Noninvasive Assessment of Renal Fibrosis with Magnetization Transfer MR Imaging: Validation and Evaluation in Murine Renal Artery Stenosis.

Purpose To test the utility of magnetization transfer imaging in detecting and monitoring the progression of renal fibrosis in mice with unilateral renal artery stenosis. Materials and Methods This prospective study was approved by the Institutional Animal Care and Use Committee. Renal artery stenosis surgery (n = 10) or sham surgery (n = 5) was performed, and the stenotic and contralateral kidneys were studied longitudinally in vivo at baseline and 2, 4, and 6 weeks after surgery. After a 16.4-T magnetic resonance imaging examination, magnetization transfer ratio was measured as an index of fibrosis (guided by parameters selected in preliminary phantom studies). In addition, renal volume, perfusion, blood flow, and oxygenation were assessed. Fibrosis was subsequently measured ex vivo by means of histologic analysis and hydroxyproline assay. The Wilcoxon rank sum or signed rank test was used for statistical comparisons between or within groups, and Pearson and Spearman rank correlation was used to compare fibrosis measured in vivo and ex vivo. Results In the stenotic kidney, the median magnetization transfer ratio showed progressive increases from baseline to 6 weeks after surgery (increases of 13.7% [P = .0006] and 21.3% [P = .0005] in cortex and medulla, respectively), which were accompanied by a progressive loss in renal volume, perfusion, blood flow, and oxygenation. The 6-week magnetization transfer ratio map showed good correlation with fibrosis measured ex vivo (Pearson r = 0.9038 and Spearman ρ = 0.8107 [P = .0002 vs trichrome staining]; r = 0.9540 and ρ = 0.8821 [P < .0001 vs Sirius red staining]; and r = 0.8429 and ρ = 0.7607 [P = .001 vs hydroxyproline assay]). Conclusion Magnetization transfer imaging was used successfully to measure and longitudinally monitor the progression of renal fibrosis in mice with unilateral renal artery stenosis. © RSNA, 2016 Online supplemental material is available for this article.

Non-invasive assessment of cardiac function in a mouse model of renovascular hypertension.

Hypertension continues to be a significant cause of morbidity and mortality, underscoring the need to better understand its early effects on the myocardium. The aim of this study is to determine the feasibility of in vivo longitudinal assessment of cardiac function, particularly diastolic function, in a mouse model of renovascular hypertension. Renovascular hypertension (RVH) was induced in 129S1/SvImJ male mice (n=9). To assess left ventricular (LV) systolic and diastolic function, M-mode echocardiography, pulsed-wave Doppler echocardiography and tissue Doppler imaging were performed at baseline, 2 and 4 weeks after the induction of renal artery stenosis. Myocardial tissue was collected to assess cellular morphology, fibrosis, extracellular matrix remodeling and inflammation ex vivo. RVH led to a significant increase in systolic blood pressure after 2 and 4 weeks (baseline: 99.26±1.09 mm Hg; 2 weeks: 140.90±7.64 mm Hg; 4 weeks: 147.52±5.91 mm Hg, P<0.05), resulting in a significant decrease in LV end-diastolic volume, associated with a significant elevation in ejection fraction and preserved cardiac output. Furthermore, the animals developed an abnormal diastolic function profile, with a shortening in the E velocity deceleration time as well as increases in the E/e' and the E/A ratio. The ex vivo analysis revealed a significant increase in myocyte size and deposition of extracellular matrix. Non-invasive high-resolution ultrasonography allowed assessment of the diastolic function profile in a small animal model of renovascular hypertension.

Commentary: improving medical education during financially challenging times.

The expectation exists that medical education will continue to improve even during financially challenging times. The authors reviewed their recent experiences in effecting positive changes and improvements in Mayo Medical School during a time of fiscal constraint. They successfully implemented numerous changes, including a major curriculum reform, while modestly reducing overall costs of the medical school and improving student satisfaction and learner outcomes. These improvements resulted from careful alignment among the institutional mission of serving the needs of the patient, communication with the faculty, involvement of the students, and streamlining of multiple processes throughout the school. The authors sought to eliminate excessive resource utilization while retaining the essence of Mayo Medical School's education process. The authors' experience can both encourage and inspire other schools to continue to improve the educational experience for their students in concert with meeting increasing financial pressures.

Comparison of low versus high tacrolimus levels in kidney transplantation: assessment of efficacy by protocol biopsies.

BACKGROUND: The use of calcineurin inhibitors is generally guided by drug blood levels. However, those levels are chosen based on clinical experience, lacking adequate titration studies. METHODS: In these analyses, we compared clinical and histologic endpoints in two groups of kidney transplant recipients: in the first (HiTAC, January 2000 to June 2002, n=245) tacrolimus levels were significantly higher than in the second (LoTAC, July 2002 to September 2004, n=330). This change in drug levels (15% reduction) was made in an attempt to reduce the incidence of polyoma virus nephropathy (PVAN). Other immunosuppressive medications were unchanged during these two time periods. RESULTS: The recipient and donor demographics were not statistically different between the two groups. Compared to HiTAC, at one year posttransplant LoTAC had: 1) lower incidence of PVAN (10.5% vs. 2.5%, P<0.0001); 2) lower fasting glucose levels; 3) higher iothalamate glomerular filtration rate (52+/-19 vs. 59+/-17 ml/min/m, P<0.0001); and 4) on protocol one-year biopsies, lower incidence and severity of interstitial fibrosis (67% vs. 45%, P=0.003) and tubular atrophy (82% vs., 66%, P=0.01). The incidence and severity of acute rejection episodes was similar between both groups (7.8% versus 7.6%). CONCLUSIONS: Modest reductions in tacrolimus exposure early posttransplant are associated with significant beneficial effects for the patient and the allograft without an increased immunologic risk.