Kremer Hovinga, T

English

This thesis adresses two aspects of renovascular disease in more detail. Our long standing interest in the effects of ACE inhibitors on kidney function has been expanded to include its use in conjunction with radioisotope methods to study both the diagnostic potential and the changes in renal function casu quo handling of different tracer materials. Secondly, the effects of renovascular disease on renal function and the possible benefits of active intervention by surgery and in particular by PTRA have been studied. ... Zie:m Summary and conclusion

Dissertations of the University of Groningen

   University of GroningenRenovascular diseaseKremer Hovinga, TIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1990Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Kremer Hovinga, T. (1990). Renovascular disease: Observations on radioisotope detection andpreservation of renal function. s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 04-06-2022d, M.; Wellons,Íery stenosis.s, G.; Wehling,raler DilatationDonohue, J.P.tioning kidney.y. A potentially1982;142:693A.J.M.; Hern,n kidney func-:terial disease.rovascular dis-H.; Hem, G.K.al angioplastyChapter 7Summary and conclusionsThis thesis adÍesses two aspects of renovascular disease in more detail. Our long standinginterest in the effects of ACE inhibitors on kidney function has been expanded to includeits use in conjunction with radioisotope methods to study both the diagnostic potential andthe changes in renal function casu quo handling ofdifferent Eacer materials. Secondly, theeffects of renovascular disease on renal function and the possible benehts of active inter-vention by surgery and in particular by PTRA have been studied.The first part of this thesis (Chapters 2 & 3) describes observations on radioisotopeinvestigations in human unilateral renal artery stenosis, before and after challenge withACE inhibitors under conrolled conditions. The case reported in chapter 2 is one of thefint among the many studies in this field, and represents the lust published case of rever-sible decreased uptake of the Eacer ee*Tc-DMSA (dimercapto succinic acid) in this situ-ation. This study delineates the now familiar concept of angiotensin-Il mediated vasocon-striction, essential to effectively maintain transmembrane filtration pressure and henceglomerular hlration in a kidney with high gnde renal aÍery st€nosis. Renal blood flowusually is maintained in this situation, but t}re handling of tracer materials, considered tobe dependent upon renal perfusion and (peri)tubular uptake is clearly altered.The diagnosric potential of different radioisotope investigations before and after ACEinhibition was subsequently studied prospectively in a larger group of patients with uni-lateral renal artery stenosis, as described in chapter 3. tzl-hippurate and es-Tc-DTPArenography and e*"Tc-DMSA scintigraphy, with their clearly different predominantmechanism of renal uptake and excretion, were studied concurrently to evaluate the use-fulness of these different methods in diagnosing renal artery stenosis, and o gain insightin ttre altered renal hemodynamics and handling of tlre tracers. The results of these diffe-rent radioisotope investigations were evaluated both visually and quantitively. Further-more (changes in) blood pressure and in particular renal function were studied. The sen-sitivity percentages for detection of renovascular disease, already high in this selectedpopulation, were fuÍher increased for all radioisotope methods after challenge with ACEinhibitors, conÍirming preliminary observations of other investigators. Despite the attimes substantial drop in blood pressure, ACE-stimulated renography and scintigraphyproved [o be rather simple and safe methods of investigations. Overall renal function usu-ally is well maintained in this situation, except in some patients with more marked renalimpairmenl Tracer handling, however, can show striking changes, most typically "reten-tion" curves in l23l-hippumte renography and diminished or even absent uptake of ee-Tc-DTPA and s*'Tc-DMSA at the stenotic side. Quantitative valuation objectivates asym-metry of kidney renography and scintigraphy and can be useful to compare results of these69methods in different centres. tzsl-hippuÍate renography and se-Tc-DMSA renal scintigra-phy are methods of choice, in situations of marked overall renal impairment, or discretesegmental stenosis respectively.Chapter 4 represents an extensive review of the literature on Íhe effects of renal arterystenosis and in particular the effects of Eeatment by surgery or angioplasty on kidneyfunction. It has become more generally accepted that preservation of renal function is animporrant factor and in selected cases the sole reason for active intervention in renovas-cular disease. Atherosclerosis and fibromuscular dysplasia, the rwo disorders responsiblefor all except a few patients with renovascular disease, have clinically clearly distinctcharacteristics, especially with regard to the risk of renal functional deterioration. In fibro-muscular dysplasia type of stenosis renal function generally is not severely impaired andthe risk of total vascular occlusion is relatively small, except in certain less frequent sub-types of this disorder. In atherosclerotic renovascular disease preservation ofrenal func-tion is most important because of the risks of progression and renal failure.A first preliminary overview is given of the effects of revascularization on renal func-tion in the different clinical situations, characteristic of this heterogenous disorder. Inshort, active intervention can lead to improved or stabilized renal function in many casesbut is unrewarding under some circumstances. The improvement in renal function usuallyis only modest" except in favourable cases of vascular occlusion or high grade stenosis tothe entire renal mass (occlusive disease in a solitary functioning kidney or bilaterally).However, perhaps more importantly, the resulting kidney function after successful revas-cularization can be maintained over long-term follow up in most patients. Unfortunatelyresults of revascularization are not universally beneficial, either because the interventionhas not been (completely) successful, has met with complications, or because too faradvanced structural renal damage already had been present. This latter situation is fre-quently present in particular in (unilateral) atherosclerotic renal artery stenosis with mar-ked decreased overall renal function and in the case of otal vascular occlusion.Increased awaÍeness of the risks to renal mass and function and fte still improvingmethods of intervention make active revascularization a more attractive, but not clearlydefined treatment option, also because of the lack of good comparative studies with medi-cal treatrnent.Chapter 5 describes results of accurate renal function measurements hortly beforeand after uncomplicated PTRA h unilateral renal artery stenosis. For this purpose glome-rular filuation rate (GFR) and effective renal plasma flow @RPF) were measuÍed by con-stant infusion methods, using tx1-ior1lalamate and l3{-hippurate, in 12 patients duringstandardized iet and either no or unchanged antihypert€nsive medication. ERPF incre-ased in the majority (7 5Vo) of paients but GFR, at least when measured within two weeksafter the procedure, increased simultaneously in only 33Vo of the patients. This modestimprovement of GFR (of líVo at most) was only seen in patients with initially a relativelywell maintained renal function. The anatomical severity of the stenosis and the extent ofdilatation, at least as calculated from the angiograms were not predictive of the responseobtained. Marked size differences and shrinkage of the kidney were prognostically unfa-70vourablerenal fun,patients \functionrenal funrstandingIn ch:introductthis perioeffect on.At that tit(42Vo) an'favourablnosis or ckedly in natinine clInitial rention, imprAlso in tlrpressure lobservedoptimal oHumatriad of ropposed tincludinglocalisedsenting aapart fronthis heteraugment.Overconsidereand adapNowadalother melficity. Oftigaphyinvasivetantly, throf renal 'iA renal scintigra-lrÍnent, Or discreteects ofrenal arteryoplasty on kidneyenal function is anrention in renovas-nrden responsibleilly clearly distincterioration. In fibro-'erely impaiÍed andn less frequent sub-ation of renal func-dlure.;ation on renal func-genous disorder. In,ction in many casesnal function usuallygh grade stenosis tolney or bilaterally).er successful revas-ients. Unfortunatelyuse the interventionor because too fartteÍ situation is fre-/ stenosis with mar-occlusion.the still improving[ive, but not clearly) studies witll medi-rents shortly beforethis purpose glome-e measured by con-l2 patiens during:ation. ERPF incre-d within two weekstients. This modestinitially a relativelyis and the extent ofive of the responserognostically unfa-vourable characteristics. As opposed to effects on blood pressure, response of (overall)renal function after successful PTRA is not positively correlated with PRA ratio. In fact,patients with the highest PRA ratio had unchanged or even somewhat decreased renalfunction after PTRA. These patients, however, were also characterised by a low initialrenal function and a small kidney size at the stenotic side, most probably reflecting longstanding structural ischemic and/or hlpertensive damage.In chapter 6, we describe the results of PTRA treatÍnent during the first 5 years afterintroduction of this technique in our clinic in 1979. A total of 43 patients were treated inthis period and in 33 of these complete reevaluation, including blood pressure response,effect on renal function and angiographic status of the dilated vessels could be performed.At that time, a relatively high peÍcentage of restenosis was found in both atherosclerosic-(427o) and, fibromuscular dysplasia type of stenosis (227o). Blood pressure response wasfavourable after successful dilatation of uni- or bilateral disease. When contralateral ste-nosis or occlusion remained unEeated, blood pressure, as expected, was no[ altered mar-kedly in mostcases. Renal function was studied, by both serum creatinine values and cre-atinine clearance estimations over long-term follow up up to 4 years after the procedure.Initial renal function was impaired to some extent in all patients. After successful dilata-tion, improvement or stabilization of renal function was seen in the majority of patients.Also in the patients of the more complicated subgroup, mentioned above, in whom bloodpressuÍe had not changed markedly after PTRA, improvement of renal function wasobserved in a more or less similar percentage of the patients. However, now the result wasoptimal only after a few months.Human renovascular disease is a rafter hetcrogeneous disorder, characterised by thetriad of compromised renovascular hemodynamics, hypertension and ischaemia. Asopposed to the situation in most animal experiments, its presentation can vary greatly,including for example the classical "therapy resistant" severely hypertensive patient withlocalised focal stenosis and patients with surreptitiously progressed bilateral disease, pre-senting acutely with left sided congestive heart failure or end stage renal disease. Evenapart from the relatively low prevalence ofrenovascular disease in Íhe general population,this heterogeneiry and the incomplete understanding of the pathophysiology thereforeaugment he difÍïculties in screening for this disease.Over the years many methods have been advocated for this purpose including twoconsidered to be "gold sÍandards": conventional angiography for anatomical diagnosisand adaptations of the Howard and Stamey tests for more physiological evaluation.Nowadays Íhese two have been abandoned, largely because of their impracticality, but noother methods of choice have emerged, showing a sufficiently high sensitivity and speci-ficity. Of the more contemporary methods under investigation, renography and renal scin-tigraphy have received (renewed) interest, in part because they are relatively simple, non-invasive and readily available methods, which also can be repeated easily. More impor-tantly, the different radionuclid give dynamic information on "functional" characteristicsof renal perfusion and glomerular filtration. Apart from technical improvements in this7 1field, intervention in the renin-angiotensin-aldosterone system (RAAS) can reveal or aug-ment changes compatible with "critical" renal artery stenosis.This demonsEation of functional significance of the stenosis is important for severalreasons. First, the presence of renal artery stenosis has been shown in healthy individualsand at autopsy, without evidence of hypertension or renal impairment. Secondly, angio-graphic "anatomical" renal arterial nanowing is an imperfectreflection of the severity andof the functional significance of the lesion, and therefore cannot be used to establish thecausal relationship with the hypertension present. Unfortunately, the evaluation of "func-tional" characteristics of renal arterial disease has not lived up to expectation at present.Studies of ACE-stimulated renography in dogs have documented a 1007o sensitivity indiagnosing unilateral renovascular disease. However, experiments in animals are usuallydone shortly after fte induction of renovascular hypertension by clamping ttre renal artery.The importance of the RAAS has clearly been established in this situation. Subsequently,a transition period can be found, where removal of the clamp still restores blood pressure,even tlough Angiotensin II levels already had returned already to pÍe-stenosis levels, butultimately no change in blood pressure is seen any longer after removal of the original ste-nosis. In the human situation, generally the severity and the duration of the stenosis areunknown and intrarenal abnormalities of various etiology can be present at the same time.Not surprisingly therefore ACE-stimulated renography and scintigraphy have not attaineda similar high degree of sensitivity, when compared to experimental animal studies.Further studies Írerefore are clearly needed, both to study ttre exact. indications, but evenbefore that, to standardize the appropriate conditions of investigation in order to maximizethe yield of these methods.Thus, although radionuclide imaging with ACE inhibitor challenge clearly is a valu-able addition o Íre diagnostic arsenal, both historical and scientific reasons hould warnagainst its indiscriminitive use as a new "ideal" screening method in hypertension. Futurediagrostic methods, however, should be selected upon their ability tn demonstrate this"functional" character of the lesion.The concept of evaluating renal hemodynamics or altered handling ofvarious tracers,before and after interference in different intrarenal regulatory mechanisms, is also veryappealing in order to further elucidate the complex intrarenal changes econdary to reno-vascular disease. One of the major clinical problems in this disorder is our inability to pro-ve beyond doubt the secondary nature of the hypertension in all cases before intervention.Also presumably somewhat different inftaÍenal facton come into play when causinghypertension or renal impairment. Contrasting effects tlerefore can be seen with regardto blood pressure and renal function after intervention, also depending on the etiology ofthe disease. ACE inhibitors can be helpful to more precisely indicate the limis of renalcontraregulatory mechanisms, activated to preserve renal perfusion and function.In fibromuscular dysplasia the main indication for treatment is ttre hypertension pre-sent. Revascularization isbest done by PTRA as results are moÍe or less equal to those ofsurgery. Effects on blood pÍessure and, if renal function is impaired, on renal functiongenerally are rewarding, obviating the need for life-long antihypertensive therapy.72Ablatirdevelolgical bralso in rThesummalthe hightion, lorblood plesions iis muchrisk patiprogresswhetherdecline rischaem,damage,tively shvessel prsystemat.conditiorat this mrreveal or aug-mt for severalhy individualscondly, angio-he severity ando establish the,ation of "func-tion at present.Zo sensitivity innals are usuallythe renal artery.r. Subsequently,blood pressure,nosis levels, but'the original ste-'the stenosis areat the same time.have not attainedanimal studies.cations, but evenrrder to maximizeclearly is a valu-tons should warnertension. Futuredemonstrate this'f various Eacers,sms, is also verycondary to reno-r inability !o pro-bre intervention.ry when causingseen with regardn the etiology ofre limits of renalfunction.ypertension pre-equal to those of'n renal functiontensive therapy.Ablative procedures hould be avoided, ifpossible, in view of the propensity for (de novo)development of new lesions contralaterally. Improvement in PTRA and especially in sur-gical both in situ and extracorporeal techniques have made intervention more feasible,also in case of extensive or branch disease.The value of intervention in atherosclerotic renovascular disease is much less easilysummarized. Revascularization both confers Íre greatest benefit, but unfortunately alsothe highest risks in this situation. Although still reduced compared to the general popula-tion, long-term survival is better in successfully revascularized patients. The degree ofblood pressure control achieved and the extent of exfrarenal significant atheroscleroticlesions are major determinants in this regard. Adequate medical antihypertensive therapyis much more feasible nowadays and can be a good treatment option, in particular in highrisk patients. Careful follow up of renal function and renal size, however, is waranted asprogressive disease is noted, especially in patients with advanced atherosclerotic stenosis,whether or not blood pressuÍe is controlled. Revascularization can arrest or reverse thedecline of renal function in many cases, Íle best results obtained, when all renal mass isischaemic. Timely intervenlion is mandatory as combined ischaemic and hypertensivedamage can lead to progressive irreversible loss ofrenal function and renal size in a rela-tively short time. Prevention of total occlusion and the possible res[oration of long-termvessel prognosis to that without stenosis aÍe encouraging findings, but the lack of largesystematic investigations and the still evolving methods of treatment in this relatively rarecondition preclude a really definitive standpoint on intervention in renovascular diseaseat this moment.

Renovascular disease:Observations on radioisotope detection and preservation of renal function.

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Renovascular disease:Observations on radioisotope detection and preservation of renal function.

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