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Xanthogranulomatous Pyelonephritis in a Renal Allograft
0022-534 7/88/1406-1512$02.00 /0 Vol. 140, December Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1988 by The Williams & Wilkins Co.
XANTHOGRANULOMATOUS PYELONEPHRITIS IN A RENAL ALLOGRAFT SEYMOUR RIBOT,* ALKIVIADIAS Y. CAMPBELL
AND
HOSSEIN ESLAMI
From the Divisions of Nephrology, Anatomic Pathology and Organ Transplantation, Newark Beth Israel Medical Center and University of Medicine and Dentistry of New Jersey, Newark, New Jersey
ABSTRACT
We report a case of xanthogranulomatous pyelonephritis in a cadaver kidney allograft. The patient had diabetic glomerulosclerosis. The predisposing factors that led to this condition included hyperglycemia, a previous rejection reaction and Escherichia coli urinary infection. Persistent fever, pyuria, bacilluria and a nonfunctioning allograft resulted in allograft nephrectomy. The diagnosis was made on histological examination. Diagnostic criteria for xanthogranulomatous pyelonephritis in the allografted kidney are similar to those in the native kidney. (J. Ural., 140: 1512-1513, 1988) Xanthogranulomatous pyelonephritis is a rare chronic infectious kidney disease found in only 18 of 3,000 consecutive nephrectomies and open kidney biopsies. 1 The name derives from the nature of the cellular infiltration with large lipid-filled cells thought to represent macrophages. 2 We report a case of xanthogranulomatous pyelonephritis in an allografted kidney. CASE REPORT
A 34-year-old woman was admitted to our medical center on November 25, 1986 because of a rapid increase in blood urea nitrogen (BUN) to 102 mg./dl. (normal 5 to 25) and creatinine to 7.5 mg./dl. (normal 0.5 to 1.4) from previous levels of 67 and 2.7 mg./dl., respectively, on November 18. She had a 22-year history of insulin-dependent diabetes mellitus. Maintenance hemodialysis was started in April 1984 and on September 16, 1986 the patient received a cadaver kidney transplant. Although there was early graft function, an acute allograft rejection reaction occurred 4 weeks after transplantation. The patient responded to a pulse dose of methylprednisone and, subsequently, she was maintained on prednisone, azathioprine and cyclosporine with stable but diminished allograft function. During the week before the current hospitalization she noticed general weakness, declining urine output and mild left lower quadrant fullness. The patient claimed compliance with antirejection treatment, except for having missed 1 day of treatment during the week before presentation. Other medications included clonidine, furosemide and insulin. Physical examination revealed a chronically ill woman with a cushingoid appearance and moderate facial hirsutism. Vision was impaired because of diabetic retinopathy. Blood pressure was 144/80 mm. Hg. There were fine crepitant rales at both subscapular areas. She had a left iliac surgical scar and the renal allograft was palpable but not enlarged or tender. There was 2+ pitting edema of the feet and legs. Laboratory data revealed a serum sodium of 128 mEq./1. (normal 135 to 148), potassium 6.8 mEq./1. (normal 3.5 to 5.3), chloride 98 mEq./1. (normal 95 to 105) and bicarbonate 13 mEq./1. (normal 24 to 31). Blood sugar was 380 mg./dl. (normal 70 to 110), BUN 130 and creatinine 7.6 mg./dl. Total proteins were 6.4 gm./dl. (normal 6.0 to 8.0) with albumin 2.0 gm./dl. (normal 3.5 to 5.0). Calcium was 9.2 mg./dl. (normal 8.5 to 10.5), phosphorus 5.0 mg./dl. (normal 2.5 to 4.5) and alkaline phosphatase 384 IU/1. (normal 90 to 282). White blood count was 11,000/mm. 3 (normal 7,800 ± 300), hemoglobin 5.9 gm./dl. (normal 14.0 ± 2) and hematocrit 17.4 per cent (normal 47 ± 5). The urinary sediment on microscopic examination showed Accepted for publication March 23, 1988. *Requests for reprints: Newark Beth Israel Medical Center, 201 Lyons Ave., Newark, New Jersey 07112.
a full field of white blood cells and clumps. Urine cultures that previously yielded no growth now showed significant colony counts of Escherichia coli. Sensitivity studies showed that the organism was sensitive to amikacin, gentamicin, tobramycin, chloramphenicol, tetracycline and all of the cephalosporins tested, including cefazolin, cefoperazone, cefotaxime, cefoxitin and cephalothin. It was resistant to ampicillin, piperacillin and ticarcillin. The urine was not cultured for anaerobes. The same organism was isolated on blood culture. The whole blood cyclo-
FIG. 1. Longitudinal sector of renal allograft demonstrates heterogeneous echogenicity of parenchyma and anechoic area in its mid region.
FIG. 2. Enlarged kidney (550 gm.) with multiple, well demarcated yellowish-brown nodules and dilated pelvis.
1512
XANTHOGRAJ\JULOiviATOUS PYELONEPHRITIS IN RENAL ALLOGRAFT
1513
FIG. 3. A, cortex shows inflammatory infiltrate in interstitium (left) and large number of foamy cells (right). H & E, reduced from X40. B, higher power view of part A shows large finely granular histiocytes. H & E, reduced from X400.
sporine level was 257 ng./ml. (normal 100 to 300). There was slight cardiomegaly on a chest x-ray. The allograft perfusion and scan demonstrated moderately decreased perfusion and markedly decreased function. An allograft ultrasound is shown in figure 1. Maintenance hemodialysis was reinstituted on admission and continued throughout the hospital stay. Because of suspected acute allograft rejection the patient received an aborted course of monoclonal anti-OKT3.* However, the antirejection treatment was stopped when a needle biopsy of the graft on November 26 demonstrated acute pyelonephritis. Antibiotic treatment with cefonicid and tobramycin was instituted. Because of irreversible loss of function and persistent fever, allograft nephrectomy was performed on hospital day 17. Ureteral obstruction or bladder pathological conditions were not demonstrated at operation. The resected renal allograft was enlarged (550 gm.) with multiple yellowish-brown nodules in the renal cortex and medulla (fig. 2). The pelvis was dilated and contained a yellow purulent exudate that yielded E. coli with the same antibiotic sensitivity as the organism isolated from the urine. Microscopically, the interstitium was infiltrated by a mixture of neutrophils, lymphocytes and a few plasma cells (fig. 3, A). The nodules revealed a large number of histiocytes with periodic acid, Schiff positive granules (fig. 3, B). Ziehl-Neelsen and Grocott's stains for acid fast organisms and fungi were negative. Calcospheres (Michaelis-Gutmann bodies) were not identified with von Kossa, Prussian blue and periodic acid, Schiff stains. The contralateral kidney from the same cadaver kidney donor was transplanted in a nondiabetic recipient at our medical center. This allograft showed early function and the recipient had an uncomplicated course without any urinary infection.
27-year-old woman 14 months after a living donor kidney transplantation. The contralateral native kidney had been removed previously because of xanthogranulomatous pyelonephritis. 5 Hoy and associates noted a urinary infection frequency of 55.4 per cent following kidney transplantation,6 which does not differ significantly from the 42 per cent reported by Masur and associates. 7 Because of this high incidence of urinary infections and the exceedingly rare occurrence of xanthogranulomatous pyelonephritis in renal allografts, the constellation of risk factors leading to allograft loss in our patient was reviewed. The organism E. coli isolated from our patient was an important pathogen in previously reported cases with xanthogranulomatous pyelonephritis involving native kidneys. It was isolated from 4 of the 19 cases reported by Goodman and associates, second in frequency to Proteus mirabilis, 3 from the majority of cases reported by Malek and associates, 1 and in 2 of 4 cases reported by Anhalt and associates.4 Diabetes mellitus is considered a major predisposing cause for E. coli urinary infections in kidney transplantation patients. 6 Renal failure and hyperglycemia have been recognized as added infection risk factors in immunosuppressed patients. 8 Urinary infection in our patient can readily be attributed to the observed predisposing conditions, although the cause of the intense xanthogranulomatous reaction remains unknown. One may speculate that the allograft rejection episode engrafted on the infection resulted in this unique cellular response. It is hoped that further experience with this rare renal allograft complication will shed light on its obscure pathogenesis. REFERENCES 1. Malek, R. S., Greene, L. F., DeWeerd, J. H. and Farrow, G. M.:
DISCUSSION
The gross and m,,,.,~.~a•""'" appearance of the allograft lesion resembled renal tumor yet the histology was readily identified as xanthogranulomatous pyelonephritis with special staining and electron micrography. The resemblance of the lesion to neoplasm has been reported others. 1 Since this lesion has never been observed in a renal allograft, it is of great interest to note the clinical, radiological and pathological similarities and differences between the disease in the native kidney as described by others 1 • 3 • 4 and in the renal allograft. Some similarities include fever and pyuria. Suppuration, a frequent finding, also was observed in the allograft kidney of our patient. Atypical features in our patient included the absence of any demonstrable obstruction and a lack of chronicity. Although the clinical features of this disease may lead to suspicion of xanthogranulomatous pyelonephritis, the diagnosis can only be confirmed by histological examination. To our knowledge there are no previous reports of xanthogranulomatous pyelonephritis in a renal allograft. However, this disease has been reported in the single native kidney of a *Orthoclone, Ortho Pharmaceutical CofP., Raritan, New Jersey.
2. 3.
4.
5. 6.
7.
8.
Xanthogranulomatous pye!onephritis. Brit. J. Urol., 44: 296, 1972. Tan, H. K. and Heptinstall, R. H.: Experimental pyelonephritis. A light and electron microscopic study of the periodic acid-Schiff positive interstitial cell. Lab. Invest., 20: 62, 1969. Goodman, M., Curry, T. and Russell, T.: Xanthogranulomatous pyelonephritis (XGP): a local disease with systemic manifestation. Report of 23 patients and review of the literature. Medicine, 58: 171, 1979. Anhalt, M. A., Cawood, C. D. and Scott, R., Jr.: Xanthogranulomatous pyelonephritis: a comprehensive review with report of 4 additional cases. J. Urol., 105: 10, 1971. Carson, C. C. and Weinerth, J. L.: Xanthogranulomatous pyelonephritis in renal transplant recipient. Urology, 23: 58, 1984. Hoy, W. E., Kissel, S. M., Freeman, R. B. and Sterling, W. A., Jr.: Altered patterns of posttransplant urinary tract infections associated with perioperative antibiotics and curtailed catheterization. Amer. J. Kidney Dis., 6: 212, 1985. Masur, H., Cheigh, J. S. and Stubenbord, W. T.: Infection following renal transplantation: a changing pattern. Rev. Infect. Dis., 4: 1208, 1982. Anderson, R. J., Schafer, L.A., Olin, D. B. and Eickhoff, T. C.: Infectious risk factors in the immunosuppressed host. Amer. J. Med., 54: 453, 1973.
THE JOURNAL OF UROLOGY
Copyright © 1988 by The Williams & Wilkins Co.
XANTHOGRANULOMATOUS PYELONEPHRITIS IN A RENAL ALLOGRAFT SEYMOUR RIBOT,* ALKIVIADIAS Y. CAMPBELL
AND
HOSSEIN ESLAMI
From the Divisions of Nephrology, Anatomic Pathology and Organ Transplantation, Newark Beth Israel Medical Center and University of Medicine and Dentistry of New Jersey, Newark, New Jersey
ABSTRACT
We report a case of xanthogranulomatous pyelonephritis in a cadaver kidney allograft. The patient had diabetic glomerulosclerosis. The predisposing factors that led to this condition included hyperglycemia, a previous rejection reaction and Escherichia coli urinary infection. Persistent fever, pyuria, bacilluria and a nonfunctioning allograft resulted in allograft nephrectomy. The diagnosis was made on histological examination. Diagnostic criteria for xanthogranulomatous pyelonephritis in the allografted kidney are similar to those in the native kidney. (J. Ural., 140: 1512-1513, 1988) Xanthogranulomatous pyelonephritis is a rare chronic infectious kidney disease found in only 18 of 3,000 consecutive nephrectomies and open kidney biopsies. 1 The name derives from the nature of the cellular infiltration with large lipid-filled cells thought to represent macrophages. 2 We report a case of xanthogranulomatous pyelonephritis in an allografted kidney. CASE REPORT
A 34-year-old woman was admitted to our medical center on November 25, 1986 because of a rapid increase in blood urea nitrogen (BUN) to 102 mg./dl. (normal 5 to 25) and creatinine to 7.5 mg./dl. (normal 0.5 to 1.4) from previous levels of 67 and 2.7 mg./dl., respectively, on November 18. She had a 22-year history of insulin-dependent diabetes mellitus. Maintenance hemodialysis was started in April 1984 and on September 16, 1986 the patient received a cadaver kidney transplant. Although there was early graft function, an acute allograft rejection reaction occurred 4 weeks after transplantation. The patient responded to a pulse dose of methylprednisone and, subsequently, she was maintained on prednisone, azathioprine and cyclosporine with stable but diminished allograft function. During the week before the current hospitalization she noticed general weakness, declining urine output and mild left lower quadrant fullness. The patient claimed compliance with antirejection treatment, except for having missed 1 day of treatment during the week before presentation. Other medications included clonidine, furosemide and insulin. Physical examination revealed a chronically ill woman with a cushingoid appearance and moderate facial hirsutism. Vision was impaired because of diabetic retinopathy. Blood pressure was 144/80 mm. Hg. There were fine crepitant rales at both subscapular areas. She had a left iliac surgical scar and the renal allograft was palpable but not enlarged or tender. There was 2+ pitting edema of the feet and legs. Laboratory data revealed a serum sodium of 128 mEq./1. (normal 135 to 148), potassium 6.8 mEq./1. (normal 3.5 to 5.3), chloride 98 mEq./1. (normal 95 to 105) and bicarbonate 13 mEq./1. (normal 24 to 31). Blood sugar was 380 mg./dl. (normal 70 to 110), BUN 130 and creatinine 7.6 mg./dl. Total proteins were 6.4 gm./dl. (normal 6.0 to 8.0) with albumin 2.0 gm./dl. (normal 3.5 to 5.0). Calcium was 9.2 mg./dl. (normal 8.5 to 10.5), phosphorus 5.0 mg./dl. (normal 2.5 to 4.5) and alkaline phosphatase 384 IU/1. (normal 90 to 282). White blood count was 11,000/mm. 3 (normal 7,800 ± 300), hemoglobin 5.9 gm./dl. (normal 14.0 ± 2) and hematocrit 17.4 per cent (normal 47 ± 5). The urinary sediment on microscopic examination showed Accepted for publication March 23, 1988. *Requests for reprints: Newark Beth Israel Medical Center, 201 Lyons Ave., Newark, New Jersey 07112.
a full field of white blood cells and clumps. Urine cultures that previously yielded no growth now showed significant colony counts of Escherichia coli. Sensitivity studies showed that the organism was sensitive to amikacin, gentamicin, tobramycin, chloramphenicol, tetracycline and all of the cephalosporins tested, including cefazolin, cefoperazone, cefotaxime, cefoxitin and cephalothin. It was resistant to ampicillin, piperacillin and ticarcillin. The urine was not cultured for anaerobes. The same organism was isolated on blood culture. The whole blood cyclo-
FIG. 1. Longitudinal sector of renal allograft demonstrates heterogeneous echogenicity of parenchyma and anechoic area in its mid region.
FIG. 2. Enlarged kidney (550 gm.) with multiple, well demarcated yellowish-brown nodules and dilated pelvis.
1512
XANTHOGRAJ\JULOiviATOUS PYELONEPHRITIS IN RENAL ALLOGRAFT
1513
FIG. 3. A, cortex shows inflammatory infiltrate in interstitium (left) and large number of foamy cells (right). H & E, reduced from X40. B, higher power view of part A shows large finely granular histiocytes. H & E, reduced from X400.
sporine level was 257 ng./ml. (normal 100 to 300). There was slight cardiomegaly on a chest x-ray. The allograft perfusion and scan demonstrated moderately decreased perfusion and markedly decreased function. An allograft ultrasound is shown in figure 1. Maintenance hemodialysis was reinstituted on admission and continued throughout the hospital stay. Because of suspected acute allograft rejection the patient received an aborted course of monoclonal anti-OKT3.* However, the antirejection treatment was stopped when a needle biopsy of the graft on November 26 demonstrated acute pyelonephritis. Antibiotic treatment with cefonicid and tobramycin was instituted. Because of irreversible loss of function and persistent fever, allograft nephrectomy was performed on hospital day 17. Ureteral obstruction or bladder pathological conditions were not demonstrated at operation. The resected renal allograft was enlarged (550 gm.) with multiple yellowish-brown nodules in the renal cortex and medulla (fig. 2). The pelvis was dilated and contained a yellow purulent exudate that yielded E. coli with the same antibiotic sensitivity as the organism isolated from the urine. Microscopically, the interstitium was infiltrated by a mixture of neutrophils, lymphocytes and a few plasma cells (fig. 3, A). The nodules revealed a large number of histiocytes with periodic acid, Schiff positive granules (fig. 3, B). Ziehl-Neelsen and Grocott's stains for acid fast organisms and fungi were negative. Calcospheres (Michaelis-Gutmann bodies) were not identified with von Kossa, Prussian blue and periodic acid, Schiff stains. The contralateral kidney from the same cadaver kidney donor was transplanted in a nondiabetic recipient at our medical center. This allograft showed early function and the recipient had an uncomplicated course without any urinary infection.
27-year-old woman 14 months after a living donor kidney transplantation. The contralateral native kidney had been removed previously because of xanthogranulomatous pyelonephritis. 5 Hoy and associates noted a urinary infection frequency of 55.4 per cent following kidney transplantation,6 which does not differ significantly from the 42 per cent reported by Masur and associates. 7 Because of this high incidence of urinary infections and the exceedingly rare occurrence of xanthogranulomatous pyelonephritis in renal allografts, the constellation of risk factors leading to allograft loss in our patient was reviewed. The organism E. coli isolated from our patient was an important pathogen in previously reported cases with xanthogranulomatous pyelonephritis involving native kidneys. It was isolated from 4 of the 19 cases reported by Goodman and associates, second in frequency to Proteus mirabilis, 3 from the majority of cases reported by Malek and associates, 1 and in 2 of 4 cases reported by Anhalt and associates.4 Diabetes mellitus is considered a major predisposing cause for E. coli urinary infections in kidney transplantation patients. 6 Renal failure and hyperglycemia have been recognized as added infection risk factors in immunosuppressed patients. 8 Urinary infection in our patient can readily be attributed to the observed predisposing conditions, although the cause of the intense xanthogranulomatous reaction remains unknown. One may speculate that the allograft rejection episode engrafted on the infection resulted in this unique cellular response. It is hoped that further experience with this rare renal allograft complication will shed light on its obscure pathogenesis. REFERENCES 1. Malek, R. S., Greene, L. F., DeWeerd, J. H. and Farrow, G. M.:
DISCUSSION
The gross and m,,,.,~.~a•""'" appearance of the allograft lesion resembled renal tumor yet the histology was readily identified as xanthogranulomatous pyelonephritis with special staining and electron micrography. The resemblance of the lesion to neoplasm has been reported others. 1 Since this lesion has never been observed in a renal allograft, it is of great interest to note the clinical, radiological and pathological similarities and differences between the disease in the native kidney as described by others 1 • 3 • 4 and in the renal allograft. Some similarities include fever and pyuria. Suppuration, a frequent finding, also was observed in the allograft kidney of our patient. Atypical features in our patient included the absence of any demonstrable obstruction and a lack of chronicity. Although the clinical features of this disease may lead to suspicion of xanthogranulomatous pyelonephritis, the diagnosis can only be confirmed by histological examination. To our knowledge there are no previous reports of xanthogranulomatous pyelonephritis in a renal allograft. However, this disease has been reported in the single native kidney of a *Orthoclone, Ortho Pharmaceutical CofP., Raritan, New Jersey.
2. 3.
4.
5. 6.
7.
8.
Xanthogranulomatous pye!onephritis. Brit. J. Urol., 44: 296, 1972. Tan, H. K. and Heptinstall, R. H.: Experimental pyelonephritis. A light and electron microscopic study of the periodic acid-Schiff positive interstitial cell. Lab. Invest., 20: 62, 1969. Goodman, M., Curry, T. and Russell, T.: Xanthogranulomatous pyelonephritis (XGP): a local disease with systemic manifestation. Report of 23 patients and review of the literature. Medicine, 58: 171, 1979. Anhalt, M. A., Cawood, C. D. and Scott, R., Jr.: Xanthogranulomatous pyelonephritis: a comprehensive review with report of 4 additional cases. J. Urol., 105: 10, 1971. Carson, C. C. and Weinerth, J. L.: Xanthogranulomatous pyelonephritis in renal transplant recipient. Urology, 23: 58, 1984. Hoy, W. E., Kissel, S. M., Freeman, R. B. and Sterling, W. A., Jr.: Altered patterns of posttransplant urinary tract infections associated with perioperative antibiotics and curtailed catheterization. Amer. J. Kidney Dis., 6: 212, 1985. Masur, H., Cheigh, J. S. and Stubenbord, W. T.: Infection following renal transplantation: a changing pattern. Rev. Infect. Dis., 4: 1208, 1982. Anderson, R. J., Schafer, L.A., Olin, D. B. and Eickhoff, T. C.: Infectious risk factors in the immunosuppressed host. Amer. J. Med., 54: 453, 1973.