Roentgenol 2008;191(1):198-206. 38. Halliday T, Baxter G. Lymphoma: Pictorial review. II. Eur Radiol 2003;13(6):1224-34. 39. Parenti GC, Feletti F, Brandini F, et al. Imaging of the scrotum: Role of MRI. Radiol Med 2009;114(3):414-24. 40. Kim W, Rosen MA, Langer JE, et al. MR imaging correlation in pathologic conditions of the scrotum. Radiographics 2007;27 (5):1239-53. 41. Breyer BN, Van den Eeden SK, Horberg MA, et al. HIV status is an independent risk factor for reporting lower urinary tract symptoms. J Urol 2011;185(5):1710-5. 42. Gaughan EM, Dezube BJ, Bower M, et al. HIV-associated bladder cancer: A case series evaluating difficulties in diagnosis and management. BMC Urol 2009;9:10. 43. Silberstein J, Downs T, Lakin C, et al. HIV and prostate cancer: A systematic review of the literature. Prostate Cancer Prostatic Dis 2009;12(1):6-12. 44. Quatan N, Nair S, Harrowes F, et al. Should HIV patients be considered a high risk group for the development of prostate cancer? Ann R Coll Surg Engl 2005;87(6):437-8. 45. Zougkas K, Kalafatis M, Kalafatis P. Nephrogenic adenoma of the urinary bladder. Int Urol Nephrol 2005;37(3):477-81. 46. Porcaro AB, DʼAmico A, Ficarra V, et al. Nephrogenic adenoma of the urinary bladder: Our experience and review of the literature. Urol Int 2001;66(3):152-5. 47. Wong-You-Cheong JJ, Woodward PJ, Manning MA, et al. From the archives of the AFIP: Inflammatory and nonneoplastic bladder masses: Radiologic-pathologic correlation. Radiographics 2006;26(6):1847-68. 48. Young RH. Tumor-like lesions of the urinary bladder. Mod Pathol 2009;22(suppl 2):S37-52.
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In the aging human immunodeficiency virus (HIV)-infected population with improved immune function under antiretroviral treatment, many different opportunistic disorders may be encountered, along with rare presentations or complicated forms of common diseases. Renal and urologic abnormalities observed in the setting of HIV infection or acquired immunodeficiency syndrome are reviewed with their imaging appearances, including renal dysfunction, urolithiasis, urinary tract infections and related complications, genitourinary tuberculosis, vascular lesions, urogenital tumors, and bladder abnormalities, with emphasis on characterization. In HIV-positive patients, early crosssectional imaging is warranted to detect uncommon disorders and complications, with the aim to preserve renal function.
Introduction Owing to the growing prevalence of human immunodeficiency virus (HIV) infection worldwide, and to the improved survival following the introduction of highly active antiretroviral therapy (HAART), clinicians and radiologists are increasingly confronted with aging HIV populations with complaints and abnormalities involving many organ systems, particularly the genitourinary tract.1-3 In HIV-positive patients, cross-sectional imaging is frequently crucial to investigate nonspecific symptoms and physical findings, because different or coexisting From the Department of Radiology, “Luigi Sacco” University Hospital, Milan, Italy. Reprint requests: Massimo Tonolini, MD, Department of Radiology, “Luigi Sacco” University Hospital, Via G.B. Grassi 74, 20157 Milan, Italy. E-mail: [email protected]. Curr Probl Diagn Radiol 2013;42:266–278. & 2013 Mosby, Inc. All rights reserved. 0363-0188/$36.00 + 0 http://dx.doi.org/10.1067/j.cpradiol.2013.04.001
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infectious and neoplastic opportunistic urogenital diseases may be encountered, along with severe complications of urinary tract infection (UTI), and with disorders resulting from side effects of HAART drugs.1,2,4,5 In this pictorial article, we present our experience, at a large teaching hospital specializing in infectious diseases, about multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) appearances of common and unusual renal and urologic disorders observed in patients with HIV infection or acquired immunodeficiency syndrome (AIDS) in the antiretroviral era, including causes of renal dysfunction, urolithiasis, UTI and related complications, hemorrhages, tumors, and urinary bladder lesions. Emphasis is placed on those findings that may be useful for differential diagnosis, together with pertinent clinical information.3
Renal Function Impairment Among HIV-positive patients, renal impairment ranging from minor or transient serum creatinine (S-Cr) level increase to end-stage renal failure is increasingly recognized as an important comorbidity. Renal dysfunction is common in untreated patients and patients with AIDS, and can be sometimes encountered even in the primary stages of HIV infection. Decreased (o60 mL/min) glomerular filtration rate (GFR) is reported in 3%-10% of HIV cohorts; however, subclinical renal damage suggested by excessive proteinuria is probably much more common.3,6,7 Mostly reported among African Americans rather than among Europeans because of a peculiar genetic susceptibility, HIV-associated nephropathy (HIVAN) is a progressive form of chronic kidney disease, histologically characterized by collapsing focal segmental
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glomerulosclerosis with microcystic tubular dilatation, podocyte proliferation, interstitial inflammation, and fibrosis, which results from direct viral infection of renal epithelial cells. Clinically, HIVAN manifests as proteinuria and rapid kidney function deterioration with increased S-Cr level, without edema and hypertension. Although in the past HIVAN represented the leading cause (nearly 50% of cases) of renal failure in HIV patients, its occurrence has been dramatically reduced by HAART and is almost limited to HAART-naïve patients.3,8,9 Definitive diagnosis of HIVAN requires renal biopsy. In HIVAN, ultrasound... ultrasound may show normal-sized or moderately enlarged kidneys with increased cortical echogenicity (which is superior that of the liver), pelvicalyceal urothelial thickening, and sometimes loss of the normal sinus fat (Fig 1 A and B). Despite MDCT and MRI findings are scarcely reported and unspecific, in our experience loss of corticomedullary differentiation may represent a useful
sign (Fig 1 C and D). In the appropriate clinical context, these bilateral appearances may support a clinical and laboratory diagnosis of HIVAN.3,8 Currently, renal dysfunction among HIV-infected patients is usually due to comorbidities (particularly diabetes), infections, drug toxicity, and noninfectious illnesses such as infiltrating tumors (mostly lymphoma). Tenofovir treatment is an independent risk factor for renal function damage, because GFR reduction related to treatment duration is observed in 50% of patients.3,10,11 Although the incidence of kidney failure is decreasing compared to the pre-HAART era, radiologists should be aware of the nonnegligible occurrence of renal impairment in relatively young patients with HIV or AIDS. Therefore, recent S-Cr measurement and GFR estimation using the Modification of Diet in Renal Disease (MDRD) or Chronic Kidney Disease Epidemiology Collaboration formulas are strongly recommended prior to contrast-enhanced CT and MRI studies.6,12
FIG 1. HIV-associated nephropathy in 2 different patients. Ultrasound (A and B) in a 34-year-old female shows enlarged kidneys (15-cm craniocaudal diameter) with increased parenchymal echogenicity and urothelial thickening of the renal pelvis (arrowheads in B). In a 46-year-old female with markedly reduced renal function (25 mL/min estimated glomerular filtration rate), unenhanced T1- (C) and T2-weighted (D) MRI images show symmetric kidneys with size at upper normal limits, normal parenchymal thickness, and loss of the normal corticomedullary differentiation.
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Urolithiasis Since the early years of HAART, indinavir was recognized to cause nephrolithiasis in up to 20% of treated HIV patients. Indinavir stones, primarily composed of crystallized protease inhibitor drug, are hypoechoic, nonradiopaque on plain abdominal radiographs, and hypoattenuating at CT, so that their presence was suggested by hydronephrosis, or detected as filling defects in the opacified collecting systems during excretory urography.3 Currently, the prevalence of urolithiasis reported in HIV populations (11%) is not significantly different from that in control groups. Furthermore, indinavir lithiasis is becoming less prevalent compared with other types of stones, which result from metabolic abnormalities including decreased urinary excretion of citrate and magnesium, plus increased urinary concentrations of oxalate, calcium, and uric acid.2,13,14 Although ultrasound remains useful as a screening modality, low-dose unenhanced MDCT currently represents a well-established modality to investigate patients with suspected urolithiasis, providing quick, accurate localization of calculi and detection of secondary signs consistent with acute renal colic such as calyceal, pyelic, or ureteral dilatation, renal enlargement, and perinephric fat stranding (Fig 2).15,16
Urinary Tract Infections In the general population, most uncomplicated UTIs are confidently diagnosed on the basis of history, physical examination, and laboratory tests and do not require radiologic investigation, so that imaging is
reserved for patients that do not respond to treatment, with atypical clinical presentation, recurrent or unusually severe symptoms. Conversely, UTI represents a major source of morbidity and mortality in immunosuppressed patients, in whom rare opportunistic pathogens, such as Candida, Aspergillus, and Pneumocystis jirovecii, may be encountered. Furthermore, severe clinical presentation with signs and symptoms of sepsis and abscess collections are not unusual. Therefore, in high-risk patients such as those with HIV infection, early imaging is beneficial to define the extent of disease and identify complications.3,17 Acute pyelonephritis (APN) is a bacterial or fungal infection of the kidney parenchyma and collecting system, which is usually diagnosed clinically and confirmed by characteristic laboratory findings and urine cultures. In the general population, APN invariably results from ascending gram-negative UTI causing bacterial invasion of the kidney. Conversely, in HIV-positive patients, urine cultures revealing gram-negative organisms indicate an ascending infection, whereas gram-positive bacteria suggest a hematogenous route particularly in association with sepsis, endocarditis, or intravenous drug abuse.2,17-19 In APN, ultrasound may show renal enlargement, diffuse hyperechoic changes with decreased corticomedullary differentiation and focal, poorly marginated hypoechoic regions from interstitial edema (Fig 3A). However, sonography is relatively insensitive with abnormal findings in only 25% of patients, as it easily misses subtle changes of mild APN and provides limited assessment of perinephric fat and structures.16-20
FIG 2. Left-sided flank pain in a 45-year-old female investigated with urgent unenhanced MDCT. Axial (A) and coronal (B) images show mild pyelocalyceal dilatation (arrowhead), perinephric fat stranding, and Gerota fascia thickening (thin arrow) consistent with acute renal colic. An 8-mm calcific calculus is detected in the ipsilateral pelvic ureter (arrow in B).
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FIG 3. Acute bacterial pyelonephritis in a 28-year-old male. Ultrasound (A) shows increased cortical echogenicity of the right kidney and minimal perinephric fluid (arrowhead). After 48 hours, contrast-enhanced MDCT (B) shows characteristic “striated nephrogram” appearance (thin arrows), which becomes inconspicuous in the excretory phase (C).
Although MDCT has the disadvantages of radiation exposure and use of iodinated contrast, it currently represents the preferred imaging modality to investigate most urologic disorders and the most consistent modality to image APN. The nephrographic phase (acquired 60-100 seconds after contrast administration) provides the maximum detection and visualization of both infectious and solid renal abnormalities in their full extent. The MDCT hallmark of uncomplicated APN is represented by the “striated nephrogram” appearance (Fig 3B), including sharply defined wedge-shaped areas, linear bands, or streaky zones of reduced enhancement radiating from the papilla toward and perpendicularly to the cortical surface. These alternating bands of hypoattenuation represent areas of nonfunctioning parenchyma due to tubular obstruction by inflammatory debris, interstitial edema,
and vasospasm, with intervening normal tubules (Fig 3B).17-20 Untreated or progressive APN causes lesions to coalesce, with appearance of peripheral round or extensive hypoattenuating areas (Figs 4 and 5). The preliminary acquisition of unenhanced images may be helpful to detect coexisting lithiasis and secondary signs, such as unilateral focal or global enlargement of the kidney, subtle decreased parenchymal attenuation (best identified with narrow window settings), perinephric fat stranding, and thickening of Gerota fascia (Fig 4). Additionally, an excretory phase MDCT acquisition may be performed when urinary obstruction, delayed nephrogram, or filling defects in the collecting systems or hypoattenuation areas are observed in nephrographic images. In pyelographic phase images, the striated nephrogram is less
FIG 4. Acute bacterial pyelonephritis in a 45-year-old woman. Unenhanced acquisition (A) detects mildly increased attenuation of perinephric fat and Gerota fascia thickening (thin arrow) on the left side, without hydronephrosis and urolithiasis. In the nephrographic phase (detailed image in B), the ipsilateral kidney shows poor, inhomogeneous contrast enhancement with a “striated” appearance and some tiny nonenhancing fluid-like foci suggesting microabscesses (arrowheads).
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FIG 5. Renal abscesses in 2 different patients. In a 37-year-old female (A), the left kidney shows a large wedge-shaped perfusion defect, in which tiny subcapsular fluid-like foci are identified (arrows), allowing diagnosis of lobar pyelonephritis with microabscesses and differentiation from infarction and lymphoma. In a 67-year-old male with acute urinary infection (B), a larger mesorenal collection (n) with enhancing peripheral rim and perinephric extension (thin arrows) is seen.
conspicuous (Fig 3C); however, delayed enhancement of hypoattenuating areas may differentiate functional from damaged parenchyma.17-19,21,22 APN changes should be reported as unilateral or bilateral, focal or diffuse, with or without focal swelling, and renal enlargement. Multiple small, nonenhancing fluid-like collections within the affected areas indicate the development of microabscesses (Figs 4B and 5), which may suggest an underlying fungal infection caused by Candida or Aspergillus species, reflecting the presence of fungal spores, hyphae, and pseudohyphae.3 Furthermore, microabscesses represent a useful feature to differentiate APN from neoplastic renal lesions, together with a poorly defined interface between the affected area and surrounding parenchyma, associated perinephric stranding and fascial thickening, and appropriate clinical and laboratory data. The differential diagnosis of focal APN mostly includes renal infarction particularly during sepsis or endocarditis, tuberculosis (TB), and tumors such as lymphoma.19,22 Extrarenal accessory signs of APN include lung base effusions, periportal tracking, and gallbladder edema (Fig 6A), which should not be confused with cholecystitis. Mild-to-moderate pelvicalyceal or ureteral thickening with increased urothelial enhancement suggesting pyeloureteritis (Fig 6 A-C) is commonly observed, most conspicuous in the nephrographic phase, and sometimes the only perceptible feature of acute UTI. Extensive and circumferential involvement is helpful to differentiate from transitional cell carcinoma. Importantly, these changes resolve after treatment (Fig 6D).19,20,23
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Although with increased cost and limited availability, MRI represents an attractive, effective modality to diagnose and follow-up APN, particularly in pregnant or young patients for whom obviating radiation exposure is recommended. Furthermore, in patients with contraindications to intravenous contrast because of allergy or renal impairment, an unenhanced MRI acquisition is usually sufficient to confirm the diagnosis and stage APN. On MRI, the affected area shows low T1- and increased T2-signal intensity, decreased corticomedullary differentiation, sometimes enlarged global edematous renal, and associated perinephric fluid. Contrast enhancement patterns closely reflect those observed using MDCT. Abscess collections have variable and inhomogeneous, mostly T1-hypointense and T2-hyperintense signal intensity depending on the amount of protein, fluid, and cellular debris. Pitfalls of MRI include limited detection of lithiasis and gas-forming infections.17,19,24
Complications of Urinary Tract Infections Owing to immune suppression, HIV-infected patients are among those at high risk for complicated UTI. In untreated APN, tiny suppurative foci can coalesce, leading to the formation of variable-sized abscess collections, which may be sometimes identified sonographically as hypoanechoic cavities without internal color flow signals. By far superior for the assessment of APN complications, MDCT consistently depicts intrarenal or perirenal abscesses as round or geographic hypoattenuating collections, often surrounded by decreased parenchymal enhancement reflecting
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FIG 6. Accessory signs of acute pyelonephritis in 2 different patients. In a 32-year-old female (A), gallbladder edema (n) is seen in association with left kidney enlargement with inhomogeneous perfusion, Gerota fascia thickening (thin arrow), and enhancing pyelourothelial thickening (arrowhead). In a 42-year-old female with clinical presentation suggesting sepsis, bilaterally preserved, symmetric renal perfusion, right-sided pelvicalyceal (B), and ureteral (C) enhancing mural thickening are seen as the only feature suggesting urinary tract infection, which resolved after antibiotic treatment (D).
nonnecrotic infected kidney. A peripheral, thickened enhancing capsule is the hallmark of the mature abscess (Fig 5B).17-19,22 In the context of UTI, untreated hydronephrosis results in persistent infection and permanent renal impairment. Pyonephrosis, defined by an infected and obstructed collecting system, represents a urologic emergency requiring intervention to prevent life-threatening sepsis and rapid, permanent loss of function.17,18 However, pyonephrosis is difficult to distinguish from noninfected dilatation by imaging. Although ultrasound readily detects hydronephrosis, echogenic intraluminal debris or a urine-debris level is exceptionally recognized. A high level of suspicion should be maintained when nonspecific MDCT signs, including renal enlargement, striated or poorly functioning nephrogram, perinephric fat inflammatory changes, and pyeloureteral thickening, are observed together with collecting system dilatation (Fig 7). Sometimes, the obstructed cavities show higher-than-water (10-50 Hounsfield
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Units, HU) attenuation due to purulent urine.15,17,18 Additionally, MR urography sequences may be performed to visualize the obstructed collecting systems and may reveal fluid-fluid levels suggesting pyonephrosis.17,19,24 In chronic, long-standing or recurrent UTI, parenchymal destruction leads to renal “scarring” with cortical thinning and decrease in size, and pyelocalyceal and ureteral distortion, resulting in permanent functional impairment (Fig 8).17 The currently exceptional nephrocutaneous fistula (NCF) involves spontaneous development of an abnormal communication between the kidney and the skin, crossing through the retroperitoneum and abdominal wall structures along the lowest resistance points represented by the Petit triangle and the Grynfeld quadrilateral. Invariably associated with chronic UTI and long-standing nephrolithiasis, NCF is clinically suggested by local tenderness and swelling near the flank or lumbar region plus urine 271
FIG 7. Pyonephrosis in a 72-year-old male with septic shock. Initial postcontrast MDCT acquisition (A) shows hypoperfused left kidney with parenchymal thinning, perinephric fat stranding (n), and Gerota fascia thickening (thin arrow). The collecting system is overdistended despite ureteral stent, with enhancing thickened urothelium (arrowheads). After stent repositioning and infected urine drainage, follow-up MDCT (B) shows resolved pyonephrosis and improved renal thickness and enhancement.
leakage from a cutaneous orifice, and usually requires nephrectomy and fistulectomy to eradicate infection.25-27
In the past, most NCFs were investigated with retrograde pyelogram or fistulography or both, directly opacifying the abnormal track and the urinary
FIG 8. Chronic urinary infection in a 44-year-old male with permanent Foley catheter. Initially, MDCT shows severe urothelial thickening with moderate contrast enhancement in the right pelvicalyceal system and left ureter (arrowheads in A), and the urinary bladder including a focal wall calcification (B). Excretory urography (C) shows diffuse caliber and contour irregularities in the left ureter and bladder. Follow-up MDCT (D) shows absent hydronephrosis and appearance of severe “scarred” parenchymal thinning in the upper third of the left kidney.
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collecting system, but without cross-sectional information concerning the surrounding anatomical structures. Currently, MDCT provides additional information about size, parenchymal thickness, and function of the kidney involved, comprehensive characterization of the underlying lithiasis or infection or both, and visualization of the fistulous track (Fig 9).26,28
Genitourinary Tuberculosis In developed countries, TB is increasingly encountered, particularly in immigrants and immunosuppressed individuals such as HIV-positive patients. Resulting from hematogenous spread and subsequent reactivation of Mycobacterium tuberculosis, genitourinary TB is one of the commonest sites of extrapulmonary involvement, not unusually without active lung infection. Recognition of genitourinary TB is important because if untreated it leads to shrunken, nonfunctioning kidneys. However, it is usually a challenging clinical diagnosis because of subtle, unspecific symptoms and time-consuming, difficult cultures.29,30 Early renal involvement mimics APN with or without abscesses on MDCT, including poor nephrographic enhancement, unspecific hypoattenuating parenchymal regions, and sometimes abscess collections (Fig 10). Focal dilatation or distortion of the pelvicalyceal structures or both should suggest the possibility of kidney TB. Late renal TB changes are well known and more specific, including amorphous calcifications (present in almost 50% of patients), focal or diffuse cortical scars, parenchymal
FIG 10. Genitourinary involvement from disseminated tuberculosis in a 48-year-old female African immigrant. Panoramic body MDCT images show supraclavicular and mediastinal necrotic adenopathies (arrows in A), small hypovascular lesions in the liver and spleen (thin arrows), hypoperfused kidneys with a “striated nephrogram” appearance, and fluid-like collection (n) consistent with left-sided salpingitis (detailed image in B).
destruction, and cavities communicating with the collecting systems.21,29,30 Other intra-abdominal manifestations may be variably associated, particularly in the peritoneum, lymph nodes, liver, and spleen. Furthermore, the ureter, urinary bladder, adnexa (Fig 10), prostate, seminal vesicles, and epididymis are often involved.21,29,30
FIG 9. Nephrocutaneous fistulization in a 45-year-old female with long-standing history of nephrolithiasis. MDCT shows left-sided hydronephrosis with enhancing thickened urothelium (arrowheads) and calcific stones in the lumbar ureter, plus an enlarged lymph node (arrow in A). Additionally, the nephrocutaneous fistula (thin arrows in B) is identified as a fluid-like track with enhancing margins, which crosses posteroinferiorly from the kidney through the posterior pararenal space, quadratus lumborum muscle, and subcutaneous fat to the cutaneous orifice draining greenish pus.
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Vascular and Bleeding Lesions In the aging HAART-treated HIV population, accelerated atherosclerosis results from an increased prevalence of dyslipidemia, insulin resistance, fat redistribution, and hypertension, sometimes causing renal artery stenosis.3 Alternatively, a necrotizing vasculitis involving small-caliber vessels may be encountered in the setting of HIV. Sharing most clinical and arteriographic features with polyarteritis nodosa, HIV-related renal vasculitis may be occasionally complicated by spontaneous hemorrhage, clinically manifesting with abdominal or flank pain and tenderness, and variable signs of hemodynamic compromise.31-34 Prompt investigation with MDCT reliably assesses presence, size, topography (subcapsular, perirenal, or pararenal), mass effect, and sometimes the cause of renal hematoma. Attenuation values vary according to clot age, with acute hematomas being typically hyperattenuating (40-70 HU) (Fig 11). Furthermore, MDCT identifies important findings suggesting the need for endovascular or surgical treatment, such as contrast medium extravasation indicating active bleeding and capsule laceration.31-34
Neoplasms In the HAART era, long-standing HIV infection is increasingly associated with the development of tumors. Among these, non-Hodgkin lymphoma (NHL) is currently the most common cancer in HIV populations and represents an AIDS-defining malignancy. Histologically, NHL is usually high-grade,
poorly differentiated with disseminated or extranodal involvement.35,36 Because of its panoramic body exploration, MDCT is optimally suited for staging and follow-up of systemic diseases such as NHL. In the genitourinary tract, the kidney is the most commonly involved organ. Often involving both kidneys, NHL most usually appears as solitary (10%-20%) or multiple (60% of cases) circumscribed masses that may sometimes diffusely replace most of the renal parenchyma. Isoattenuating to slightly hyperattenuating on unenhanced MDCT images, NHL characteristically shows minimal contrast enhancement and is best depicted in the nephrographic phase as hypovascular compared with the renal parenchyma (Fig 12 A-D). The absence of clinical and imaging signs suggesting infection and the association of lymphadenopathies or other involved organs help in the differentiation of NHL from APN. Conversely, lesion heterogeneity and hypervascularization indicate a different diagnosis, such as renal cell carcinoma (Fig 12 E and F), or metastases (Fig 12G).36-38 Alternatively, in 25% of cases, the kidneys may get involved by direct extension of bulky soft-tissue lymphomatous retroperitoneal masses to the perinephric space, causing displacement or encasement of blood vessels (Fig 12H). Hydronephrosis may result from ureteral obstruction or compression by enlarged retroperitoneal lymph nodes.36 Currently, tumors such as NHL represent a not unusual cause underlying renal impairment in HIV patients.2,3,11,37 Heralded by firm, painless scrotal enlargement, NHL may involve the testis or epididymis or both,
FIG 11. Spontaneous perinephric hematoma in a 43-year-old male presenting with abdominal pain and hypotension. At admission, unenhanced MDCT due to renal failure (A) detects fairly large hyperattenuating (60-65 HU) blood collection (n) compressing the right kidney. Days later, with improved renal function, follow-up contrast-enhanced MDCT (B) shows stable subcapsular hematoma without enhancing tissue nor contrast extravasation indicating ongoing bleeding.
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FIG 12. Different renal neoplasms in HIV-positive patients. In a 45-year-old male with history of treated mediastinal non-Hodgkin lymphoma, axial (A) and coronal (B) nephrographic phase MDCT images show a hypovascular lobulated mass at the upper right renal pole, consistent with lymphoma relapse. In a 52-year-old woman (C and D), a large isoattenuating, poorly enhancing lymphomatous mass with tiny calcifications replaces most of the left kidney. In a 42-year-old woman, T2-(E) and contrast-enhanced T1-weighted (F) MRI images show a 3.5-cm left-sided intrarenal mass with inhomogeneous intensity with a moderate, eccentric enhancement. Surgical resection demonstrated papillary renal cell carcinoma. In a 49-year-old male (G) with known hepatocellular carcinoma (n), follow-up MDCT detects appearance of a vascularized, inhomogeneous left kidney mass with necrosis and calcification consistent with metastasis. Retroperitoneal soft-tissue lymphoma tissue encasing the left renal vessels is seen in a 68-year-old male (H).
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FIG 13. Non-Hodgkin lymphoma in a 35-year-old male presenting with firm, nontender right scrotal enlargement. Ultrasound shows roundish 2-cm hypoechoic intratesticular lesion on the right (A) and 2 tiny similar lesions on the left side (B). MRI (C) confirms lesion bilaterality with hypointense T2signal (thin arrow). Body CT staging (D) detects innumerable small-sized hypovascular foci in both kidneys.
mostly in association with nodal or other visceral sites.36,37 Ultrasound with high-frequency linear transducers depicts either homogeneously hypoechoic
enlarged testes in cases of diffuse infiltration or variable-sized hypoechoic focal lesions (Fig 13), sometimes with intralesional flow signals at color or power
FIG 14. Nephrogenic adenoma (NA) of the urinary bladder in a 36-year-old male with chronic urinary infections. Ultrasound (A) shows broadbased endoluminal vegetation along the right bladder wall. Unenhanced (B) and postcontrast (C) MDCT images depict diffuse mural thickening of the anterior and right bladder wall with solid density and moderate enhancement suggesting carcinoma, without involvement of the perivesical fat planes and adenopathies. Cystoscopy confirmed multiple vegetations with irregular mucosal surfaces. Histology on extensive transurethral endoscopic resection diagnosed NA. Follow-up MDCT urography 3 months later (D) visualized well-distended opacified bladder with disappeared abnormalities.
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Doppler. Although an intratesticular topography and bilaterality suggest malignancy, sometimes NHL may invade the epididymis, which then appears enlarged and hypoechoic, causing diagnostic uncertainty with epididymo-orchitis.38 As MRI is increasingly used as an ideal second-line modality for scrotal disorders, NHL may be appreciated as focal masses or diffusely infiltrating tissue, T2hypointense relative to normal testicular tissue (Fig 13).39,40
Urinary Bladder Abnormalities HIV infection is an independent risk factor for lower urinary tract complaints.41 In the setting of HIV, bladder urothelial and prostate cancers are increasingly encountered often at a younger age than that in noninfected people, with similar behavior and imaging features. Therefore, hematuria in HIV warrants a thorough evaluation, including urinary cytology, cystoscopy, and MDCT urography.42 The male HIV population is considered a high-risk group to receive strict clinical and prostate-specific antigen screening.43,44 In our experience, male HIV-infected patients may sometimes develop urinary bladder nephrogenic adenoma (NA), which closely mimics transitional cell carcinoma clinically, endoscopically, and at imaging. Despite its name, NA is a rare, nonmalignant urinary tract lesion, which is believed to represent a reactive metaplastic process of the urothelium following chronic mucosal irritation by recurrent infection, lithiasis, intravesical instrumentation, or surgery. By far most frequent in the bladder, NA is histologically characterized by proliferation of tubules, cysts, and papillae lined by low cuboidal to columnar epithelium. Although NA is not premalignant, surveillance is needed as a result of the high (63%) recurrence rate.45-47 Sonographically detected as endoluminal vegetations or sessile masses, NA lesions at MDCT appear as polypoid or plaque-like mural bladder lesions that moderately enhance in the nephrographic phase, and are seen as endoluminal vegetations against opacified urine in the excretory phase (Fig 14). Circumferential wall thickening may be observed with widespread lesions.45-47 Most usually diagnosed on endoscopic biopsy and resection specimens, NA may be suggested considering the younger age of most patients compared to that of urothelial cancer, the presence of typical risk factors such as immunosuppression and
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chronic urinary infection, history of previous endoscopic or surgical procedures, the absence of calcifications, and invasion of the perivesical fat planes.45,48
Conclusion In the aging HIV-infected population with improved immune function and survival under HAART, symptoms and signs related to the genitourinary tract involve a wide differential diagnosis. Therefore, cross-sectional imaging, most usually with MDCT, is required to provide a quick and reliable diagnosis, with the aim to reduce morbidity and preserve renal function. State-of-the-art MDCT and MRI technology, knowledge of pertinent clinical information, and familiarity with common and unusual infectious, neoplastic diseases allow radiologists to confidently detect and characterize renal and urologic abnormalities on abdominopelvic studies performed in HIV-infected patients.
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