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Long-term follow up of renal transplant artery stenosis by doppler
Long-Term Follow Up of Renal Transplant Artery Stenosis by Doppler J. Buturovic´-Ponikvar, A. Zˇupunski, A. Urbancˇicˇ, A. Kandus, M. Malovrh, A. Gucˇek, A. Bren, and R. Ponikvar
T
HE INCIDENCE of renal transplant artery stenosis after renal transplantation ranges from 2% to 12%. True incidence is difficult to assess because renal angiography is not performed in all patients; it can be even up to 23%.1– 4 Stenosis can cause hypertension and/or deterioration of renal function. Diagnosing and treating stenosis is important because it can cause graft loss. Introducing duplex Doppler and color Doppler ultrasonography in late 1980s enabled noninvasive diagnosing of stenosis, assessment of its localization and hemodynamic significance, assessment of revascularization success, and follow-up of stenosis in the long term.5,6 We have observed some patients with high-grade stenosis after unsuccessful revascularization, to be stable over years. The purpose of our study was to assess the rate of progression of renal transplant artery stenosis in long-term patients by regular Doppler examination and to study the influence of stenosis on renal function and hypertension.
peak systolic velocity of ⬎2 m/sec (so-called stenotic jet) at the stenotic site. In the case of a normal resistance index at the level of the renal parenchymal vessels, the stenosis was judged to be in the range of 50% to 75%. If a distal »parvus-tardus« pattern was joined to stenotic »jet« of ⬎2 m/sec, the stenosis was considered to be in the range of 75% to 90%.7 All Doppler studies were performed by nephrologists experienced in the technique, using an ultrasound monitor Acuson 128 XP/10 and convex 3.5 MHz probe. The patients were followed for at least 3 and up to 11 years. The peak systolic velocity at the stenotic site, the resistance index at the intrarenal segmental and parenchymal arteries, serum creatinine value, hemoglobin level, blood pressure, and number of hypertensive medications were analysed on a yearly basis. The main indication for angiography and revascularization was deterioration of renal function. Thirteen percutaneous transluminal renal angioplasties (PTRA) of stenosis were performed in 12 patients and four surgical revascularizations in 4 patients. In one patient surgical revascularization followed unsuccessful PTRA. Spontaneous regression of stenosis to nonsignificant level (⬍50%) was observed in 5 of 27 (19%) patients.
PATIENTS AND METHODS
RESULTS
The study included 27 recipients of cadaveric kidneys, 13 men and 14 women, aged 42 ⫾ 13 years. 24/27 patients (89%) received their first and the other 3 their second, renal graft. Fifteen of 27 (56%) were treated with cyclosporine (Neoral) and steroids as maintenance immunosuppression; 12 of 27 were on triple immunosuppressive therapy (Neoral, steroids, azathioprine, or mycophenolate mofetil). Nine acute cellular rejections occurred in 8 of 27 patients (30%). All patients received diltiazem as a standard part of immunosuppressive protocol. All patients were diagnosed to have at least 50% stenosis of the renal transplant artery. Stenoses were primarily diagnosed and regularly followed (at least once yearly and in every occasion when renal function was deteriorating and/or hypertension increasing) by duplex Doppler. In 17 patients, 21 renal angiographic studies were performed (4 patients had angiography performed twice). All of the angiographies confirmed the stenosis previously diagnosed by duplex Doppler. The Doppler criterion to diagnose stenosis was a
The data concerning peak systolic velocity, resistance index, serum creatinine value, hemoglobin level, average blood pressure, and number of antihypertensive medications (excluding diuretics) are presented in Table 1. In the group as a whole (both revascularized or not) there was a tendency toward decreased peak systolic velocity and a corresponding increase in resistance index (which was always within From the Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenija. Supported in part by Ministry of Education, Science and Sport (Grant No L3-1369 and J3-3480). Address reprint requests to Prof Dr Jadranka Buturovic´Ponikvar, Department of Nephrology, University Medical Center Ljubljana, Zalosˇka 7, 1525 Ljubljana, Slovenija.
Table 1. Various Data in Patients With Renal Transplant Artery Stenosis During 3-Year Follow Up (n ⴝ 27)
1 year 2 years 3 years
PSV
RI
Cr
Hb
BP
Th
2.2 ⫾ 0.5 2.0 ⫾ 0.6 1.9 ⫾ 0.5
60 ⫾ 11 64 ⫾ 10 64 ⫾ 9
139 ⫾ 81 117 ⫾ 48 119 ⫾ 52
138 ⫾ 19 138 ⫾ 18 134 ⫾ 20
147/89 138/85 136/84
2.3 ⫾ 1.0 2.6 ⫾ 1.0 2.7 ⫾ 1.2
Abbreviations: PSV, peak systolic velocity (m/s); RI, resistance index (%); Cr, serum creatinine (mol/L); Hb, hemoglobin (g/L); BP, blood pressure (mm Hg); Th, number of antihypertensive medications. Values are presented as mean ⫾ SD.
0041-1345/01/$–see front matter PII S0041-1345(01)02460-5
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3390
Transplantation Proceedings, 33, 3390–3391 (2001)
LONG-TERM FOLLOW UP BY DOPPLER
3391
Table 2. Data for Revascularized (REV; n ⴝ 15) and Nonrevascularized (nREV; n ⴝ 12) Patients With Renal Transplant Artery Stenosis During 3-Year Follow Up
1 year REV nREV 2 years REV nREV 3 years REV nREV
PSV
RI
Cr
Hb
BP
Th
2.3 ⫾ 0.5 2.1 ⫾ 0.4
57 ⫾ 10 63 ⫾ 12
143 ⫾ 81 132 ⫾ 75
135 ⫾ 23 141 ⫾ 13
156/92 139/82
2.1 ⫾ 1.1 2.4 ⫾ 1.2
2.1 ⫾ 0.6 1.9 ⫾ 0.5
64 ⫾ 10 63 ⫾ 12
128 ⫾ 62 100 ⫾ 32
136 ⫾ 21 140 ⫾ 18
148/89 132/80
2.6 ⫾ 1.1 2.5 ⫾ 1.1
2.0 ⫾ 0.6 1.7 ⫾ 0.5
66 ⫾ 9 63 ⫾ 10
130 ⫾ 58 100 ⫾ 35
135 ⫾ 22 132 ⫾ 16
140/86 130/78
2.7 ⫾ 1.2 2.6 ⫾ 1.2
Abbreviations: PSV, peak systolic velocity (m/s); RI, resistance index (%); Cr, serum creatinine (mol/L); Hb, hemoglobin (g/L); BP, blood pressure (mm Hg); Th, number of antihypertensive medications. Values are presented as mean ⫾ SD.
normal limits). The serum creatinine gradually decreased, hemoglobin level was stable and average blood pressure decreased over time along with an increasing number of antihypertensive medications. Diltiazem, as a regular part of immunosuppressive protocol, was included in the number of antihypertensive medications. Table 2 compares the same parameters for patients who were revascularized (by PTRA or surgically) versus those who were only treated conservatively. The trend towards improving stenosis (assessed by decreasing peak systolic velocity in the long-term) is present in both groups. Compared to nonrevascularized patients the revascularized group had a higher peak systolic velocity and a lower resistance index at the beginning, indicating a higher degree of stenosis at the time of diagnosis. DISCUSSION
According to our results, the long-term natural course of renal transplant artery stenosis, whether the patient is revascularized or not, seems to be stable or possibly even regressive. Even spontaneous regression of stenosis to a nonsignificant level (⬍50%) was observed. The majority of stenoses were in the range of 50% to 75% (according to Doppler criteria). Duplex Doppler seems to be an excellent test for monitoring stenosis in the long term. As far as we know, this is the first report of long-term measurement of peak systolic velocity inside the stenosis, together with estimates of the corresponding resistance index. Peak systolic velocity at the stenotic site reflected pretty accurately the grade of stenosis. Regular duplex Doppler examinations seems to help assess the progression of the stenosis and to guide the timing for intervention in individual patients. They also help to detect the regression of the stenosis that was observed in not inconsiderable number of patients (19%). The possibility of reversible stenosis had been reported previously by Chan et al.8 We did not consider hypertension alone as the indication
for revascularization, since this condition is usually multifactorial in renal transplant recipients. In addition, the antihypertensive medications presently available are superior to those prescribed a decade ago. In the same fashion, as there is a tendency to be reluctant to revascularize atherosclerotic stenosis of native renal arteries for hypertension alone,9 we are also more conservative to revascularize stenosis in renal transplant recipients based upon hypertension alone, although the mechanism of stenosis is different, namely it may be due to technical factors or immunological events.10 In conclusion, renal transplant artery stenosis, whether revascularized or treated conservatively, can be monitored by Doppler and tends to be stable over time. The number of antihypertensive medications increases with time, however the blood pressure tends to be lower. Renal function during a 3-year period of follow-up was stable or even improved suggesting the possibility of spontaneous regression of stenosis in at least some patients. REFERENCES 1. Roberts JP, Ascher NL, Fryd DS, et al: Transplantation 480:580, 1989 2. Smith RB, Cosimi AB, Lordon R, et al: J Urol 115:639, 1979 3. Sankari BR, Geisinger M, Zelch M, et al: J Urol 155:1860, 1996 4. Fervenza FC, Lafayette RA, Alfrey EJ, et al: Am J Kidney Dis 31:142, 1998 5. Merkus JW, Hoitsma AJ, van Asten WNJC, et al: Clin Transplant 9:383, 1995 6. Rengel M, Gomes-da-Silva G, Inchaustegui L, et al: Kidney Int 54:S99, 1998 7. Krumme B, Blum U, Schwertfeger E, et al: Kidney Int 50:1288, 1996 8. Chan YT, Ng WD, Ho CP, et al: Br J Surg 72:454, 1985 9. van Jaarsveld BC, Krijnen P, Pieterman H, et al: N Engl J Med 342:1007, 2000 10. Wong W, Fynn SP, Higgins RM, et al: Transplantation 61:215, 1996
T
HE INCIDENCE of renal transplant artery stenosis after renal transplantation ranges from 2% to 12%. True incidence is difficult to assess because renal angiography is not performed in all patients; it can be even up to 23%.1– 4 Stenosis can cause hypertension and/or deterioration of renal function. Diagnosing and treating stenosis is important because it can cause graft loss. Introducing duplex Doppler and color Doppler ultrasonography in late 1980s enabled noninvasive diagnosing of stenosis, assessment of its localization and hemodynamic significance, assessment of revascularization success, and follow-up of stenosis in the long term.5,6 We have observed some patients with high-grade stenosis after unsuccessful revascularization, to be stable over years. The purpose of our study was to assess the rate of progression of renal transplant artery stenosis in long-term patients by regular Doppler examination and to study the influence of stenosis on renal function and hypertension.
peak systolic velocity of ⬎2 m/sec (so-called stenotic jet) at the stenotic site. In the case of a normal resistance index at the level of the renal parenchymal vessels, the stenosis was judged to be in the range of 50% to 75%. If a distal »parvus-tardus« pattern was joined to stenotic »jet« of ⬎2 m/sec, the stenosis was considered to be in the range of 75% to 90%.7 All Doppler studies were performed by nephrologists experienced in the technique, using an ultrasound monitor Acuson 128 XP/10 and convex 3.5 MHz probe. The patients were followed for at least 3 and up to 11 years. The peak systolic velocity at the stenotic site, the resistance index at the intrarenal segmental and parenchymal arteries, serum creatinine value, hemoglobin level, blood pressure, and number of hypertensive medications were analysed on a yearly basis. The main indication for angiography and revascularization was deterioration of renal function. Thirteen percutaneous transluminal renal angioplasties (PTRA) of stenosis were performed in 12 patients and four surgical revascularizations in 4 patients. In one patient surgical revascularization followed unsuccessful PTRA. Spontaneous regression of stenosis to nonsignificant level (⬍50%) was observed in 5 of 27 (19%) patients.
PATIENTS AND METHODS
RESULTS
The study included 27 recipients of cadaveric kidneys, 13 men and 14 women, aged 42 ⫾ 13 years. 24/27 patients (89%) received their first and the other 3 their second, renal graft. Fifteen of 27 (56%) were treated with cyclosporine (Neoral) and steroids as maintenance immunosuppression; 12 of 27 were on triple immunosuppressive therapy (Neoral, steroids, azathioprine, or mycophenolate mofetil). Nine acute cellular rejections occurred in 8 of 27 patients (30%). All patients received diltiazem as a standard part of immunosuppressive protocol. All patients were diagnosed to have at least 50% stenosis of the renal transplant artery. Stenoses were primarily diagnosed and regularly followed (at least once yearly and in every occasion when renal function was deteriorating and/or hypertension increasing) by duplex Doppler. In 17 patients, 21 renal angiographic studies were performed (4 patients had angiography performed twice). All of the angiographies confirmed the stenosis previously diagnosed by duplex Doppler. The Doppler criterion to diagnose stenosis was a
The data concerning peak systolic velocity, resistance index, serum creatinine value, hemoglobin level, average blood pressure, and number of antihypertensive medications (excluding diuretics) are presented in Table 1. In the group as a whole (both revascularized or not) there was a tendency toward decreased peak systolic velocity and a corresponding increase in resistance index (which was always within From the Department of Nephrology, University Medical Center Ljubljana, Ljubljana, Slovenija. Supported in part by Ministry of Education, Science and Sport (Grant No L3-1369 and J3-3480). Address reprint requests to Prof Dr Jadranka Buturovic´Ponikvar, Department of Nephrology, University Medical Center Ljubljana, Zalosˇka 7, 1525 Ljubljana, Slovenija.
Table 1. Various Data in Patients With Renal Transplant Artery Stenosis During 3-Year Follow Up (n ⴝ 27)
1 year 2 years 3 years
PSV
RI
Cr
Hb
BP
Th
2.2 ⫾ 0.5 2.0 ⫾ 0.6 1.9 ⫾ 0.5
60 ⫾ 11 64 ⫾ 10 64 ⫾ 9
139 ⫾ 81 117 ⫾ 48 119 ⫾ 52
138 ⫾ 19 138 ⫾ 18 134 ⫾ 20
147/89 138/85 136/84
2.3 ⫾ 1.0 2.6 ⫾ 1.0 2.7 ⫾ 1.2
Abbreviations: PSV, peak systolic velocity (m/s); RI, resistance index (%); Cr, serum creatinine (mol/L); Hb, hemoglobin (g/L); BP, blood pressure (mm Hg); Th, number of antihypertensive medications. Values are presented as mean ⫾ SD.
0041-1345/01/$–see front matter PII S0041-1345(01)02460-5
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
3390
Transplantation Proceedings, 33, 3390–3391 (2001)
LONG-TERM FOLLOW UP BY DOPPLER
3391
Table 2. Data for Revascularized (REV; n ⴝ 15) and Nonrevascularized (nREV; n ⴝ 12) Patients With Renal Transplant Artery Stenosis During 3-Year Follow Up
1 year REV nREV 2 years REV nREV 3 years REV nREV
PSV
RI
Cr
Hb
BP
Th
2.3 ⫾ 0.5 2.1 ⫾ 0.4
57 ⫾ 10 63 ⫾ 12
143 ⫾ 81 132 ⫾ 75
135 ⫾ 23 141 ⫾ 13
156/92 139/82
2.1 ⫾ 1.1 2.4 ⫾ 1.2
2.1 ⫾ 0.6 1.9 ⫾ 0.5
64 ⫾ 10 63 ⫾ 12
128 ⫾ 62 100 ⫾ 32
136 ⫾ 21 140 ⫾ 18
148/89 132/80
2.6 ⫾ 1.1 2.5 ⫾ 1.1
2.0 ⫾ 0.6 1.7 ⫾ 0.5
66 ⫾ 9 63 ⫾ 10
130 ⫾ 58 100 ⫾ 35
135 ⫾ 22 132 ⫾ 16
140/86 130/78
2.7 ⫾ 1.2 2.6 ⫾ 1.2
Abbreviations: PSV, peak systolic velocity (m/s); RI, resistance index (%); Cr, serum creatinine (mol/L); Hb, hemoglobin (g/L); BP, blood pressure (mm Hg); Th, number of antihypertensive medications. Values are presented as mean ⫾ SD.
normal limits). The serum creatinine gradually decreased, hemoglobin level was stable and average blood pressure decreased over time along with an increasing number of antihypertensive medications. Diltiazem, as a regular part of immunosuppressive protocol, was included in the number of antihypertensive medications. Table 2 compares the same parameters for patients who were revascularized (by PTRA or surgically) versus those who were only treated conservatively. The trend towards improving stenosis (assessed by decreasing peak systolic velocity in the long-term) is present in both groups. Compared to nonrevascularized patients the revascularized group had a higher peak systolic velocity and a lower resistance index at the beginning, indicating a higher degree of stenosis at the time of diagnosis. DISCUSSION
According to our results, the long-term natural course of renal transplant artery stenosis, whether the patient is revascularized or not, seems to be stable or possibly even regressive. Even spontaneous regression of stenosis to a nonsignificant level (⬍50%) was observed. The majority of stenoses were in the range of 50% to 75% (according to Doppler criteria). Duplex Doppler seems to be an excellent test for monitoring stenosis in the long term. As far as we know, this is the first report of long-term measurement of peak systolic velocity inside the stenosis, together with estimates of the corresponding resistance index. Peak systolic velocity at the stenotic site reflected pretty accurately the grade of stenosis. Regular duplex Doppler examinations seems to help assess the progression of the stenosis and to guide the timing for intervention in individual patients. They also help to detect the regression of the stenosis that was observed in not inconsiderable number of patients (19%). The possibility of reversible stenosis had been reported previously by Chan et al.8 We did not consider hypertension alone as the indication
for revascularization, since this condition is usually multifactorial in renal transplant recipients. In addition, the antihypertensive medications presently available are superior to those prescribed a decade ago. In the same fashion, as there is a tendency to be reluctant to revascularize atherosclerotic stenosis of native renal arteries for hypertension alone,9 we are also more conservative to revascularize stenosis in renal transplant recipients based upon hypertension alone, although the mechanism of stenosis is different, namely it may be due to technical factors or immunological events.10 In conclusion, renal transplant artery stenosis, whether revascularized or treated conservatively, can be monitored by Doppler and tends to be stable over time. The number of antihypertensive medications increases with time, however the blood pressure tends to be lower. Renal function during a 3-year period of follow-up was stable or even improved suggesting the possibility of spontaneous regression of stenosis in at least some patients. REFERENCES 1. Roberts JP, Ascher NL, Fryd DS, et al: Transplantation 480:580, 1989 2. Smith RB, Cosimi AB, Lordon R, et al: J Urol 115:639, 1979 3. Sankari BR, Geisinger M, Zelch M, et al: J Urol 155:1860, 1996 4. Fervenza FC, Lafayette RA, Alfrey EJ, et al: Am J Kidney Dis 31:142, 1998 5. Merkus JW, Hoitsma AJ, van Asten WNJC, et al: Clin Transplant 9:383, 1995 6. Rengel M, Gomes-da-Silva G, Inchaustegui L, et al: Kidney Int 54:S99, 1998 7. Krumme B, Blum U, Schwertfeger E, et al: Kidney Int 50:1288, 1996 8. Chan YT, Ng WD, Ho CP, et al: Br J Surg 72:454, 1985 9. van Jaarsveld BC, Krijnen P, Pieterman H, et al: N Engl J Med 342:1007, 2000 10. Wong W, Fynn SP, Higgins RM, et al: Transplantation 61:215, 1996