0022-5347/78/1192-0275$02.00/0 The Journal of Urology Copyright © 1978 by The Williams & Wilkins Co.
Vol. 119, February Printed in U.SA.
DISSEMINATED MUCORMYCOSIS WITH RENAL INVOLVEMENT A. SCOTT DANSKY, CHARLES M. LYNNE
AND
VICTOR A. POLITANO
From the Department of Urology, University of Miami School of Medicine and Jackson Memorial Hospital, Miami, Florida
ABSTRACT
A case of fatal disseminated mucormycosis causing bilateral renal artery thrombosis, parenchymal and collecting system invasion and destruction, and extrinsic perirenal and proximal ureteral compression is presented. In addition to acute renal failure meningoencephalitis, cerebral hemorrhagic infarction and septic enterocolitis were contributing causes of death. Fungi of the various species of Mucorales are ubiquitous saprophytes and opportunistic pathogens that cause the most acutely fatal fungal disease known. 1 Healthy individuals are infected rarely and renal involvement is unusual. Prout and Goddard reported a case of mucormycosis in an alcoholic limited solely to the kidney, cured by nephrectomy and amphotericin B therapy. 2 Langston and associates described bilateral renal mucormycosis with no other organ involvement in a multiple trauma patient who died despite amphotericin B treatment. 3 Several cases of disseminated disease with minimal renal involvement have been documented at autopsy. 4-7 Herein we describe a case of acute renal failure caused by a combination of diminished renal blood flow, intrinsic renal disease and obstructive uropathy, secondary to disseminated mucormycosis.
with persistent anuria but it was terminated after 3¼ hours because of severe hypotension, despite volume expanders and dopamine pressor drip. The patient died the next day. Autopsy revealed multiple focal abscesses and hemorrhagic
CASE REPORT
L. J., a 39-year-old black man, was hospitalized with the chief complaint of right epigastric and flank pain, weakness, and dizziness 7 days in duration. Two weeks previously he had complained of dysuria and frequency with terminal gross hematuria without clots. There was no significant medical history and routine physical examination, complete blood count, SMA-6, creatinine, chest x-ray and electrocardiogram were normal 9 weeks before admission to the hospital. Blood pressure was 90 palpable, pulse 160, respirations 30, temperature 99.4F, blood urea nitrogen (BUN) 49 and creatinine 4.5. Urinalysis revealed 100 red and 20 to 30 white blood cells, and no bacteria per high power field. Excretory urography showed only faint opacification of the left collecting system and ureter at 24 hours and non-function on the right side. On the afternoon of admission to the hospital the patient became febrile and anuric, despite fluid challenges and diuretics. Retrograde pyelography was normal on the left side. There were multiple filling defects with distortion of the right renal pelvis and upper ureter with questionable extravasation under low pressure injection of contrast material (fig. 1). There was no evidence of distal obstruction. A triple renal scan revealed no flow to or function of the right kidney. The left kidney was small with diminished flow and severe tubular dysfunction with no evidence of excretion. Arteriography was suggested but deferred because of the rapidly deteriorating status of the patient and further risk of compromised renal function. Despite supportive therapy for fluid and electrolyte balance the BUN and creatinine continued to increase. An extracorporeal shunt was inserted and dialysis was done the second hospital day. A second run was initiated 4 days after hospitalization for fluid overload, metabolic acidosis and azotemia Accepted for publication September 16, 1977. Read at annual meeting of Southeastern Section, American Urological Association, New Orleans, Louisiana, March 27-31, 1977. 275
Fm. 1. Right retrograde pyelogram shows multiple filling defects of renal pelvis and upper ureter.
infarcts of the brain, lungs, liver, adrenals and intestines. Both kidneys were of normal size and encased in a 4 cm. thickness of indurated gray putty-like perirenal fat (fig. 2). Both renal arteries were thrombosed at their origins with no discernible lumen. Neither renal vein was involved. The cellular architecture of most glomeruli and tubules was destroyed. Both renal pelves contained abundant necrotic debris to the level of the mid ureter. There was bilateral extrinsic
276
DANSKY, LYNNE AND POLITANO
proximal ureteral compression from retroperitoneal necrotic tissue extending from the lower pole of both kidneys. Large, branching, non-septate hyphae were demonstrated easily in all involved microscopic specimens (fig. 3). DISCUSSION
Mucormycosis is a rapidly fatal fungal infectious pathogen that appears most commonly in the presence of impaired host resistance. Before 1943 it had never been described in this country and only 5 cases could be found in the literature. 8 The primary site of infection is generally the nasal mucosa with contiguous spread to the paranasal sinuses, orbit, cribriform plate, meninges and brain with aspiration, tracheobronchial invasion and arterial infiltration. Clinical forms include rhinocerebral, most commonly associated with uncontrolled diabetic acidosis;9-11 pulmonary, primarily a disease of patients with leukemia or lymphoma 12- 14 and gastrointestinal, encountered most frequently in malnourished individuals. 15• 16 The use of corticosteroids 17 and immunosuppressives 1s-2o has been implicated. The disseminated variety is far less common. Early diagnosis, metabolic regulation and prompt combined surgical and antifungal therapy have reduced mortality to approximately 50 per cent in recent series but disseminated disease remains fulminating and fatal within 8 to 10 days. 21- 23 In our patient no definite portal of entry was found. There
Fm. 2. Left kidney at autopsy reveals severe perirenal and periureteral encasement.
were no obvious conditions predisposing to infection. Antecedent renal failure was ruled out by normal renal function tests 9 weeks before hospitalization. It appears that hematogenous spread led to bilateral renal artery thrombosis with subsequent infiltration of the parenchyma. Capsular invasion with contamination of Gerota's fat with perirenal and periureteral dissection were significant components at autopsy to the etiology of the renal failure. Ante mortem diagnosis was not made, since the history, presenting symptoms and constellation of signs were so.atypical. It;is,doubtful whether, even with dialysis, amphotericin Band bilateral nephrectomy, this patient could have survived such disseminated disease. REFERENCES
1. Baker, R. D.: Resectable mycotic lesions and acutely fatal mycoses. J.A.M.A., 150: 1579, 1952. 2. Prout, G. R., Jr. and Goddard, A. R.: Renal mucormycosis. Survival after nephrectomy and amphotericin B therapy. New Engl. J. Med., 263: 1246, 1960. 3. Langston, C., Roberts, D. A., Porter, G. A. and Bennett, W. M.: Renal phycomycosis. J. Urol., 109: 941, 1973. 4. Zimmerman, L. E.: Fatal fungal infections complicating other diseases. Amer. J. Clin. Path., 25: 46, 1955. 5. Baker, R. D.: Pulmonary mucormycosis. Amer. J. Path., 32: 287, 1956. 6. Straatsma, B. R., Zimmerman, L. E. and Gass, J. D.: Phycomycosis. A clinicopathological study of fifty-one cases. Lab. Invest., 11: 963, 1962. 7. Nishimura, K., Ogata, T. and Kiyota, S.: An autopsy case of mucormycosis with acute renal failure. J. Kumamoto Med. Soc., 44: 345, 1970. 8. Gregory, J.E., Golden, A. and Haymaker, W.: Mucormycosis of the central nervous system. Johns Hopkins Hosp. Bull., 73: 405, 1943. 9. Abramson, E., Wilson, D. and Arky, R. A.: Rhinocerebral phycomycosis in association with diabetic ketoacidosis. Report of two cases and a review of clinical and experimental experience with amphotericin B therapy. Ann. Intern. Med., 66: 735, 1967. 10. Price, D. L., Wolpaw, E. R. and Richardson, E. P.: Intracranial phycomycosis: a clinicopathological and radiological study. J. Neurol. Sci., 14: 359, 1971. 11. Deshpande, D. H. and Desai, A. P.: Cerebral phycomycosis in cases ofrenal failure. Neurol. India, 24: 20, 1976. 12. Meyer, R. D., Rosen, P. and Armstrong, D.: Phycomycosis complicating leukemia and lymphoma. Ann. Intern. Med., 77: 871, 1972. 13. Utz, J. P.: Pulmonary infection due to opportunistic fungi. Brit. J. Psychiat., 116: 427, 1970. 14. Blank, N., Castellino, R. A. and Shah, V.: Radiographic aspects of pulmonary infection in patients with altered immunity. Ra-
,I
r
Fm. 3. Hematoxylin and eosin stain of left kidney microabscess shows typical large non-septate hyphae of mucormycosis
DISSEMINATED MUCORMYCOSIS WITH RENAL INVOLVEMENT
diol. Clin. N. Amer., 11: 175, 1973. Lawson, H. H. and Schmaman, A.: Gastric phycomycosis. Brit. J. Surg., 61: 743, 1974. Madhaven, M. and Reddy, D. J.: Mucormycosis of intestine. Indian J. Path. Bact., 12: 46, 1969. Baker, R. D.: Mucormycosis-a new disease? J.A.M.A., 163: 805, 1957. Low, A. I., Tulloch, A.G. S. and England, E. J.: Phycomycosis of the kidney associated with a transient immune defect and treated with chlortrimazole. J. Urol., 111: 732, 1974. Gallis, H. A., Berman, R. A., Cate, T. R., Hamilton, J. D.,
20.
21. 22. 23.
277
Gunnells, J.C. and Steckel, D. L.: Fungal infections following renal transplantation. Arch. Intern. Med., 135: 1163, 1975. Hammer, G. S., Bottone, E. J. and Hirschman, S. Z.: Mucormycosis in a transplant recipient. Amer. J. Clin. Path., 64: 389, 1975. Ripon, J. W.: Medical Mycology. Philadelphia: W. B. Saunders Co., chapt. 21, pp. 430-447, 1974. Case records of the Massachusetts General Hospital. Case 481968. New Engl. J. Med., 279: 1220, 1968. Neame, P. and Rayner, D.: Mucormycosis: a report of twentytwo cases. Arch. Path., 70: 261, 1960.
Vol. 119, February Printed in U.SA.
DISSEMINATED MUCORMYCOSIS WITH RENAL INVOLVEMENT A. SCOTT DANSKY, CHARLES M. LYNNE
AND
VICTOR A. POLITANO
From the Department of Urology, University of Miami School of Medicine and Jackson Memorial Hospital, Miami, Florida
ABSTRACT
A case of fatal disseminated mucormycosis causing bilateral renal artery thrombosis, parenchymal and collecting system invasion and destruction, and extrinsic perirenal and proximal ureteral compression is presented. In addition to acute renal failure meningoencephalitis, cerebral hemorrhagic infarction and septic enterocolitis were contributing causes of death. Fungi of the various species of Mucorales are ubiquitous saprophytes and opportunistic pathogens that cause the most acutely fatal fungal disease known. 1 Healthy individuals are infected rarely and renal involvement is unusual. Prout and Goddard reported a case of mucormycosis in an alcoholic limited solely to the kidney, cured by nephrectomy and amphotericin B therapy. 2 Langston and associates described bilateral renal mucormycosis with no other organ involvement in a multiple trauma patient who died despite amphotericin B treatment. 3 Several cases of disseminated disease with minimal renal involvement have been documented at autopsy. 4-7 Herein we describe a case of acute renal failure caused by a combination of diminished renal blood flow, intrinsic renal disease and obstructive uropathy, secondary to disseminated mucormycosis.
with persistent anuria but it was terminated after 3¼ hours because of severe hypotension, despite volume expanders and dopamine pressor drip. The patient died the next day. Autopsy revealed multiple focal abscesses and hemorrhagic
CASE REPORT
L. J., a 39-year-old black man, was hospitalized with the chief complaint of right epigastric and flank pain, weakness, and dizziness 7 days in duration. Two weeks previously he had complained of dysuria and frequency with terminal gross hematuria without clots. There was no significant medical history and routine physical examination, complete blood count, SMA-6, creatinine, chest x-ray and electrocardiogram were normal 9 weeks before admission to the hospital. Blood pressure was 90 palpable, pulse 160, respirations 30, temperature 99.4F, blood urea nitrogen (BUN) 49 and creatinine 4.5. Urinalysis revealed 100 red and 20 to 30 white blood cells, and no bacteria per high power field. Excretory urography showed only faint opacification of the left collecting system and ureter at 24 hours and non-function on the right side. On the afternoon of admission to the hospital the patient became febrile and anuric, despite fluid challenges and diuretics. Retrograde pyelography was normal on the left side. There were multiple filling defects with distortion of the right renal pelvis and upper ureter with questionable extravasation under low pressure injection of contrast material (fig. 1). There was no evidence of distal obstruction. A triple renal scan revealed no flow to or function of the right kidney. The left kidney was small with diminished flow and severe tubular dysfunction with no evidence of excretion. Arteriography was suggested but deferred because of the rapidly deteriorating status of the patient and further risk of compromised renal function. Despite supportive therapy for fluid and electrolyte balance the BUN and creatinine continued to increase. An extracorporeal shunt was inserted and dialysis was done the second hospital day. A second run was initiated 4 days after hospitalization for fluid overload, metabolic acidosis and azotemia Accepted for publication September 16, 1977. Read at annual meeting of Southeastern Section, American Urological Association, New Orleans, Louisiana, March 27-31, 1977. 275
Fm. 1. Right retrograde pyelogram shows multiple filling defects of renal pelvis and upper ureter.
infarcts of the brain, lungs, liver, adrenals and intestines. Both kidneys were of normal size and encased in a 4 cm. thickness of indurated gray putty-like perirenal fat (fig. 2). Both renal arteries were thrombosed at their origins with no discernible lumen. Neither renal vein was involved. The cellular architecture of most glomeruli and tubules was destroyed. Both renal pelves contained abundant necrotic debris to the level of the mid ureter. There was bilateral extrinsic
276
DANSKY, LYNNE AND POLITANO
proximal ureteral compression from retroperitoneal necrotic tissue extending from the lower pole of both kidneys. Large, branching, non-septate hyphae were demonstrated easily in all involved microscopic specimens (fig. 3). DISCUSSION
Mucormycosis is a rapidly fatal fungal infectious pathogen that appears most commonly in the presence of impaired host resistance. Before 1943 it had never been described in this country and only 5 cases could be found in the literature. 8 The primary site of infection is generally the nasal mucosa with contiguous spread to the paranasal sinuses, orbit, cribriform plate, meninges and brain with aspiration, tracheobronchial invasion and arterial infiltration. Clinical forms include rhinocerebral, most commonly associated with uncontrolled diabetic acidosis;9-11 pulmonary, primarily a disease of patients with leukemia or lymphoma 12- 14 and gastrointestinal, encountered most frequently in malnourished individuals. 15• 16 The use of corticosteroids 17 and immunosuppressives 1s-2o has been implicated. The disseminated variety is far less common. Early diagnosis, metabolic regulation and prompt combined surgical and antifungal therapy have reduced mortality to approximately 50 per cent in recent series but disseminated disease remains fulminating and fatal within 8 to 10 days. 21- 23 In our patient no definite portal of entry was found. There
Fm. 2. Left kidney at autopsy reveals severe perirenal and periureteral encasement.
were no obvious conditions predisposing to infection. Antecedent renal failure was ruled out by normal renal function tests 9 weeks before hospitalization. It appears that hematogenous spread led to bilateral renal artery thrombosis with subsequent infiltration of the parenchyma. Capsular invasion with contamination of Gerota's fat with perirenal and periureteral dissection were significant components at autopsy to the etiology of the renal failure. Ante mortem diagnosis was not made, since the history, presenting symptoms and constellation of signs were so.atypical. It;is,doubtful whether, even with dialysis, amphotericin Band bilateral nephrectomy, this patient could have survived such disseminated disease. REFERENCES
1. Baker, R. D.: Resectable mycotic lesions and acutely fatal mycoses. J.A.M.A., 150: 1579, 1952. 2. Prout, G. R., Jr. and Goddard, A. R.: Renal mucormycosis. Survival after nephrectomy and amphotericin B therapy. New Engl. J. Med., 263: 1246, 1960. 3. Langston, C., Roberts, D. A., Porter, G. A. and Bennett, W. M.: Renal phycomycosis. J. Urol., 109: 941, 1973. 4. Zimmerman, L. E.: Fatal fungal infections complicating other diseases. Amer. J. Clin. Path., 25: 46, 1955. 5. Baker, R. D.: Pulmonary mucormycosis. Amer. J. Path., 32: 287, 1956. 6. Straatsma, B. R., Zimmerman, L. E. and Gass, J. D.: Phycomycosis. A clinicopathological study of fifty-one cases. Lab. Invest., 11: 963, 1962. 7. Nishimura, K., Ogata, T. and Kiyota, S.: An autopsy case of mucormycosis with acute renal failure. J. Kumamoto Med. Soc., 44: 345, 1970. 8. Gregory, J.E., Golden, A. and Haymaker, W.: Mucormycosis of the central nervous system. Johns Hopkins Hosp. Bull., 73: 405, 1943. 9. Abramson, E., Wilson, D. and Arky, R. A.: Rhinocerebral phycomycosis in association with diabetic ketoacidosis. Report of two cases and a review of clinical and experimental experience with amphotericin B therapy. Ann. Intern. Med., 66: 735, 1967. 10. Price, D. L., Wolpaw, E. R. and Richardson, E. P.: Intracranial phycomycosis: a clinicopathological and radiological study. J. Neurol. Sci., 14: 359, 1971. 11. Deshpande, D. H. and Desai, A. P.: Cerebral phycomycosis in cases ofrenal failure. Neurol. India, 24: 20, 1976. 12. Meyer, R. D., Rosen, P. and Armstrong, D.: Phycomycosis complicating leukemia and lymphoma. Ann. Intern. Med., 77: 871, 1972. 13. Utz, J. P.: Pulmonary infection due to opportunistic fungi. Brit. J. Psychiat., 116: 427, 1970. 14. Blank, N., Castellino, R. A. and Shah, V.: Radiographic aspects of pulmonary infection in patients with altered immunity. Ra-
,I
r
Fm. 3. Hematoxylin and eosin stain of left kidney microabscess shows typical large non-septate hyphae of mucormycosis
DISSEMINATED MUCORMYCOSIS WITH RENAL INVOLVEMENT
diol. Clin. N. Amer., 11: 175, 1973. Lawson, H. H. and Schmaman, A.: Gastric phycomycosis. Brit. J. Surg., 61: 743, 1974. Madhaven, M. and Reddy, D. J.: Mucormycosis of intestine. Indian J. Path. Bact., 12: 46, 1969. Baker, R. D.: Mucormycosis-a new disease? J.A.M.A., 163: 805, 1957. Low, A. I., Tulloch, A.G. S. and England, E. J.: Phycomycosis of the kidney associated with a transient immune defect and treated with chlortrimazole. J. Urol., 111: 732, 1974. Gallis, H. A., Berman, R. A., Cate, T. R., Hamilton, J. D.,
20.
21. 22. 23.
277
Gunnells, J.C. and Steckel, D. L.: Fungal infections following renal transplantation. Arch. Intern. Med., 135: 1163, 1975. Hammer, G. S., Bottone, E. J. and Hirschman, S. Z.: Mucormycosis in a transplant recipient. Amer. J. Clin. Path., 64: 389, 1975. Ripon, J. W.: Medical Mycology. Philadelphia: W. B. Saunders Co., chapt. 21, pp. 430-447, 1974. Case records of the Massachusetts General Hospital. Case 481968. New Engl. J. Med., 279: 1220, 1968. Neame, P. and Rayner, D.: Mucormycosis: a report of twentytwo cases. Arch. Path., 70: 261, 1960.
