Evaluation of Renal Fibrosis Using Magnetization Transfer Imaging at 1.5T and 3T in a Porcine Model of Renal Artery Stenosis.

Renal fibrosis is an important marker in the progression of chronic kidney disease, and renal biopsy is the current reference standard for detecting its presence. Currently, non-invasive methods have only been partially successful in detecting renal fibrosis. Magnetization transfer imaging (MTI) allows estimates of renal fibrosis but may vary with scanning conditions. We hypothesized that MTI-derived renal fibrosis would be reproducible at 1.5T and 3T MRI and over time in fibrotic kidneys. Fifteen pigs with unilateral renal artery stenosis (RAS, n = 9) or age-matched sham controls (n = 6) underwent MTI-MRI at both 1.5T and 3T 6 weeks post-surgery and again 4 weeks later. Magnetization transfer ratio (MTR) measurements of fibrosis in both kidneys were compared between 1.5T and 3T, and the reproducibility of MTI at the two timepoints was evaluated at 1.5T and 3T. MTR at 3T with 600 Hz offset frequency successfully distinguished between normal, stenotic, and contralateral kidneys. There was excellent reproducibility of MTI at 1.5T and 3T over the two timepoints and no significant differences between MTR measurements at 1.5T and 3T. Therefore, MTI is a highly reproducible technique which is sensitive to detect changes in fibrotic compared to normal kidneys in the RAS porcine model at 3T.

Incidental diagnosis of presacral ganglioneuroma in a patient with hematuria.

Ganglioneuromas are benign neuroblastic tumors seen most in pediatric population. The most common locations are mediastinal, retroperitoneal and adrenal regions. Ganglioneuromas rarely occur in presacral space. We present one such case of an incidentally diagnosed presacral ganglioneuroma in an asymptomatic 71-year-old male who initially presented with hematuria.

Renal fibrosis detected by diffusion-weighted magnetic resonance imaging remains unchanged despite treatment in subjects with renovascular disease.

Tissue fibrosis is an important index of renal disease progression. Diffusion-weighted magnetic resonance imaging's (DWI-MRI) apparent diffusion coefficient (ADC) reveals water diffusion is unobstructed by microstructural alterations like fibrosis. We hypothesized that ADC may indicate renal injury and response to therapy in patients with renovascular disease (RVD). RVD patients were treated with medical therapy (MT) and percutaneous transluminal renal angioplasty (MT + PTRA) (n = 11, 3 bilaterally, n = 14 kidneys) or MT (n = 9). ADC and renal hypoxia (R2*) by blood-oxygen-level-dependent MRI were studied before (n = 27) and 3 months after (n = 20) treatment. Twelve patients underwent renal biopsies. Baseline ADC values were correlated with changes in eGFR, serum creatinine (SCr), systolic blood pressure (SBP), renal hypoxia, and renal vein levels of pro-inflammatory marker tumor necrosis-factor (TNF)-α. Renal oxygenation, eGFR, and SCr improved after MT + PTRA. ADC inversely correlated with the histological degree of renal fibrosis, but remained unchanged after MT or MT + PTRA. Basal ADC values correlated modestly with change in SBP, but not in renal hypoxia, TNF-α levels, or renal function. Lower ADC potentially reflects renal injury in RVD patients, but does not change in response to medical or interventional therapy over 3 months. Future studies need to pinpoint indices of kidney recovery potential.

Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement: A Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: We assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Individuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life. RESULTS: Of 48 subjects randomized, 41 completed total liver volume measurements (n=29 pasireotide long-acting release and n=12 placebo). From baseline, there were -99±189 ml/m absolute and -3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (P<0.001 for both). Total kidney volumes decreased by -12±34 ml/m and -1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (P=0.05 for both). Changes in eGFR were similar between groups. Among the n=48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; P<0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (P=0.001). CONCLUSIONS: Another somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes). CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Pasireotide LAR in Severe Polycystic Liver Disease, NCT01670110 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3.

Peristenotic Collateral Circulation in Atherosclerotic Renovascular Disease: Association With Kidney Function and Response to Treatment.

The significance of peristenotic collateral circulation (PCC) development around a stenotic renal artery is unknown. We tested the hypothesis that PCC is linked to loss of kidney function and recovery potential in patients with atherosclerotic renovascular disease (ARVD). Thirty-four patients with ARVD were assigned to medical-therapy with or without revascularization based on clinical indications. The PCC was visualized using multidetector computed tomography and defined relative to segmental arteries in patients with essential hypertension. PCC number before and 3 months after treatment was correlated with various renal parameters. Thirty-four stenotic kidneys from 30 patients were analyzed. PCC number correlated inversely with kidney volume. ARVD-stenotic kidneys with baseline PCC (collateral ARVD [C-ARVD], n=13) associated with elevated 24-hour urine protein and stenotic kidney vein level of tumor necrosis factor-α, lower single-kidney volume and blood flow, and greater hypoxia than in stenotic kidneys with no PCC (no collateral ARVD [NC-ARVD], n=17). Revascularization (but not medical-therapy alone) improved stenotic kidney function and reduced inflammation in both NC-ARVD and C-ARVD. In C-ARVD, revascularization also increased stenotic kidney volume, blood flow, and oxygenation to levels comparable to NC-ARVD, and induced PCC regression. However, revascularization improved systolic blood pressure, plasma renin activity, and filtration fraction only in NC-ARVD. Therefore, patients with C-ARVD have greater kidney dysfunction, atrophy, hypoxia, and inflammation compared with patients with NC-ARVD, suggesting that PCC does not effectively protect the stenotic kidney in ARVD. Renal artery revascularization improved in C-ARVD stenotic kidney function, but not hypertension or renin-angiotensin system activation. These observations may help direct management of patients with ARVD.

Two Non-gadolinium-based, Innovative Approaches to Preoperative Lymphangiography.

Most magnetic resonance lymphangiography techniques employ intravenous gadolinium-based contrast agents, which carry a US Food and Drug Administration warning about gadolinium retention in the body when used intravenously. Because of this, there may be reluctance to perform intradermal injections of gadolinium-based contrast agents in patients with obstructed lymphatic drainage due to concerns about gadolinium retention in the skin and soft tissues and potential-related toxicity. The aim of this study was to show proof of concept of 2 preoperative lymphangiographic techniques that do not use gadolinium-based contrast agents. One technique used contrast-enhanced ultrasound with intradermal injections of microbubbles (Lumason) in a patient with stage 3, nonpitting left upper extremity edema. Another technique used magnetic resonance imaging with intradermal injections of 0.03 mg/mL or 0.003% ferumoxytol (Feraheme) in a patient with stage 3, nonpitting right lower extremity edema. Both contrast-enhanced ultrasound with microbubbles and magnetic resonance lymphangiogram with ferumoxytol were able to identify candidates for lymphovenous bypass surgery. These candidates were not identified by conventional indocyanine green injections. The authors conclude that (1) low-dose ferumoxytol is a potentially effective non-gadolinium-based contrast alternative to gadolinium-based contrast agent in magnetic resonance lymphangiography and (2) contrast-enhanced ultrasound can identify candidate lymphatic vessels for anastomosis.

A phase I study of the VEGFR kinase inhibitor vatalanib in combination with the mTOR inhibitor, everolimus, in patients with advanced solid tumors.

Purpose Combining small-molecule inhibitors of different targets was shown to be synergistic in preclinical studies. Testing this concept in clinical trials is, however, daunting due to challenges in toxicity management and efficacy assessment. This study attempted to evaluate the safety and efficacy of vatalanib plus everolimus in patients with advanced solid tumors and explore the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies as a predictive biomarker. Patients and Methods This single-center, phase I trial containing 70 evaluable patients consisted of a dose escalation proportion based on the traditional "3 + 3" design (cohort IA and IB) and a dose expansion proportion (cohort IIA and IIB). Toxicity was evaluated using the Common Terminology Criteria of Adverse Events. Antitumor activity was assessed using the Modified Response Evaluation Criteria in Solid Tumors. Results The maximum tolerated doses were determined to be vatalanib 1250 mg once daily or 750 mg twice daily in combination with everolimus 10 mg once daily. No treatment-related death occurred. The most common toxicities were hypertriglyceridemia, hypercholesterolemia, fatigue, vomiting, nausea and diarrhea. There was no complete response. Nine patients (12.9%) had partial response (PR) and 41 (58.6%) had stable disease (SD). Significant antitumor activity was observed in neuroendocrine tumors with a disease-control rate (PR + SD) of 66.7% and other tumor types including renal cancer, melanoma, and non-small-cell lung cancer. Conclusions The combination of vatalanib and everolimus demonstrated reasonable toxicity and clinical activity. Future studies combining targeted therapies and incorporating biomarker analysis are warranted based on this phase I trial.

In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure.

Atherosclerotic renovascular disease (ARVD) reduces tissue perfusion and eventually leads to loss of kidney function with limited therapeutic options. Here we describe results of Phase 1a escalating dose clinical trial of autologous mesenchymal stem cell infusion for ARVD. Thirty-nine patients with ARVD were studied on two occasions separated by three months. Autologous adipose-derived mesenchymal stem cells were infused through the renal artery in 21 patients at three different dose levels (1, 2.5 and 5.0 × 105 cells/kg) in seven patients each. We measured renal blood flow, glomerular filtration rate (GFR) (iothalamate and estimated GFR), renal vein cytokine levels, blood pressure, and tissue oxygenation before and three months after stem cell delivery. These indices were compared to those of 18 patients with ARVD matched for age, kidney function and blood pressure receiving medical therapy alone that underwent an identical study protocol. Cultured mesenchymal stem cells were also studied in vitro. For the entire stem cell treated-cohort, mean renal blood flow in the treated stenotic kidney significantly increased after stem cell infusion from (164 to 190 ml/min). Hypoxia, renal vein inflammatory cytokines, and angiogenic biomarkers significantly decreased following stem cell infusion. Mean systolic blood pressure significantly fell (144 to 136 mmHg) and the mean two-kidney GFR (Iothalamate) modestly but significantly increased from (53 to 56 ml/min). Changes in GFR and blood pressure were largest in the high dose stem cell treated individuals. No such changes were observed in the cohort receiving medical treatment alone. Thus, our data demonstrate the potential for autologous mesenchymal stem cell to increase blood flow, GFR and attenuate inflammatory injury in post-stenotic kidneys. The observation that some effects are dose-dependent and related to in-vitro properties of mesenchymal stem cell may direct efforts to maximize potential therapeutic efficacy.

MRI feature tracking strain is prognostic for all-cause mortality in AL amyloidosis.

OBJECTIVES: Cardiac involvement is a major determinate of mortality in light chain (AL) amyloidosis. Cardiac magnetic resonance imaging (MRI) feature tracking (FT) strain is a new method for measuring myocardial strain. This study retrospectively evaluated the association of MRI FT strain with all-cause mortality in AL amyloidosis. MATERIALS AND METHODS: Seventy-six patients with newly diagnosed AL amyloidosis underwent cardiac MRI. 75 had images suitable for MRI FT strain analysis. MRI delayed enhancement, morphologic and functional evaluation, cardiac biomarker staging and transthoracic echocardiography were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. RESULTS: There were 52 deaths. Median follow-up of surviving patients was 1.7 years. In univariate analysis, global radial (Hazard Ratio (HR) = 0.95, p <.01), circumferential (HR = 1.09, p < .01) and longitudinal (HR = 1.08, p < .01) strain were associated with all-cause mortality. In separate multivariate models, radial (HR = 0.96, p = .02), circumferential (HR = 1.09, p = .03) and longitudinal strain (HR = 1.07, p = .04) remained prognostic when combined with presence of biomarker stage 3. CONCLUSIONS: MRI FT strain is associated with all-cause mortality in patients with AL amyloidosis.

Magnetic Resonance Imaging and Computed Tomography of Cardiac Masses and Pseudomasses in the Atrioventricular Groove.

The atrioventricular (AV) groove constitutes the anatomic space separating the atria and ventricles. The AV groove is often difficult to visualize at echocardiography, and suspected lesions can be further assessed with cardiac computed tomography or magnetic resonance imaging. AV groove lesions may originate from within the AV groove or extend into this space from adjacent structures. The differential diagnosis for AV groove lesions is often wide, but a precise diagnosis can sometimes be made. This pictorial essay illustrates the magnetic resonance imaging and computed tomography appearance of common and uncommon AV groove lesions, and attempts to provide a logical framework for differential diagnosis when confronted with a known or suspected lesion at cross-sectional imaging.

Inflammatory hepatic adenomas: Characterization with hepatobiliary MRI contrast agents.

PURPOSE: To characterize the MRI appearance of inflammatory hepatic adenomas using hepatobiliary contrast agents. MATERIALS AND METHODS: MRI was performed using hepatobiliary contrast agents (3 with gadobenate dimeglumine and 24 with gadoxetic acid) in 27 patients with immunohistochemistry-confirmed diagnosis of inflammatory hepatic adenoma. The appearance of the lesions on T2 and diffusion-weighted images, pre-gadolinium T1-weighted images, dynamic post-gadolinium images, and hepatobiliary phase images was assessed. RESULTS: Seven lesions (26%) showed predominant hyperenhancement on hepatobiliary phase images in comparison with adjacent hepatic parenchyma: 1 lesion showed diffuse, mildly heterogeneous hyperenhancement, and the remaining 6 lesions showed peripheral hyperenhancement and central hypoenhancement. Twenty lesions (74%) were predominantly hypoenhancing compared to adjacent liver on hepatobiliary phase images. Nine lesions showed a pattern of peripheral hyperenhancement and central hypoenhancement on hepatobiliary phase images; in 6 of these lesions a majority of the mass appeared hyperenhancing, while the remaining 3 lesions showed predominant hypoenhancement. CONCLUSIONS: This investigation shows that a significant percentage of inflammatory hepatic adenomas appear isointense or hyperintense in comparison to adjacent normal liver on hepatobiliary phase images, and therefore this feature should not be used to distinguish hepatic adenomas from focal nodular hyperplasia without additional supporting evidence.

Autologous Mesenchymal Stem Cells Increase Cortical Perfusion in Renovascular Disease.

Atherosclerotic renovascular disease (RVD) reduces renal blood flow (RBF) and GFR and accelerates poststenotic kidney (STK) tissue injury. Preclinical studies indicate that mesenchymal stem cells (MSCs) can stimulate angiogenesis and modify immune function in experimental RVD. We assessed the safety and efficacy of adding intra-arterial autologous adipose-derived MSCs into STK to standardized medical treatment in human subjects without revascularization. The intervention group (n=14) received a single infusion of MSC (1.0 × 105 or 2.5 × 105 cells/kg; n=7 each) plus standardized medical treatment; the medical treatment only group (n=14) included subjects matched for age, kidney function, and stenosis severity. We measured cortical and medullary volumes, perfusion, and RBF using multidetector computed tomography. We assessed tissue oxygenation by blood oxygen level-dependent MRI and GFR by iothalamate clearance. MSC infusions were well tolerated. Three months after infusion, cortical perfusion and RBF rose in the STK (151.8-185.5 ml/min, P=0.01); contralateral kidney RBF increased (212.7-271.8 ml/min, P=0.01); and STK renal hypoxia (percentage of the whole kidney with R2*>30/s) decreased (12.1% [interquartile range, 3.3%-17.8%] to 6.8% [interquartile range, 1.8%-12.9%], P=0.04). No changes in RBF occurred in medical treatment only subjects. Single-kidney GFR remained stable after MSC but fell in the medical treatment only group (-3% versus -24%, P=0.04). This first-in-man dose-escalation study provides evidence of safety of intra-arterial infusion of autologous MSCs in patients with RVD. MSC infusion without main renal artery revascularization associated with increased renal tissue oxygenation and cortical blood flow.

Taxonomy and Imaging Manifestations of Systemic Amyloidosis.

Amyloidosis is a heterogeneous group of disorders that are characterized by extracellular deposition of misfolded and aggregated autologous proteins leading to organ dysfunction. Amyloid deposits produce diverse clinical syndromes depending on their type, location, and the amount of deposition. Clinical and imaging features of amyloidosis in various organ systems are described.

Magnetic Resonance Imaging of Perirenal Pathology.

The perirenal space can be involved by a variety of neoplastic, inflammatory, infectious, and proliferative disorders. Magnetic resonance imaging is often an ideal technique for identification and staging of lesions arising within the perirenal space, with its superior soft tissue characterization as well as its ability to visualize extension into blood vessels and adjacent organs. This pictorial essay describes the magnetic resonance imaging appearance of a variety of pathologies which can arise from or involve the perirenal space, and provides a framework for categorization and differential diagnosis of these lesions.

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease.

BACKGROUND AND OBJECTIVES: Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured. RESULTS: Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001). CONCLUSIONS: These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines.

Efficacy of 4 Years of Octreotide Long-Acting Release Therapy in Patients With Severe Polycystic Liver Disease.

OBJECTIVE: To observe the effect on total liver volume (TLV) on and off therapy in selected symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PLD) who received octreotide long-acting release (OctLAR) for up to 4 years. PATIENTS AND METHODS: Twenty-eight of 42 participants in a prospective 2-year clinical trial of OctLAR (40 mg monthly) consisting of double-blind, randomized (year 1) and open-label treatment (year 2) phases reenrolled in a 2-year open-label extension (OLE) study after being off OctLAR a mean of 8.3 months (original study: July 1, 2007, through June 30, 2013). Participants underwent magnetic resonance imaging at baseline, years 1 and 2, reenrollment, and study completion. Primary end point: change in TLV; secondary end points: changes in total kidney volume, glomerular filtration rate, quality of life (QoL), safety, vital signs, and laboratory parameters. RESULTS: Twenty-five participants (59.5%) completed the OLE. Off therapy, TLVs increased a mean ± SD of 3.4%±8.2% per year; after resuming therapy, TLVs decreased a mean ± SD of -4.7%±6.1% per year. Despite regrowth off treatment, overall reductions were observed, with a median (interquartile range) TLV of 4047 mL (3107-7402 mL) at baseline and 3477 (2653-7131 mL) at study completion (-13.2%; P<.001) and with improved health-related QoL. Total kidney volumes increased, and glomerular filtration rates declined from 58.2 mL/min to 54.5 mL/min (n=16) in patients with ADPKD on therapy from baseline to study completion. CONCLUSION: Therapy with OctLAR over 4 years in selected patients with symptomatic PLD arrested PLD progression, alleviating symptoms and improving health-related QoL. Discontinuation led to organ regrowth. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00426153.

Evaluation of apical subtype of hypertrophic cardiomyopathy using cardiac magnetic resonance imaging with gadolinium enhancement.

Apical hypertrophic cardiomyopathy (HC) is an uncommon variant of HC. We sought to characterize cardiac magnetic resonance imaging (MRI) findings among apical HC patients. This was a retrospective review of consecutive patients with a diagnosis of apical HC who underwent cardiac MRI examinations at the Mayo Clinic (Rochester, MN) from August 1999 to October 2011. Clinical and demographic data at the time of cardiac MRI study were abstracted. Cardiac MRI study and 2-dimensional echocardiograms performed within 6 months of the cardiac MRI were reviewed; 96 patients with apical HC underwent cardiac MRI examinations. LV end-diastolic and end-systolic volumes were 130.7 ± 39.1 ml and 44.2 ± 20.9 ml, respectively. Maximum LV thickness was 19 ± 5 mm. Hypertrophy extended beyond the apex into other segments in 57 (59.4%) patients. Obstructive physiology was seen in 12 (12.5%) and was more common in the mixed apical phenotype than the pure apical (19.3 vs 2.6%, p = 0.02). Apical pouches were noted in 39 (40.6%) patients. Late gadolinium enhancement (LGE) was present in 70 (74.5%) patients. LGE was associated with severe symptoms and increased maximal LV wall thickness. In conclusion, cardiac MRI is well suited for studying the apical form of HC because of difficulty imaging the cardiac apex with standard echocardiography. Cardiac MRI is uniquely suited to delineate the presence or absence of an apical pouch and abnormal myocardial LGE that may have implications in the natural history of apical HM. In particular, the presence of abnormal LGE is associated with clinical symptoms and increased wall thickness.

Unveiling nonischemic cardiomyopathies with cardiac magnetic resonance.

Cardiomyopathy is defined as a heterogeneous group of myocardial disorders with mechanical or electrical dysfunction. Identification of the etiology is important for accurate diagnosis, treatment and prognosis, but continues to be challenging. The ability of cardiac MRI to non-invasively obtain 3D-images of unparalleled resolution without radiation exposure and to provide tissue characterization gives it a distinct advantage over any other diagnostic tool used for evaluation of cardiomyopathies. Cardiac MRI can accurately visualize cardiac morphology and function and also help identify myocardial edema, infiltration and fibrosis. It has emerged as an important diagnostic and prognostic tool in tertiary care centers for work up of patients with non-ischemic cardiomyopathies. This review covers the role of cardiac MRI in evaluation of nonischemic cardiomyopathies, particularly in the context of other diagnostic and prognostic imaging modalities.

Stent revascularization restores cortical blood flow and reverses tissue hypoxia in atherosclerotic renal artery stenosis but fails to reverse inflammatory pathways or glomerular filtration rate.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow, glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulointerstitial injury in the poststenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. METHODS AND RESULTS: Inpatient studies were performed in patients with ARAS (n=17; >60% occlusion) before and 3 months after stent revascularization, or in patients with essential hypertension (n=32), during fixed Na(+) intake and angiotensin converting enzyme/angiotensin receptors blockers Rx. Single kidney cortical, medullary perfusion, and renal blood flow were measured using multidetector computed tomography, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R(2)*) were measured by blood oxygen level-dependent MRI at 3T, as was fractional kidney hypoxia (percentage of axial area with R(2)*>30/s). In addition, we measured renal vein levels of neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Pre-stent single kidney renal blood flow, perfusion, and GFR were reduced in the poststenotic kidney. Renal vein neutrophil gelatinase-associated lipocalin, tumor necrosis factor-α, monocyte chemoattractant protein-1, and fractional hypoxia were higher in untreated ARAS than in essential hypertension. After stent revascularization, fractional hypoxia fell (P<0.002) with increased cortical perfusion and blood flow, whereas GFR and neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and tumor necrosis factor-α remained unchanged. CONCLUSIONS: These data demonstrate that despite reversal of renal hypoxia and partial restoration of renal blood flow after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly explains the limited clinical benefit of renal stenting. These results identify potential therapeutic targets for recovery of kidney function in renovascular disease.

Somatostatin analog therapy for severe polycystic liver disease: results after 2 years.

BACKGROUND: We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.® (OctLAR(®)) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O → O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P → O). METHODS: The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters. RESULTS: Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P → O) showed substantial reduction in TLV after treatment with OctLAR in Year 2 (Δ% -7.66 ± 9.69%, P = 0.011). The initial reduction of TLV in the OctLAR group (O → O) was maintained for 2 years (Δ% -5.96 ± 8.90%), although did not change significantly during Year 2 (Δ% -0.77 ± 6.82%). OctLAR inhibited renal enlargement during Year 1 (Δ% +0.42 ± 7.61%) in the (O → O) group and during Year 2 (Δ% -0.41 ± 9.45%) in the (P → O) group, but not throughout Year 2 (Δ% +6.49 ± 7.08%) in the (O → O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O → O patients and Year 2 for P → O patients, average reduction in TLV was -6.08 ± 7.58% (P = 0.001) compared to net growth of 0.9 ± 8.35% in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups. CONCLUSION: Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.