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Postinfectious glomerulonephritis in a renal allograft associated with a mycotic aneurysm of a coronary artery
Postinfectious Glomerulonephritis in a Renal Allograft Associated with a Mycotic Aneurysm of a Coronary Artery
HENRY G. NEBEKER, M.D., Ph.D. GAVRIL HERCZ, M.D. GREGORY K. FELD, M.D. THOMAS M. STANLEY, M.D. JACK W. COBURN, M.D. KIYOSHI KUROKAWA, - M.D. Los Angeles, California
Postinfectious giomeruionephritis is well known to occur after various infections but is rare in renal allografts, perhaps as a result of immunosuppressive therapy. This report describes a 47-year-old man who, seven years after receiving a cadaveric renal transplant, had biopsy-proved crescentic giomerulonephritis presenting with gross hematuria and rapidly progressive renal failure. The patient underwent cardiac surgery to define an abnormal structure shown on echocardiography, and a mycotic aneurysm of the left circumflex artery was discovered. Such aneurysms are uncommon and rarely diagnosed during life. This case appears to be the first report of glomerulonephritis associated with a mycotic aneurysm of a coronary artery and one of the few reports of postinfectious glomerulonephritis in a renal allograft. Glomerulonephritis develops after streptococcal infections of the throat and skin, bacterial endocarditis, and infections of atrioventricular shunts. However, postinfectious glomerulonephritis is rare in renal allograft recipients [ 11, perhaps because of immunosuppressive therapy. This report describes an unusual case of crescentric glomerulonephritis associated with a mycotic aneurysm of a coronary artery. Mycotic aneurysms of a coronary artery are uncommon [ 21; they usually arise secondary to bacterial endocarditis and are rarely diagnosed during life [3]. Thus, two uncommon disease processes occurred together in this renal transplant recipient and appear to be causally related. CASE REPORT
From the Medical, Laboratory, and Research Services, Veterans Administration Wadsworth Medical Center, and the Departments of Medicine and Pathology, University of California at Los Angeles School of Medicine, Los Angeles, California. This work was supported by the Veterans Administration. Dr. Nebeker is a fellow supported by National Institutes of Health Training Grant A21351. Requests for reprints should be addressed to Dr. Henry Nebeker, Nephrology Section (Wl 1 lL), Veterans Administration Wadsworth Hospital, Los Angeles, California 90073. Manuscript accepted June 23, 1983.
940
May 1984
A 47-year-old man was hospitalized at the Veterans Administration Wadsworth Medical Center because of gross hematuria. End-stage renal disease had developed at age 38, with a clinical diagnosis of chronic glomerulonephrltis, and was treated with maintenance hemodialysis. At age 42, he received a cadaveric renal transplant, and during the next five years, he did well with serum creatinine levels between 1.0 and 1.5 mg/dl while receiving immunosuppressive (prednisone 20 mg every other day and azathioprine 150 mg every day) and antihypertensive therapy. Two months before admission, fever and chills developed, and he was hospitalized elsewhere. Blood cultures grew Staphylococcus aureus, and he was treated with intravenous oxacillin for three weeks. No apparent source of infection was discovered; results of echocardiography were interpreted as normal. On discharge, the serum creatinine level was 1.9 mg/dl. Two weeks after discharge, the patient noted gross hematuria, and cystoscopy showed blood emanating from the ureteral orifice of the transplant. After two weeks of persistent hematuria, he came to this hospital for evaluation. On examination, the temperature was 37.3%, and a new III/VI holosystolic
The American Journal of Medlclne
Volume 76
POSTINFECTIOUS GLOMERULONEPHRITIS IN A RENALALLOGRAFT-NEBEKER ET AL
murmur was heard at the apex. Thare was no graft tenderness nor pedal edema. The serum creatinine value was 2.4 mg/dl, and the serum urea nitrogen level was 42 mg/dl. Urinalysis showed 3-I protein, 200 red cells and 10 white cells per high-power field, and no casts. Blood and urine cultures later showed no pathogens, but the patient was given intravenous oxacillin because of possible endocarditis. Ultrasound study of the renal graft showed no evidence of obstruction, and renal scintiscanning showed good perfusion and tubular function. Within two days after admission, the serum creatinine level increased to 3.6 mg/dl. A biopsy specimen of the graft was obtained, and frozen sections showed diffuse crescentic. glomerulonephritis. Echocardiography showed no evidence of valvular vegetations, but a 2 cm cystic structure lateral to the left ventricular wall was noted. The composition of the structure was unclear, and it was unchanged on repeated echocardiography two days later. The serum C3 level was 132 mg/dl (normal 60 to 120). Antiglomerular basement membrane antibodies were not detected in serum, and sarum immune complexes were not detected by Clq binding, Raji cell, and polyethylene glycol assays. The permanent sections of the renal biopsy specimen revealed diffuse endocapillary hypercellularity and central lobular polymorphonuclear cell infiltrates, with six of 13 glomeruli showing small to medium-sized extracapillary crescents (Figure 1). The basement membranes were not thickened, and the vessels appeared normal. The interstitium was edematous and contained a mild infiltrate of acute and chronic inflammatory cells with slight diffuse interstitial fibrosis and tubular atrophy. Technical difficulty resulted in suboptimal immunofluorescent study, but there was no marked staining for IgG, IgM, IgA, or C3. Electron microscopy revealed the glomerular basement membrane to be of normal width with occasional subendothelial and intramembranous deposits of low and medium density. The patient was initially treated with plasmapheresis, azathioprine, and 1 g of methylprednisolone intravenously for three days followed by high-dose prednisone. Multiple blood and urine cultures showed no growth, but oxacillin was continued because of the recent history of staphylococcal bacteremia. The serum creatinine level rose to 4.2 mg/dl after two weeks in the hospital but then progressively fell. He continued to receive azathioprine, with gradual reduction in the dosage of prednisone; after seven weeks, the serum creatinine level had decreased to 1.6 mg/dl. The patient then underwent cardiac catheterization to define the structure seen on echocardiography. An anomalous structure on the left lateral-posterior wall with rapid filling from the left circumflex coronary artery was evident. Two days later, surgery was performed, and a mycotic aneurysm of the mid-left circumflex coronary artery, which contained 50 ml of necrotic material, was discovered. The structure extended into the myocardium but did not reach the endocardium. Detailed descriptions of cardiac findings are reported elsewhere [4]. Direct exploration of the left atrium and mitral valve showed no evidence of previous or current endocarditis. The aneurysm and surrounding necrotic material were resected, and a saphenous vein bypass graft was placed. Culture and stains of the resected tissue disclosed no organisms. Several days after
Figure 1. Renal allograft biopsy specimen showing a glomerulus with hypercellularity of the glomerular tuft and an extracapillary crescent (periodic acid-Schiff stain; original magnification X 320).
surgery, the patient had a cardiac arrest, cerebral infarction developed, and he eventually died; postmortem examination was not performed. COMMENTS
The glomerulonephritis in this patient was temporally related to the infection in the left circumflex artery and was probably causally related, perhaps as a result of immune complex deposition. Diffuse proliferative glomerulonephritis with extracapillary crescents secondary to bacterial endocarditis [5] or visceral abscesses [6] has been reported. The histologic findings in this case were not characteristic of transplant rejection, and it is unlikely that the nephritis represented a recurrence of the disease that involved his native kidneys. The absence of detectable immune complexes in the serum of this patient could be due to prior antibiotic treatment, since immune complexes may disappear from the circulation in patients with endocarditis during treatment, at the same time that blood culture results become negative [7]. The absence of immunofluorescent staining for immunoglobulins or C3 is not unexpected, since other investigators have found negative immunofluorescent results in a significant number of patients with glomerulonephritis complicating subacute bacterial endocarditis [ 5,8]. The mechanism of glomerular injury in these cases remains speculative.
May 1984
The American Journal of Medicine
Volume 76
941
POSTINFECTIOUS
GLOMERULONEPHRlTlS
IN A RENAL ALLOGRAFT-NEBEKER
ET AL
Of interest is the fact that maintenance immunosuppression to prevent graft rejection did not prevent nephritis, possibly of immunologic origin, in this case. A recent report described a patient with a renal allografi
artery, but there was no evidence of glomerulonephritis [9]. This case appears to be the first report of glomerulonephritis associated with a mycotic aneurysm of a coronary artery as well as a rare instance of post-
who died of a ruptured mycotic
infectious
aneurysm
of a coronary
glomerulonephritis
in a renal graft.
REFERENCES 1.
2. 3. 4.
5.
942
Sonnabend W, Kistler GS, Thiel G, et al: Chronische Herdglomerulitis und chronisch persistierende Hepatitis nach Nierentransplantation: Nachweiss von Hepatitis 6 und Epstein-Barr-virus Antigen. Schweiz Med Wochenschr 1974; 104: 1205-1217. Case records of the Massachusetts General Hospital (case 6-1967). N Engl J Med 1967; 276: 338-345. Crook BRM, Raftery EB, Oram S: Mycotic aneurysms of coronary arteries. Br Heart J 1979; 35: 107-109. Feld G, Tei C, Nebeker HG, et al: Ruptured mycotic aneurysm of the circumflex artery as a late sequela of staphylococcal bacteremia. Submitted. Morel-Maroger L, Sraer J-D, Herveman G, Godeau P: Kid-
May 1984
The American Journal ol Medicine
Volume 76
6.
7.
8.
9.
ney in subacute endocarditis. Arch Pathol 1972; 94: 205213. Beaufils M, MoreCMaroger L, Sraer J-D, Kanfer A, Kourilsky 0, Richet G: Acute renal failure of glomerular origin during visceral absesses. N Engl J Med 1976; 295: 185-189. Bayer AS, Theofilopoulos AN, Eisenberg R, Dixon FJ. Guze LB: Circulating immune complexes in infective endocarditis. N Engl J Med 1976; 295: 1500-1505. BouttonJones JM, Sissons JGP, Evans DJ, Peters DK: Renal lesions of subacute infective endocarditis. Br Med J 1974; 2: 11-14. McGee MB, Khan MY: Ruptured mycotic aneurysm of a coronary artery. Arch Intern Med 1980; 140: 1097-1098.
HENRY G. NEBEKER, M.D., Ph.D. GAVRIL HERCZ, M.D. GREGORY K. FELD, M.D. THOMAS M. STANLEY, M.D. JACK W. COBURN, M.D. KIYOSHI KUROKAWA, - M.D. Los Angeles, California
Postinfectious giomeruionephritis is well known to occur after various infections but is rare in renal allografts, perhaps as a result of immunosuppressive therapy. This report describes a 47-year-old man who, seven years after receiving a cadaveric renal transplant, had biopsy-proved crescentic giomerulonephritis presenting with gross hematuria and rapidly progressive renal failure. The patient underwent cardiac surgery to define an abnormal structure shown on echocardiography, and a mycotic aneurysm of the left circumflex artery was discovered. Such aneurysms are uncommon and rarely diagnosed during life. This case appears to be the first report of glomerulonephritis associated with a mycotic aneurysm of a coronary artery and one of the few reports of postinfectious glomerulonephritis in a renal allograft. Glomerulonephritis develops after streptococcal infections of the throat and skin, bacterial endocarditis, and infections of atrioventricular shunts. However, postinfectious glomerulonephritis is rare in renal allograft recipients [ 11, perhaps because of immunosuppressive therapy. This report describes an unusual case of crescentric glomerulonephritis associated with a mycotic aneurysm of a coronary artery. Mycotic aneurysms of a coronary artery are uncommon [ 21; they usually arise secondary to bacterial endocarditis and are rarely diagnosed during life [3]. Thus, two uncommon disease processes occurred together in this renal transplant recipient and appear to be causally related. CASE REPORT
From the Medical, Laboratory, and Research Services, Veterans Administration Wadsworth Medical Center, and the Departments of Medicine and Pathology, University of California at Los Angeles School of Medicine, Los Angeles, California. This work was supported by the Veterans Administration. Dr. Nebeker is a fellow supported by National Institutes of Health Training Grant A21351. Requests for reprints should be addressed to Dr. Henry Nebeker, Nephrology Section (Wl 1 lL), Veterans Administration Wadsworth Hospital, Los Angeles, California 90073. Manuscript accepted June 23, 1983.
940
May 1984
A 47-year-old man was hospitalized at the Veterans Administration Wadsworth Medical Center because of gross hematuria. End-stage renal disease had developed at age 38, with a clinical diagnosis of chronic glomerulonephrltis, and was treated with maintenance hemodialysis. At age 42, he received a cadaveric renal transplant, and during the next five years, he did well with serum creatinine levels between 1.0 and 1.5 mg/dl while receiving immunosuppressive (prednisone 20 mg every other day and azathioprine 150 mg every day) and antihypertensive therapy. Two months before admission, fever and chills developed, and he was hospitalized elsewhere. Blood cultures grew Staphylococcus aureus, and he was treated with intravenous oxacillin for three weeks. No apparent source of infection was discovered; results of echocardiography were interpreted as normal. On discharge, the serum creatinine level was 1.9 mg/dl. Two weeks after discharge, the patient noted gross hematuria, and cystoscopy showed blood emanating from the ureteral orifice of the transplant. After two weeks of persistent hematuria, he came to this hospital for evaluation. On examination, the temperature was 37.3%, and a new III/VI holosystolic
The American Journal of Medlclne
Volume 76
POSTINFECTIOUS GLOMERULONEPHRITIS IN A RENALALLOGRAFT-NEBEKER ET AL
murmur was heard at the apex. Thare was no graft tenderness nor pedal edema. The serum creatinine value was 2.4 mg/dl, and the serum urea nitrogen level was 42 mg/dl. Urinalysis showed 3-I protein, 200 red cells and 10 white cells per high-power field, and no casts. Blood and urine cultures later showed no pathogens, but the patient was given intravenous oxacillin because of possible endocarditis. Ultrasound study of the renal graft showed no evidence of obstruction, and renal scintiscanning showed good perfusion and tubular function. Within two days after admission, the serum creatinine level increased to 3.6 mg/dl. A biopsy specimen of the graft was obtained, and frozen sections showed diffuse crescentic. glomerulonephritis. Echocardiography showed no evidence of valvular vegetations, but a 2 cm cystic structure lateral to the left ventricular wall was noted. The composition of the structure was unclear, and it was unchanged on repeated echocardiography two days later. The serum C3 level was 132 mg/dl (normal 60 to 120). Antiglomerular basement membrane antibodies were not detected in serum, and sarum immune complexes were not detected by Clq binding, Raji cell, and polyethylene glycol assays. The permanent sections of the renal biopsy specimen revealed diffuse endocapillary hypercellularity and central lobular polymorphonuclear cell infiltrates, with six of 13 glomeruli showing small to medium-sized extracapillary crescents (Figure 1). The basement membranes were not thickened, and the vessels appeared normal. The interstitium was edematous and contained a mild infiltrate of acute and chronic inflammatory cells with slight diffuse interstitial fibrosis and tubular atrophy. Technical difficulty resulted in suboptimal immunofluorescent study, but there was no marked staining for IgG, IgM, IgA, or C3. Electron microscopy revealed the glomerular basement membrane to be of normal width with occasional subendothelial and intramembranous deposits of low and medium density. The patient was initially treated with plasmapheresis, azathioprine, and 1 g of methylprednisolone intravenously for three days followed by high-dose prednisone. Multiple blood and urine cultures showed no growth, but oxacillin was continued because of the recent history of staphylococcal bacteremia. The serum creatinine level rose to 4.2 mg/dl after two weeks in the hospital but then progressively fell. He continued to receive azathioprine, with gradual reduction in the dosage of prednisone; after seven weeks, the serum creatinine level had decreased to 1.6 mg/dl. The patient then underwent cardiac catheterization to define the structure seen on echocardiography. An anomalous structure on the left lateral-posterior wall with rapid filling from the left circumflex coronary artery was evident. Two days later, surgery was performed, and a mycotic aneurysm of the mid-left circumflex coronary artery, which contained 50 ml of necrotic material, was discovered. The structure extended into the myocardium but did not reach the endocardium. Detailed descriptions of cardiac findings are reported elsewhere [4]. Direct exploration of the left atrium and mitral valve showed no evidence of previous or current endocarditis. The aneurysm and surrounding necrotic material were resected, and a saphenous vein bypass graft was placed. Culture and stains of the resected tissue disclosed no organisms. Several days after
Figure 1. Renal allograft biopsy specimen showing a glomerulus with hypercellularity of the glomerular tuft and an extracapillary crescent (periodic acid-Schiff stain; original magnification X 320).
surgery, the patient had a cardiac arrest, cerebral infarction developed, and he eventually died; postmortem examination was not performed. COMMENTS
The glomerulonephritis in this patient was temporally related to the infection in the left circumflex artery and was probably causally related, perhaps as a result of immune complex deposition. Diffuse proliferative glomerulonephritis with extracapillary crescents secondary to bacterial endocarditis [5] or visceral abscesses [6] has been reported. The histologic findings in this case were not characteristic of transplant rejection, and it is unlikely that the nephritis represented a recurrence of the disease that involved his native kidneys. The absence of detectable immune complexes in the serum of this patient could be due to prior antibiotic treatment, since immune complexes may disappear from the circulation in patients with endocarditis during treatment, at the same time that blood culture results become negative [7]. The absence of immunofluorescent staining for immunoglobulins or C3 is not unexpected, since other investigators have found negative immunofluorescent results in a significant number of patients with glomerulonephritis complicating subacute bacterial endocarditis [ 5,8]. The mechanism of glomerular injury in these cases remains speculative.
May 1984
The American Journal of Medicine
Volume 76
941
POSTINFECTIOUS
GLOMERULONEPHRlTlS
IN A RENAL ALLOGRAFT-NEBEKER
ET AL
Of interest is the fact that maintenance immunosuppression to prevent graft rejection did not prevent nephritis, possibly of immunologic origin, in this case. A recent report described a patient with a renal allografi
artery, but there was no evidence of glomerulonephritis [9]. This case appears to be the first report of glomerulonephritis associated with a mycotic aneurysm of a coronary artery as well as a rare instance of post-
who died of a ruptured mycotic
infectious
aneurysm
of a coronary
glomerulonephritis
in a renal graft.
REFERENCES 1.
2. 3. 4.
5.
942
Sonnabend W, Kistler GS, Thiel G, et al: Chronische Herdglomerulitis und chronisch persistierende Hepatitis nach Nierentransplantation: Nachweiss von Hepatitis 6 und Epstein-Barr-virus Antigen. Schweiz Med Wochenschr 1974; 104: 1205-1217. Case records of the Massachusetts General Hospital (case 6-1967). N Engl J Med 1967; 276: 338-345. Crook BRM, Raftery EB, Oram S: Mycotic aneurysms of coronary arteries. Br Heart J 1979; 35: 107-109. Feld G, Tei C, Nebeker HG, et al: Ruptured mycotic aneurysm of the circumflex artery as a late sequela of staphylococcal bacteremia. Submitted. Morel-Maroger L, Sraer J-D, Herveman G, Godeau P: Kid-
May 1984
The American Journal ol Medicine
Volume 76
6.
7.
8.
9.
ney in subacute endocarditis. Arch Pathol 1972; 94: 205213. Beaufils M, MoreCMaroger L, Sraer J-D, Kanfer A, Kourilsky 0, Richet G: Acute renal failure of glomerular origin during visceral absesses. N Engl J Med 1976; 295: 185-189. Bayer AS, Theofilopoulos AN, Eisenberg R, Dixon FJ. Guze LB: Circulating immune complexes in infective endocarditis. N Engl J Med 1976; 295: 1500-1505. BouttonJones JM, Sissons JGP, Evans DJ, Peters DK: Renal lesions of subacute infective endocarditis. Br Med J 1974; 2: 11-14. McGee MB, Khan MY: Ruptured mycotic aneurysm of a coronary artery. Arch Intern Med 1980; 140: 1097-1098.