Improved Results of Vascular Reconstruction in Pediatric and Young Adult Patients with Renovascular Hypertension

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Pediatric Articles IMPROVED RESULTS OF VASCULAR RECONSTRUCTION IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH RENOVASCULAR HYPERTENSION ARTURO MARTINEZ, ANDREW C. NOVICK,* ROBERT CUNNINGHAM AND MARLENE GOORMASTIC From the Departments of Urology and Pediatrics, Cleveland Clinic Foundation, Cleveland, Ohio

ABSTRACT

From 1955 to 1988, 56 patients 21 years old or younger underwent surgical treatment for renovascular hypertension at our clinic. The cause of renal artery disease was fibrous dysplasia in 53 patients, Takayasu's arteritis in 2 or an arterial aneurysm in 1. Bilateral or branch renal artery disease, and extrarenal arterial disease were present in 16, 23 and 11 patients, respectively. The results of 28 patients treated from 1955 to 1977 (group 1) were compared to those of 28 patients treated from 1978 to 1988 (group 2). Hypertension was cured or improved postoperatively in 83% of the patients from group 1 and in 96% from group 2 (p = 0.07). However, this outcome was achieved through surgical revascularization in only 48% of the patients from group 1 compared to 96% from group 2 (p = 0.0002). A multivariate analysis revealed that the only significant variable related to clinical outcome was the era of treatment, which reflects the improved technical efficacy of revascularization during the last decade. Aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. It currently is possible to achieve amelioration of hypertension and preservation of renal function in most young patients with renal artery disease. (J. Ural., 144: 717-720, 1990) Renal artery disease is a relatively common cause of surgically correctable hypertension in children and is second in frequency only to coarctation of the thoracic aorta in this regard. Although renal revascularization has been established for more than 25 years as an effective form of treatment for adult renovascular hypertension, the initial results in children were less satisfactory. 1 • 2 However, during the last decade successful renovascular reconstruction and amelioration of hypertension have become attainable goals for most young patients with this disease_ 3 - 7 We document and delineate the basis for the improved results of surgical treatment in children and young adults with renovascular hypertension. MATERIALS AND METHODS

The study population comprises 56 patients 21 years old or younger who underwent surgical treatment for renovascular hypertension at our clinic from November 1955 to June 1988. This series includes 33 female and 23 male patients 10 months to 21 years old. The pathological cause of renal artery disease was medial fibroplasia in 11 patients, perimedial fibroplasia in 17, intimal fibroplasia in 25, Takayasu's arteritis in 2 and an arterial aneurysm in 1. Renal artery disease was present unilaterally in 40 patients and bilaterally in 16. A total of 23 patients had branch renal artery disease. In 11 patients extrarenal arterial disease was present, which involved the abdominal aorta (2), or mesenteric (8), carotid (2) or iliac (1) arteries. Surgical treatment of renal artery disease was indicated for severe associated hypertension in all patients. Preoperatively, all patients were evaluated with aortography, which demonstrated the location and extent of renal artery disease. Rapid Accepted for publication January 26, 1990. *Requests for reprints: Department of Urology, Cleveland Clinic Foundation, 1 Clinic Center Dr., Cleveland, Ohio 44195. 717

sequence excretory urography (IVP) was obtained in 21 patients and an abnormality indicative of renal artery stenosis was observed in 17. Differential renal vein plasma renin assays were obtained in 29 patients and lateralization to I kidney with a ratio of 1.5 or greater was observed in 26. The preoperative serum creatinine level was less than 2.0 mg./dl. in all patients (normal level 0.7 to 1.4 mg./dl.). All patients were evaluated postoperatively with serial blood pressure recordings, serum creatinine determinations and either an IVP or isotope renography. If either of the latter 2 studies suggested diminished renal perfusion, or in the event of persistent or recurrent postoperative hypertension renal angiography also was performed. Followup information was obtained from a review of medical records as well as from direct contact with the patients or the referring physicians. Postoperative followup ranged from 1 to 30 years. Specific criteria were used to judge the effect of surgical treatment on preoperative hypertension. Patients were considered cured if the most recent blood pressure was normal for age on no medication. Improved were patients who had a decrease in diastolic pressure of 15 mm. Hg or more, or who were normotensive on medication. Failures were patients who did not qualify for either of the aforementioned categories. The study population was divided into 2 groups for purposes of comparison. Group 1 comprised 28 patients treated from 1955 to 1977 and group 2 comprised 28 patients treated from 1978 to 1988. Comparison of continuous factors between the 2 groups for clinical outcome were done with Student's t test. Chi-square tests were used to test for significant association of categorical factors with groups or clinical outcome. An a level of 0.05 was considered statistically significant. A logistic regression was used to test for factors with independent association

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TABLE

1. Preoperative clinical characteristics of pediatric and young

adult patients with renal artery disease No. pts. Mean age (yrs.) Male-to-female ratio Mean mos. of hypertension Mean blood pressure (mm. Hg) Extent of renal artery disease: Unilat. Bilat. Branch

Group 1

Group 2

P Value

28 11.5 14:14 11.7 190/126 (39)*

28 14 9:19 27.4 168/107 (16)*

0.06 0.17 0.03 0.02 0.0001

21 7 11

17 11 13

0.41

* Mean value (mm. Hg) above the 95th percentile for diastolic blood pressure according to patient age. TABLE

2. Primary surgical treatment for renal artery disease Group 1 (28 pts.)

Total nephrectomy Partial nephrectomy Surgical revascularization: Unilat. Bilat. (staged)

TABLE 3.

Group 2 (28 pts.)

7

1

2

0

19 15

27 20

4

7

Methods of primary surgical revascularization for renal artery disease

Aortorenal bypass Renal autotransplantation Aortorenal reimplantation Resection and reanastomosis Splenorenal bypass Local aneurysmectomy

Group 1 (23 pts.)

Group 2 (34 pts.)

8

15 18*

1 2 4 7

0

1

1

0 0

* Includes 15 extracorporeal branch repairs.

with cure rate. Mean postoperative followup in groups 1 and 2 was 138 and 44 months, respectively. RESULTS

The preoperative clinical characteristics of patients in groups 1 and 2 are provided in table 1. The blood pressure is expressed as a mean systolic and diastolic level, and as a mean increment above the 95th percentile for diastolic blood pressure according to patient age. Patients in group 1 had a shorter duration of hypertension (p = 0.03) and more severe hypertension (p = 0.02) compared to patients in group 2. There was no significant difference in the 2 groups with respect to patient age, sex,

unilateral versus bilateral disease or the presence of branch renal artery disease. Table 2 depicts the primary surgical treatment done in both groups. Of 28 patients in group 1, 9 were managed with total (7) or partial (2) nephrectomy and 19 underwent renal revascularization. Of 28 patients in group 2, only 1 was managed with nephrectomy and 27 underwent renal revascularization. Staged bilateral renal revascularizations were performed in 4 patients in group 1 and 7 in group 2. The specific vascular reconstructive techniques used in each group are listed in table 3. A variety of revascularization techniques were used in group 1. By comparison, 33 of 34 revascularizations in group 2 were done by an aortorenal bypass (15) or renal autotransplantation (18). All of the aortorenal bypasses in group 2 were done with an autogenous graft of the hypogastric artery or saphenous vein (fig. 1). The most common indication for autotransplantation in group 2 was the presence of branch renal artery disease requiring extracorporeal vascular repair (15, fig. 2). Postoperatively, there were 9 unsuccessful revascularizations in group 1 due to stenosis or thrombosis of the repaired renal artery. The initial operation in these patients was a splenorenal bypass in 5 and segmental resection with reanastomosis in 4. The management of these 9 technical failures was by secondary nephrectomy in 4 patients, successful secondary revascularization in 1 and medical antihypertensive therapy in 4. One revascularization in group 2 was technically unsuccessful due to postoperative obstruction of the repaired renal artery. The technical failure rate after primary renal revascularization operations was 39% (9 of 23 patients) in group 1 and 3% (1 of 34) in group 2. The results of surgical treatment for renovascular hypertension were determined according to patient status at the most recent followup. In group 1, 15 patients (54%) were cured, 8 (29%) were improved and 5 (17%) failed, compared to 22 (78% ), 5 (18%) and 1 (4%), respectively, in group 2. The difference in outcome between groups 1 and 2 is not statistically significant (p = 0.07). However, there is an important difference between the 2 groups in whether a successful clinical outcome (that is cured or improved) was achieved with or without preservation of the involved kidney. In group 1 cure or improvement of hypertension was achieved through total or partial nephrectomy in 12 patients (52%) and through revascularization in 11 (48%). In group 2 cure or improvement of hypertension was achieved through nephrectomy in 1 patient (4 %) and through revascularization in 26 (96%, p = 0.0002). Univariate analysis of patient characteristics with respect to clinical outcome revealed that the clinical failures tended to be younger (p = 0.09), had a shorter duration of hypertension (p

FIG. 1. A, aortogram in 9-year-old boy shows bilateral renal artecy stenosis from intimal fibroplasia. B, completed right aortorenal bypass with autogenous hypogastric artery graft. C, postoperative aortogram shows patent right aortorenal graft. Child subsequently underwent left renal autotransplantation.

VASCULAR RECONSTRUCTION FOR RENOVASCULAR HYPERTENSION

719

FIG. 2. A, left renal arteriogram in 19-year-old woman shows aneurysmal and stenosing fibrous disease involving main renal artery and 3 branches. B, completed extracorporeal revascularization with branched graft of hypogastric artery. C, arteriogram after autotransplantation shows patent main renal artery and repaired branches. Reprinted with permission from Novick, A. C.: Microvascular reconstruction of complex branch renal artery disease. Urol. Clin. N. Amer., 11: 465, 1984.

= 0.048) and had higher diastolic blood pressures (p = 0.015). When the differences in patient ages, and duration of and degree of hypertension were adjusted for in the multivariate analysis, using a Cox proportional hazards model, only era was significantly related to clinical outcome (p = 0.0001). DISCUSSION

The most common cause of renovascular hypertension in children or young adults is fibrous dysplasia of the renal artery. Other causative renovascular lesions in this age group include an arterial aneurysm, arteriovenous malformation, Takayasu's arteritis, neurofibromatosis, thromboembolic disease and trauma. 8 The typical clinical presentation for these disorders is an asymptomatic patient with recently discovered hypertension upon routine physical examination. Renal artery disease should be considered in the differential diagnosis of any child or young adult with hypertension. If there is no obvious cause for hypertension renal angiography should be done. Renal vein renin assays may be indicated if the relationship between renal artery disease and hypertension is not clear. In children and young adults with renal artery disease bilateral or branch renal artery involvement is common, particularly with the fibrous dysplasias, and extrarenal vascular disease also may be present. 9 • 10 1\/[any renovascular lesions in younger patients, such as intimal and perimedial fibroplasia, also are known to cause progressive vascular obstruction. 11 Therefore, treatment must be directed not only at relief of hypertension but also at preservation of functioning renal parenchyma. There currently are 3 therapeutic options available to manage patients with renovascular hypertension, namely medical treatment, an operation (nephrectomy or revascularization) and percutaneous transluminal angioplasty. Notwithstanding the improved recent efficacy of medical antihypertensive therapy, this approach has no role in the definitive treatment of young patients, since it would entail a lifelong commitment to drug therapy with the attendant risk of losing renal function from progressive disease. Percutaneous transluminal angioplasty is effective in some cases but often is not technically possible due to the small size of the diseased vessels, involvement of renal artery branches, or presence of multiple lesions, aneurysmal disease or perivascular scarring in cases of arteritis. 12 For most young patients surgical treatment currently offers the best prospect to ameliorate hypertension and preserve renal function. We compared our experience with surgical treatment of renovascular hypertension in young patients before (group 1) and after (group 2) 1978 to delineate the evolving role of

operative therapy in this patient age group. While hypertension was cured or improved in most patients from both groups, this was achieved through revascularization in 96% of the patients in group 2 but in only 48% in group 1 (p = 0.0002). Several of the earlier patients also required 2 operations due to a failed initial revascularization. The patients in group 2 tended to be somewhat older with a longer duration and diminished severity of hypertension. The latter 2 findings are probably due to more effective medical antihypertensive therapy during the last decade. Notwithstanding these observations, a multivariate analysis revealed that the only significant variable related to clinical outcome was the era of treatment. We believe that this reflects the improved technical efficacy of surgical revascularization during the last decade. The results of surgical renal revascularization in young patients have improved due to the development of microvascular techniques and a better appreciation of specific operative approaches that are most likely to be effective. Aortorenal bypass is the mainstay revascularization technique and a graft of autologous hypo gastric artery is preferred. 13 A saphenous vein graft may be used in postpubertal children but should be avoided in the small child in whom postoperative aneurysmal graft expansion may occur. 14 When an aortorenal bypass is not possible due to peripheral renal artery disease or aortic hypoplasia renal autotransplantation is the treatment of choice. The ability to perform extracorporeal microvascular repair of branch renal artery lesions has extended the feasibility of revascularization to patients who would previously have been considered inoperable, or candidates for total or partial nephrectomy.15 In our study 5 patients from group 1 who underwent nephrectomy currently would be considered suitable for microvascular branch arterial reconstruction. Our early experience with revascularization in children also has shown that splenorenal bypass and segmental resection with reanastomosis are not effective in this patient age group. 16 In summary, renovascular hypertension in the child or young adult is a potentially curable disease and surgical revascularization is the treatment of choice. The technical efficacy of renovascular reconstruction has improved and it currently is possible to achieve cure or improvement of hypertension with preservation of renal function in most patients. REFERENCES

1. Foster, J. H., Pettinger, W. A., Oates, J. A., Rhamy, R. K., Klatte, E. C., Burko, H. C., Bolasny, B. L., Gordon, R., Puyau, F. A. and

Younger, R. K.: Malignant hypertension secondary to renal artery stenosis in children. Ann. Surg., 164: 700, 1966.

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2. Coran, A. G. and Schuster, S. R.: Renovascular hypertension in childhood. Surgery, 64: 672, 1968. 3. Kyriakides, G. K. and Najarian, J. S.: Renovascular hypertension in childhood: successful treatment by renal autotransplantation. Surgery, 85: 611, 1979. 4. Coran, A. G., Whitehouse, W. M., Jr. and Stanley, J. C.: Technical considerations in the surgical management of renovascular hypertension in children. J. Ped. Surg., 16: 890, 1981. 5. Stanley, J. C. and Fry, W. J.: Pediatric renal artery occlusive disease and renovascular hypertension. Etiology, diagnosis, and operative treatment. Arch. Surg., 116: 669, 1981. 6. Hendren, W. H., Kim, S. H., Herrin, J. T. and Crawford, J. D.: Surgically correctable hypertension of renal origin in childhood. Amer. J. Surg., 143: 432, 1982. 7. Jordan, M. L., Novick, A. C. and Cunningham, R. L.: The role of renal autotransplantation in pediatric and young adult patients with renal artery disease. J. Vase. Surg., 2: 385, 1985. 8. Novick, A. C.: Renal vascular hypertension in children. In: Clinical Pediatric Urology, 2nd ed. Edited by P. P. Kelalis, L. R. King and A. B. Belman. Philadelphia: W. B. Saunders Co., chapt. 29, pp. 1046-1072, 1984. 9. Rybka, S. J. and Novick, A. C.: Concomitant carotid, mesenteric

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and renal artery stenosis due to primary intimal fibroplasia. J. Urol., 129: 798, 1983. Kaufman, J. J.: The middle aortic syndrome: report of a case treated by renal autotransplantation. J. Urol., 109: 711, 1973. Schreiber, M. J., Pohl, M.A. and Novick, A. C.: The natural history of atherosclerotic and fibrous renal artery disease. Urol. Clin. N. Amer., 11: 383, 1984. Hayes, J. M., Risius, B., Novick, A. C. Geisinger, M., Zelch, M., Gifford, R. W., Jr., Vidt, D. G. and Olin, J. W.: Experience with percutaneous transluminal angioplasty for renal artery stenosis at the Cleveland Clinic. J. Urol., 139: 488, 1988. Novick, A. C., Stewart, B. H. and Straffon, R. A.: Autogenous arterial grafts in the treatment of renal artery stenosis. J. U rol., 118: 919, 1977. Stanley, J. C., Ernst, C. B. and Fry, W. J.: Fate of 100 aortorenal vein grafts: characteristics of late graft expansion, aneurysmal dilatation, and stenosis. Surgery, 74: 931, 1973. Novick, A. C.: Management of intrarenal branch arterial lesions with extracorporeal microvascular reconstruction and autotransplantation. J. Urol., 126: 150, 1981. Novick, A. C., Straffon, R. A., Stewart, B. H. and Benjamin, S.: Surgical treatment of renovascular hypertension in the pediatric patient. J. Urol., 119: 794, 1978.