Vol. 11 4 . ~overnher Printed in [ T.S.A.

T,rnJ OCRNAL OF lJRO l.0(;\

Copyright © l!l,~ hv T he Williams & Wilki ns Co.

Review Article REN OVASCULAR HYPERTE NSIOJ\:: THE ROLE OF THE UROLOGIST WILLI AM H. FAIH From the Department of SurRerv. Dil'isiun of C:enitourinar_,. S tir#f'r\". WashinRlon Uni1·ersit,· School of M Pdicine . St. /,r,uis. Missouri

More than 40 yea rs a go Goldblatt and a ssociates demonstrated t hat unilatera l constriction of the renal a rtery could lead to t he development of hypertension in the experimen tal a nimal. 1 Two decad es later Howard and associat es a pplied the lessons learned from the an ima l model t o parallel situations in huma ns and reported cure of hy pertension aft er nephrectomy in 4 patient s with demonstrable unilatera l rena l a rt ery obstru ction. 2 T his re port occasioned much enthus ias m amon g clinic ia ns for the identification a nd repa ir of renal artery lesions in hypertensive ind ividua ls . Based solely on the assu mption t hat the stenotic lesion was responsible many patients were operated on for repa ir or removal of a kidney with arteria l narrowing only to have no improvement in the hypertension. It soon beca me obv ious t hat not a ll obstructions of t he rena l a rtery we re etiologically responsible for hype rtension. S ince this early experience t he en t hus iasm with which physicia ns have approached the evaluation of patients wi th hypertension in a n attempt t o identify those with a renovascular etiology has waxed a nd wa ned . oft en stimulated hv the introduction of new a nd bett er diagnost ic ~ a neu ve rs . The intimate involve ment of t he u rologist in a fie ld of hypertension was occasioned hv the need for techn iq ues of cystoscopy and ureter; ! catheterization com mon to urology for t he a d equate perform ance of the div ided rena l studies advocated by Howard and Connor. 3 It is clear that finding a rena l arterial lesion a lone is not sufficie nt justification to warrant a n operation in every hype rte ns ive patient. The lesion must be fun ctiona ll y significa nt , t hat is it red uces blood fl ow t o the ki dne:, by a n a mount suffi cient t o render at least a portion of t he kidney ischemic. T he d iagnos is of surgically correctable renovascular hypertens ion ( RVH) can be made only by verification of a significa nt differen ce in the fun ctiona l capacity of the involved kidney as compa red t o t he contrala t eral (a nd pres uma bly norma l) one. Currently, t he measu re ment of pressor substances ( renin a nd angiotensin) in the Rec ipient of Research Career Development Award '.\o. S K 04 Al70 107, ~ational Institute of Allergy and Infec-

tious Diseases, National Institutes of Health. Unit ed States Public Healtb Service.

peripheral a nd rena l venous efflue nt and the ratio of the rena l ve in re ni n concent ra tion bet wee n the 2 kidn e:,.:s is the most commonl y· used test to de monst ra te this fu n ct ion a l d ifference. However, blind fai th in a " m agic nu m ber" such as that obt a ined hy calculating the renal vein renin ratio (RVRR) may lead the physician t o adopt a mechanistic approa ch t o the difficult dec is ion as t o whet her an opera tion is required in a gi ven pa t ient. Moreover, if the dec is ion fo r surgical int ervention is based sole ly on the result s oft he a rt e riogra m a nd t he RVRR, t here is little defe nse against the state ment t ha t the general or vasc ula r surgeo n working in concert with the ra diologist a nd internist is equally a ble to a pply the " magic number" a nd make t he d ec ision for surgical intervention wit hou t benefit of urologic opinion . T he urologist, when as ked to evaluate a patient wit h sus pect ed RVH. should b ring his spec ia li zed knowledge of rena l fun ction a nd phys iology. kidney anatomy and arc hitecture, and u rologic investi gat ive a nd surgica l techniques to hear upon the patient 's proble m in a n effort to assess the s ituation a nd to develop a logical, ind ividua lized d iagnostic "game pla n" . T o simply fo llow a stereot y ped invest igative rou ti ne in every case may eventua lly' lead referring physicians t o assu me that t he u rologist has no s pec ia li zed kn owledge to contrib ut e a nd t ha t hy following a give n diagnost ic approac h the pa tient may be referred di rect lv t o a vasc ul a r surgeon for correction of the lesion . This would d env the u rologist the opportuni ty t o direct the d iag~ostic an d surgica l a tt ac k and may· res ul t in less tha n opt im um patient care. It seems appropriate, in this rev iew, to consider t he current state of t he a rt in the diagnos is a nd t reat ment of RV J-1. the ra tionale fo r surgi,:al correct ion versus medical treatment , a suggest ed approac h for the p roper assess ment of the proble m a nd t he techniques a nd results of surgery. WH Y I N\ 'Ec,TI C:ATE')

Befo re consid ering t he var ious modalit ies used t o assess t he funct iona l lesion in a patient with s uspect ed RVH we must first answer t he more immedia te query . H ow necessa ry is it t o eval uate a

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hypert ens ive indiv idua l l'or renovascular disease'1 renal a rterv st enosis as the etiologic agent 111 his Should not these investi ga tions into poss ible renal hvpert ens i\·e patients. involvemen t be cons ide red on i'.' in pat ient s with I NCIIJENCE AN D CLI N ICAL CHAH A('TEHI STI CS clinical or laborat ory ev idence of renal disease or when medical therapy fa ils t o adequat elv control The inc idence of RVH in the ge neral hypert enthe blood pressure') Long-term followup of medi- sive population is unknown. Of the 2.442 patients cally a nd surgicallv treated patients with apparent evaluated in the Cooperative Study of RenovasRVH has been reported in d et a iL' Of :214 patie nt s cular Hyperte nsion. 9 179 had proved RVH as select ed pros pectively and followed by the sa me judged by a good response to correct ive surgerygroup of investi gators for 7 to 14 years with a mean an incidence of , .:l pe r cent in t his selected followu p of a pproxima t e!'.' 10 vea rs 100 were series, Other a uthors sta te tha t RV H is the un de rtrea t ed surgica lly a nd I 14 werP treat ed med ical lv . 1:','ing et iology in about 2 to 15 per cen t. of paThe groups werP simila rly constitut ed except in l tients with diastolic hypertens ion. •0 - 12 import a nt rega rd , that is more t han 80 per cent of There are no absolut ely re lia ble distinguishing patient s assigned to the surgical group had fail ed clinical characieristics to a id the physician in to respond satisfactorily to a :m to 90-da\· trial of ma king a diagnosis, RVH is more likely to appear intensive medical ant ihv pertensive the rapy and at a later age ( more than 50 years old) than is were cons idered medical management fa ilures, ln essential h\pertens ion. Although in practical terms add ition, 16 of the initia l 11 4 medica l pat ients most patient s who present wit h the onset of subsequentl,v requ ired surgica l int ervent ion be - hypertension after the age of 50 years will have cause of inability to control by pert ension. progres- essential hype rtens ion, 9 High blood pressure ocsive d ecrease in renal functional capacitv or pa- curring in child hood or in young female adults tient refusal to continue with medical manage- should be. in part icu lar, thoroughly investigated ment. In t he lat est report ed followup the compa ri- as be ing caused by renal artery d isease, the son between the 2 groups was striking, 5 The mean incidence of f'ibromuscular diseases (FMD) of the diastoli c blood pressure was almos t 20 mm. Hg rena l a rtery being espec ia lly high in t his palower in the surgical group , More importa nt!:,,,·. tient population, 9 While the presence of a n however. the over- a ll mortalit y rate in the s urgi- up per abdominal bruit may be fou nd in many cally treated patients was 16 per cent contrasted to thin normote ns ive individuals this clinical sign 40 per cent in those treat ed medicalh·, In addition. is found 6 to 9 times more often in patients the surgicall y t reated pa tients had a far smaller with RVH than it is in those patients with incidence of fatal myocardia l infarction. cere- essential hy pert ension, However, since the over-all brovasc ular accidents a nd severe rena l failure incidence of essential hy pertens ion is much higher requiring dialysis or t ransp lanta tion than those than RVH the finding of a n a bdominal bruit in a treated solely with medication , given patient mav not be part icularly helpfuL The natural history of ma nv renal a rt e ria l le- RVH is uncommon in black subjects, 90 per cent of sions is one of grad ua l progression. 6 Also. it is now the cases occurring in the white population. 9 clear that individuals with even moderate blood pressure elevations experience more morbidity a nd DIA(;NOSTIC TESTS earlier mortality than normote ns ive indi\·iduals . 1 · • T hus, t he physicia n who opts fo r medical control of Because of t he lac k of cl inical s igns or symptoms hyperte nsion in pa tients with rena l a rteria l lesions to aid the p hys ician in distinguishing patients with must ensure tha t the patients will be un de r con - RVH from t hose wi th essentia l hypertens ion , relistant , close m ed ica l surveilla nce , In assess ing the a nce must be placed upon various diagnostic blood p ressure response to medica l treatment one techniques . T he most commonly used tests a nd must not judge the effectiveness of a given thera - the ir value in ident ifying RVH will be considered, peutic regimen solely on the response of the blood Excretorv uro~raphv ([VP), The rapid sequence pressure to the medication. Quality of life. which !VP can be of considerable va lue as a screening test can oft en be seriously diminished as the result of t o select those ind ividu a ls to be investigated in side effects of potent ant ihypertensive agents. more detail for a poss ible renovascul a r et iology of must a lso be eva luated, In our experience. excel- the hype rt ens ion. The most common ab normality lent control of diastolic blood pressure with a pla n seen in patie nts with proved RVH and the most of med ical m a nagement acceptable to the patient relia ble feat ure in distinguishing essent ial hyperis not easily accomplished. The maintenance of t ension from unilateral renovascular disease is a normal blood pressure without disturbing s ide delay in t he caliceal a ppearance time on the side of effects of the m edication is a fo rmidable task in the involved kidne'.'," For this reason, failure t o many patients, Prompt a nd acc ura t e assess me nt of obt a in early films 1 t o ;J minutes after injection of renal arterial lesions and improvement in operati\·e t he cont rast agen t means tha t t he most valuable tec hniques have led to cu re or s ignifi cant lowering in form a t ion to be obtained from t he IVP is lost, of blood pressure in t he majority of patient s The other major a bnorm a lities in the TVP of t reated s urgically, For t hese reasons. the conscien - patients with RVH-dispa rity in rena l lengt h and tious physician should make an effort to excl ude la te hyperconcentration of contrast -are found

RENOVASCULAR HYPERTENS ION: ROLE OF UROLOGIST

considerably less often than the delay in appearance time. The routine use of the conventional IVP, in which the first film is taken 5 minutes or more after contrast administration, in evaluating patients for t he etiology of high blood pressure, is inadequate, a waste of time and money. and is ethically indefensible in light of current knowledge. Ancillary urographic features. such as ureteral notching caused by collateral circulation to t he kidney v ia ureteral vessels, a decreased volume of t he collecting system a nd thin spidery cal ices on the involved side, while occasiona lly hel pful in a given patient are generally unreliable diagnostic aids. We must also keep in mind that the IVP is not a test of renal function and can he totally normal even in the presence of complete occlusion of the main renal artery supply ing a kidn ey. 13 The IVP also cannot be considered a means of predicting surgical success in patients with a demonstrated renal artery lesion. In the cooperative study of RVH slightly more than 80 per cent of the patient s who had a favorable response t o an operation had an abnormal IVP preoperati vely . However. the same percentage of abnormal IVPs were found in the group of patients not res ponding to an operation a nd considered surgical failures. Also. :28 of :ll patients (77 per cent) with a norma l IVP. despite documented renal artery stenosis, responded favorably to an operation. Radioactive reno14raphy. The rapidity of performance, patient acceptability and relative economy of the ren ogram make its use appealing. Many attempts have been m ade to obta in functional and quantitative information from various phases of the renogram curves with little success and the visual comparison of the slope of the excretory curves remains as the most common!:-,· used indica tor of an ab normal tracing."· 1 5 Analysis of the cooperative study data indicated that 7G per cent of patients with greater than 50 per cent st enosis on renal arteriography had an ab norma l renogram. However, no charact eristic patt ern has been found to differentiate renovascular lesions from parenchymal disease and there is a high inc idence of falsely positive renograms in patients with essen tial hypert ens ion. 1 '· 16 Although conventional renography has little to recommend it for the functional assess ment of' a renal arteria l lesion. newer rad ioisotope t echn iques offer considerable promise in obta ining in formation on the function of t he individua l kidne_,·s without the requ irement for ureteral catheterization. In a recent study compa ring the results of the renal perfusion/ excretion determination (RP / ED) with split rena l function studies (SRFS) in a sma ll number of patient s the urine flow ratios. hippu ra t e concentrat ion differences, total renal plasma fl ow and differential perfusion between the right a nd left kidneys revealed good agreement between the 2 t ests. 1 7 If add it iona l experience with ra dioisotope differential rena l function studies (which re-

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quire only a simple venipuncture) confirms the early promise-this test should suppla nt the existing renogram a nd may add cons iderab ly to our diagnostic accuracy in ident ifying patients with RVH. Pending the further t esting of newer techniques the renogram is best thought of as a screening test in h ypertensive patients that, along with the IVP, may help to identify those pat ients most likely to warrant more sophisticated investigational studies. The role of renal arteriowaphy. Along with the observat ion that hypertension could be experimenta lly induced by renal a rt ery constriction. the major stimulus for detection and correction of RVH in hum a ns resulted from dramatic improve ments in the safetv and technique of angiography. The introduct ion of selective renal arte riography great ly enha nced the ability of the radiologist to demonstrate stenotic narrow ing occurring at the origin of the renal arteries from the aort a a nd vascular occl usions involving branches of the ma in renal artery. that is segmental or branch stenoses. However, it soon became obvious that not all renal artery stenoses could be implica ted as causing hypertension. In the earl\· pa rt of' the last decade :2 important reports were added to the lit e rature. stressing that rena l a rterial lesions may be found in a high percentage of normotensive individuals. Evler and associates studied 409 patients subjected to angi ograplrv· for a va riet v of vascular prob lems a nd found renal arterial disease in 98 of :\04 normotensive individuals (:l:2 per centl. ' " Furthermore. th ese authors a lso found that "all t:-,'))es of major re na l art erial disease tha t were present in the hype rt ensive patients were also founrl in the normotensive group" an rl in add ition. "se\·ere stenoses. even it bilateral and accompanied IP, postste notic dilatation . we re not necessarily associated with hypertens ion". Shortlv aft er the latter article was reported . Holley a nd associates. in a clinicopat hologic stud_,. of normot e nsive and hype rt ens ive individuals. observed moderate or severe athernm a tous renal ar ter,, stenosis in 49 per cent of :2:'i(i unselecterl individuals wit h a docume nt ed negative hist or,· of hypertension. exam ined at necropsv. 19 Of the I :2(i normotensive indi, iduals with autopsy e,·id ence of' rena l arterv stenosis. a lmost two-thirds ( 8:\) had evidence of bilateral disease. Fost er anc! ,1ssociates report ed on 1.0,0 pa tients referred to a specia li zed cent er for resea rch on hypert ension. 2 ° Forty-three per cent ( 46()) of the hypertensive patients ha d evidence of' renal artery stenosis. However. onl:, :\9 per cent of those with a rteria l lesions ( IG per cent of th e entire group) had surgically proved RVH. These a uthors also stressed the importance of obt ain ing ob lique project ions to proper!:-,- v isualize t he renal arteries and reported on a number of pat ient s in whom the routine a nteroposterior aortogram fa iled t o show a renal a rtery st enos is which was clearl y delineated on the

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oblique arteriogram. 21 Similarly, failure to obtain an arteriogram via a direct aortic injection of contrast medium before doing selective arteriography may obscure an arteriosclerotic lesion localized to the orifice of the renal artery. Better angiographic techniques also have led to a greater appreciation of the frequency with which stenosis is bilateral and aid in distinguishing between fibromuscular lesions and those caused by atherosclerosis. About two-thirds of renal artery lesions are caused hy atherosclerosis with a maleto-female ratio of approximately :2 to 1. 20 · 22 The left renal artery is more commonly involved than the right one and the vast majority (more than 80 per cent) of occlusive atherosclerotic lesions occur at the orifice or in the proximal third of the artery. In contrast, FMD appears to be primarily a disorder of young female subjects. 70 to 80 per cent of the cases occurring in women and typically involv ing the middle and distal third of the right renal artery. In more than 4fi per cent of the cases of FMD the segmental arterial branches are also involved with the disease. 22 · " In recent years efforts have been made to sub classifv the non-atherosclerotic vascular lesions in an att.e mpt to correlate the arterial changes with the natural historv of the disease. Although the non-atherosclerotic lesions may he considered under the common term, fibromuscular dvsplasia. the actual pathologic findings consist mainly of severe medial hyperplasia involving chiefly the fibrous elements of the media rather than hyperplasia of smooth muscle celis or elements. 24 The Mayo Clinic group suggested a radiologic classification of FMD, depending on whet her the disease was multifocal-the typical string of beads effect so commonly seen, focal-consisting of a solitary stenosis less than l cm. in length. tubular-an elongated. smooth. concentric stenosis or mixedin which :2 or more forms are present in the same patient. 23 · 24 At the last report on ,'i5 patients who had serial angiographic studies. all forms of the disease showed progression but the multifocal form was less likely to do so than the other categories.• At the Cleveland Clinic a classification is used. which is based more on the pathologic changes. In those pa tients with suharh·ential fihroplasia and intimal or true fihr()]nuscular hyperplasia (rare) progression of the disease process was found to occur frequenth·. In contrast. in patients diagnosed as having medial fihrnplasia (the most common tvpe of lesion). onlY a few patients showed progression. More importantly. in patients more than 40 years old with medial film, plasia the lesions appeared to he relatiHh· stable. although more than fi() per cent of the patient,; were followed for onl:v :2 years or less. ' ·' \'-ihile interesting. at the present ti me these arteriographic and pathologic distinction,; have little value in a given patient. The physician must keep in mind that all types of lesions-at,heroscl e rot ic or non-atherosclerotic-may progress and follow the patient accordingly.

The incidence of bilateral involvement of the renal arteries with FMD is higher than formerly recognized and bilateral arterial disease is found in 25 to '. l9 per cent of cases. 22 · 23 Just as the demonstration of a renal artery stenosis does not indicate that the patient is hypertensive , or if so, that the hypertension does not result from the renal artery occlusion, so. too, the arteriogram cannot be used in predicting the response of the patient to surgical treatment of the occlusion. The recent l:,,: published reports of the cooperative study on RVH again confirm the observation that "in spite of the availabilit:,' of the arteriogram to detect renal artery stenosis , it has only limited value in predicting the response to surgerv". 22 Analvsis of renal angiograms in 502 patients undergoing nephrectomy or reconstructive renovascular surgery, followed by the study group for at least l:2 months. revealed that the presence of collateral circulation was of no significant value in predicting the success or failure of an operation and the presence or absence of post-stenotic dilatation showed no correlation with surgical results. As with any major diagnostic procedure renal arteriograph:,,· has complications with a minor complication rate of around 3 per cent and a major non-fatal complication rate of 0.4 to 1.:2 per cent. 2 •- 23 The majoritv of major complications are caused by thromboses or hemorrhages but direct renal injury has occurred following renal arteriography. either as a result of a toxic reaction to contrast media or arterial damage. Indeed. RVH has been reported to occur as a complication of renal arteriographv. 29 There is a high!:,· significant correlation between neurologic complications and arteriography performed b_v the transbrachial or transaxillary route and evidence suggests that the procedure is not entirely safe. 27 OIJ\·iously most patients in whom the upper extremity technique is used are judged not suitable candidates for the transfemoral approach as a result of severe atherosclerosis involving the iliac and femoral vessels. In these cases translumbar aortographv should be used although selective arteriographic techniques cannot be used and the diagnostic yield may be less than that obtained via catheter studies. There is no difference in the rate of ('omplications between the transfemoral and translumbar approaches. If it is absolutely necessary to use an upper extremity approach it should be done by someone highly skilled and experienced in the technique. The most important factor leading to a high rnmplication rate is thought to be inexperience on the part oft he ope rat or. 27 Because of the possibility of renal injurv or hemorrhage following angiography it is imperat i,·e that renal function, as measured by the serum creatinine or blood urea nitrogen (BUN). and the hematocrit be checked the day following the procedure. If the creatinine or BUN is elevated any planned surgical procedure should he delaved until renal function returns to normal.

HENO VA S(T I.AH IIYPEHTEr\ S IO N: IWI.E OF l ' HOI.OCI ST

In the coo perat ive st ud y report on rnmplications noted in th e performance of 2.,19 a rt e riogram s invol v ing 15 ce nters , th ere we re :l reported fa t a li ties (0.11 per cen t). An a dditional l.6 pe r cent of studi es were "t echnica ll y unsatisfactory .. . " Plasma renin activity (PRA). While th e prec ise m ec han is m s gove rning sec ret ion a nd rel ease of renin bv th e kidn eys are still not full y und e rstood. it is clear th a t this enzyme manufactured or a t leas t stored in th e juxt aglomerular cel ls of the afferent a rt e riol e plays an impo rt a nt rol e in th e pa thoph ysio logy of m a n y hy pert ens i\·e st a t es . pa rti cul a rly RVH. The d ete rmin at io n of PRA has been of grea t va lue in identif,ving patients with signifi ca nt ren a l artery ste nos is. At present. the me as ureme nt of re nin activity is th e most widely used s tudy in judgin g whet her an a rte ri a l les ion d e m onstrat ed on a rt eriog rap h y is. in fad. functi onall v s ignifica nt . As suc h , in most m edic a l centers. the d ec is ion to at tempt s urgi ca l correct ion of RVH is base d prim ar ily on the resu lt oft he re nin studies. It is now generally acce pt ed th a t the le\·el of re nin obt a ined in a blood sam pl e from a periph eral vein m ay s impl y be a refl ec tion of th e state of sodium balance of th e individual a nd th a t c ur e of RVH occurs in a significant numb er of indi\ idu a ls with no dem onstra bl e e levat ion of renin leve b in periphe ral vein blood. 30 · 31 At prese nt. the det ermination most co mmonl y used to indi cate the s ignifica nc e of a re nal a rt e ry s t en os is and the one on whi ch the d ec is ion to operate is mos t oft en based is a comparison of the PRA in the venous e ff1u e nt from the isc hem ic kidn e:v· with that draining th e norm a l kidney. th a t is the RVRR. Whil e virtual un a nimity ex ist s among investi ga tors th a t th e RVRR is a use ful mean s of eva lua ting pa tient s with re n a l arter:v· st e nos is. th e re still is cons iderable d e ba t e as to what co nstitutes a positive ratio. E a rly re port s indica ted that a 2 to 1 ratio betwee n th e ischemi c kidney and the contralateral kidn ev was required before a lesion could be considered s ignifi ca nt 32 but th e rece nt trend has been to libera lize th e interpretation of the RVRR The most common figure cit ed as indi cat ive of a positive ra tio has bee n 1.5 to I. 33 a lthough so me im·esti ga tor s have suggested a ratio of 1. 4 to l or less may be of more value as a prognost ic guide. 34 Howe\·e r. a tt e mpt ,to libera li ze th e int erpreta tion of th e RVRR b~, th e use of a lowe r ratio for a pos iti ve test should be d o ne with co n s idera ble ca ution. M a rk s a nd Maxwell rev iewed the results of re na l ve in renin measurements in '22, pa tients in whom essen ti a l hy pertension a nd normal renal a na tom y were we ll do cum ent ed and in whom no acute stimul a ti on of the renin-an giote ns in syste m was used prior to obt a inin g the renal ve in sa mpl es ."" Twe nt y pe r ce nt of these pat ient s ha d a RVRR of 1.5 or greate r: a ratio of l.96 or m ore would be ex pected to exc lud e 95 per ce nt of pati ent s with esse nti a l hy pe rt ens ion (95 per ce nt confid e n ce limit s). Assay variability must a lso he co nsi d ered. Stockigt and associates. usi ng a sens iti\·e im -

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munoa ssa., t ec hniqu e to d e ter mine PRA. found th a t a t levels of renin a ct iv it v less th a n 4 n g. per ml. for :\ hours. the standard de\·ia tion oft he assay a pproac hed 8 per l'l'lll o ft he m ea n. Thu:-. a RVRR greater th a n 1 is poss ibl e sole lv as a res ult of assav tec hnique a nd does not necessarily indicat e high e r levels in one of th e re na l ve in sa mpl es. Howe\· er. the prob a bilit y that assav va riation alone could cause a RVRR of 1. 5 or greater is v irtu a ll y non ex iste nt eve n a t ex tre m e ly low leve ls of PRA. 33 The RVRR has a high degree of an·urac\· in predi ctin g th e res ponse of th e pa ti e nt with a renal a rt erv stenosis to ne phrec tom y or a reco nstructiv e opera tion. In a re\· iew of 1: \ publi s hed se ri es of pa ti e nts with su rg ica ll v pro ve d unil a t era l main re na l a rt en· s te nos is, Rus se ll coll ec t ed a tot a l of 1,5 pat ie nt s with preu pera ti,·e re na l ,·e in re nin st udi es who were followed a t leas t l vear posto peratively . 36 Of th ese l, f> pat ie n ts 11;-, had a RVRR of 1. f"> or greater. A :v·ear aft er th e ope ra t ion 106 (92. l per cent) of th ese indi v idu a ls ha d a cure or s ignifi ca nt imprm·e m e nt in th e hy pe rt e ns ion. However. of 60 patients operated on with a RVRR less than 1. ,-l. :21 pa ti e nts (:l:> pe r ce nt of the tot a l ) we re a lso cu re d or impro ve d by an ope ra t ion. In toto. the clini ca l success or failure was predict ed by th e R\' RR in 14S of the l, Pi pa t ie nts . that is the RVRR was 8:\ per cent al'c urat e in predicti ng th e res pon se of the pa ti e nt s to a n operation. Other a uthors ha ,·e reported th e RVRR to be predicti\·e in a pproximat e!\· 80 to Sf> per ce nt of cases w ith unil atera l les ions, 37 a finding in agreement w ith our own ex perien ce.'" While m os t im·estigat ors find few falsely pos 1t ive re na l vein rat ios a greate r probl e m in clini ca l m a na ge ment is occas ion ed hy falsely nega tive res ult s. In his se ri es Ru sse ll not ed a sa ti sfactory res pon ,-;e to s urger~· in more t han a third of th e pati e nts with a nega tive RVRR. Poutasse and as soci a t es re port ed cure or improvement of h:.;pe rt ens ion in fi of 6 pati e nt s opera t ed on d esp ite a RVRR less than 1. :i. 39 These authors also s tressed th e ex tre m e care necessarv in the perform a nce and int erpr et a tion of renin d e t ermin a tions a nd enumerated th e mor e common causes of falsely nega t i\· e ra tios. Proper diet a ry pre para tion . pa tient pos iti on ing a nd assu rant' e th a t th e sa mplin g cathet e r is ac tu a lly in th e ren a l \·e in (easilv deter min ed by m easu ring oxvgen sa turation or para a min ohippu ra t e [PAH] ext rac ti o n in th e renal ve nous blood ) will grea t!\· redu ce th e lik elihood of a fa lse ly nega ti\·e st ud y . The diffi c ult y of predictin g s urgi ca l res pon se in pat ie nt s with bil a t e ra l re n a l a rt e ry disease in les ions involving th e seg m e ntal arterial bran c hes is a formidable one. H oweve r, in a rece nt exce llent stud y b y Schambelan a nd assoc ia tes se lecti ve intrarena l ca th e te rizat ion was used to obta in ve nous blood from a n isc he mic seg m e nt oft he kidn ey in 5 hy pe rt e ns ive pa ti e nts w ith no s ignifica nt diffe rence in RVRR not ed bet ween th e blood sa mpl es obtained from th e main ren a l ve in. 4 0 In eac h of these pa ti ent s the renin ac tivit y in th e blood

t

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FAIH

draining the involved segment was more than I .;J times that found in the hlood from the contralateral main renal vein. Therefore. this techni4ue should be considered in a ll patients in whom a segmental lesion is suspected. Additional criteria have been proposed to improve the diagnostic and predictive accuracy of peripheral renal vein renin determinations. Evi dence of suppression of renin release in the contra latera l kidney seem s to have added value in forecasting the response to surgery " · 41 and lac k of such suppression may indicate a bnorma l blood flow to the contralateral kidney , tha t is ischem ic changes present in the small vessels of the oppos ite normal kidney may be respons ible for persistence of the h~,pertension even when the st enotic lesion is corrected. Importance of the functional status of the contralat era! kidney in determining the out come of an operation is well recognized. The combinat ion analysis score defined by Vaughan and associates, hased on an elevated peripheral renin. evidence of an abnormally increased re nal vein renin content relative to the arterial renin activit y from the suspected kidney and suppression of renin secretion from the contralat eral kidney . appears to improve the predictive accurac:,,· of renin determinations a nd may be of value in identif\ing bila teral ischemi c disease.' 1 " However. the ultimat e usefulness of this measurem ent in clinical practice awa its confirmation by other investigators in a larger number of patients. SRFS. The physiologic basis for SRFS is based on the demonstration of excessive sod ium a nd water reabsorption occurring in the ischem ic kidney as compared to the contra latera l and presumably norma l one. The classic techni4ue for performing SRFS as originally proposed by Howard and Connor 3 was later modified by us ing an infus ion of inulin, PAH and antidiuretic hormone, under a urea saline diuresi s to accentuate the disparity in the salt a nd water reabsorption between the 2 kidneys. 43 The functional lesion characteristic of ischemia was demon strated to be qualitatively identical in main renal artery obstruction and occlusion of a major segmental branch oft he renal artery. This observation made possible an accurate, reproducible means of evaluating the functional significance of rena l arterial lesions, even those involving branches of the renal a rtery producing segmenta l renal is chemia. In recent yea rs the use of SRFS as a diagnostic and prognostic indicator of sign ificant renal ischemia h as declined markedly. T he necessity for the SRFS to be performed under regional anesthesia, the length of time involved to adequately perform the test and the fact that many urologist s are untra ined in the technique of differential function stud ies have a ll cont ributed to the diminution in the popula rity of the SRFS. Also, major a nd minor complications, such as temporary ureteral colic following cat heter removal a nd posi tive urine cultures, occur in about 11 per cent of

patients following the study." Nonetheless. the SRFS are unsurpassed for accuracy in assessing t he fun ctio na l significance of st enotic renal a rt erial lesions. To quote Hunt a nd St rong. "Although differential renal funct ion studies which re4uire c\·stoscopy and cat heterization of both ureters unde r spinal anest hesia. have been performed less fre4uentl11 in our insti t ut ion since the advent of sat isfactorv and reproducihle m easurement of renin act ivit v in the renal plasma. we continue to cons ider the technique the yardstick by whic h othe r methods of assess ing functionally significant lesions must be com pared''.' These words. from astut e investigators with a wealth of experience in the diagnosis and treatment of patients with renal hvpert ension , a de4uately sum up t he relative role of renal function studies in evaluating rena l a rt er:-,· st enos is. For th is reason the tec hnique should be familiar to everv urologist a nd be considered part of the urologic a rma me ntarium . Leav ing one or both ureteral catheters in place for 1:2 to :24 hours following a SRFS and the proper catheter care will do much to mini mize the incidence of ureteral colic and urinary tract infection, which are the most frequent complications encountered. SRFS and RVRR in predicting clinical response to surgery. A strict comparison bet ween the :2 methods is not easi ly obtained prima rily owing to the wide variat ion that exists from institution to institution in the performance of the SRFS. Thus, in the series compiled by Russell from 1:3 published reports, 36 some of the tests were done under general anesthesia, ot he rs wit hout t he use of PAH, inulin or proper dietary preparation (for example test done wh ile the pat ient was sodium depleted or on a ntihype rtensive medication). However, of 141 patients with SRFS perfo rmed preoperatively and followed for a minimum of l yea r after surgical correction the studies correctly predicted the results in 106 or 75 per cent of the patients, a slightl y lower accuracy than that obtained with renal vein ren in activity determina tions in the same compilat ion. In those re ports in which re nin act ivity and SRFS were performed in the same patients by investigators skilled in both techniques. the SRFS has heen found to be e4ual or s uperior in prognostic ability to the RVRR. Foster and associates, by comb ining results of the Howard and Stamey tests, found the SRFS to be greater t han 95 per cent accurate in predicting surgical response in 101 patients. 2 0 In a later publication from the same institution, the a uthors stress that in many patients the RVRR and SRFS are complementary a nd concluded t ha t omission of either SRFS or renin determinations would have resulted in falsely negati ve findin gs in 8 to l O per ce nt of t heir cases.•• Several groups have been crit ica l of the origina l criteria proposed for calling the SRFS positive (a to l difference in urine f1ow and :200 per cent or more increase in PAH concentration in cases of

,l

RENOV ASCULAR HYPERTENSION : ROLE OF l"ROLOCIST

main renal artery stenosis and at least 2 to 1 difference in urine volume with a 16 per cent or greater increase in PAH concentration in the urine from kidneys with segmental ischemia), and suggested that the criteria be liberalized to improve the diagnost ic accuracy of the SRFS. " · 4 ·' Our experience with differential renal function studies in segmental renal ischemia would support the concept of the necessity for less stringent criteria. 38 · 46

Indications for SRFS and renal vein renin determinations. It is evident that SRF'S and renal vein renin studies afford valuable information in selecting patients with potentially curable hypertension owing to renal artery stenosis. The relative ease of sampling renal venous blood just prior to performance of the renal arteriogram makes the routine use of RVRR appealing. In addition, the necessit y of subjecting the patient to spinal anest hesia and the complications that may occur as the result of bilateral ureteral catheterization tend to make the routine performance of SRFS unattractive. SRFS are of limited value in patients with pyelonephritis, since the water a nd salt-losing characteristics of the pyelonephritic kidney m ay mask significant renal ischem ia . In these patient;,. as well as those with a non -functioning kidney or hydronephros is, the rena l vei n study is clearly the diagnostic test of choice. In addition, the added morbidity possibl e as a result of function studies is not routinely warranted in the patient who presents with an elevated peripheral renin. arteriographic evidence of severe renal artery stenosis and a RVRR of 1.5 or greater with evidence of suppression of renin secretion by the contralatera l kidney. However, if the peripheral and renal ve in renins do not afford convincing evidence of signifi: ant renal ischemia in a patient with radiographic evidence of unilateral renal artery stenosis. SRFS should be performed to more accurately and reliably diagnose possible RVH. Lastly, both rena l vein renin determ inat ions and SRFS may be required in those patients presenting with evidence of bilateral renal a rt ery ~tenosis in order to judge the necessity of and proper approach to treatment a nd also may he important in the preoperative evaluation of the contralateral renal function in those patients in whom unilateral nephrectomy is being considered. The attendant morbidit y of carefully performed SRFS does not approach the morbidity and mortality associa ted with an unnecessarv operation or inadequate I~· treated hypertension. Although we have several methods to diagnose the lesion of rena l ischemia. we lack a simply performed, rel iable indicator of which patients will be cured by an operation. Pending the development of simpler, more precise diagnostic maneu vers, the most accurate tests in predicting success following correction of the renal artery lesion are the use of SRFS and the RVRR. Thus. it is

661

important for the urologist to be full y aware and cognizant of the indications and use of these tests as applied to the individual patient. SL' KCICAI. HESLLTS

The initial enthusiasm for surgical treatment of virtually every stenotic lesion of the rena l artery was dampened by reports that many patients were not improved by a n operation. 47 However. since that time. improveme nts in diagnostic a bilit:v, greater care a nd prudence in selecting patients for an operation a nd recent advances in vascular surgical techniques and approaches have led to the situation where we can current!:-, expect cure or improvement of hypertension in the majoritv of patients treated surg ica lly. In the cooperative study 66 per cent of all s urgica lly treated patients were cured or had significant improvement lll the level of the hypert ension.•• Fifty -six per cent of patients with bilateral lesions were significantly benefited by an operation compared to more than 70 per cent success in patient s with unilateral disease. A s ignifica ntly higher percentage of pati ents with unilateral FMD were cured or improved by an operat ion (80 per cent) than were those with unilateral atherosclerot ic disease (6;J per cent). Of particular interest are the results of surgerv in those patients who had demonstrated evidence of functionally significant stenosis by diagnost ic tests prior to operat-ion and who had an anatomically successful operation. In this group. \ll per cent of those with F'MD a nd 8:l per cent of patients with at herosclerot ic disease were cured or improved. Even more encouraging reports a re appearing from si ngle cent ers with a particular interest in tbis problem. Foster and associates reported that 90 per cent of 1:2:2 patients operated upon for RVH and followed for (i months to 11 vears postoperatively were cured or s ignifica ntly improved ." ' In the series with the longest followup published to date. Hunt a nd assoc iates reported on the status of 8-+ of 100 surgical I\· treated patients who were alive, to 14 years postoperat ivelv . 5 Fifty -one of the pat ients were normotensi\·e and an a dditional :2, were normotensi\"l' with the use of a mild antihvpertensive agent. Other authors report cure or improvement in about 80 to 90 per cent of patients treated surgically.••-" The results in ch ildren are particularly encouragin g. 51 In all series quoted pa tient s with FMD respond better to an operation than do patients with atherosclerosis. Palmer reported improvement in 17 of 19 patients (89 per cent) with FMD compared to onl:-,· :21 of :tl pati ents (64 per cent I with a therosd erot ic disease." He implied that generalized small ves:;el disease in the opposite kidney wit b the resultant decrease in renal pl asma flo w to the contralateral kidnev might serve as an important guide to prognosis. Other a uthors have not found the contralateral renal pl asma flow to be of

662

FAIR

such value in predicting which patients will have a good surgical response 53 and an operation should not be denied a patient solely on the basis of a low contralateral PAH clearance. Not surprisingly, younger individuals, many of whom have FMD, responded better to an operation than older people. However, even in considering the patients with FMD as an isolated group, the patients who failed to respond to an operation were almost 10 years older and had a duration of hypertension more than 2 years longer than those who were cured. 9 In most series it appears that women are more likely to benefit from corrective surgery than men. However, this may he a reflection of the fact that the large majority of cases of FMD are found in young female subjects, while atherosclerotic disease as a cause of renal hypertension is more common in older men. The over-all mortality rate of surgery to correct renal artery stenosis has been reported to be between 5 and 11 per cent, 20 · 48 · 54 the majority of deaths occurring in older patients with diffuse atherosclerot ic disease. The improvement in surgical techniques has led to a more aggressive approach to renal arterial lesions. While formerly nephrectomy was the most commonly used form of corrective surgery for RYH attempts at revascularization are the primary approach to treatment today and nephrectomy as a primary procedure is performed in only 20 to~() per cent of cases.2°· 55 Nephrectomy should be considered only for 1) elderly or poor risk patients who may have difficulty in withstanding a more timeconsuming and technically difficult revascularization procedure, 2) patients in whom the hyperten sion is caused by a non-functioning or poorly functioning ischemic kidney and with a normal contra lateral kidney, 3) patients with extensive disease of the distal renal arterial branches in whom reconstruction or clilatation 51 · 56 of the multiple stenoses is not feasible, 4) patients with a scarred pyelonephritic kidney suspected on the basis of renal functional evaluation of being responsible for hypertension. with a normal opposite kidney and ii) patients in whom a revascularization procedure has failed previously. The surgeon dealing with operative treatment of RYH must be thoroughly familiar with a variety of surgical techniques: nephrectomy. partial nephrectomy. segmental artery resection and reanastomo sis, reimplantation of the renal artery into a new site on the aorta, aortic and renal artery enclarterectomy , vein patch angioplasty and renal autotransplantation have all been used with favorable results. On the left side a splenorenal anastomosis is often possible, although in patients with FMD or aneurysms of the renal artery. the splenie vessel should be carefully inspected before use. The vascular changes present in the renal artery can occasionally be found to involve the splenic arter:,,· also. 55 The use of dacron or other synthet ie materials as

grafts for renal arterial bypass has, in many centers , been replaced by autogenous vessel grafts. However, Kaufman prefers the use of velour dacron grafts as a bypass or interposition graft in an individual middle aged or older. 55 Wylie has had good results with the use of a hypogastric artery as a free arterial graft. 57 These authors also report using the external ij_iac artery (which is in turn replaced by a dacron graft) as a bypass graft with good results. In children the common iliac artery has been clividecl, turned upwards and an encl-to-end anastomosis between the common iliac and renal artery performed in a few patients with cure of hy pertension. No ill effects ensue as a result of ligating the common iliac, presumably owing to the development of collateral vessels. 58 However, the most common bypass operation used is the saphenous vein bypass. 20 · 21 · ' 0 · 59 Prior to clamping the renal artery, heparin and mannitol are usually administered systemically. The graft is placed on the lateral side of the aorta below the original renal arter:,c and passes obliquely upward (on the right side usuallv but not strictly necessarilv behind the vena cava) to the kiclnev. An e~cl-to-encl or end -to-side anastomosis between the vein graft and the renal artery is used, although the end-to -end anastomosis may lessen the likelihood of postoperative graft thrombosis. 51 The use of monofilament pol:,,·propvlene suture material is superior to braided polyester suture in reducing blood leakage through the suture line and minimizes the requirement for blood transfusion. 20 Technical failures leading to graft occlusion by thrombosis or stenosis have been reported to occur in 12 to 21 per cent of bypass grafts. 60 · 61 If thrombosis of the graft occurs it usually presents within the first week postoperatively. A normal rapid sequence IYP does not ensure a patent graft. 61 If the physician serious!:,,· considers the possibility of graft occlusion an arteriogram in the early postoperative period will make the definitive diagnosis. Recently several groups have expressed concern over the long-term fate of saphenous vein aortorenal bypass grafts. 60 · 61 The Vanderbilt group reported thrombosis in l•t per cent of 89 aortorenal saphenous vein grafts but stressed the fact that no thromboses developed bevoncl the early postoperative period and were probably related to technical failures. 61 More importanth·. lfi of 89 grafts (17 per cent) developed stenot ic lesions. alt hough only one of these required reoperation. Of :l9 grafts followed with serial studies for l2 to 108 months postoperative!:,,·. (i2 per cent remained normal, 20 per cent had a mild uniform dilatation of the graft which did not progress on further examination. and 2 of :rn (:J per cent) de,·eloped true aneur:-·sm formation. In the '.\1ichigan study 40 per cent of 7,! vein grafts were normal when examined 8 to 109 months after opPrntion."" Fort_,·-four per cent had a mild

t

HE NO VA SC l ' LAH HYPEHTE:'-/SIO'.'i : HOLE OF l HOLOCIST

dilatation throughout the le ngth of the ve in whi('h parall eled th e in crease in diamet er of th e renal artery. Of partic ul a r interes t was th e fact that JG per cent of the 74 vein graf"ts ha yea rs old) or patients in whom it is not poss ible to control the blood pressure in the norm a l range on a medical reg imen that is acce pt a bl e to t he pati ent a nd does not se riou sly impai r the qu a lit y of his life. as well as in patients with rece nt onset of severe diastolic hype rten s ion , one should proceed to a se lect ive re na l a rt e riogram with front a l a nd oblique projections. If the arteriogram d e mon strat es a re na l arten· les ion this les ion must be assessed for its functional significance befo re a rational d ec ision with respec t to a n operation can be reached . The rela ti ve ease of sa mpling re na l ,·e nous blood just prior to perform a nce of th e re nal arteriogram makes th e routin e use of re na l ve in renin d etermina tion appealing. If the peripheral and re na l ve in renin d etermination s do not afford convincing ev ide nce of s ignificant ren a l isc hemia in a pat ie nt with radiographic ev idence of unilateral renal artery ste nosis. SRFS should be performed to more ac curat e h- a nd reliabl v diagnose poss ibl e RVH. Th e mode rn urologis t with his knowl edge of anatonw. ph)·s iology, and cliagnost ic and surgical a pproac hes in elucidating the na ture of surgical disease should functi on as the central fi gure in th e ha ndling of th ese pa ti e nt s. Th e urologist must be ca pable of pe rforming anl .. Goodman. S. and Roguska. ,J.· Plasma renin activitv in primary and secondary hypertension. Medicine. 46: 475, 1967. Hussain, R. A.. Gifford, R. W., ,Jr.. Stewart. B. H., Meane:,-. T. F., McCormack. L. ,J., Vidt. D. G. and Humphrey. D. C.: Differential renal venous renin activity in diagnosis of renovascular hvpertension. Review of :2:J cases. Amer. ,J. Cardiol.. :32: 707. 19,:l. Gunnells. ,J. C .. ,Jr.. McGuffin. W. L., ,Jr .. ,Johnsrude. I. and Robinson. R R.: Peripheral and renal venous plasma renin activity in h:,,pertension. Ann Intern. Med .. 71: "''''· 1969. Stockigt, ,J_ R., Noakes. C. A., Collins. R. D., Schambelan, M. and Biglieri. E. G.: Renal-vein renin in various forms of renal hypertension. Lancet, 1: 119-1. 197:2. Ernst, C. B .. Rookstein, ,J. ,J., Montie. ,J.. Baumgartel, E., Hoobler. S. W. and Frv. W. ,J.: Renal vein renin ratios and collateral vessels in renovascular hypertension. Arch. Surg .. 104: 4'.JG. 197:2. Marks. L. S. and Maxwell, M. H.: Renal vein renin. Value and limitations in the prediction of operative results. llrol. Clin. N. Amer .. 2: :n1, 197fi. Russell. R. P.: Renal hvpertension. Surg. Clin. N. Amer .. 54: :)49. 1'.174. Bourgoignie. ,J., Kurz. S., Cantanzaro, F. ,J., Serirat, I'. and Perry. H. M., ,Jr .. Renal venous renin in h:,pertension. Amer. ,J. Med .. 48: :i:1:2, 1970. Schaeffer. A. ,J. and Fair. W.R.: Comparison of split function ratios with renal vein renin ratios in patients with curable hypertension caused by um lateral renal arterv stenosis. ,J. Crol.. 112: 697. 1974. Poutasse. E. F .. Marks, L. S .. Wisoff. C. P., Vinson. A. M. and Wan. A. T .. Renal vein renin determina tions in hvpertension: falselv negative tests. ,J. llrol.. 110: :1,1, 197;1_ Schambelan. M .. Glickman. M. Stockigt. ,J. R. and Biglieri. E.G.: Selective renal vein renin samplin~

RENOV ASCULAI{ HYPEHTENSIO N: HOLE OF l iROLOGI ST

41.

42.

4:,.

44.

4,'>.

46.

4,.

48.

49.

,'iO.

in h y perten s iv e pati e nt s with seg ment a l renal les ions . New En g l. ,J. Med. , 290: I J;'i:l. 19,4. Va ughan. E. D., ,Jr. , Bi.ihl er, F. R.. Laragh. J. H .. Sealey·. J. E., Baer, L. and Bard. R. H. : Re novascular h y perten s ion: renin m eas ure m e nt s to indi cate h y persec retion and contralatera\ su ppress io n. estimate renal plasma flow. and sco re of s urgical curability. Amer. J. Med., 55 : 402. 1973. Vaughan. E. D. , ,Jr . and L a ragh. ,J. H.: N ew concepts oft h e renin syst e m and of vasoconstrict ion -vo lume m ec han isms. Di agnos is a nd treatment of re nov asc ular and renal hy p e rtens ion s . Urn \. C lin. N. Amer .. 2: 2:37. 1975 . S t a m ev. T. A. , Nudelman, I. ,J. . Good. P . H .. Schwentker. F. N. a nd Hendri cks. F.: Functional c h a ract e ris tics of renova sc ular hype rt e ns ion. Med ic ine. 40: 347. 1961. O"Conor. V. ,J.. ,Jr. and S imon. N . M.· Are divid ed fun ction studies n ecessa rv in the treatment of renovasc ular hy pe rt e nsio n'' ,J. U rol.. 103: 11 9. 1970. De a n. R. H. a nd Fost e r. ,J. H.· Criter ia for the diagnosis of re nov asc ul ar hype rt e ns ion . ~-iu rge n ·. 74: 926. 197:l F a ir. W. R. a nd S tam ey. T. A.: Diffe re nti a l re nal fun ction studi es in seg m ent a l rena l isc he mi a . .J.A.M .A .. 217: 790. 1971. Shapiro. A. P .. P erez-Sta hl e, E .. Scheib. E.T.. Hron. K .. Moutsos . S. E .. Berg. G. a nd Misage. ,J. R .: Re n a l artery s t en os is and hy·pertension. Ohs en·ation s on current sta tu s of th era pv from a s tud,· of 11 5 pa ti e nt s . Am e r. ,J. M ed .. 47: 17fi. 1969 . F ost e r, .J. H .. M axwell. M . H .. Franklin. S. S .. Bl e ife r. K. H .. Trippe l. 0 . H .. ,Julian. 0 . C .. D eCamp. P. T. a nd Varady. P. T.: Renornseular occlusi,·e di sease. Resu lt s of operati,·e trea tm e nt. ,J.A.M.A .. 231: 1()4:l . 197i'i. Jun cos. L. l., Strong. C. G. a nd Hunt. .J. C'. : Predic t ion of res ult s of s urgery· for renal and renovasc ul a r hv pert ens ion. Arch. Int ern. M ed .. 134: 655. 1974. Ernst. C .R .. S t a nl ey· . ,J.C .. M a rshall. F. F. a nd Frv. W. J. · Autoge no u s sap he nou s ,·ei n aor t ore1rn I graft s . A t e n -year exper ience. Arch. Surg .. 105: 8,i,i. 19,:2.

665

ii i. Frv. W. ,J.. Brink. R. E. a nd Thompson. N. W. : '.\Jew t ec hniques in th e trea tment of ex t e ns ive fihromu sc ul a r disease in volv ing th e re na l a rt e ri es. S urge ry·. 68: 9!i9. 19,0 . .'i:2. Palmer. ,J. M: Prognostic valueofcontralateral renal plasma flow in re novascu lar hy-perte ns i,,n. An a l\"s is of fi5 s ur~i ca \\y trea t ed patients with prove d unilateral les ions . ,J.A.M.A .. 217: 794. 19,1. 5:L Mendonca. P. P .. de and Young. ,J. D .. ,Jr.: RennY ascular status a ft e r re n a l surgerv for hy pe rt e nsion . .J.A.M.A.. 201: G9:2. 1~167. !i4. K au fman. ,J. ,J.. Lupu. A. N. a nd M a xwell. M. H .: Furth e r ex pe ri e nc es in th e diagnosis an d trea t men l of reno vascu lar h v perten si on. II. Surgical tre atment of hvpe rt e ns ion secondary· to re na l artery stenosis. ll rol. Int . 24: 1:2. 19(i9. ""· K au fm a n ..J. ,J. · Dac ron grafts a nd sp le norena l ll\·pa ss in th e su rgical trea tm e nt of stenosing les io ns of th e re nal a rt e n ·. Urn\. C'lin. N. Amer .. 2: :\6fi. 197:i. :i6 . Morris. C. C. ,Jr .. Lec hl er. A. a nd DeHakev. M. E.: Surgical treat m en t of fihromuscular diseas e of the carotid a rt e ri es . Arc h. Surg .. 96: (j;\fi. 1,168. WYiie. E. ,J.· Endart erectom \" a nd a uto geno us a rt eri a l grafts in th e surgical trea tnH: nt of ste nosi ng les ion s of th e re na l a rtPrv . ll rol. Clin. N. Amer .. 2: ;\;'i I. :ill. Owen. h:.· Curable causes of hvpe rt c nsi o n . Hrit .. J. Hos p. M ed .. II: ii:,:l. 111,-l. ,i9. K a ufm a n. ,J. .J. a nd Lupu. A. "I. : Treatme nt of rena l a rt e r~,; stenos is u:-.ing h~·pogast ric arte r.v autograhs. ,J. llrol.. ltHi: 9. 19, 1. 60. Stanlev .. J.C .. Ern s t . C.H. a nd Fn. W . . J.· Fate of IOO aor tore na l ,·e in gra ft s : c harac t e ri s tics of lat e gra ft ex pa ns inn . anf'ur _,·s n1al dilatation. an