Renal Aspergilloma Due to Aspergillus flavus

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Renal Aspergilloma Due to Aspergillus flavus Zia u. Khan, G. Gopalakrishnan, Khaleel A1-Awadi, Ram K. Gupta, Sami A. Moussa, Tulsi D. Chugh, and Dimitrolos Krajci

From the Departments of Microbiology, Surgery, Nephrology, and Anatomy, Faculty of Medicine, Kuwait University, and Mubarak AI-Kabeer Hospital, Kuwait

Renal aspergillomas have been reported only rarely. We report a case of Aspergillusjlavus colonization of the renal pelvis and upper ureter of a patient with concomitant urinary schistosomiasis. The diagnosis was based on the demonstration of characteristic hyphal elements on direct microscopy and isolation ofthe fungus in culture. The patient was successfully treated with liposomal amphotericin B. This case emphasizes the importance of direct microscopic examination of urine specimens for prompt diagnosis of fungal infections of the urogenital system. Renal aspergilloma should be considered in the differential diagnosis of filling defects of the urinary tract, especially in patients who are immunocompromised.

urine cultures were negative. He was advised to undergo extracorporeal shock wave lithotripsy for treatment of his left renal calculus. The patient was readmitted 3 months later for evaluation of acute pain in the right flank, pyrexia, and abnormal renal func-

Case Report A 36-year-old Egyptian male was admitted to the urology unit of Mubarak Al-Kabeer Hospital (Kuwait) in January 1993 for evaluation of right flank pain and episodic pyrexia of 4 months' duration. He had undergone right lower ureteric surgery for removal of a calculus in 1983. Investigations showed abnormal renal function (blood urea nitrogen level, 11.4 mmol/L and serum creatinine level, 700 J.tmollL) and abnormal liver function (a low albumin level and elevated levels of aspartate aminotransferase [207 DIL] and alanine aminotransferase [108 DILl). Serology demonstrated antibodies to hepatitis C virus. Obstructive uropathy with urinary schistosomiasis and membranoproliferative glomerulonephritis, leading to chronic renal failure and liver dysfunction, were diagnosed. Ultrasonograms revealed two calculi in the left lower and midpolar renal calices. The right kidney was grossly hydronephrotic, and hydroureter, which subsequently proved to be due to a lower ureteric stricture at the site of the earlier surgery, was noted. The patient underwent retrograde dilatation of the stricture, and a double J stent was fixed in the right kidney. On discharge, his serum creatinine level was 380 J.tmol/L, and

Received 16 May 1994; revised 31 October 1994. Reprints or correspondence: Dr. Zia U. Khan, Department of Microbiology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Kuwait. Clinical Infectious Diseases 1995;21:210-2 © 1995 by The University of Chicago. All rights reserved. 1058-4838/95/2101-0032$02.00

Figure 1. Antegrade pyelogram via a percutaneous nephrostomy catheter showing filling defects in the pelvis and upper ureter of a patient with a renal aspergilloma.

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Aspergilli that commonly exist as saprobes have a low pathogenicity for humans unless immunity is impaired [1]. Renal aspergillosis most frequently occurs as a sequel to hematogenous dissemination of pulmonary disease [2]. Isolated aspergillar infection of the renal collecting system is rarely reported. We describe an unusual case of renal aspergilloma due to Aspergillus flavus in an Egyptian male with concomitant urinary schistosomiasis.

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Figure 2. A, scanning electron micrograph of a cross section of the patient's stent showing a mycelial mass (A. jiavus) in the lumen (magnification, X 80; bar, 10 j.tm). B, one of the hyphae is seen adhering to the stent wall (arrow) (magnification, X 850; bar, 10 j.tm).

tion (serum creatinine level, 880 JLmol/L). An ultrasonogram revealed right-sided hydronephrosis despite placement of the stent. A right percutaneous nephrostomy was performed, and antegrade examination showed multiple lucent filling defects in the midureter (figure I). Direct microscopic examination of the urine samples demonstrated numerous fragments of hyaline and septate hyphae, and cultures yielded pure growth of A. jfavus. The fungus was also growing on the stent and blocking its lumen (figure 2). Moreover, A. jfavus-specific precipitating antibodies were demonstrated with use of the Ouchterlony test. Because the patient's renal function continued to deteriorate (as evidenced by an increase in the level of serum creatinine

to 900 JLmollL), it was decided to treat him with liposomal amphotericin B (AmBisome; Vestar, Cambridge, England) irrigation at a dose of 50 mg/L via the percutaneous nephrostomy catheter. A total dose of 630 mg was administered over a period of 4 weeks, after which the cultures became negative. His double J stent was removed prior to the start of treatment out of concern that it would serve as a nidus for fungal colonization. There was no worsening of renal or liver function during the course of therapy. Following the treatment, his serum creatinine and serum albumin levels stabilized at 328 p,mol/L and 21 giL, respectively; the total protein concentration was 50 giL. A posttreatment nephrostogram showed no obstruction or lower

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ureteric stricture. The patient did well during 6 months of follow-up after his discharge from the hospital on 1 May 1993.

Discussion

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of local or systemic antifungal therapy when necessary. Amphotericin B is the most potent and reliable agent with known efficacy against aspergillosis that is currently available. However, its major drawbacks include severe toxicity, minimal urinary excretion, and poor tolerability. Now that liposomal amphotericin B is available, the problem of toxicity has been largely overcome [13]. Our patient was treated with liposomal amphotericin B irrigation, and no signs of nephrotoxicity or other side effects were observed. Experiences in treating renal aspergillosis with amphotericin B have been limited. The duration of therapy is usually related to the prognosis in each case and the rate of clearance of Aspergillus from the infected site. Acknowledgments

The authors thank: Mrs. R. Chandy for technical assistance and Mr. P. K. Akbar for typing the manuscript. References 1. Andriole VT. Infections with Aspergillus species. Clin Infect Dis 1993; 17(suppl 2):S481-6. 2. Wise GJ, Silver DA. Fungal infections of the genitourinary system. J Urol 1993; 149:1377-88. 3. Flechner SM, McAninch JW. Aspergillosis of the urinary tract: ascending route of infection and evolving patterns of disease. J Urol 1981; 125:598-601. 4. Comings DE, Thurbow BA, Callahan DH, Waldstein SS. Obstructing aspergillus cast of the renal pelvis. Arch Intern Med 1962; 110:25561. 5. Bibler MR, Gianis IT. Acute ureteral colic from an obstructing renal aspergilloma. Rev Infect Dis 1987; 9:790-4. 6. Godec CJ, Mielnick A, Hilfer 1. Primary renal aspergillosis. Urology 1989;34:152-4. 7. Halpern M, Szabo S, Hochberg E, et al. Renal aspergilloma: an unusual cause of infection in a patient with the acquired immunodeficiency syndrome. Am J Med 1992;92:437-40. 8. Baird RW, Lancaster DJ. Diabetic ketoacidosis and the presentation of renal aspergilloma. Am J Med 1988;85:453-4. 9. Picketty C, George F, Weiss L, Lavarde V, Hernigou A, Kazatchkine MD. Renal aspergilloma in AIDS. Am J Med 1993;94:557-8. 10. Davies SP, Webb WJS, Patou G, Murray WK, Denning DW. Renal aspergilloma. A case illustrating the problems of medical therapy. Nephrol Dial Transplant 1987;2:568-72. 11. Tronchin G, Bouchara ]P, Robert R, Senet IM. Adherence of Candida albicans germ tubes to plastic: ultrastructural and molecular studies of fibrillar adhesins. Infect Immun 1988;56:1987-93. 12. Annaix V, Bouchara J, Larcher G, Chabasse D, Tronchin G. Specific binding of human fibrinogen fragment D to Aspergillus fumigatus conidia. Infect Immun 1992;60:1747-55. 13. Schmitt H-J. New methods of delivery of amphotericin B. Clin Infect Dis 1993; 17(suppl 2):S501-6.

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According to Flechner and McAninch [3], aspergillus infection of the kidney can evolve through three disease patterns. The first pattern is commonly seen in immunocompromised patients with disseminated aspergillosis that results from hematogenous spread. The second pattern has been described among patients who had Aspergillus casts in the renal pelvis that were associated with obstructive uropathy; our patient's case appears to represent this pattern of progression. In the third pattern, the ascending urinary tract has been suggested as the possible route of infection involving the urethra, bladder, ureters, and kidneys. Since the first case of renal aspergilloma (which occurred in a 27-year-old female diabetic) was reported in 1962 [4], 15 additional cases of the disease have been described in the English-language literature [3, 5-10]. Our patient, who was colonized with Aspergillus in the renal pelvis and upper ureter, represents the 17th such case. He appeared to have been immunocompromised in view of his renal insufficiency, gross proteinuria, and abnormal liver function due to hepatitis C virus infection. Furthermore, his case was similar to a case described by Davies et al. [10]: both of the patients had undergone surgery for renal calculi, cultures yielded A. flavus, and both patients had antibodies to the fungus. However, concomitant urinary schistosomiasis was the unique feature of our case. In both instances, infection was most likely introduced during the surgical procedure. While contaminated suture material was the probable source of infection in the patient described by Davies et al. [10], implantation of a contaminated stent might have been the source in our case. Fungal colonization of the stent lumen, with hyphae adhering to its surface, was observed (figure 2). In this context, it would be interesting to determine whether fibrillar adhesins, which have been shown to mediate adherence of Candida albicans to plastic surfaces, are also expressed on Aspergillus hyphae [11]. Recent studies have demonstrated that Aspergillus conidia possess receptors for fibrinogen that could act as mediators of conidial adherence to host tissue [12]. It is possible that this mechanism also facilitates aspergillar colonization of fibrinogen-coated foreign bodies. The cornerstone of successful treatment of renal aspergillorna is evacuation of the obstructing mass and administration

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