Michael A. McKusick

The Management of Patients with Advanced Carcinoid Tumors and Islet Cell Carcinomas

Among the rarest of cancers, the gastrointestinal neuroendocrine tumors (islet cell carcinomas and carcinoid tumors) present difficult and complex challenges for individual patient management. When the tumors metastasize, patients have a variety of clinical presentations including manifestations of tumor bulk and bizarre syndromes resulting from massive hormone production. Table 4. SI Units When physicians analyze therapeutic options for patients with metastatic carcinoid tumors or islet cell carcinomas, they should consider the course of the patients malignant disease, the distribution of metastasis, the severity of clinical manifestations, and the relative contributions of the hormonal syndromes and tumor bulk to symptoms and disability. The oncologist must be conservative, because these diseases frequently run an indolent course, allowing years of comfortable life with no treatment whatsoever. However, aggressive approaches may be justified when the patient develops disabling symptoms because tumor debulking or correction of mechanical problems may sometimes provide the patient with additional years of comfortable life. If the patient has a clinically dominant hormonal syndrome and has no imminent threat from tumor bulk, it is frequently possible to produce substantial palliation with minimal therapeutic risk. In earlier years, only patients with gastrinoma could be helped in this manner by the use of histamine-2 blockers (for example, adequate doses of cimetidine or ranitidine or, more recently, omeprazole [Prilosec, Merck and Company, West Point, Pennsylvania]). The development and clinical application of an analog of somatostatin (octreotide; Sandostatin, Sandoz Pharmaceuticals, East Hanover, New Jersey) has provided a novel and frequently highly effective tool for control of almost all the endocrine syndromes. Striking decreases in hormonal levels and substantial or complete relief from symptoms can be achieved in approximately 80% of patients [1, 2]. Although octreotide usually produces only minimal immediate side effects, gallstones are a frequent long-term complication. However, octreotide therapy is cumbersome to the patient and is costly. Further, most patients become resistant to this therapy; for patients with carcinoid tumor, the median interval is about 1 year and for patients with islet cell carcinomas, only a few months. For these reasons, octreotide therapy for the carcinoid syndrome should be reserved for patients with severe flushing or diarrhea. In those with islet cell carcinomas, it should be used primarily to restore the patient to a better general and nutritional status so that more aggressive and definitive therapy can be undertaken with an acceptable risk. Regression rates after systemic chemotherapy or immunotherapy (using either single drugs or drug combinations) for metastatic carcinoid tumors and islet cell carcinomas have been variable, as is typical for solid tumors [3]. For carcinoid tumors, regression rates (even with our most effective regimens) seldom exceed 20%, and the discouragingly short duration of these responses hardly justifies the risks and side effects of treatment. For this reason, we urge that systemic therapy for carcinoid tumors be carried out in a research setting. For islet cell carcinoma, however, treatment may be of true clinical value. Streptozocin (Zanosar, The Upjohn Company, Kalamazoo, Michigan) seems to have specific cytotoxicity for the islet cell carcinoma and produces credible tumor regressions in about 30% of patients. Because of its minimal hematologic toxicity, it is useful in drug combinations with chemotherapeutic agents that are dose limited by leukopenia and thrombocytopenia. In a randomized trial, fluorouracil plus streptozocin was found to produce a 45% regression rate and seemed to improve survival when compared with streptozocin alone [4]. In a recent randomized trial, the combination of doxorubicin and streptozocin increased the regression rate to 69% and produced a statistically significant increase in survival [5]. However, fewer than one third of patients have a substantive and prolonged response to chemotherapy, and it produces considerable toxicity. A special consideration in managing these patients is the usually dominant involvement of the liver in the metastatic process. For selected patients, the surgeon can make a major and usually long-lasting contribution by resection of large solitary tumor masses or well-localized clusters of metastatic lesions [6]. With modern surgical technology, operative morbidity and mortality have been reduced to acceptable levels. Among 40 such patients reported by McEntee and colleagues [6], only a single postoperative death occurred. Usually, however, the diffuse nature of hepatic metastasis precludes effective surgical debulking. Therefore, hepatic artery infusion of various drugs has been attempted but with little documented evidence of success. Occlusion of hepatic arterial flow is attractive, because metastatic tumor neovascularity and oxygenation derive almost entirely from the hepatic artery. In contrast, hepatocytes are resilient, and viability may be maintained through the portal vein until rearterialization occurs. Although many researchers have shown that hepatic artery occlusion effectively shrinks primary or metastatic cancer in the liver, for the more common and more aggressive malignant diseases, tumor regrowth occurs so quickly that any net gain is difficult to discern. Because carcinoid tumors and islet cell carcinomas usually grow slowly, lasting benefit may be possible using hepatic artery occlusion. This review documents our experience with hepatic arterial occlusion, by either surgical ligation or embolization, in selected patients with neuroendocrine tumors and hepatic-dominant metastatic disease. Although frequent and substantial tumor regressions were produced, the duration of these regressions, even with these indolent neoplasms, was discouragingly short. We therefore developed and tested a regimen of sequential hepatic arterial occlusion and chemotherapy with the hope that regressions could be enhanced and prolonged. For chemotherapy, we elected to give each of the drugs that have been most active for these tumors when used alone (that is, fluorouracil, streptozocin, doxorubicin, and dacarbazine [DTIC]). Methods Patient Selection All patients selected for study had histologically confirmed carcinoid tumor or islet cell carcinoma with metastasis clinically limited to or dominant in the liver. They were ambulatory and maintaining a reasonable state of oral nutrition (at least 1200 calories daily). One or more measurable parameters of malignant disease were required to serve as objective indicators of response to therapy. For liver metastasis, this required clearly demarcated lesions on liver imaging that measured at least 5 cm in greatest diameter using radioisotope scanning or at least 3 cm in diameter using computed tomography or magnetic resonance imaging. Alternatively, if the patient had malignant hepatomegaly with a distinct liver edge extended at least 5 cm below the xiphoid or costal margins on quiet respiration, this was also used as a marker for response to therapy. In the absence of measurable liver involvement, hormonal assays could be used alone as markers for response to therapy, if they were greater than twice the upper limit of normal. Contraindications to study entry were a total serum bilirubin level more than 51.3 mol/L (3 mg/dL), previous radiation therapy to the liver or hepatic arterial chemotherapy, and the standard contraindications for each of the involved cytotoxic drugs. In practice, protocol entry was limited to those patients who, in the judgment of the physician, had clinically significant symptoms related to tumor bulk or to the endocrine syndrome or had extensive metastasis associated with abnormal test results for liver function. Treatment Hepatic artery occlusion was done by surgical ligation in those patients who had other specific indications for abdominal surgery (for example, an obstructing carcinoid tumor of the small bowel) or for those patients in whom catheterization and embolization were not considered to be technically feasible. For all other patients, occlusion was done by catheterization and embolization. Before hepatic artery occlusion by either method, the anatomy of the hepatic vasculature was determined by angiography. If any evidence of portal vein occlusion or compromise of portal vein flow was noted, occlusion was not done. In patients having operative tumor devascularization, the hepatic artery was approached for ligation through the gastrohepatic ligament of the lesser omentum. The primary right and left hepatic arteries were ligated and divided individually distal to the gastroduodenal artery. Dearterialization was completed by division of the entire gastrohepatic omentum from the diaphragm to the bile duct. Any accessory or replaced hepatic arteries were also identified, ligated, and divided; lymphoareolar tissue in the hepatoduodenal ligament was also divided. Cholecystectomy was done to avoid gallbladder ischemia. For occlusion by embolization, the hepatic artery was selectively catheterized with injection of embolic material, usually gel foam or polyvinyl alcohol or both. Because of the technical difficulty encountered in the procedure, the pretreatment impairment of liver function, and the total mass and distribution of hepatic metastasis, eight patients had embolization done at two or three sittings separated by 3 to 4 work-week intervals. After hepatic artery occlusion, the patient was observed in the hospital for a minimum of 5 days to monitor complications. In some instances, prophylactic antibiotics were used. The patient was released from hospital when there was no clinical evidence of complications, definite recovery of abnormal test results for liver function, and reduction of fever. Sequential chemother

Incidental Renal Artery Stenosis Among a Prospective Cohort of Hypertensive Patients Undergoing Coronary Angiography

OBJECTIVE To determine the feasibility, safety, and clinical yield of angiographic screening among hypertensive patients undergoing coronary angiography. PATIENTS AND METHODS This study was a prospective cohort analysis of hypertensive patients who underwent cardiac catheterization at a tertiary care referral center from July 1998 to March 1999. Abdominal aortography was performed to screen for renal artery stenosis, the percentage of which was measured. RESULTS The mean +/- SD age of the 297 study patients was 64.9+/-10.2 years; 58.6% were male, and 98.0% were white. Mean +/- SD systolic/diastolic blood pressure was 142.8+/-22.5/79.6+/-11.4 mm Hg. Aortography required a mean incremental dose of 62+/-9 mL of nonionic contrast agent. No complications were attributable to aortography. Of 680 renal arteries, 611 (90%) were visualized adequately. Also, 53% of patients had normal renal arteries, 28% had stenoses less than 50%, and 19.2% had stenoses of 50% or more. Renal artery stenosis was bilateral in 3.7% of patients and high grade (>70% stenosis) in 7%. Patients with renal artery stenosis were more likely to have had a previous coronary intervention. In multivariate analysis, systolic blood pressure (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.03-138; P=.02), history of stroke or transient ischemic attack (OR, 2.7; 95% CI, 1.27-5.78; P=.01), and cancer (OR, 2.0; 95% CI, 1.02-3.82; P=.04) independently correlated with renal artery stenosis of 50% or more. CONCLUSION The prevalence of incidental renal artery stenosis among hypertensive patients undergoing coronary catheterization is significant. Therefore, screening abdominal aortography should be considered in these patients to better define their risk of cardiovascular complications.

Gastric mucosal responses to intrahepatic portosystemic shunting in patients with cirrhosis

BACKGROUND & AIMS The response of gastric mucosal lesions in cirrhotic patients with portal hypertension, namely, portal hypertensive gastropathy (PHG) and gastric vascular ectasia (GVE), to transjugular intrahepatic portosystemic shunts (TIPS) is not known. METHODS Clinical and laboratory evaluation, upper gastrointestinal endoscopy, and Doppler ultrasonography were performed before placement of TIPS and 6 weeks, 3 months, and 6 months after TIPS in 54 patients. Thirty patients had mild PHG, 10 had severe PHG, and 14 had GVE. RESULTS Approximately 75% of the patients with severe PHG responded to TIPS as shown by improvement in endoscopic findings and by a decrease in transfusion requirements; 89% of patients with mild PHG had endoscopic resolution. Patients with GVE had neither endoscopic resolution nor a decrease in transfusion requirements after TIPS. There was no difference in mortality between the 2 groups. CONCLUSIONS The results support the position that severe PHG and GVE may be different lesions. Mild and severe PHG respond to TIPS. Because GVE does not respond to TIPS, we recommend that TIPS be avoided for the treatment of gastrointestinal bleeding associated with GVE.

Outcomes of Atherosclerotic Renal Artery Stenosis Managed Without Revascularization

OBJECTIVE To determine how often patients with renal artery stenosis (RAS) managed without revascularization progress to accelerated hypertension and/or renal failure. PATIENTS AND METHODS We examined the outcomes of 68 patients (mean +/- SEM age, 71.8 +/- 0.9 years) with high-grade (>70%) RAS identified between 1989 and 1993 who were treated without renal revascularization for at least 6 months after angiography. The time to last follow-up averaged 38.9 +/- 2.8 months. Other vascular beds were affected in 66 of the 68 patients. End points were revascularization, nephrectomy, dialysis, or death. RESULTS The mean +/- SEM serum creatinine level rose from 1.4 +/- 0.1 to 2.0 +/- 0.2 mg/dL (P<.001). Mean +/- SEM blood pressure did not change (157 +/- 3/83+/-2 vs 155 +/- 3/79 +/- 2 mm Hg), but the need (mean +/- SEM) for medication increased from 1.6+/-0.1 to 1.9+/-0.1 drugs (P=.02). Four patients (5.8%) eventually underwent renal revascularization for refractory hypertension (1 patient), for progressive stenosis (1 patient), and during aortic reconstruction (2 patients). One additional patient underwent nephrectomy to improve blood pressure control. Five others (7.4%) developed end-stage renal disease (ESRD) for reasons other than progressive vascular disease, namely, diabetes (3 patients), atheroemboli (1 patient), and contrast toxicity without RAS progression (1 patient). In 1 further case, the reason for ESRD was unknown, and it may have been caused by vascular occlusion. During follow-up, 19 patients died of unrelated causes, including myocardial infarction and stroke. CONCLUSIONS These data indicate that antihypertensive medication requirements increased and renal function deteriorated modestly in a subset of patients with atherosclerotic RAS managed initially without vascular intervention. Many achieved stable blood pressure for many years. Deterioration of renal function and mortality risk were greatest in patients with bilateral stenosis or stenosis to a solitary functioning kidney. These results reinforce the need for meticulous follow-up for disease progression but underscore the role of competing risks and high mortality from other cardiovascular diseases, which primarily determine the outcomes in patients with RAS and widespread atherosclerotic disease.

Surgical technique and preliminary results of endoscopic subfascial division of perforating veins.

PURPOSE Direct surgical ligation of incompetent perforating veins has been reported to effectively treat severe chronic venous insufficiency. It is associated, however, with significant wound complications. We evaluate our early experience with endoscopic subfascial division of the perforating veins. METHODS From August 5, 1993, to December 31, 1994, 11 legs in nine patients (five male and for female) were treated with endoscopic subfascial division of perforating veins. Nine of the 11 legs had active or recently healed venous ulcers. Mean duration of the ulcerations was 5.6% years. Standard laparoscopic equipment with 10-mm ports was used to perform clipping and division of medial perforating veins through two small incisions made just below the knee, avoiding the area of ulcer and lipodermatosclerosis. Carbon dioxide was insufflated at a pressure of 30 mm Hg into the subfascial space to facilitate dissection, and a pneumatic thigh tourniquet was used to obtain a bloodless operating field. Concomitant removal of superficial veins was performed in eight limbs. Mean follow-up was 9.7 months (range, 2 to 13 months). RESULTS A mean of 4.4 perforating veins (range, 2 to 7) were divided; tourniquet time averaged 58 minutes (range, 30 to 72). Wound infection of a groin incision and superficial thrombophlebitis were early complications; each occurred in one patient. In seven legs the ulcer healed or did not recur and symptoms resolved. In three legs, the ulceration improved, and in one it was unchanged. CONCLUSIONS Endoscopic subfascial division of perforating veins seems to be a safe technique, with favorable early results obtained in a small number of patients. This preliminary experience supports further clinical trials to evaluate this technique.

Common iliac artery aneurysm: expansion rate and results of open surgical and endovascular repair.

OBJECTIVES To assess expansion rate of common iliac artery aneurysms (CIAAs) and define outcomes after open repair (OR) and endovascular repair (EVAR). METHODS Clinical data of 438 patients with 715 CIAAs treated between 1986 and 2005 were retrospectively reviewed. Size, presentations, treatments, and outcomes were recorded. Kaplan-Meier method with log-rank tests and chi2 test were used for analysis. RESULTS Interventions for 715 CIAAs (median, 4 cm; range, 2-13 cm) were done in 512 men (94%) and 26 women (6%); 152 (35%) had unilateral and 286 (65%) had bilateral CIAAs. Group 1 comprised 377 patients (633 CIAAs) with current or previously repaired abdominal aortic aneurysm (AAA). Group 2 comprised 15 patients (24 CIAAs) with associated internal iliac artery aneurysm (IIAA). Group 3 comprised 46 patients (58 isolated CIAAs). Median expansion rate of 104 CIAAs with at least two imaging studies was 0.29 cm/y; hypertension predicted faster expansion (0.32 vs 0.14 cm/y, P = .01). A total of 175 patients (29%) were symptomatic. The CIAA ruptured in 22 patients (5%, median, 6 cm; range, 3.8-8.5 cm), and the associated AAA ruptured in 20 (4%). Six (27%) ilioiliac or iliocaval fistulas developed. Repairs were elective in 396 patients (90%) and emergencies in 42 (10%). OR was performed in 394 patients (90%) and EVAR in 44 (10%). The groups had similar 30-day mortality: 1% for elective, 27% for emergency repairs (P < .001); 4% after OR (elective, 1%; emergency, 26%), and 0% after EVAR. No deaths occurred after OR of arteriovenous fistula. Complications were more frequent and hospitalization was longer after OR than EVAR (P < .05). Mean follow-up was 3.7 years (range, 1 month-17.5 years). The groups had similar 5-year primary (95%) and secondary patency rates (99.6%). At 3 years, secondary patency was 99.6% for OR and 100% for EVAR (P = .66); freedom from reintervention was similar after OR and EVAR (83% vs 69%, P = .17), as were survival rates (76% vs 77%, P = .70). CONCLUSIONS The expansion rate of CIAAs is 0.29 cm/y, and hypertension predicts faster expansion. Because no rupture of a CIAA <3.8 cm was observed, elective repair of asymptomatic patients with CIAA >or=3.5 cm seems justified. Although buttock claudication after EVAR remains a concern, results at 3 years support EVAR as a first-line treatment for most anatomically suitable patients who require CIAA repair. Patients with compressive symptoms or those with AVF should preferentially be treated with OR.

Preserved Oxygenation Despite Reduced Blood Flow in Poststenotic Kidneys in Human Atherosclerotic Renal Artery Stenosis

Atherosclerotic renal artery stenosis reduces blood flow and perfusion pressures to the poststenotic kidney producing renovascular hypertension and threatening glomerular filtration rate. Little is known regarding regional tissue oxygenation in human renovascular disease that develops slowly. We compared stenotic and contralateral kidneys regarding volume, tissue perfusion, blood flow measured by multidetector computed tomography, and blood oxygen level–dependent magnetic resonance values in the cortex and medulla in 14 patients with unilateral stenosis (mean: 71% by quantitative computed tomography) and in 14 essential hypertensive patients during 150 mEq/d of sodium intake and renin-angiotensin blockade. Stenotic kidney volume was reduced compared with the contralateral kidney (118.6±9.9 versus 155.4±13.7 mL; P<0.01), as was total blood flow (269.7±42.2 versus 383.7±49; P=0.02), mainly because of reduced cortical volume. Tissue perfusion was similar but lower than essential hypertension (1.5 versus 1.2 mL/min per milliliter; P<0.05). Blood oxygen level–dependent MR at 3 T confirmed elevated R2* values (a measure of deoxyhemoglobin) in deep medullary regions in all 3 sets of kidneys (38.9±0.7 versus cortex 17.8±0.36 s−1; P<0.0001). Despite reduced blood flow, R2* values did not differ between atherosclerotic and essential hypertensive kidneys, although furosemide-suppressible fall in medullary R2* was reduced in stenotic kidneys (5.7±1.8 versus 9.4±1.9 s−1; P<0.05). Renal venous oxygen levels from the stenotic kidney were higher than those from essential hypertensives (65.1±2.2 versus 58.1±1.2; P=0.006). These data indicate that, although stenosis reduced blood flow and volume, cortical and medullary oxygenation was preserved under these conditions.

Most patients with abdominal aortic aneurysm are not suitable for endovascular repair using currently approved bifurcated stent-grafts.

Strict morphologic criteria must be used for patient selection to achieve durable success with endovascular aortic aneurysm repair (EVAR). The goal of this study was to assess morphologic suitability (MS) of abdominal aortic aneurysms (AAAs) for 2 currently approved bifurcated stent grafts and identify reasons for exclusion from EVAR. The authors reviewed the electronic charts of 1,795 consecutive patients who were diagnosed as having AAA between January 1999 and July 2001 at their institution. Three hundred and twenty patients had an AAA with a diameter of =5.0 cm, measured on computed tomography (CT). The records of 301 patients, 254 men, 47 women, with a mean age of 74 years were available for review, and these patients constituted the study cohort. Criteria used for MS included a proximal neck length =15 mm; neck diameter between 18 and 26 mm; neck angulation =60°; common or external iliac artery (CIA or EIA) diameters of 7–16 mm and 8–13 mm, respectively, for AneuRx (Medtronic Ave, Santa Rosa, CA) and Ancure (Guidant Cardiac and Vascular Division, Menlo Park, CA) bifurcated grafts. AAAs were suitable for AneuRx device in 14% of patients (43 of 301; 95% CI = 11–19%) and for Ancure in 5% (16 of 301; 95% CI = 3.1–9%). The main reason for exclusion was an inadequate proximal aortic neck (73%). The neck was too short in 49.5%, too wide in 64% and badly angulated in 12% of the patients. Iliac artery morphology precluded EVAR with AneuRx and Ancure devices in 52% and 80%. Both CIAs were too wide for EVAR in 43% and 77%, respectively. When iliac artery diameter =20 mm was accepted, iliac suitability for AneuRx increased from 49% to 70% and overall suitability increased from 14% to 20%. When more permissive criteria were used for MS (neck length =10 mm, neck diameter =30 mm, CIA =20), 39% of patients became candidates for EVAR. More than three fourths of the patients with an AAA =5.0 cm in size, seen in a tertiary referral center, are morphologically not suitable for EVAR using 2 currently approved bifurcated endografts. The main reasons for exclusion are a short or wide proximal aortic neck. Considerable changes in size of the devices and in proximal attachment techniques have to occur before most AAAs will be suitable for EVAR.

Blood Oxygen Level–Dependent Magnetic Resonance Imaging Identifies Cortical Hypoxia in Severe Renovascular Disease

Atherosclerotic renal artery stenosis has a range of manifestations depending on the severity of vascular occlusion. The aim of this study was to examine whether exceeding the limits of adaptation to reduced blood flow ultimately leads to tissue hypoxia, as determined by blood oxygen level dependent MRI. We compared 3 groups of hypertensive patients, 24 with essential hypertension, 13 with “moderate” (Doppler velocities 200–384 cm/s), and 17 with “severe” atherosclerotic renal artery stenosis (ARAS; velocities >384 cm/s and loss of functional renal tissue). Cortical and medullary blood flows and volumes were determined by multidetector computed tomography. Poststenotic kidney size and blood flow were reduced with ARAS, and tissue perfusion fell in the most severe lesions. Tissue medullary deoxyhemoglobin, as reflected by R2* values, was higher as compared with the cortex for all of the groups and did not differ between subjects with renal artery lesions and essential hypertension. By contrast, cortical R2* levels were elevated for severe ARAS (21.6±9.4 per second) as compared with either essential hypertension (17.8±2.3 per second; P<0.01) or moderate ARAS (15.7±2.1 per second; P<0.01). Changes in medullary R2* after furosemide administration tended to be blunted in severe ARAS as compared with unaffected (contralateral) kidneys. These results demonstrate that severe vascular occlusion overwhelms the capacity of the kidney to adapt to reduced blood flow, manifest as overt cortical hypoxia as measured by blood oxygen level–dependent MRI. The level of cortical hypoxia is out of proportion to the medulla and may provide a marker to identify irreversible parenchymal injury.

Comparison of 1.5 and 3 T BOLD MR to study oxygenation of kidney cortex and medulla in human renovascular disease.

Objectives:Imaging of the kidney using blood oxygen level dependent MR presents a major opportunity to examine differences in tissue oxygenation within the cortex and medulla applicable to human disease. We sought to define the differences between regions within kidneys and to optimize selection of regions of interest for study with 1.5 and 3 Tesla systems. Materials and Methods:Studies in 38 subjects were performed under baseline conditions and after administration of furosemide intravenously to examine changes in R2* as a result of suppressing oxygen consumption related to medullary tubular solute transport. These studies were carried out in patients with atherosclerotic renal artery stenosis (n = 24 kidneys) or essential hypertension or nonstenotic kidneys (n = 39). All patients but one were treated with agents to block the renin angiotensin system (ACE inhibitors or angiotensin receptor blockers). For each kidney, 3 levels (upper pole, hilum, and lower pole) were examined, including 3 individual segments (anterior, lateral, and posterior). Results:Low basal R2* levels in kidney cortex (12.06 ± 0.84 s−1) at 1.5 Tesla reflected robust blood flow and oxygenation and agreed closely with values obtained at 3.0 Tesla (13.62 ± 0.56 s−1, NS). Coefficients of variation ranged between 15% and 20% between segments and levels at both field strengths. By contrast, inner medullary R2* levels were higher at 3 T (31.66 ± 0.74 s−1) as compared with 1.5 T (22.19 ± 1.52 s−1, P < 0.01). Medullary R2* values fell after furosemide administration reflecting reduced deoxyhemoglobin levels associated with blocked energy-dependent transport. The fall in medullary R2* at 3.0 Tesla (−12.61 ± 0.97 s−1) was greater than observed at 1.5 T (−6.07 ± 1.38 s−1, P < 0.05). Cortical R2* levels remained low after furosemide and did not vary with field strength. Correlations between measurements of defined cortical and medullary regions of interest within kidneys were greater at each sampling level and segment at 3.0 T as compared to 1.5 T. For patients studied with 3.0 T, furosemide administration induced a lesser fall in R2* in poststenotic kidneys at 3.0 T (−10.61 ± 1.61 s−1) versus nonstenotic kidneys (−13.21 ± 0.72 s−1, P < 0.05). This difference was not evident in comparisons made at 1.5 T. The magnitude of furosemide-suppressible oxygen consumption at 3.0 T (−43%) corresponded more closely with reported experimental differences observed during direct measurement with tissue electrodes (45%–50%) than changes measured at 1.5 T. Conclusion:These results indicate that blood oxygen level dependent MR measurements at high field strength can better distinguish discrete cortical and inner medullary regions of the kidney and approximate measured differences in oxygen tension. Maneuvers that reduce oxygen consumption related to tubular solute transport allow functional evaluation of the interstitial compartment as a function of tissue oxygenation. Impaired response to alterations in oxygen consumption can be detected at 3 T more effectively than at 1.5 T and may provide real-time tools to examine developing parenchymal injury associated with impaired oxygenation.