z RENOGRAM INIS-mf —11322 RENOVASCULAR HYPERTENSION G.G. Geyskes STELLINGEN Behorende bij het proefschrift THE RENOGRAM IN RENOVASCULAR HYPERTENSION door G.G. Geyskes \ "n. it f 1 VII Het captopril renogratn kan de diagnostische PTA zoals door Maxwell Paranormale geneeskunde bij patiënten met hypertensie heeft meer bepleit vrijwel vervangen. subjectieve dan objectieve effecten. M.H. Maxwell. A.V. Walu. Hyptritnsion 1914.6:589-392. II VIII Bij dubbelzijdige nierarteriestenose geeft ncfrectomie van een kleine Het lijkt mogelijk de ontwikkeling van diabetische nefropathie af te nier in combinatie met PTA van de contralaterale nier vaak verbetering remmen door medicamenteuze antihypertensieve therapie, speciaal met van de totale nierfunktie. converting enzyme inhibitors. Ill IX Onderdrukking van de PRA is een antihyperteniief mechanisme van Het roken van sigaretten kan een oorzaak van renovaculaire hyperten- betaMokkers. sie zijn. G.G. Geyskts. J. Vos. P. Boer. E.J. Dorhoul Mets. Lmcei 1976:1049-1051. CE. Grimm el al. Nrphron 1986. 44 SI: 96-100. IV Contractie van het extracellulair volume is een antihyperteniief mecha- Het metaiodobenzylguanidine scintigram is een aanwinst bij de diag- nisme van diuretka. nostiek van het feochromocytoom. De opname van deze stof kan ook U.A.M. van Seht». G.G. Geyskti. J.C. Hom. El Dorhoul Mees. therapeutische consequenties hebben. CKn Phorm è Vier 1986. 39:6044, XI Bij veroordeling voor een /.waar misdrijf kan men 't best een levenslange Het clonidine withdrawal syndroom is een vrij sterke contraindicatie tegen het gebruik van dit antihyptttensivum. strul geven die verkort wordt bij verbetering van de mentaliteit. G.G. Geyskts. P. Boer. E.J. vtn Dorhoul Met$. Br. J. Clln Pharm 1979. 7:33-62. XII VI Als men de schoonheid van traditionele houten schepen op de Neder- landse wateren wil behouden moeten snel financiële steunmaatregelen De combinatie natriurese en vaat verwijding it een gunstig werkingspro- genomen worden, sneller dan het hout rot. fiel van ntcardipwe voor de tNmfic van essentiële hypertensie. ».A.M. VM Sehmk. G.G. Geyikes. Br. J. Clln Pharm 1984. 18:57-63. XIII Een korte waarschuwingstoon die tijdens een telefoongesprek aangeeft dat het toestel wordt opgeroepen zou de telefonische communicatie aanzienlijk kunnen verbeteren. XIV Vergclijking van de nierfunktie van muis en olifant verheldert het inzicht in het gegeven dat voor een patient de ernst van zijn uraemie belangrijker is dan het aantal milliliters klaring waarmee dit wordt bereikt. XV De promotie van een wetenschapper heeft veel kenmerken van de wespenproef bij de Oajana indianen. Or. D.C. Gryskes: Met «/<• ()ajana\ up slap. Vilgave Department landhmnrproefstaiion Surinam? 1942. Utrecht, 9 juni 1987 THE RENOGRAM IN RENOVASCULAR HYPERTENSION HET RENOGRAM BIJ RENOVASCULAIRE HYPERTENSIE (met een samenvatting in het Nederlands) PROEFSCHRIFT Ter verkrijging van de graad van doctor in de geneeskunde aan de rijksuniversiteit te Utrecht, op gezag van de rector magnificus Prof. Dr. J.A. van Ginkel volgens besluit van het college van dekanen in het openbaar te verdedigen op dinsdag 9 juni 1987 des namiddags te 14.30 uur door GIJSBERT GERARD GEYSKES geboren op 11 juli 1934 ). te Woudenberg ) Schotanus & Jens Utrecht b.v. Promotoren: - Prof. Dr. E.J. Dorhout Mees - Prof. Dr. C.B.A.J. Puylaert Copromotor: - Dr. H.Y. Oei De publicatie van dit proefschrift werd financieel gesteund door de Kliniek voor Inwendige Geneeskunde en door de Van 't Hoog Stichting, beiden te Utrecht. CONTENTS Chapter 1. Introduction and questions 1 Chapter 2. The radioisotope renogram 4 Chapter 3. Autoregulation of renal blood flow and GFR 8 Chapter 4. Study 1: Follow up study of 70 patients with renal artery stenosis treated by percutaneous transluminal dilatation 17 Chapter 5. Study 2: Renography: prediction of blood pressure after dilatation of renal artery stenosis 29 Chapter 6. Study 3: Renography with captopril. Changes in a patient with hypertension and unilateral renal artery stenosis 47 Chapter 7. Study 4: Renovascular hypertension identified by captopril-induced changes in the renogram 59 Chapter 8. Study 5: Renovascular hypertension. The small kidney updated 81 Chapter 9. Conclusions and answers to the questions 103 Chapter 10. Supplementary discussion of captopril renography 111 Chapter 11. Summary 117 Samenvatting in het Nederlands 121 List of publications on the subject of renal artery stenosis and PTA 129 Dankwoord 133 Curriculum vitae 135 Aan Kathinka - %•: CHAPTER 1 Introduction and questions The studies reported in this thesis were done because of our interest in renovascular hypertension. The interest of our group was intensified by the development of a new treatment of renal artery stenosis, balloon catheter dilatation or percutane- ous transluminal angioplasty (PTA) in 1978. Our earliest results, the first report in the litterature on PTA in a group of patients with renovascular hypertension, was pu- blished in 1979 (1). This innovative way of treating patients with renal artery stenosis has led to an enthousiastic and fruitfull cooperation among the departments of radiology, nucleair medicine and nephrology. An account of the scientific cooperation of these departments on the subject of renal artery stenosis and PTA, is given in the list of publications, abstracts and full papers, to be found at the end of this thesis. This thesis comprises five reports on studies with renograms, radionuclide investigations of individual renal function in pa- tients suspected of renovascular hypertension. More informa- tion about/he radioisotope renogram is given in chapter 2. The main question was to determine wether the renogram could trace functional changes in a kidney with a stenosed artery, before and after PTA treatment. In a given patient these ._ functional changes could provide information on the signifi- cance of the artery stenosis as a cause of that patient's hyperten- i sion, and to some extend predict the bloodpressure response ! after PTA treatment. i ; An important issue in these studies is the registration of the ) renal effects created by captopril on the renogram. This drug ' with its specific inhibition of the conversion of angiotensine I to angiotensine II, amplifies the impairment of the glomerular I filtration rate (GFR) in a kidney behind a stenosis. This is . 1 ¥ attributed to the dependency of the GFR on angiotensin II in a kidney with a low perfusion pressure: converting enzyme inhi- bition disturbs the angiotensin Il-dependent autoregulation of the GFR (2). A short overview of the pathophysiology of autoregulation of renal blood flow and GFR with emphasis on the contribution of angiotensin II, is given in chapter 3. As shown in our studies, captopril-induced deterioration of the GFR can be shown by renography, especially when it occurs in only one of two kidneys and for that reason does escape detection by overall renal function studies. Our group has introduced the captopril-induced change in the renogram as a test for a functional renal artery stenosis (3,4). This test can detect abnormalities in flow as well as in renal renin activity, two main components of the sequence of events that are thought to be of importance in the causation of renovascular hypertension. Questions posed in this thesis. 1. Is it possible to predict the effect of PTA on bloodpressure by the 131 I-hippurate renogram. 2. Does the 131 I-hippurate renogram change after PTA, and is this change related to the blood pressure response to PTA. 3. Are renograpic methods able to demonstrate captopril-in- duced unilateral changes in renal function in a patient with renovascular hypertension. 4. Do captopril induced changes in the renogram improve specificity or sensitivity of the renogram without captopril for the diagnosis of renovascular hypertension. 5. Do what extent can patients with hypertension and one very poorly perfused kidney (one that has relative hippura- te uptake of that kidney /total renal uptake of 25% as shown by renography) benefit from PTA treatment. References 1. Geyskes G.G., Puylaert C.B.A.J., Oei H.Y., Boomsma J. H.B. Intraluminal dilatation of renal artery stenosis. Clin Science 1979, 57,4415-4435. 2. Blythe W.B. Captopril and renal autoregulations. N. Eng- land J. of Med 1983, 308, 390-391. 3. Geyskes G.G., Oei H.Y., Dorhout Mees EJ. Captopril induced renographic alterations in unilateral renal artery stenosis. Book of abstracts I Oth Scientific Meeting Intern. Soc. Hypertension Interlaken, Switzerland 1984 p 388. 4. Oei H.Y., Geyskes G.G., Dorhout Mees EJ., Puylaert C.B. A.J. Captopril induced renographic alterations in uni- lateral renal stenosis. J. Nucl. Med. 1984, 25, P36. CHAPTER 2 The radioisotope renogram In 1956 Taplin and Winter (1) developed the radioisotope renogram as a test to detect unilateral renal artery disease in hypertensive patients. They interpreted the time activity curves by a visual comparison of the two tracings and this method is still widely utilized. However differences in interpretation of this qualitative method have led to more objective quantitative interpretations of the various parameters derived from these curves. There are divergent opinions about criteria to be employed in interpretation of renogram curves. Unavoidable technical dif- ficulties and lack of an accepted standardized technique may partially account for discrepancy in published results. This was especially true when single probes were placed above each kidney, but thickness of body wall, size of renal pelvis and asymmetric rate of pelvic emptying, especially when the diure- sis is slow, are still causing considerabel variations in the amplitudo and shape of the curves in a normal individual. In a overview of 12 studies false positive renograms were reported in 20% (range 0 - 33%) of 357 patients with essentiel hyperten- sion, true positive tests in 84% (range 54 -100%) of 348 patients with proven renal artery stenosis (2). Over the passed decade, the use of more advanced gamma camera equipment and computer system enabling accurate background subtraction have improved the accuracy of reno- graphy to such extent that measurment of divided renal func- tion has achieved a high level of reliability (1,3,4).