Exercise renography in essential hypertension.

Exercise renography is an investigative procedure used to visualize a renal functional disturbance of essential hypertension (EH). The exercise protocol was developed to intensify a renal functional abnormality observed in standing hypertensive patients, when it appeared that this disturbance was directly associated with EH. Clearance determinations during light ergometric exercise showed that the abnormal scintigraphic images of the exercise renogram result from a prominent contraction of glomerular filtration rate (GFR), while effective renal plasma flow (ERPF) remained comparatively stable. The results obtained at present with exercise renography and clearance determinations suggest that afferent-efferent glomerular vessel dysfunction disrupts the stable relationship between GFR and ERPF in EH. This relationship is severely disturbed, and most readily recognized, during exercise. It is suspected that this functional abnormality results in the activation of the renin-angiotensin axis. A particularly exciting consequence of this research is the recognition that scintigraphy permits recognition of a disruption of the stable relationship of GFR and ERPF. This opens the door to a broad area of research unrelated to EH, since initial results in renovascular disease and urinary tract obstruction indicate that the fixed relationship between GFR and ERPF can be disturbed in these and other diseases as well.

[Static-dynamic MR urography. Comparison with excretory urography and scintigraphy in experimentally-induced urinary tract obstruction]. / Statisch-dynamische MR-Urographie. Vergleich mit Ausscheidungsurographie und Szintigraphie bei experimentell induzierter Harntransportstörung (HTS).

PURPOSE: To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction. METHODS: Static-dynamic MRU--combination study with a respiratory-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA and furosemide--was obtained in comparison with 99mTc-MAG3 diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US) in 29 healthy piglets and in 20 piglets with surgically induced ureteric stenosis (total of 50 postoperative examination blocks). RESULTS: MRU allowed complete depiction of the urinary tract in all controls, in operated piglets the stenosis was always correctly identified. Quality of MRU was superior to EU in 36 of 43 comparative studies. Calculation of single kidney function from parenchymal renograms, and assessment of urinary excretion from whole-kidney renograms resulted in a highly significant agreement of MRU with DRS. CONCLUSION: Static-dynamic MR urography allows excellent depiction of experimentally induced urinary tract obstruction, and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out, it does not require radiation and it permits a functional-morphological correlation.

Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction. I. Evaluation of the normal status in an animal model.

OBJECTIVE: A new approach, combined static-dynamic MR urography is evaluated to determine its potential utility for the functional-morphological diagnosis of paediatric urinary tract obstruction. In this initial investigation we sought to evaluate the procedure by imaging the urinary tract of piglets. MATERIALS AND METHODS: Twenty-nine healthy piglets were studied with MR urography (MRU), 99mTc-MAG3 diuretic renal scintigraphy (DRS), ultrasound (US) and excretory urography (EU). The functional and morphological findings were compared. For MRU we combined a respiration-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA injection. RESULTS: MRU depicted the complete urinary tract with superior image quality compared to EU. Calculation of time-intensity curves from the dynamic sequence permitted determination of single kidney function from parenchymal ROIs and urinary excretion using the whole kidney ROI. MRU and DRS showed significant agreement in the assessment of both single kidney function and urinary excretion. Disturbances of urinary drainage were generally caused by an overfilled bladder. CONCLUSIONS: Combined static-dynamic MRU is well suited for the depiction of the complete urinary tract and for the determination of individual kidney function and urinary excretion in the piglet.

Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction. II. Findings in experimentally induced ureteric stenosis.

PURPOSE: To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction in the piglet. MATERIALS AND METHODS: In 20 piglets unilateral ureteric stenosis was created operatively. Post-surgery repeated comparative examinations were obtained with MRU, diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US). MRU was performed as a combination study with a static 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA with frusemide administration. RESULTS: MRU allowed complete depiction of the prestenotic urinary tract and of the stenosis in all cases. In 43 comparative studies MRU was superior to EU in 36, EU to MRU in 2. When single kidney function was calculated with both MRU and DRS, results were highly correlated (r = 0.92). When urinary excretion was compared, significant agreement was achieved with concordant findings in 86% and slightly discordant results in 12%. CONCLUSIONS: Static-dynamic MR urography permits excellent depiction of experimentally induced urinary tract obstruction in piglets and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out--it does not require radiation and it permits functional-morphological correlation.

Afferent-efferent vessel dysfunction appears to be a specific characteristic of a large subset of patients with essential hypertension.

Exercise renography makes it possible to subdivide essential hypertensives (EHs) into two distinct populations. Fifty to 60% develop exercise-mediated renal dysfunction and a transitory, severe reduction of glomerular filtration. The other subset of EHs does not have exercise-mediated renal dysfunction. We hoped to learn whether the disturbance is also present while EHs rest. Twenty-six EHs and 21 normotensive controls were studied with a resting sequential renogram using Tc-99m-mercaptoacetyl-triglycine (MAG3), a tracer excreted primarily by proximal tubular cells. EHs also had an exercise renogram. All persons had three consecutive 10-min dual-tracer infusion clearance determinations with 111In-DTPA and 131I-hippurate, for the simultaneous determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). To demonstrate the accuracy of the clearance procedure we sought to reproduce Hollenberg's results which show greater flow variability in EH than in normotension. Following this, the variability (VAR) of the GFR and ERPF as well as the variability fraction (VF), the ratio of GFR variability divided into the ERPF variability, were calculated. Hollenberg's results were reproduced. Sixteen of 26 essential hypertensives developed exercise-mediated renal dysfunction. GFR-VAR in EH differed from controls. The VF suggests that EHs with a bilateral abnormal exercise renogram have a more pronounced GFR variability than those EH with a normal exercise renogram. The results point to intraglomerular pressure fluctuations in patients with EH, and the VF suggests that this may be more pronounced in EHs with a bilateral abnormal exercise renogram than in those with a normal exercise renogram. It is hypothesized that the variable GFR provokes renin secretion in EH.

Renal hemodynamic changes during smoking: effects of adrenoreceptor blockade.

BACKGROUND: Cigarette smoking accelerates progression of renal failure in diabetic and nondiabetic renal disease. Renal hemodynamics during smoking are characterised by a reversible decrease in glomerular filtration rate (GFR) and filtration fraction (FF) accompanied by increased renovascular resistance (RVR), systemic blood pressure, heart rate and plasma catecholamine concentrations. MATERIALS AND METHODS: To further assess the role of sympathetic overactivity we compared the effects of different pharmacological interventions on smoking-induced changes of renal hemodynamics in occasional smokers. In a first series, placebo pretreatment plus smoking was compared to Prazosin pretreatment (3 mg) plus smoking. In a second study, placebo pretreatment plus smoking was compared to Atenolol pretreatment (50 mg) plus smoking. RESULTS: Basal blood pressure was significantly lower with Prazosin and Atenolol. On placebo, GFR and FF decreased significantly during smoking and RVR increased. With Prazosin pretreatment compared to placebo pretreatment no statistically significant differences for the changes of GFR, FF, RPF and RVR were seen. In contrast, with Atenolol pretreatment compared to placebo pretreatment, the smoking-induced changes in active renin, GFR and RVR were significantly smaller. CONCLUSION: It is suggested that the acute renal hemodynamic effects of smoking are mediated, at least in part, via increased sympathetic activity operating mainly through beta-1 adrenergic mechanisms.

[Nuclear medicine in kidney diagnosis]. / Nuklearmedizinische Nierendiagnostik.

A brief review of frequently requested examinations is presented. The clinical physiology associated with characteristic function images observed in obstruction, urinary leaks, hypertension, renal failure, and in renal transplantation are presented, as is the use of function images in the patient with renal malignancy.

The exercise renogram and its interpretation.

UNLABELLED: The exercise renogram is a rarely used diagnostic procedure, but it may visualize an exercise-induced change in renal function related to the pathophysiology of essential hypertension, which could greatly increase interest in this examination. The aim of this study was to demonstrate the interpretative approach and the terminology which is used to describe results of exercise renography, using a population of hypertensives with renovascular disease. METHODS: We reviewed the examinations of 70 hypertensives who had supine renography as well as exercise renography with a 60-80 W work load. Forty-eight patients were examined with 99mTc-MAG3 and 22 with 131I hippurate. The renographic and angiography results were recorded as well as the antihypertensive drugs used and the site of vascular lesions. RESULTS: Thirty-three hypertensives developed a bilateral-abnormal exercise renogram, which appears to be associated with primary hypertension. Eight individuals responded to exercise with a unilateral-abnormal exercise renogram, in a kidney behind a stenosis. Only 19 patients had a normal exercise renogram, and 10 had only one functioning kidney. Pathology recognized but unrelated to the intervention included nonfunctioning and small kidneys and pelvic retention. CONCLUSION: Exercise renography's only indication is for recognition of pathology unique to hypertension, since other function disturbances were recognized in resting renograms.

Exercise activates renal dysfunction in hypertension.

A bilateral, exercise-mediated renal functional abnormality was first described more than a decade ago. The disturbance is specific for hypertension, is seen in different forms of hypertension, and has been studied most extensively in hypertensives with renovascular disease. The bilateral-abnormal exercise renogram identifies the disturbance. Hypertensives with unilateral renovascular disease were studied in the continuing evaluation of the bilateral function disturbance. We examined 31 hypertensives with documented unilateral renovascular disease, all of whom had renography at rest and during 60 to 80 W ergometric exercise. An additional seven normotensives and 17 essential hypertensives served as controls, and had the same sequence of studies. All patients reported upon continued on to an infusion clearance with 131I-hippurate and 111In-diethylenetriamine pentaacetic acid to determine glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) at rest, and during 25 W ergometric exercise. Eighteen of 31 hypertensives with unilateral renovascular disease were found to have a bilateral-abnormal exercise renogram. Clearance examinations in these identified a prominent reduction of the GFR and a lesser decrease in the ERPF during exercise. Hypertensives with normal exercise renograms did not have the exercise mediated abnormal clearance pattern. Similar results were observed in the control population of essential hypertensives, 65% of whom developed the functional disturbance. The seven normotensives controls did not exhibit the exercise mediated function changes. We conclude that an exercise-mediated bilaterally occurring functional disturbance exists in certain hypertensives, who then have a bilateral-abnormal exercise renogram. Associated with this is a distinctly abnormal clearance during exercise which is characterized by a low filtration fraction.

Serum albumin (SA) accumulation by bronchogenic tumours: a tracer technique may help with patient selection for SA-delivered chemotherapy.

Systemic toxicity and inadequate tumour uptake of chemotherapeutic agents limit effective therapy of disseminated malignant disease. We seek to use macromolecules for improved delivery of therapeutic agents to tumours, and hope to use radiotracer procedures to identify those malignancies able to accumulate the transport molecule. A literature search identified in vitro and animal experimental data which indicated that serum albumin is taken up in malignancies. Selected cytostatic drugs can be bound to albumin, which suggests the suitability of the molecule as a potential transport vehicle. We therefore evaluated indium-111 labelled human serum albumin (HSA) to determine the frequency of its accumulation in bronchogenic tumours. Single-photon emission tomographic (SPET) images were obtained in 23 patients 48 h after intravenous injection of 1.5 mCi 111In diethylenetriamine penta-acetic acid (DTPA)-HSA. SPET imaging with technetium-99m labelled erythrocytes was included in the protocol to assess the influence which vascularity has on the HSA-based images. All patients went on to surgery. We documented the histological diagnosis, T-stage and differentiation grade. The scintigraphic examination demonstrated HSA uptake in three squamous cell carcinomas and four adenocarcinomas. Of these, six malignancies accumulating HSA had 2.2-5.4 times, the tracer concentrations observed in comparable background regions. Small cell carcinoma failed to accumulate the labelled HSA during the 2-day scintigraphic evaluation. The HSA images did not appear to represent tumour vascularity. T-stage and differentiation grade failed to predict which tumours would demonstrate HSA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeat exercise renograms in hypertension identify persistent renal dysfunction.

BACKGROUND: Hypertensives may develop bilateral trapping of para-aminohippurate analogues in the tissue of the kidneys during light exercise, as can be demonstrated using radioactively labelled [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine. Tracer accumulation in the kidneys during exercise results in a typical renographic pattern, the bilateral-abnormal exercise renogram. The disturbance is common during exercise, being found in almost 60% of all hypertensives, regardless of aetiology. OBJECTIVE: To determine whether bilateral-abnormal exercise renograms are spurious phenomena, or whether the results of exercise renography are reproducible. DESIGN: We reviewed the renographic examinations of 27 hypertensive patients, each of whom had undergone at least one resting and two [131I]-hippurate or [99mTc]-mercaptoacetyl-triglycine gamma-camera exercise renograms. The status of the renal artery at the time of scintigraphy was documented, using available arteriograms. The causes of vascular lesions were noted, as were revascularization procedures and the antihypertensive medication being taken at the time of scintigraphy. RESULTS: The average time between exercise renograms was 15.5 months, and 24 of the 27 hypertensive patients had comparable results in the first and the follow-up exercise renogram, divergent results being noted for the other three patients. Re-evaluation of the scintigrams of the three hypertensive patients with divergent results suggested that intermittent pelvic retention might have caused errors of interpretation in two. We found it notable that neither revascularization nor a change in antihypertensive drug therapy influenced the results of exercise renography. Exercise renograms were reproducible over long periods, and potential extraneous influences on blood flow, such as antihypertensive drugs or revascularization, failed to alter the results. CONCLUSION: The results are considered relevant, because a direct relationship appears probable between hypertension and the disturbance investigated. Reproducible results suggest that the exercise-mediated disturbance is fixed to the kidneys, that it can be reactivated repeatedly and that it may play a role in maintaining hypertension.

Studies with positron emission tomography after systemic administration of fluorine-18-uracil in patients with liver metastases from colorectal carcinoma.

Fluorouracil (FU) is the most common cytostatic agent used for chemotherapy in patients with colorectal tumors. Fifty patients with 78 hepatic metastases from colorectal tumors were examined with positron emission tomography (PET) following intravenous infusion of 18F-FU. The uptake of the cytostatic agent was evaluated in normal liver parenchyma, liver metastases and the aorta. Tracer uptake was expressed with the standardized uptake value (SUV). The maximum liver activity was 11.3 SUV (mean value) with a standard deviation of 1.85 SUV. The highest activity concentrations were noted 30 min (mean value) postinjection. In comparison, the activity concentration of individual metastasis was low. Two hours after tracer injection, the mean activity in metastases was 1.3 SUV, but notable individual variation in uptake was seen. Fluorine-18 concentration values 2 hr after FU infusion were approximately 44% of the FU uptake 20 min postinfusion. Fifty-three metastases were also examined with 15O-labeled water. The examination was performed to compare the uptake of the nonmetabolized tracer with FU uptake. We noted a statistically significant correlation between 15O-water concentration, uptake of nonmetabolized FU 8 min after the end of the infusion and FU retention (120 min postinjection) in a subgroup of metastases. The results suggest that FU retention in different metastases is highly variable and mainly dependent on early FU uptake into tumor cells.

Renovascular hypertension: a perfusion disturbance that escaped recognition.

A bilateral, exercise-mediated, hippurate transport disturbance was previously described when patients with fixed renovascular hypertension were imaged with o-iodo-hippurate. This study sought to test the hypothesis that patients with an abnormal exercise scintigram have a perfusion abnormality characterized by dysregulation of renal blood flow. We imaged 23 patients with hypertension and angiographically documented renovascular disease in the supine position, as well as during upright exercise. Seven normotensive volunteers served as controls. We measured the resting glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) with a single compartment radiotracer infusion clearance. The clearance examination also included a measurement period with 25 watt ergometric exercise. Nine hypertensive patients had normal exercise renograms. These patients had age-appropriate clearance values at rest and during exercise, as well as age-appropriate best-organ (generally without stenosis) GFR and ERPF values. The filtration fraction (FF) was 0.21 at rest and 0.22 during exercise. Fourteen hypertensive patients had a bilateral, exercise-induced disturbance of hippurate transport. In these patients, the global resting GFRs and ERPFs were decreased 40% from age-appropriate predicted values. The FF remained at 0.20. Light exercise caused a pronounced contraction of GFR and a less severe reduction in the ERPF. During exercise the mean filtration fraction was only 0.12. The exercise-induced reduction in the clearance values was bilateral, which indicated that the perfusion of nonstenosed organs was compromised as well. We suggest that the described perfusion abnormality occupies a relevant position during the maintenance phase of fixed renovascular hypertension.

Renal artery aneurysm: surgical indications and results.

The clinical course of 23 patients with 28 renal artery aneurysms (RAAs) is reported. The RAAs were recorded over a period of 10 years. Thirty-five per cent of the RAAs (eight of 23 patients) were detected during the investigation of hypertension, whereas 26% (six of 23 patients) were discovered incidentally while imaging atherosclerotic arterial disease in the aorto-iliac region by angiography. Twenty-two aneurysms were treated surgically and primary nephrectomy was necessary in one case. The surgical technique used was excision of the aneurysm with bypass grafting in 13 cases (seven Dacron, five vein, one arterial bypass), a running suture following aneurysm excision in four cases and an end-to-end anastomosis in two cases. The results (for a period of 1-10 years) were excellent in all but three cases: two early graft occlusions (vein interposition) and one late occlusion (Dacron bypass) in the course of a re-operation which had become necessary because of a ruptured aneurysm of the gastro-epiploic artery after 3 months. Three of 23 patients were treated by embolisation of four intraparenchymal aneurysms. The follow-up of a non-treated saccular aneurysm showed a total thrombosis of the aneurysm within 4 years and fixed renal hypertension developed later in this patient. We suggest surgical repair of an RAA regardless of its size and the clinical symptoms, in order to prevent microembolism into the renal parenchyma and to avoid the development of fixed renal hypertension. Intrarenal aneurysms can be treated by embolisation to stop severe haematuria thus preserving the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Design of compounds having enhanced tumour uptake, using serum albumin as a carrier--Part II. In vivo studies.

In the present in vivo study the uptake kinetics of radioiodinated albumin were determined in normal organs, and tumours of rats using sequential scintigraphy. Rat serum (RSA) was radioiodinated either directly at a tyrosine residue (d-RSA), or indirectly at a residualizing marker tagged to the albumin (rm-RSA). These labelling procedures did not alter the kinetics of labelled albumin, as shown by blood disappearance curves. Directly labelled albumin was shown to have tumour uptake. Residualizing markers like tyramine-cellobiose (TCB), tyramine-deoxysorbitol (TDS) and aminonaphthaltyrimide-deoxysorbitol (ANTDS) are metabolically inert. After the intracellular degradation of the albumin carrier the TCB-, TDS- and ATNDS-residues accumulate in the lysosomes, particularly those of tumour cells. It was able to be demonstrated that residualizing-marker tagged albumin-bound radioactivity was five times higher after 72 h than the tumour radioactivity after use of directly labelled RSA. These data found support when whole-body retention of directly labelled RSA, and residualizing marker-RSAs, were determined. After 72 h, 60% of 131I bound to RSA directly had been excreted, compared to only 25% of the activity attached indirectly to RSA with a residualizing marker. Whole-body autoradiography of rats injected with directly labelled RSA, or residualizing marker-RSA, support these results. Most of the radioactivity of directly labelled RSA was excreted within 24 h, whereas labelled residualizing marker-RSAs were also stored in tumour and liver tissue. ANTDS bound to RSA allows fluorescence microscopy. Cryosections of tumours from rats preinjected 10 min and 24 h with ANTDS-RSA before dissection, demonstrated that the fluorescence is localized on and in tumour cells. This indicates that cellular uptake of the marker takes place. Fluorescence was not observed in muscle tissue. This appears to suggest that the albumin uptake is greater in tumours than in normal tissue, and that it is metabolized in the tumour cells.

[Measurement of the blood flow velocity in the pulmonary arteries using the magnetic resonance technique]. / Messung der Blutflussgeschwindigkeit in den Pulmonalarterien mit Hilfe der Magnetresonanztechnik.

MR blood velocity measurements were performed by the RACE technique in a plane perpendicular to the flow of the pulmonary arteries. MR findings were correlated with those of perfusion scintigraphy, Doppler US and right heart catheter (thermodilution). The ratio of MR blood flow measurements of right and left pulmonary arteries correlated well with the results of perfusion scintigraphy (RPA to LPA) and Doppler. Poor correlation was found when comparing MR blood flow measurements with right heart catheter since absolute flow measurements can be superimposed by neighboring blood vessels in complex anatomic situations.

Renal studies in nuclear medicine.

Research in nephrologic nuclear medicine is presently concentrated in two well-defined areas: interventional procedures and the use of mercaptoacetyltriglycine. The ongoing evaluation of mercaptoacetyltriglycine continues to be a source of interesting research activity, with the distribution volume and the extent of hepatic excretion remaining points of discussion. This tracer permits quantitative determination of renal function. As an imaging agent, mercaptoacetyltriglycine compares favorably with hippurate and with diethylenetriamine penta-acetic acid, particularly in evaluating renal insufficiency. Renal function studies obtained during pharmacologic or physiologic intervention dominate research in hypertension and obstructive uropathy. Angiotensin-converting enzyme inhibition improved the renographic detection of renovascular lesions. Interventional renography with angiotensin-converting enzyme inhibition or ergometric exercise were both capable of generating useful prognostic data on the posttherapy blood pressure response in patients with renovascular hypertension. Interventional diuretic renography with furosemide permits surgical intervention to be reserved for organs at immediate risk because the degree of obstruction and the extent of renal function compromise are easily recognized.

Renovascular hypertension: predicting surgical cure with exercise renography.

Renal artery stenosis with resultant renovascular hypertension has attracted clinical attention because the disease is potentially curable and because numerous diagnostic and therapeutic modalities compete for clinical acceptance. An exercise-mediated disturbance of renal hippurate transport was recently described, and has been implicated as having a role in nephrogenic fixed hypertension. To predict the final course of renovascular hypertension before operation we carried out a prospective study with the goal of verifying the predictive value of exercise hippurate scintigraphy. The study was to test the hypothesis that patients with disturbance of renal hippurate transport (pathologic renogram) induced by exercise would have stabilized hypertension and would continue to be hypertensive after operation. Thirty-one patients with hypertension who had unilateral or bilateral renovascular stenosis documented on angiography were referred to rest and exercise hippurate scintigrams before operation. The results of the examinations at rest served as standard and were compared with the exercise scintigrams. In 19 of the 31 (61%) patients a disturbance of transrenal hippurate transport evolved during exercise, whereas 12 (39%) patients failed to respond to exercise with altered hippurate kinetics. Twenty-six patients went on to renovascular operations; five had percutaneous transluminal angioplasty. Revascularization results differed markedly when the blood pressure response of patients with positive results on exercise (abnormal) and patients with negative results on exercise (normal) were compared. Ten of 12 patients with hypertension who had normal exercise renograms were cured. In comparison, blood pressure values were little influenced by therapy in patients with an abnormal response, where 17 of 19 patients continued to have hypertensive disease after therapy.(ABSTRACT TRUNCATED AT 250 WORDS)