Korean J Hematol 2010; 45(4):
Published online December 31, 2010
https://doi.org/10.5045/kjh.2010.45.4.275
© The Korean Society of Hematology
1Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
2Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Correspondence to : Correspondence to Soo Jeong Kim, M.D. Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2227-4226, Fax: +82-2-393-6884, ALVIN97@yuhs.ac
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Invasive aspergillosis (IA) is a leading cause of infectious mortality in patients who have undergone a hematopoietic stem cell transplant (HSCT); the mortality due to IA ranges from 70% to 93% in HSCT patients. Early diagnosis and treatment are the cornerstones for the good prognosis of IA. Primary renal aspergillosis is an extremely rare presentation in patients who have undergone HSCT, and the risk factor for this uncommon presentation is not well known. We report a patient who developed primary renal aspergillosis and renal stones in both the kidneys after HSCT. Invasive renal aspergillosis was diagnosed after a nephrectomy, which was performed to treat massive renal hematoma.
Keywords Primary renal aspergillosis, Hematopoietic stem cell transplant, Renal stones
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients who have undergone a hematopoietic stem cell transplant (HSCT). The common sites of IA include lung, central nervous system, and paranasal sinuses. Primary renal aspergillosis is extremely rare; it has been mostly reported in immunocompromised patients. In Korea, only 3 cases of primary renal aspergillosis have been reported [1-3], but none were associated with HSCT. We report a patient who developed primary renal aspergillosis and renal stones in both the kidneys after HSCT. Invasive renal aspergillosis was diagnosed after nephrectomy, which was performed to treat massive renal hematoma.
A 33-year-old man was hospitalized after experiencing general weakness for 1 month. His medical history was unremarkable. Bone marrow examination revealed acute myeloid leukemia (AML). He received induction chemotherapy comprising continuous infusion of cytarabine (100 mg/m2) for 7 days and bolus injection of idarubicin (12 mg/m2) for 3 days. He achieved complete remission, and the same drugs were administered during consolidation chemotherapy. At the end of the first consolidation chemotherapy, he visited the outpatient clinic because of severe headache. Cerebrospinal fluid (CSF) cytology confirmed leukemia relapse in the central nervous system (CNS). Bone marrow examination did not show any evidence of hematologic relapse. Isolated CNS relapse was treated by intrathecal injection of methotrexate (12 mg; twice weekly). After the 4th injection, leukemic blasts in the CSF were unidentifiable. Therefore, methotrexate injection was discontinued after 2 additional courses. The patient received allogeneic peripheral blood SCT from a HLA-2-mismatched unrelated donor. Abdominal ultrasonography before the transplant had revealed renal stones with hydronephrosis in the right kidney. Since the patient had no specific symptoms related to renal stones, HSCT was continued without further treatment for renal stones. The conditioning regimen comprised busulphan (3.2 mg/kg; IV; 4 days) and cyclophosphamide (60 mg/kg; IV; 2 days). Tacrolimus and short-course methotrexate were administered for the prophylaxis of graft-versus-host disease (GVHD). Micafungin (50 mg daily; IV) was administered for anti-fungal prophylaxis from the 1st day of conditioning chemotherapy until engraftment. After engraftment, itraconazole (200 mg) solution was orally administered daily.
On the 19th day of transplantation, complete engraftment was achieved, and the absolute neutrophil count was 1,015/µL. The patient was discharged on day 27. Nonoliguric acute renal failure developed during the transplant period. The estimated glomerular filtration rate (as per Modification of diet in renal disease equation) was steady between 40 and 70 mL/min/m2; this was considered as a side effect of the calcineurin inhibitor. There were no symptoms and signs of acute GVHD. The serum was negative for
On day 74, he presented with right flank pain. Abdominal ultrasonography and non-contrast-enhanced abdominal computed tomography (CT) revealed multiple renal and ureteral stones with right hydronephrosis (Fig. 1) but no radiologic evidence of fungal infection in the kidney.
After urologic consultation, the patient was scheduled for extracorporeal shock wave lithotripsy (ESWL) for stone removal, but a febrile episode occurred. No pathogen was identified in the blood, sputum, and urine culture. PCR showed positive findings for cytomegalovirus (CMV) before the febrile episode, but the result of the consecutive test was negative without any anti-CMV treatment.
On day 75, serum analysis yielded positive findings for
On day 96, the patient was admitted because of headache and right flank pain. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal leukemic infiltration, and CSF cytology confirmed the presence of CNS leukemia. Abdominal CT revealed residual multiple renal and ureteral stones in both kidneys. The serum
On day 109, emergency radical nephrectomy was performed (Fig. 3), and a ruptured area in the mid-portion of the lateral side of the right kidney was observed. Moreover, multiple fungal hyphae with septae and branching at acute angles in the renal parenchyma with vascular invasion, which was morphologically consistent with renal aspergillosis, were observed (Fig. 4). The identity of the causative fungal pathogen was inconclusive. The abscess-like lesion in the prostate was not manipulated because of the risk for hemorrhage. The patient was initially treated with meropenem and vancomycin for broad-spectrum antibacterial coverage and amphotericin B deoxycholate for empirical antifungal coverage after the development of fever. After confirmation of renal aspergillosis, voriconazole was administered instead of amphotericin B deoxycholate at the intensive care-unit after the operation, but the patient died on day 113 because of sepsis progression.
IA is a leading cause of infectious mortality after HSCT. Although supportive care has improved and new antifungal agents and sensitive tests such as
In 2008, the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) classified IFI into proven, probable, or possible disease [7]. The
In our patient, the positive finding of serum galactomannan was first reported on day 75, and the subsequent tests were positive, with a continuously high titer. According to the EORTC/MSG classification, we diagnosed the patient with possible fungal infection and treated him with amphotericin B deoxycholate. Unfortunately, after 2 weeks of treatment, the serum galactomannan levels did not decrease, which may be attributed to the following reasons. First, although amphotericin B is used as a standard therapy for IA, only 13.3% of patients who had undergone allogenic HSCT had shown a favorable response [10]. Second, since amphotericin B is excreted mainly via the biliary tract (42%) and only a low percentage is excreted via the kidney (24%) [3], there is a possibility that the amphotericin B deoxycholate concentration is not sufficient to eliminate
In the only report of primary renal aspergillosis following HSCT, the patient had a stone in the renal pelvis [12]; this clinical presentation was similar to that observed in our patient. Many other reports have described the simultaneous presentation of renal aspergillosis and urinary tract stones. Haq et al. [13] reported primary renal aspergillosis in a diabetic patient with renal stones and Godec et al. and Eisenberg et al. reported cases with primary renal aspergillosis and obstruction at the ureteropelvic junction [14, 15]. These findings may suggest that urinary stasis induced by urinary tract obstruction may play some role in the development of renal aspergillosis.
In conclusion, the development of primary renal aspergillosis following HSCT is extremely rare, but if fungal infection is suspected in a patient with a urinary tract obstruction, especially with renal stones, renal aspergillosis must be considered in the differential diagnosis.
Images of the renal parenchymal tearing with active bleeding, subcapsular hematoma in the right kidney (left panel), and prostate abscess (right panel).
Renal biopsy showing renal parenchymal and vascular invasion by
Korean J Hematol 2010; 45(4): 275-278
Published online December 31, 2010 https://doi.org/10.5045/kjh.2010.45.4.275
Copyright © The Korean Society of Hematology.
Hyunsung Park1, Mi Jung Lee1, Yundeok Kim1, Yoo Hong Min1, Soo Jeong Kim1*, and Dokyung Kim2
1Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
2Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
Correspondence to: Correspondence to Soo Jeong Kim, M.D. Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. Tel: +82-2-2227-4226, Fax: +82-2-393-6884, ALVIN97@yuhs.ac
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Invasive aspergillosis (IA) is a leading cause of infectious mortality in patients who have undergone a hematopoietic stem cell transplant (HSCT); the mortality due to IA ranges from 70% to 93% in HSCT patients. Early diagnosis and treatment are the cornerstones for the good prognosis of IA. Primary renal aspergillosis is an extremely rare presentation in patients who have undergone HSCT, and the risk factor for this uncommon presentation is not well known. We report a patient who developed primary renal aspergillosis and renal stones in both the kidneys after HSCT. Invasive renal aspergillosis was diagnosed after a nephrectomy, which was performed to treat massive renal hematoma.
Keywords: Primary renal aspergillosis, Hematopoietic stem cell transplant, Renal stones
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients who have undergone a hematopoietic stem cell transplant (HSCT). The common sites of IA include lung, central nervous system, and paranasal sinuses. Primary renal aspergillosis is extremely rare; it has been mostly reported in immunocompromised patients. In Korea, only 3 cases of primary renal aspergillosis have been reported [1-3], but none were associated with HSCT. We report a patient who developed primary renal aspergillosis and renal stones in both the kidneys after HSCT. Invasive renal aspergillosis was diagnosed after nephrectomy, which was performed to treat massive renal hematoma.
A 33-year-old man was hospitalized after experiencing general weakness for 1 month. His medical history was unremarkable. Bone marrow examination revealed acute myeloid leukemia (AML). He received induction chemotherapy comprising continuous infusion of cytarabine (100 mg/m2) for 7 days and bolus injection of idarubicin (12 mg/m2) for 3 days. He achieved complete remission, and the same drugs were administered during consolidation chemotherapy. At the end of the first consolidation chemotherapy, he visited the outpatient clinic because of severe headache. Cerebrospinal fluid (CSF) cytology confirmed leukemia relapse in the central nervous system (CNS). Bone marrow examination did not show any evidence of hematologic relapse. Isolated CNS relapse was treated by intrathecal injection of methotrexate (12 mg; twice weekly). After the 4th injection, leukemic blasts in the CSF were unidentifiable. Therefore, methotrexate injection was discontinued after 2 additional courses. The patient received allogeneic peripheral blood SCT from a HLA-2-mismatched unrelated donor. Abdominal ultrasonography before the transplant had revealed renal stones with hydronephrosis in the right kidney. Since the patient had no specific symptoms related to renal stones, HSCT was continued without further treatment for renal stones. The conditioning regimen comprised busulphan (3.2 mg/kg; IV; 4 days) and cyclophosphamide (60 mg/kg; IV; 2 days). Tacrolimus and short-course methotrexate were administered for the prophylaxis of graft-versus-host disease (GVHD). Micafungin (50 mg daily; IV) was administered for anti-fungal prophylaxis from the 1st day of conditioning chemotherapy until engraftment. After engraftment, itraconazole (200 mg) solution was orally administered daily.
On the 19th day of transplantation, complete engraftment was achieved, and the absolute neutrophil count was 1,015/µL. The patient was discharged on day 27. Nonoliguric acute renal failure developed during the transplant period. The estimated glomerular filtration rate (as per Modification of diet in renal disease equation) was steady between 40 and 70 mL/min/m2; this was considered as a side effect of the calcineurin inhibitor. There were no symptoms and signs of acute GVHD. The serum was negative for
On day 74, he presented with right flank pain. Abdominal ultrasonography and non-contrast-enhanced abdominal computed tomography (CT) revealed multiple renal and ureteral stones with right hydronephrosis (Fig. 1) but no radiologic evidence of fungal infection in the kidney.
After urologic consultation, the patient was scheduled for extracorporeal shock wave lithotripsy (ESWL) for stone removal, but a febrile episode occurred. No pathogen was identified in the blood, sputum, and urine culture. PCR showed positive findings for cytomegalovirus (CMV) before the febrile episode, but the result of the consecutive test was negative without any anti-CMV treatment.
On day 75, serum analysis yielded positive findings for
On day 96, the patient was admitted because of headache and right flank pain. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal leukemic infiltration, and CSF cytology confirmed the presence of CNS leukemia. Abdominal CT revealed residual multiple renal and ureteral stones in both kidneys. The serum
On day 109, emergency radical nephrectomy was performed (Fig. 3), and a ruptured area in the mid-portion of the lateral side of the right kidney was observed. Moreover, multiple fungal hyphae with septae and branching at acute angles in the renal parenchyma with vascular invasion, which was morphologically consistent with renal aspergillosis, were observed (Fig. 4). The identity of the causative fungal pathogen was inconclusive. The abscess-like lesion in the prostate was not manipulated because of the risk for hemorrhage. The patient was initially treated with meropenem and vancomycin for broad-spectrum antibacterial coverage and amphotericin B deoxycholate for empirical antifungal coverage after the development of fever. After confirmation of renal aspergillosis, voriconazole was administered instead of amphotericin B deoxycholate at the intensive care-unit after the operation, but the patient died on day 113 because of sepsis progression.
IA is a leading cause of infectious mortality after HSCT. Although supportive care has improved and new antifungal agents and sensitive tests such as
In 2008, the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) classified IFI into proven, probable, or possible disease [7]. The
In our patient, the positive finding of serum galactomannan was first reported on day 75, and the subsequent tests were positive, with a continuously high titer. According to the EORTC/MSG classification, we diagnosed the patient with possible fungal infection and treated him with amphotericin B deoxycholate. Unfortunately, after 2 weeks of treatment, the serum galactomannan levels did not decrease, which may be attributed to the following reasons. First, although amphotericin B is used as a standard therapy for IA, only 13.3% of patients who had undergone allogenic HSCT had shown a favorable response [10]. Second, since amphotericin B is excreted mainly via the biliary tract (42%) and only a low percentage is excreted via the kidney (24%) [3], there is a possibility that the amphotericin B deoxycholate concentration is not sufficient to eliminate
In the only report of primary renal aspergillosis following HSCT, the patient had a stone in the renal pelvis [12]; this clinical presentation was similar to that observed in our patient. Many other reports have described the simultaneous presentation of renal aspergillosis and urinary tract stones. Haq et al. [13] reported primary renal aspergillosis in a diabetic patient with renal stones and Godec et al. and Eisenberg et al. reported cases with primary renal aspergillosis and obstruction at the ureteropelvic junction [14, 15]. These findings may suggest that urinary stasis induced by urinary tract obstruction may play some role in the development of renal aspergillosis.
In conclusion, the development of primary renal aspergillosis following HSCT is extremely rare, but if fungal infection is suspected in a patient with a urinary tract obstruction, especially with renal stones, renal aspergillosis must be considered in the differential diagnosis.
Multiple renal and ureteral stones (arrow) with hydronephrosis.
Images of the renal parenchymal tearing with active bleeding, subcapsular hematoma in the right kidney (left panel), and prostate abscess (right panel).
Right kidney with perirenal hematoma after radical nephrectomy.
Renal biopsy showing renal parenchymal and vascular invasion by
Multiple renal and ureteral stones (arrow) with hydronephrosis.
|@|~(^,^)~|@|Images of the renal parenchymal tearing with active bleeding, subcapsular hematoma in the right kidney (left panel), and prostate abscess (right panel).
|@|~(^,^)~|@|Right kidney with perirenal hematoma after radical nephrectomy.
|@|~(^,^)~|@|Renal biopsy showing renal parenchymal and vascular invasion by