Primary Renal Candidiasis

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1 Case Series Primary Renal Candidiasis Importance of Imaging and Clinical History in Diagnosis and Management Barry J. Sadegi, MD, Bhargavi K. Patel, MD, Andrew C. Wilbur, MD, Anil Khosla, MD, Ejaz Shamim, MD Objective. Primary renal candidiasis is rare but increasing in incidence. The purpose of this series is to provide imaging and clinical findings for diagnosing candidiasis and to discuss imaging in the management of this disease. Methods. Ten sonographic, 8 retrograde pyelographic, 2 intravenous pyelographic, 2 antegrade pyelographic, and 2 computed tomographic examinations of 5 patients (4 adult male patients and 1 16-year-old female patient) were reviewed. Results. The clinical presentation was variable. Sonography showed renal pelvic wall thickening (n = 5), echogenic debris (n = 4), and fungus balls (n = 2). Papillary necrosis (n = 4), filling defects due to debris (n = 3), and fungus balls (n = 2) were seen on retrograde pyelography. Conclusions. Untreated candidiasis may progress to fungus ball or abscess formation. Sonography is commonly used as the initial imaging procedure. Retrograde and antegrade pyelography are used for biopsy, diagnosis, and treatment. Awareness of this condition and knowledgeable imaging evaluation can help detect and define the site, infection severity, and subsequent therapy. Key words: fungus ball; papillary necrosis; pyelography; renal candidiasis; sonography. Abbreviations CT, computed tomography; HIV, human immunodeficiency virus Received October 17, 2008, from the Department of Radiology, University of Illinois, Chicago, Illinois USA (B.J.S., B.K.P., A.C.W., E.S.); and Veterans Administration Medical Center, John Cochran Division, St Louis, Missouri USA (A.K.). Revision requested December 1, Revised manuscript accepted for publication December 22, Address correspondence and to Bhargavi K. Patel, MD, Department of Radiology, University of Illinois, 1740 W Taylor St, M-C 931, Room 2483, Chicago, IL USA. Primary renal candidiasis is an invasive infection of the upper urinary tract that involves the renal pelvis and medulla. Although rare, it is increasing in incidence. 1,2 The risk for developing primary renal candidiasis (primary Candida pyelonephritis) is increased after urinary tract surgery or when host defenses are compromised because of diabetes, prior antibiotics, malignancy, or immunosuppressive therapy. 1,3,4 Inconsistencies remain in the diagnosis of primary renal candidiasis because patients usually have variable clinical presentations or have no systemic signs and symptoms of infection, unlike patients with renal candidiasis secondary to disseminated infection. 1,3 5 Sonography is commonly performed as the initial imaging modality. Retrograde and antegrade pyelography are useful for biopsy, diagnosis, and therapy during the course of patient treatment. Because untreated disease may gradually progress to fungus ball (mycetoma) or abscess formation, appropriate imaging at the outset may result in 2009 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2009; 28: /09/$3.50

2 Primary Renal Candidiasis earlier treatment and prevent these complications and the resulting need for surgical or other invasive intervention. In the literature, the few published reports on primary renal candidiasis describe imaging findings in neonates, children, and female patients. This series describes the imaging features on sonography, retrograde pyelography, intravenous pyelography, antegrade pyelography, and computed tomography (CT) in 5 patients, including 4 adult men, with histologically proven primary urinary tract candidiasis. Materials and Methods Ten sonographic, 8 retrograde pyelographic, 2 intravenous pyelographic, 2 antegrade pyelographic, and 2 CT examinations of 5 patients (4 adult male patients and 1 16-year-old female patient) with the diagnosis of primary renal candidiasis during an approximately 5-year period were retrospectively reviewed (Table 1). Imaging findings were correlated with the clinical histories, laboratory values, blood culture results, urinalysis results, and urine culture results. Retrograde and antegrade pyelography were performed to allow urinary drainage, to extract debris and fungus balls for tissue biopsies and treatment, and to locally instill antifungal medications. Longitudinal and transverse sonography and color Doppler sonography were performed with 5- to 2-MHz transducers. Oblique and coronal views and magnification were used to better visualize findings. The diagnosis of primary renal candidiasis was confirmed by histopathologic analysis of specimens obtained from urinary debris or fungus balls within the renal pelvis during ureteroscopy in 4 patients and urinalysis in 1. Results Four adult male patients between 54 and 68 years underwent renal sonography and retrograde pyelography; 2 had intravenous excretory pyelography; 2 had antegrade pyelography and nephrostomy; and 2 had contrast-enhanced CT (Table 2). A 16-year-old female patient had renal sonography. Sonography showed pyelocalyceal uroepithelial wall thickening (n = 5; Figures 1, 2A, 3A, and 4), debris in the calyces and renal pelvis (n = 4; Figures 2B, 3B, and 5A), avascular fungus balls in the renal pelvis (n = 2; Figure 3, B and C), and loss of corticomedullary differentiation and papillitis (n = 4; Figures 2A, 3A, and 5A and Table 2). Color and power Doppler (n = 3) studies showed diffuse increased vascularity in the renal sinus and peripelvic region (n = 2; Figures 1 and 3B). Retrograde pyelography showed papillary necrosis (n = 4; Figure 2C), a filling defect in calyces and the renal pelvis (n = 4; Figure 2C), and a filling defect due to large fungus ball masses (n = 2; Table 2). Antegrade nephrostogaphy showed a molded filling defect due to fungus masses (n = 2; Figure 3D). Excretory pyelography showed papillary necrosis and a filling defect due to debris (n = 2; Figure 5B). Computed tomography showed Table 1. Clinical Features and Imaging Procedures in 5 Patients With Primary Renal Candidiasis Age, Clinical Imaging Procedures Case y/sex Risk Factors Presentations Urinalysis Performed 1 66/M DM, TURP, UTI, antibiotics Fever, flank pain C albicans Sonography, intravenous pyelography, retrograde pyelography 2 68/M DM, postoperative rectal CA, Fever, flank pain, C albicans, Sonography, CT, retrograde pyelography, pelvic abscess, pneumonia, hematuria, polyuria C tropicalis antegrade nephrostomy antibiotic 3 66/M DM, AK amputation, antibiotic Flank pain, hematuria, C albicans Sonography, CT, retrograde pyelography, renal failure antegrade nephrostomy 4 54/M HIV, diabetes mellitus Fever, hematuria, C albicans, Sonography, intravenous pyelography, renal failure C tropicalis retrograde pyelography 5 16/F Cerebral palsy, neurogenic Fever, flank pain C albicans Sonography bladder, frequent bladder catheterization AK indicates above-the-knee; CA, carcinoma; DM diabetes mellitus; F, female; M, male; TURP, transureteral resection of the prostate; and UTI, urinary tract infection. 508 J Ultrasound Med 2009; 28:

3 Sadegi et al renal medullary enhancement (n = 1) and caliectasis (n = 2; Figure 2, D and E, and Table 2). Clinically, risk factors for immunocompromise included diabetes mellitus (n = 4), antibiotic therapy (n = 3), human immunodeficiency virus (HIV; n = 1), colon carcinoma (n = 1), transurethral prostatectomy (n = 1), and a neurogenic urinary bladder (n = 1; Table 3). The clinical presentations included fever (n = 4), painless hematuria (n = 3), flank pain (n = 4), and acute renal failure (n = 2; Table 1). All patients had candiduria and negative blood culture results for Candida albicans. Specimens obtained from the renal pelvis in the 4 adult male patients (tissue and debris) showed inflammatory and necrotic material with C albicans in all 4 cases (Figure 3E) and Candida tropicalis in 2 cases. Discussion Asymptomatic Candida colonization of the urine is common and increasingly detected in hospitalized patients. Invasive primary urinary tract infection with Candida is rare unless host defenses are weakened. 1,5 In our series, associated medical and immunocompromise risks included diabetes mellitus, recent antibiotic therapy, HIV, colon cancer, and previous prostate surgery (Table 3). Primary renal candidiasis should be suspected in immunocompromised patients with persistent candiduria and abnormal renal imaging findings. The filamentous form of Candida can cause ascending invasive infection with a predilection for urinary drainage structures when the opportunity arises. 4 6 It is characterized by a subacute or chronic clinical course and the absence of fungemia. It is associated with a superficial mat of fungal growth (uroepithelial thrush) on pyelocalyceal mucosa, vasculitis, and the presence of pseudohyphae in the interstitium and results in invasive inflammatory changes. 6 This leads to sloughing of tissue and debris formation. Mycelia form clumps over inflammatory necrotic debris and form fungus balls. 3,4,6 Systemic candidiasis is an acute hematogenous infection, which predominantly involves the cortex and medulla with microabscess formation. 5,6 It is associated with involvement of other organs, commonly the heart, and fungemia is present. Table 2. Imaging Findings in 5 Patients With Primary Renal Candidiasis Imaging Finding Patients, n Sonography (n = 5) Wall thickening of renal pelvis and calyces 5 Caliectasis and echogenic debris 4 Loss of the corticomedullary differentiation, papillitis 4 Hydronephrosis 2 Fungus ball in renal pelvis 2 Retrograde pyelography (n = 4) Papillary necrosis, irregular calyces 4 Caliectasis 4 Calyceal filling defects 3 Hydronephrosis 2 Large molded filling defect in the renal pelvis 2 Intravenous pyelography (n = 2) Irregular calyces and blunting of the fornices 2 Caliectasis 2 Calyceal filling defects 2 Hydronephrosis 1 Large filling defect in the renal pelvis 1 Antegrade nephrostomy (n = 2) Caliectasis and papillary necrosis 2 Filling defect due to fungus ball 2 Hydronephrosis 2 Contrast-enhanced CT (n = 2) Caliectasis 2 Irregular medullary enhancement 1 Figure 1. Image from a 66-year-old male patient with diabetes mellitus and recent antibiotic therapy for a urinary tract infection after transurethral prostatectomy who had flank pain and fever. Transverse color Doppler sonography of the left kidney shows wall thickening and increased vascularity (long arrow) of the renal pelvis. A thin hyperechoic line at the mucosa (short arrow), a thick hypoechoic layer at the submucosa, and a thick hyperechoic muscularis outer layer (arrowhead) of the renal pelvis are shown. J Ultrasound Med 2009; 28:

Primary Renal Candidiasis A Renal abscess formation is more likely to occur than renal fungus ball formation.

and the presence of associated diseases and because affected patients usually lack systemic signs and symptoms.

Images from a 68-year-old male patient with diabetes mellitus, rectal carcinoma, and recent antibiotic therapy for urinary tract infection who had flank

A thin hyperechoic line at the mucosa (short arrow), a hypoechoic layer at the submucosa, and a deeper thick hyperechoic layer (arrowhead) are shown.

B, Longitudinal sonography of the right kidney shows echogenic debris (long arrow) within the mildly dilated and irregular calyces (short arrows).

4 Primary Renal Candidiasis A Renal abscess formation is more likely to occur than renal fungus ball formation. The clinical diagnosis of primary renal candidiasis or primary Candida pyelonephritis is usually difficult because of variable clinical presenting features and the presence of associated diseases and because affected patients usually lack systemic signs and symptoms. 7 9 The clinical presentations in our series were variable: 4 patients had fever; 4 flank pain or pain; 3 had painless B C Figure 2. Images from a 68-year-old male patient with diabetes mellitus, rectal carcinoma, and recent antibiotic therapy for urinary tract infection who had flank pain, fever, and acute renal failure. A, Transverse sonography of the right kidney shows layered wall thickening of the renal pelvis. A thin hyperechoic line at the mucosa (short arrow), a hypoechoic layer at the submucosa, and a deeper thick hyperechoic layer (arrowhead) are shown. Loss of corticomedullary differentiation and hypoechoic pyramids (long arrow) are visible. B, Longitudinal sonography of the right kidney shows echogenic debris (long arrow) within the mildly dilated and irregular calyces (short arrows). C, Right retrograde pyelography shows filling defects within the mildly dilated and irregular calyces (arrow) due to debris. Papillary necrosis (arrowheads) is shown. D, Contrast-enhanced CT shows enlargement of the right kidney and irregular medullary enhancement (arrows). E, Delayed phase CT shows bilateral caliactasis (arrows). D E 510 J Ultrasound Med 2009; 28:

Sadegi et al hematuria; and 2 had acute renal failure. C albicans was present in urine but not in blood cultures in all 5 patients.

Images from a 66-year-old male patient with diabetes mellitus, left above-the-knee amputation, and recent antibiotic therapy who had gross hematuria.

A thin hyperechoic line at the mucosa (arrow), a hypoechoic layer at the submucosa, and a thick outer hyperechoic layer (arrowhead) are shown.

echogenic mass (long arrows) of a fungal ball formation, resulting in dilatation of the renal pelvis (curved arrows) and a dilated calyx (arrowhead).

5 Sadegi et al hematuria; and 2 had acute renal failure. C albicans was present in urine but not in blood cultures in all 5 patients. Urine cultures are nonspecific because the number of fungal Figure 3. Images from a 66-year-old male patient with diabetes mellitus, left above-the-knee amputation, and recent antibiotic therapy who had gross hematuria. A, Sonography of the right kidney shows layered wall thickening of a dilated calyx. A thin hyperechoic line at the mucosa (arrow), a hypoechoic layer at the submucosa, and a thick outer hyperechoic layer (arrowhead) are shown. B, Transverse power Doppler sonography at the midrenal area shows an avascular echogenic fungus mass (arrow) in the renal pelvis and extending into the calyx, mild hydronephrosis, and vessels (arrowheads) in the peripelvic area. C, Transverse oblique sonography of the right kidney (short arrows) with magnification and focusing in the renal pelvis at 3 weeks follow-up for persistent symptoms shows a large obstructing echogenic mass (long arrows) of a fungal ball formation, resulting in dilatation of the renal pelvis (curved arrows) and a dilated calyx (arrowhead). D, Antegrade nephropyelography via percutaneous nephrostomy (long thin arrow) confirms the presence of a large, irregular filling defect due to a fungus ball (thick arrows) in the renal pelvis and calyces. E, Histopathologic examination of tissue obtained from a biopsy specimen of a fungus ball in the renal pelvis shows budding septated hyphae of C albicans (arrowheads) and necrotic and inflammatory material (arrows). colonies does not differentiate asymptomatic colonization from infection of the bladder or kidney. 1,8 Clinically, the problem that arises is whether substantial candiduria requiring treatment is present. 8,9 Safdar et al 10 reported candiduria in about 11% of renal transplant patients. 11 In high-risk patients who have candiduria but do not have invasive infection, there is reportedly no increased benefit from treating the candiduria alone Imaging allows assessment of the disease in patients with candiduria, and this assists in patient treatment and poten- C A D B E J Ultrasound Med 2009; 28:

Primary Renal Candidiasis Figure 4. Image from a 16-year-old female patient with cerebral palsy and a neurogenic urinary bladder who had fever and flank pain.

renal pelvis. tially can favorably change the course and outcome of this disease. 1,3,11 Limitations of our observation include the small size of the series.

correlate with our imaging findings. Because patients with primary renal candidiasis frequently have renal dysfunction, sonography is often the first radiologic examination performed.

6 Primary Renal Candidiasis Figure 4. Image from a 16-year-old female patient with cerebral palsy and a neurogenic urinary bladder who had fever and flank pain. Transverse sonography of the right kidney (arrowheads) shows wall thickening (curved arrow) and hyperechoic mucosa (short arrow) of the renal pelvis with echogenic debris (long arrow) within the renal pelvis. tially can favorably change the course and outcome of this disease. 1,3,11 Limitations of our observation include the small size of the series. Biopsy of tissue and urinalysis were performed for identification of Candida pseudohyphae for final diagnosis, although there was a lack of histopathologic or uroepithelial wall changes to directly correlate with our imaging findings. Because patients with primary renal candidiasis frequently have renal dysfunction, sonography is often the first radiologic examination performed. There is very little in the literature about the sonographic features of primary renal candidiasis in adult patients. 1,2,6 All sonographic studies in our series showed renal pelvic and calyceal wall thickening. A pattern of layered wall thickening consisting of an inner echogenic rim representing the damaged mucosa, a middle hypoechoic layer probably caused by submucosal edema and infiltration, and a thick hyper - echoic outer layer of muscularis may be seen. This pattern of layered wall thickening is a nonspecific sonographic finding and can be seen in other forms of pyelitis, although in our experience, it was noted in all cases. This feature of renal candidiasis may be due to invasive inflammation and vasculitis in Candida pyelonephritis. Color Doppler imaging showed increased vascularity in the peripelvic and renal sinus areas. Ureter and renal pelvis wall thickening are Figure 5. Images from a 54-year-old male patient with HIV and diabetes mellitus who had fever, hematuria, and acute renal failure. A, Longitudinal sonography of the right kidney shows mild dilatation of the renal pelvis (arrow) and calyces, papillary necrosis, irregular calyces (arrowhead), and loss of the corticomedullary region. B, Excretory intravenous pyelography shows the renal pelvis (arrow), papillary necrosis, and calyceal filling defects (arrowheads). A B 512 J Ultrasound Med 2009; 28:

7 Sadegi et al described as sonographic findings of ureteritis cystica, acute tuberculosis, and transitional cell neoplasms and should be clinically differentiated. 6 Loss of the sonographic corticomedullary region and papillitis, although nonspecific, were present in 3 patients. As the infection progresses, sloughed papilla from papillary necrosis serve as a nidus for fungal ball formation. 1,3,4 Echogenic debris within dilated calyces, the renal pelvis, and the ureter may be seen in early fungus ball formation. Once a fungus ball has formed, a mobile, molded echogenic, avascular mass without an acoustic shadow can be seen in the renal pelvis, often obstructing the collecting system and resulting in hydronephrosis. 3,4,12 Mobility of an intraluminal echogenic avascular mass, along with diffuse wall thickening of the renal pelvis, favors an inflammatory process over a neoplasm. Evidence of papillary necrosis, calyceal filling defects due to debris from sloughed papilla, large filling defects in the renal pelvis due to fungal ball formation, and caliectasis and hydropelvis are seen on excretory intravenous pyelography and retrograde and antegrade pyelography. 2,3,6 Papillary necrosis is most often seen with analgesic use, diabetes mellitus, and sickle cell disease. However, associated wall thickening seen on sonography and the presence of candiduria favors candidiasis. If filling defects due to debris from sloughed papilla or large filling defects in the renal pelvis due to fungal ball formation are identified, further evaluation with antegrade nephrostomy or retrograde pyelography is useful to facilitate biopsy for histopathologic diagnosis and to evaluate the extent of involvement. Antegrade nephrostomy and retrograde pyelography are frequently used to guide therapy with local amphotericin B irrigation, extraction of fungal balls, and placement of stents to relieve hydronephrosis. 1,4,8,9 Multiple debris extractions and irrigations are frequently needed after Candida has invaded into the interstitium. 1 8 A filling defect in the renal pelvis should be differentiated from a blood clot, nonopaque renal calculus, transitional cell neoplasm, or ureteritis cystica, especially in adult patients. 4,6 In our series, all adult patients had retrograde pyelography and tissue biopsies. Antegrade nephrostomies were used for urinary drainage in 2 cases with fungus balls in the renal pelvis. Table 3. Risk Factors in 5 Patients With Primary Renal Candidiasis Medical Risk Factor Although CT is typically not the first examination, it may be performed when a renal mass or renal calculus is suspected. Thickening of the renal pelvic wall and hydronephrosis may be seen on CT, although these findings were better appreciated on sonography in 2 of our cases. When there is invasion of the renal parenchyma, multiple small hypoattenuated foci representing microabscesses may be shown, as in 1 of our patients. In conclusion, primary renal candidiasis is a rare opportunistic infection with variable clinical presentations and imaging findings. Imaging findings due to renal pelvic wall uroepithelial thickening, urinary debris, papillary inflammation, and hydronephrosis are seen. Sonography is the commonly used initial imaging modality and is also used for follow-up of treatment. Although the sonographic findings are nonspecific, several suggestive findings are often present. Retrograde pyelography and antegrade nephrostomy are secondary imaging modalities used during management for obtaining tissue biopsy specimens for diagnosis, for extracting debris and fungal balls, and for local instillation of drugs and urinary drainage for obstruction in advanced disease. Familiarity with the imaging findings associated with Candida involvement of the renal collecting system plays an important role in the management of primary renal candidiasis and complications in the appropriate clinical setting. References 1. Lundstrom T, Sobel J. Nosocomial candiduria: a review. Clin Infect Dis 2001; 32: Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999; 27: Patients, n Diabetes mellitus 4 Recent antibiotic therapy 3 HIV 1 Colon carcinoma 1 Transurethral prostatectomy 1 Cerebral palsy, neurogenic urinary bladder 1 J Ultrasound Med 2009; 28:

8 Primary Renal Candidiasis 3. Gerle RD. Roentgenographic features of primary renal candidiasis: fungus ball of the renal pelvis and ureter. Am J Roentgenol Radium Ther Nucl Med 1973; 119: Dembner AG, Pfister AC. Fungal infections of the urinary tract: demonstration by antegrade pyelography and drainage by percutaneous nephrostomy. AJR Am J Roentgenol 1977; 129: Fisher JF, Chew WH, Shadomy S, Duma RJ, Mayhall CG, House WC. Urinary tract infections due to Candida albicans. Rev Infect Dis 1982; 4: Pollack HM. Clinical Urography: An Atlas and Textbook of Urological Imaging. Vol I. Philadelphia, PA: WB Saunders Co; Ang BS, Telenti A, King B, Steckelberg JM, Wilson WR. Candidemia from a urinary tract source: microbiological aspects and clinical significance. Clin Infect Dis 1993; 17: Kauffman CA, Vazquez JA, Sobel JD, et al. Prospective multicenter surveillance study of funguria in hospitalized patients. National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis 2000; 30: Sobel JD, Kauffman CA, McKinsey D et al. Candiduria: a randomized, double blind study of treatment with fluconazole and placebo. National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis 2000; 30: Safdar N, Slattery WR, Knasinski V, et al. Predictors and outcomes of candiduria in renal transplant recipients. Clin Infect Dis 2005; 40: Matignon M, Botterel F, Audard V, et al. Outcome of renal transplantation in eight patients with Candida sp. contamination of preservation fluid. Am J Transplant 2008; 8: Patel B, Khosla A, Chenoweth J. Bilateral fungal bezoars in the renal pelvis. Br J Urol 1996; 78: J Ultrasound Med 2009; 28:

Candida Bezoars with Urinary Tract Obstruction in Two Women without Immunocompromising Conditions

Case Study TheScientificWorldJOURNAL (2011) 11, 1168 1172 TSW Urology ISSN 1537-744X; DOI 10.1100/tsw.2011.119 Candida Bezoars with Urinary Tract Obstruction in Two Women without Immunocompromising Conditions