ARTERIOVENOUS
FISTULA
COMPLICATING
RENAL TRANSPLANTATION W. M. BENNETT, D. STRONG, J. R&SCH,
M.D.
M.D.
M.D.
From the Departments of Medicine, Urology, and Radiology, University of Oregon Health Sciences Center, Portland, Oregon
ABSTRACT -A case of arteriovenous fktula of the major transplant vessels contributing to posttransplant hypertension and severe microangiopathic hemolytic anemia is reported. lmprovement in blood pressure and correction of anemia followed ligation of thefistula. This case reinforces the needfor diagnostic evaluation of all patients with sustained post-transplant hypertension.
In the angiographic assessment of patients with post-transplant hypertension, a high incidence of major vascular lesions has been reported.‘,’ The importance of proper diagnosis for correction of hypertension and preservation of renal function was emphasized by Bennett et a1.3 The present report concerns a patient investigated because of post-transplant hypertension who was shown to have an arteriovenous fistula between the major vessels of the transplant. Ligation of the fistula corrected a severe microangiopathic hemolytic anemia and improved management of the patient’s hypertension. Case Report A 28-year-old Caucasian male with renal failure, hypertension, and chronic glomerulonephritis underwent a cadaver renal transplant on April 26, 1974. The donor kidney had two main renal arteries which were spatulated and then sewn together to form a single orifice which was anastomosed to the recipient internal iliac artery. Warm ischemia time was twenty-four minutes. Postoperatively, although an allograft bruit was noted on the first day, there was a five-day period of oliguria necessitating one hemodialysis treatment. Technetium-99m radioisotope scans on days 1 and 3 showed even perfusion of the entire
254
renal mass except for the upper pole where uptake was delayed. On the fifth postoperative day diuresis began, and by the tenth postoperative day serum creatinine was 0.8 mg. per 100 ml. A presumed rejection episode on the twenty-first postoperative day was treated for five days with intravenous methylprednisolone and local graft irradiation with prompt improvement in renal function. Daily immunosuppressive regimen at discharge on the thirty-fifth postoperative day was azathioprine 50 mg., prednisone 20 mg., and 8 ml. of equine antilymphocyte serum. Because of persistent hypertension the patient was also maintained on hydralazine, propranolol, and furosemide (Lasix). Creatinine clearance was 72 ml. per minute. In August, 1974, the patient was readmitted to the hospital to investigate persistent diastolic hypertension of 120 mm. Hg and a drop in creatinine clearance to 52 ml. per minute. On physical examination the bruit over the transplant was considerably louder than had been noted previously. A distinct thrill over the graft was palpable. A grade 3/6 systolic ejection murmur was noted at the base of the heart. With added intravenous methylprednisolone, graft irradiation, antihypertensives, and dipyridamole, creatinine clearance improved to 70 ml. per minute and diastolic pressures were stable between
UROLOGY
/ SEPTEMBER
1976 / VOLUME
VIII,
NUMBER
3
FIGURE 1. (A) Selective arteriogram of transplanted kidney with injection 0; contrast medium at anastomotic site. There are two renal arteries. From segmental branch of one renal artery about 2 cm. from anastomotic site, large polar renal vein (arrowheads) and its enlarged intrarenal branches $11.Via intrarenal venous anastomoses, contrast medium visualizes main renal (arrows) and iliac veins and distal inferior caval vein. There is only poor visualization of arterial system of transplanted kidney. (B) Selective arteriogram of transplanted kidney with injection of contrast medium directly into arteriovenous j&tulu. There is detailed visualization of enlarged polar vein branches, their intrarenal connections, main renal, iliac, and distal inferior caval veins.
90 and 100. The ggmT~ (technetium-99m) radioisotope scan showed again decreased capillary perfusion of the superior pole; and although an open renal biopsy showed only minimal changes, rejection was considered the most likely diagnosis. Hematocrit at discharge was 32. In October, 1974, the patient began to complain of fatigue. Blood pressure was 180/120 mm. Hg, the transplant bruit and thrill were louder, and the heart murmur was noted again. Erythroid values showed a severe normocytic anemia with many nucleated red blood cells and schistocytes in the peripheral blood film. Hematocrit was 16 with 2.8 red cells per cubic centimeter. Bone marrow aspiration revealed erythroid hyperplasia with a 4 per cent peripheral reticulocytosis. Stool was repeatedly negative for occult blood, and upper gastrointestinal series, barium enema, and sigmoidoscopy revealed no bleeding lesions. Platelets were 170,000 per cubic centimeter, and white courlt was 3,600. Liver function tests, folic acid, B12, and serum iron were normal, and the Goombs test was negative. There was no
evidence of disseminated intravascular coagulation. Antinuclear antibody and antinative deoxyribonucleic acid antibody binding was also normal. Urinalysis was normal, blood urea nitrogen was 27 mg. and serum creatinine 1.5 mg. per 100 ml., and creatinine clearance 60 ml. per minute. Daily medications were prednisone 20 mg., azathioprine 50 mg., dipyridamole 150 mg., methyldopa 2 Gm., hydralazine 200 mg., propranolol 320 mg., and furosemide 160 mg. After three days on a lo-mEq. sodium diet, the patient underwent renal transplant arteriography and venous sampling from the transplant vein and his own diseased kidneys for renin activity determined by radioimmunoassay of angiotensin I. The arteriogram demonstrated an arteriovenous fistula 2 cm. from the anastomotic site between a segmental branch of renal artery and a large polar vein (Fig. 1A and B). The renin values are shown in Table I. On October 28, 1974, the patient underwent surgical exploration. A fistulous connection between one of the two main renal arteries and an
upper pole vein was noted 2 cm. distal to the internal iliac anastomosis. The palpable thrill disappeared when the fistula was ligated. The patient’s postoperative course was complicated by an ipsilateral thrombosis of the right external iliac artery, which tias managed conservatively. Blood urea nitrogen was 31 mg. and creatinine 1.2 mg.
per 100 ml. Angiography was repeated in December, 1974, and showed a 50 per cent narrowing of the transplant artery at the site of fistula ligation and good cortical perfusion. Postoperative renin activities are shown in Table I. TABLE I.
Sampling Site Internal iliac below transplant Transplant vein Internal iliac above transplant Vena cava below kidneys Right renal vein Left renal vein Vena cava above kidneys
Renin activity
-Renin Activity*After Fistula Before Fistula Ligation Ligation 16.3 16.0
12.0 15.0
17.8
15.3
18.0 30.0 30.5
16.4 51.4 50.8
18.6
16.5
*Nanograms per milliliter per hour on lo-mEq. diet.
sodium
The patient’s erythroid values rose rapidly, and two months after fistula ligation his hematocrit was 36, hemoglobin 8.4 Gm. per 100 ml., and red blood count 4.2 million per cubic centimeter. No schistocytes were seen in the peripheral blood. Blood pressure normalized on his usual medications to 150/80 mm. Hg. The patient was last seen four months after fistula ligation feeling well with a blood pressure of 155/80 mm. Hg, hematocrit 32, blood ‘urea nitrogen 31 mg. and creatinine 1.6 mg. per 100 ml., and creatinine clearance 61 ml. per minute. No heart murmur was audible. Comment Hypertension in the post-transplant period is relatively common and has usually been attributed to the recipient’s old kidneys or corticosteroid therapy. 4*5Bennett et al. have found a high incidence of vascular disease in the major transplant vessels as well as in smaller vessels of hypertensive post-transplant patients and emphasized an aggressive diagnostic approach to exclude potentially reversible causes of increased blood
256
pressure in these patients.3 In the course of such an evaluation a large arteriovenous fistula between the major transplant vessels was discovered. There have been no previous reports of this major vessel complication. Nivani, Christos, and Athanasoulis6 and Diaz-Buxo, Kopen, and Donadio7 described intrarenal arteriovenous fistulas in allografts following needle biopsy of the transplant. Our patient had abnormal perfusion isotope scans, hypertension, and a thrill over his allograft prior to his renal biopsy. Further, the anatomic location of the fistula 2 cm. from the anastomotic site makes the biopsy remote as an etiologic factor. Injury to the major transplant vessels, either surgical or immunologic, could be postulated as more likely causes of this complication The need to connect the two donor arteries at the time of transplant is of interest in this regard. It is possible that one of the renal arteries was in fact a thick-walled vein. In the absence of pathologic examination of the whole kidney, the exact cause must remain speculative. The cause of the patient’s hypertension and the precise role of the arteriovenous fistula is unclear. Renal scans appeared to indicate some upper pole renal ischemia from the time of transplant; however, the lack of a significant differential elevation of renin activity in the venous drainage of the allograft with the patient on a low-sodium diet is evidence against a significant ischemic process. Also, there was no histologic evidence of vascular disease on either the angiogram or the renal biopsy to implicate the small vessel abnormalities which so frequently accompany rejection. The relatively small daily dose of prednisone cannot be ignored; however, it does not usually cause pressure elevations this severe, especially when allograft function is maintained. It then becomes necessary to implicate the old diseased kidneys or the hemodynamic effects of the fistula itself. Indeed, Cohen5 and Papadimitriov, Shackman, and Chisholm’ believed that old kidneys were a frequent etiologic factor in post-transplant hypertension; however, other authors have shown that significant numbers of normotensive posttransplant patients have not been nephrectomized.3 Furthermore, hypertension develops in many transplant patients despite pretransplant bilateral nephrectomy. In view of the marked improvement in blood pressure following fistula ligation, nephrectomy was not believed to be necessary. Since no hemodynamic studies were done before and after fistula ligation, it is impossible to prove conclu-
UROLOGY /
SEPTEMBER 1976 /
VOLUME VIII, NUMBER 3
sively a major role for the fistula. The postoperative disappearance of the fistula, thrill, and the heart murmur, combined with correction of the microangiopathic hemolytic anemia, and improvement in blood pressure control are suggestive of a relationship. This is especially true since the old kidneys are still in situ, and the major artery to the transplanted kidney was slightly narrowed by the corrective surgery. Portland, Oregon 97201 (DR. BENNETT) References 1. SMELLIE. W. A. B., VINIK, M., and HUME, D. M.: Angiographic investigation of hypertension complicating human renal transplantation, Surg. Gynecol. Obstet. 128: 963 (1969). 2. MORRIS, P. J., et al. : Renal artery stenosis in renal
UROLOGY
transplantation, Med. J. Aust. 1: 1255 (1971). 3. BENNETT, W. M., MCDONALD, W. J.. LAWSON, R. K., hypertension: and PORTER, G. A. : Post-transplant studies of cortical blood flow and the renal pressor system, Kidney Int. 6: 99 (1974). 4. POPOVTZER, M. M., et al. : Variations in arterial blood pressure after kidney transplantation: relation to renal function, plasma renin activity and the dose of prednisone, Circulation 47: 1297 (1973). 5. COHEN, S. L. : Hypertension in renal transplant recipients: role of bilateral nephrectomy. Br. Med. J. 3: 78 (1973). 6. NIVANI, S., CHRISTOS, F. F., and A~HANASOULIS, spectrum of angioA. : Renal homotransplantation: graphic findings of the kidney, Am. J. Roentgenol. Radium Ther. Nucl. Med. 113: 433 (1971). 7. DIAZ-BUXO, J. A., KOPEN, D. F., and DONADIO, J. V. : Renal allograft arteriovenous fistula following percutaneous biopsy, J. Urol. 112: 577 (1974). 8. PAPADIMITRIOV, M., SHACKMAN, R., and CHISHOLM, G. D.: Hypertension in patients on regular dialysis and after renal allotransplantation, Lancrt 1: 902 (1969).
/ SEYtYEMBER 1976 / VOLUME VIII, NUMBER 3
257
FISTULA
COMPLICATING
RENAL TRANSPLANTATION W. M. BENNETT, D. STRONG, J. R&SCH,
M.D.
M.D.
M.D.
From the Departments of Medicine, Urology, and Radiology, University of Oregon Health Sciences Center, Portland, Oregon
ABSTRACT -A case of arteriovenous fktula of the major transplant vessels contributing to posttransplant hypertension and severe microangiopathic hemolytic anemia is reported. lmprovement in blood pressure and correction of anemia followed ligation of thefistula. This case reinforces the needfor diagnostic evaluation of all patients with sustained post-transplant hypertension.
In the angiographic assessment of patients with post-transplant hypertension, a high incidence of major vascular lesions has been reported.‘,’ The importance of proper diagnosis for correction of hypertension and preservation of renal function was emphasized by Bennett et a1.3 The present report concerns a patient investigated because of post-transplant hypertension who was shown to have an arteriovenous fistula between the major vessels of the transplant. Ligation of the fistula corrected a severe microangiopathic hemolytic anemia and improved management of the patient’s hypertension. Case Report A 28-year-old Caucasian male with renal failure, hypertension, and chronic glomerulonephritis underwent a cadaver renal transplant on April 26, 1974. The donor kidney had two main renal arteries which were spatulated and then sewn together to form a single orifice which was anastomosed to the recipient internal iliac artery. Warm ischemia time was twenty-four minutes. Postoperatively, although an allograft bruit was noted on the first day, there was a five-day period of oliguria necessitating one hemodialysis treatment. Technetium-99m radioisotope scans on days 1 and 3 showed even perfusion of the entire
254
renal mass except for the upper pole where uptake was delayed. On the fifth postoperative day diuresis began, and by the tenth postoperative day serum creatinine was 0.8 mg. per 100 ml. A presumed rejection episode on the twenty-first postoperative day was treated for five days with intravenous methylprednisolone and local graft irradiation with prompt improvement in renal function. Daily immunosuppressive regimen at discharge on the thirty-fifth postoperative day was azathioprine 50 mg., prednisone 20 mg., and 8 ml. of equine antilymphocyte serum. Because of persistent hypertension the patient was also maintained on hydralazine, propranolol, and furosemide (Lasix). Creatinine clearance was 72 ml. per minute. In August, 1974, the patient was readmitted to the hospital to investigate persistent diastolic hypertension of 120 mm. Hg and a drop in creatinine clearance to 52 ml. per minute. On physical examination the bruit over the transplant was considerably louder than had been noted previously. A distinct thrill over the graft was palpable. A grade 3/6 systolic ejection murmur was noted at the base of the heart. With added intravenous methylprednisolone, graft irradiation, antihypertensives, and dipyridamole, creatinine clearance improved to 70 ml. per minute and diastolic pressures were stable between
UROLOGY
/ SEPTEMBER
1976 / VOLUME
VIII,
NUMBER
3
FIGURE 1. (A) Selective arteriogram of transplanted kidney with injection 0; contrast medium at anastomotic site. There are two renal arteries. From segmental branch of one renal artery about 2 cm. from anastomotic site, large polar renal vein (arrowheads) and its enlarged intrarenal branches $11.Via intrarenal venous anastomoses, contrast medium visualizes main renal (arrows) and iliac veins and distal inferior caval vein. There is only poor visualization of arterial system of transplanted kidney. (B) Selective arteriogram of transplanted kidney with injection of contrast medium directly into arteriovenous j&tulu. There is detailed visualization of enlarged polar vein branches, their intrarenal connections, main renal, iliac, and distal inferior caval veins.
90 and 100. The ggmT~ (technetium-99m) radioisotope scan showed again decreased capillary perfusion of the superior pole; and although an open renal biopsy showed only minimal changes, rejection was considered the most likely diagnosis. Hematocrit at discharge was 32. In October, 1974, the patient began to complain of fatigue. Blood pressure was 180/120 mm. Hg, the transplant bruit and thrill were louder, and the heart murmur was noted again. Erythroid values showed a severe normocytic anemia with many nucleated red blood cells and schistocytes in the peripheral blood film. Hematocrit was 16 with 2.8 red cells per cubic centimeter. Bone marrow aspiration revealed erythroid hyperplasia with a 4 per cent peripheral reticulocytosis. Stool was repeatedly negative for occult blood, and upper gastrointestinal series, barium enema, and sigmoidoscopy revealed no bleeding lesions. Platelets were 170,000 per cubic centimeter, and white courlt was 3,600. Liver function tests, folic acid, B12, and serum iron were normal, and the Goombs test was negative. There was no
evidence of disseminated intravascular coagulation. Antinuclear antibody and antinative deoxyribonucleic acid antibody binding was also normal. Urinalysis was normal, blood urea nitrogen was 27 mg. and serum creatinine 1.5 mg. per 100 ml., and creatinine clearance 60 ml. per minute. Daily medications were prednisone 20 mg., azathioprine 50 mg., dipyridamole 150 mg., methyldopa 2 Gm., hydralazine 200 mg., propranolol 320 mg., and furosemide 160 mg. After three days on a lo-mEq. sodium diet, the patient underwent renal transplant arteriography and venous sampling from the transplant vein and his own diseased kidneys for renin activity determined by radioimmunoassay of angiotensin I. The arteriogram demonstrated an arteriovenous fistula 2 cm. from the anastomotic site between a segmental branch of renal artery and a large polar vein (Fig. 1A and B). The renin values are shown in Table I. On October 28, 1974, the patient underwent surgical exploration. A fistulous connection between one of the two main renal arteries and an
upper pole vein was noted 2 cm. distal to the internal iliac anastomosis. The palpable thrill disappeared when the fistula was ligated. The patient’s postoperative course was complicated by an ipsilateral thrombosis of the right external iliac artery, which tias managed conservatively. Blood urea nitrogen was 31 mg. and creatinine 1.2 mg.
per 100 ml. Angiography was repeated in December, 1974, and showed a 50 per cent narrowing of the transplant artery at the site of fistula ligation and good cortical perfusion. Postoperative renin activities are shown in Table I. TABLE I.
Sampling Site Internal iliac below transplant Transplant vein Internal iliac above transplant Vena cava below kidneys Right renal vein Left renal vein Vena cava above kidneys
Renin activity
-Renin Activity*After Fistula Before Fistula Ligation Ligation 16.3 16.0
12.0 15.0
17.8
15.3
18.0 30.0 30.5
16.4 51.4 50.8
18.6
16.5
*Nanograms per milliliter per hour on lo-mEq. diet.
sodium
The patient’s erythroid values rose rapidly, and two months after fistula ligation his hematocrit was 36, hemoglobin 8.4 Gm. per 100 ml., and red blood count 4.2 million per cubic centimeter. No schistocytes were seen in the peripheral blood. Blood pressure normalized on his usual medications to 150/80 mm. Hg. The patient was last seen four months after fistula ligation feeling well with a blood pressure of 155/80 mm. Hg, hematocrit 32, blood ‘urea nitrogen 31 mg. and creatinine 1.6 mg. per 100 ml., and creatinine clearance 61 ml. per minute. No heart murmur was audible. Comment Hypertension in the post-transplant period is relatively common and has usually been attributed to the recipient’s old kidneys or corticosteroid therapy. 4*5Bennett et al. have found a high incidence of vascular disease in the major transplant vessels as well as in smaller vessels of hypertensive post-transplant patients and emphasized an aggressive diagnostic approach to exclude potentially reversible causes of increased blood
256
pressure in these patients.3 In the course of such an evaluation a large arteriovenous fistula between the major transplant vessels was discovered. There have been no previous reports of this major vessel complication. Nivani, Christos, and Athanasoulis6 and Diaz-Buxo, Kopen, and Donadio7 described intrarenal arteriovenous fistulas in allografts following needle biopsy of the transplant. Our patient had abnormal perfusion isotope scans, hypertension, and a thrill over his allograft prior to his renal biopsy. Further, the anatomic location of the fistula 2 cm. from the anastomotic site makes the biopsy remote as an etiologic factor. Injury to the major transplant vessels, either surgical or immunologic, could be postulated as more likely causes of this complication The need to connect the two donor arteries at the time of transplant is of interest in this regard. It is possible that one of the renal arteries was in fact a thick-walled vein. In the absence of pathologic examination of the whole kidney, the exact cause must remain speculative. The cause of the patient’s hypertension and the precise role of the arteriovenous fistula is unclear. Renal scans appeared to indicate some upper pole renal ischemia from the time of transplant; however, the lack of a significant differential elevation of renin activity in the venous drainage of the allograft with the patient on a low-sodium diet is evidence against a significant ischemic process. Also, there was no histologic evidence of vascular disease on either the angiogram or the renal biopsy to implicate the small vessel abnormalities which so frequently accompany rejection. The relatively small daily dose of prednisone cannot be ignored; however, it does not usually cause pressure elevations this severe, especially when allograft function is maintained. It then becomes necessary to implicate the old diseased kidneys or the hemodynamic effects of the fistula itself. Indeed, Cohen5 and Papadimitriov, Shackman, and Chisholm’ believed that old kidneys were a frequent etiologic factor in post-transplant hypertension; however, other authors have shown that significant numbers of normotensive posttransplant patients have not been nephrectomized.3 Furthermore, hypertension develops in many transplant patients despite pretransplant bilateral nephrectomy. In view of the marked improvement in blood pressure following fistula ligation, nephrectomy was not believed to be necessary. Since no hemodynamic studies were done before and after fistula ligation, it is impossible to prove conclu-
UROLOGY /
SEPTEMBER 1976 /
VOLUME VIII, NUMBER 3
sively a major role for the fistula. The postoperative disappearance of the fistula, thrill, and the heart murmur, combined with correction of the microangiopathic hemolytic anemia, and improvement in blood pressure control are suggestive of a relationship. This is especially true since the old kidneys are still in situ, and the major artery to the transplanted kidney was slightly narrowed by the corrective surgery. Portland, Oregon 97201 (DR. BENNETT) References 1. SMELLIE. W. A. B., VINIK, M., and HUME, D. M.: Angiographic investigation of hypertension complicating human renal transplantation, Surg. Gynecol. Obstet. 128: 963 (1969). 2. MORRIS, P. J., et al. : Renal artery stenosis in renal
UROLOGY
transplantation, Med. J. Aust. 1: 1255 (1971). 3. BENNETT, W. M., MCDONALD, W. J.. LAWSON, R. K., hypertension: and PORTER, G. A. : Post-transplant studies of cortical blood flow and the renal pressor system, Kidney Int. 6: 99 (1974). 4. POPOVTZER, M. M., et al. : Variations in arterial blood pressure after kidney transplantation: relation to renal function, plasma renin activity and the dose of prednisone, Circulation 47: 1297 (1973). 5. COHEN, S. L. : Hypertension in renal transplant recipients: role of bilateral nephrectomy. Br. Med. J. 3: 78 (1973). 6. NIVANI, S., CHRISTOS, F. F., and A~HANASOULIS, spectrum of angioA. : Renal homotransplantation: graphic findings of the kidney, Am. J. Roentgenol. Radium Ther. Nucl. Med. 113: 433 (1971). 7. DIAZ-BUXO, J. A., KOPEN, D. F., and DONADIO, J. V. : Renal allograft arteriovenous fistula following percutaneous biopsy, J. Urol. 112: 577 (1974). 8. PAPADIMITRIOV, M., SHACKMAN, R., and CHISHOLM, G. D.: Hypertension in patients on regular dialysis and after renal allotransplantation, Lancrt 1: 902 (1969).
/ SEYtYEMBER 1976 / VOLUME VIII, NUMBER 3
257
