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Reversible renal artery stenosis in renal transplantation
REVERSIBLE
RENAL ARTERY STENOSIS
IN
RENAL TRANSPLANTATION
P. J. VAN CANGH, J. DAUTREBANDE, Y. PIRSON,
M.D. M.D.
M.D.
C. VAN YPERSELE G. P. J. ALEXANDRE,
DE
STRIHOU,
M.D.
M.D.
From the Departments of Uroldgy, Radiology, Nephrology, and Transplantation, Cliniques Universitaires St-Luc, and University of Louvain Medical School, Belgium
ABSTRACT - Spontaneous regression of an arterial stenosis in a renal transplant recipient is documented. Implications of this observation and possible pathogenic mechanisms are discussed.
Sustained blood pressure elevation remains a serious problem in transplanted patients.’ To unravel its cause, much energy has been devoted to the discovery of transplant artery stenosis with a hope to obtain a surgical cure. Renal artery stenosis, described in up to 25 per cent of renal transplant recipients in a systematic study,’ is by no means always associated with hypertension. Conversely, hypertension may be unrelated to concomitant arterial stenosis of the graft; a fact that should lead to a cautious approach to surgical repair in hypertensive patients. To support this thesis, we present a case report of spontaneous regression of renal transplant artery stenosis. Case Report This eight-year-old girl had been on chronic hemodialysis since January, 1976, for end stage renal disease. A left nephrectomy had been performed in 1973 for hypertension and urinary tract infection. Pathologic examination disclosed renal hypoplasia with extensive pyelonephritic On July 5, 1976, the mother’s right scarring. kidney was transplanted into the left iliac fossa. At that time blood pressure averaged 130/70 mm. Hg. The two renal arteries were anastomosed, respectively, end to side to the com-
UROLOGY
/ MAY 1979
/ VOLUME
XIII,
NUMBER
5
mon iliac and end to end to the internal iliac arteries with interrupted 6-O monofilament sutures. On the seventh postoperative day, a mild rejection episode was easily reversed by intravenous corticoids, antilymphocyte globulin, and local graft irradiation (150 r). At the time of discharge, on August 5, 1976, the girl had a normal blood pressure (130/70 mm. Hg) without antihypertensive medication. Her serum creatinine was 0.7 mg./dl. A second, severe, rejection episode occurred in October, 1976. Serum creatinine rose to 4.8 mg./dl. Transplant biopsy revealed signs of acute rejection without vascular lesions. Blood pressure rose transiently during the intravenous administration of high doses of steroids. At the time of discharge, blood pressure was maintained at 130/70 mm. Hg with clonidine (Catapres)” 0.1 mg. three times a day. Serum creatinine was 0.9 mg./dl. One month later, the patient was readmitted with a blood pressure of 240/130 mm. Hg. An abdominal angiogram performed on January 24, 1977, disclosed a high-grade stenosis (> 90 per cent) of the main renal artery at a short distance distal to the anastomosis and another lesion with moderate stenosis (50 per cent) in the lower *Boehringer-Ingelheim,
Ridgefield,
Connecticut
06877.
529
FIGURE 1. Abdominal angiograms: (A) shows high-grade stenosis of main renal artery at short distance distal to anastomosis and another lesion with moderate stenosis in lower artery; (B) shows marked decrease of both renal artery stenoses and disappearance of poststenotic dilatation.
artery (Fig. 1A). Medical treatment consisting of low-salt diet, 125-250 mg. a-methyldopa three times a day, and 100 mg. (oral diuretic) chlorthalidone” daily returned blood pressure to an average of 130/80 mm. Hg for more than one year. In February, 1978, her blood pressure rose again to 230/100 mm. Hg in the absence of any sign of rejection. Serum creatinine remained at 0.8 mg./dl. A repeat angiogram on February 24, 1978, revealed a marked decrease of both renal artery stenoses (Fig. 1B) and the disappearance of the poststenotic dilatation. Plasma renin activity was normal both in the peripheral and transplant veins but markedly elevated (10 times normal values) in the remaining native kidney. This observation strongly suggests that the patient’s own kidney was responsible for perpetuating the hypertension. At the present time, blood pressure remains at 120/80 mm. Hg with antihypertensive therapy consisting of a low-salt diet, chlorthalidone 50 mg. daily, and a-methyldopa 250 mg. three times a day. Serum creatinine is stable at 0.9 mg./dl.
“Boehringer-Ingelheim,
530
Ridgefield,
Connecticut
06877.
Comment We believe this is the second case in which spontaneous regression of a renal transplant artery stenosis is reported.3 How often such a phenomenon occurs is unknown. However, its existence should be taken into account when surgical repair is contemplated. A definite explanation of our observation cannot be provided. The possibility of an x-ray artefact is remote in view of the importance of the lesion and the existence of a poststenotic dilatation. It is also unlikely that the evolution of the stenosis was related to a transient traumatic or technical defect associated with the vascular suture. The stenoses occurred in both renal arteries and were located distal to the site of anastomosis. Furthermore, the nephrectomy of the living donor was uneventful, and the graft’s arteries were not cannulated. The hypothesis that both the development and the regression of the arterial stenoses were related to immunologic injury with subsequent healing remains an intriguing possibility. There is experimental evidence that circulating immune complexes can produce stenotic lesions of medium size arteries.4
UROLOGY
/ MAY 1979 / VOLUME
XIII,
NUMBER 5
IgM and C3 deposits have been identified in the removed segment of stenotic renal transplant arteries in 3 patients.596 Interestingly, Kaufman, Ehrlich, and Dornfeld’ have reported 4 cases of renal artery stenosis discovered in young patients in a context of acute inflammatory disease. In one of them, the stenotic artery contained IgM, and C3, and fibrinogen deposits. In another one renal artery stenosis recurred after autotransplantation coincidentally with the removal of the tonsils. Spontaneous improvement was demonstrated nine and eighteen months later on repeated angiograms. This latter observation was tentatively attributed to the healing of an immunologically induced lesion of the artery. Whatever its explanation, our observation of the spontaneous regression of a severe renal artery stenosis recommends a conservative attitude when such a lesion is identified in a hypertensive transplant recipient. Surgical repair with its attendant risk should be under-
UROLOGY
/
MAY 1979
/
VOLUME
XIII,
NUMBER
5
taken only if severe hypertension proves resistant to medical therapy or if renal function deteriorates rapidly. 1200 Brussels, Belgium (DR. VAN CANGH)
References 1. Bachy C, Alexandre GP, and van Ypersele de Strihou C: Hypertension after renal transplantation, Br. Med. J. 2: 1287 (1976). 2. Lacombe M: Arterial stenosis complicating renal allotransplantation in man: a study of 38 cases, Ann. Surg. 181: 283 (1975). 3. Vegter AJ, Bosch E, Westra D, and Linschoten H: Spontaneous reversible renal artery stenosis after renal allotransplantation, Br. Med. J. 1: 1028 (1978). 4. Germuth FG: A comparative histologic and immunologic study in rabbits of induced hypersensitivity of serum sickness type, J. Exp. Med. 97: 257 (1953). 5. Smith RB, et al: Diagnosis and management of arterial stenosis causing hypertension after successml renal transplantation, J. Ural. 115: 639 (1976). 6. Kaufman JJ, Ehrhch RM, and Dornfeld L: Immunologic considerations in renovascular hypertension, ibid. 116: 142 (1976).
531
RENAL ARTERY STENOSIS
IN
RENAL TRANSPLANTATION
P. J. VAN CANGH, J. DAUTREBANDE, Y. PIRSON,
M.D. M.D.
M.D.
C. VAN YPERSELE G. P. J. ALEXANDRE,
DE
STRIHOU,
M.D.
M.D.
From the Departments of Uroldgy, Radiology, Nephrology, and Transplantation, Cliniques Universitaires St-Luc, and University of Louvain Medical School, Belgium
ABSTRACT - Spontaneous regression of an arterial stenosis in a renal transplant recipient is documented. Implications of this observation and possible pathogenic mechanisms are discussed.
Sustained blood pressure elevation remains a serious problem in transplanted patients.’ To unravel its cause, much energy has been devoted to the discovery of transplant artery stenosis with a hope to obtain a surgical cure. Renal artery stenosis, described in up to 25 per cent of renal transplant recipients in a systematic study,’ is by no means always associated with hypertension. Conversely, hypertension may be unrelated to concomitant arterial stenosis of the graft; a fact that should lead to a cautious approach to surgical repair in hypertensive patients. To support this thesis, we present a case report of spontaneous regression of renal transplant artery stenosis. Case Report This eight-year-old girl had been on chronic hemodialysis since January, 1976, for end stage renal disease. A left nephrectomy had been performed in 1973 for hypertension and urinary tract infection. Pathologic examination disclosed renal hypoplasia with extensive pyelonephritic On July 5, 1976, the mother’s right scarring. kidney was transplanted into the left iliac fossa. At that time blood pressure averaged 130/70 mm. Hg. The two renal arteries were anastomosed, respectively, end to side to the com-
UROLOGY
/ MAY 1979
/ VOLUME
XIII,
NUMBER
5
mon iliac and end to end to the internal iliac arteries with interrupted 6-O monofilament sutures. On the seventh postoperative day, a mild rejection episode was easily reversed by intravenous corticoids, antilymphocyte globulin, and local graft irradiation (150 r). At the time of discharge, on August 5, 1976, the girl had a normal blood pressure (130/70 mm. Hg) without antihypertensive medication. Her serum creatinine was 0.7 mg./dl. A second, severe, rejection episode occurred in October, 1976. Serum creatinine rose to 4.8 mg./dl. Transplant biopsy revealed signs of acute rejection without vascular lesions. Blood pressure rose transiently during the intravenous administration of high doses of steroids. At the time of discharge, blood pressure was maintained at 130/70 mm. Hg with clonidine (Catapres)” 0.1 mg. three times a day. Serum creatinine was 0.9 mg./dl. One month later, the patient was readmitted with a blood pressure of 240/130 mm. Hg. An abdominal angiogram performed on January 24, 1977, disclosed a high-grade stenosis (> 90 per cent) of the main renal artery at a short distance distal to the anastomosis and another lesion with moderate stenosis (50 per cent) in the lower *Boehringer-Ingelheim,
Ridgefield,
Connecticut
06877.
529
FIGURE 1. Abdominal angiograms: (A) shows high-grade stenosis of main renal artery at short distance distal to anastomosis and another lesion with moderate stenosis in lower artery; (B) shows marked decrease of both renal artery stenoses and disappearance of poststenotic dilatation.
artery (Fig. 1A). Medical treatment consisting of low-salt diet, 125-250 mg. a-methyldopa three times a day, and 100 mg. (oral diuretic) chlorthalidone” daily returned blood pressure to an average of 130/80 mm. Hg for more than one year. In February, 1978, her blood pressure rose again to 230/100 mm. Hg in the absence of any sign of rejection. Serum creatinine remained at 0.8 mg./dl. A repeat angiogram on February 24, 1978, revealed a marked decrease of both renal artery stenoses (Fig. 1B) and the disappearance of the poststenotic dilatation. Plasma renin activity was normal both in the peripheral and transplant veins but markedly elevated (10 times normal values) in the remaining native kidney. This observation strongly suggests that the patient’s own kidney was responsible for perpetuating the hypertension. At the present time, blood pressure remains at 120/80 mm. Hg with antihypertensive therapy consisting of a low-salt diet, chlorthalidone 50 mg. daily, and a-methyldopa 250 mg. three times a day. Serum creatinine is stable at 0.9 mg./dl.
“Boehringer-Ingelheim,
530
Ridgefield,
Connecticut
06877.
Comment We believe this is the second case in which spontaneous regression of a renal transplant artery stenosis is reported.3 How often such a phenomenon occurs is unknown. However, its existence should be taken into account when surgical repair is contemplated. A definite explanation of our observation cannot be provided. The possibility of an x-ray artefact is remote in view of the importance of the lesion and the existence of a poststenotic dilatation. It is also unlikely that the evolution of the stenosis was related to a transient traumatic or technical defect associated with the vascular suture. The stenoses occurred in both renal arteries and were located distal to the site of anastomosis. Furthermore, the nephrectomy of the living donor was uneventful, and the graft’s arteries were not cannulated. The hypothesis that both the development and the regression of the arterial stenoses were related to immunologic injury with subsequent healing remains an intriguing possibility. There is experimental evidence that circulating immune complexes can produce stenotic lesions of medium size arteries.4
UROLOGY
/ MAY 1979 / VOLUME
XIII,
NUMBER 5
IgM and C3 deposits have been identified in the removed segment of stenotic renal transplant arteries in 3 patients.596 Interestingly, Kaufman, Ehrlich, and Dornfeld’ have reported 4 cases of renal artery stenosis discovered in young patients in a context of acute inflammatory disease. In one of them, the stenotic artery contained IgM, and C3, and fibrinogen deposits. In another one renal artery stenosis recurred after autotransplantation coincidentally with the removal of the tonsils. Spontaneous improvement was demonstrated nine and eighteen months later on repeated angiograms. This latter observation was tentatively attributed to the healing of an immunologically induced lesion of the artery. Whatever its explanation, our observation of the spontaneous regression of a severe renal artery stenosis recommends a conservative attitude when such a lesion is identified in a hypertensive transplant recipient. Surgical repair with its attendant risk should be under-
UROLOGY
/
MAY 1979
/
VOLUME
XIII,
NUMBER
5
taken only if severe hypertension proves resistant to medical therapy or if renal function deteriorates rapidly. 1200 Brussels, Belgium (DR. VAN CANGH)
References 1. Bachy C, Alexandre GP, and van Ypersele de Strihou C: Hypertension after renal transplantation, Br. Med. J. 2: 1287 (1976). 2. Lacombe M: Arterial stenosis complicating renal allotransplantation in man: a study of 38 cases, Ann. Surg. 181: 283 (1975). 3. Vegter AJ, Bosch E, Westra D, and Linschoten H: Spontaneous reversible renal artery stenosis after renal allotransplantation, Br. Med. J. 1: 1028 (1978). 4. Germuth FG: A comparative histologic and immunologic study in rabbits of induced hypersensitivity of serum sickness type, J. Exp. Med. 97: 257 (1953). 5. Smith RB, et al: Diagnosis and management of arterial stenosis causing hypertension after successml renal transplantation, J. Ural. 115: 639 (1976). 6. Kaufman JJ, Ehrhch RM, and Dornfeld L: Immunologic considerations in renovascular hypertension, ibid. 116: 142 (1976).
531