Attitudes towards chiropractic: a repeated cross-sectional survey of Canadian family physicians.

BACKGROUND: Many primary care patients receive both medical and chiropractic care; however, interprofessional relations between physicians and chiropractors are often suboptimal which may adversely affect care of shared patients. We surveyed Canadian family physicians in 2010 to explore their attitudes towards chiropractic and re-administered the same survey a decade later to explore for changes in attitudes. METHODS: A 50-item survey administered to a random sample of Canadian family physicians in 2010, and again in 2019, that inquired about demographic variables, knowledge and use of chiropractic. Imbedded in our survey was a 20-item chiropractic attitude questionnaire (CAQ); scores could range from 0 to 80 with higher scores indicating more positive attitudes toward chiropractic. We constructed a multivariable regression model to explore factors associated with CAQ scores. RESULTS: Among eligible physicians, 251 of 685 in 2010 (37% response rate) and 162 of 2429 in 2019 (7% response rate) provided a completed survey. Approximately half of respondents (48%) endorsed a positive impression of chiropractic, 27% were uncertain, and 25% held negative views. Most respondents (72%) referred at least some patients for chiropractic care, mainly due to patient request or lack of response to medical care. Most physicians believed that chiropractors provide effective therapy for some musculoskeletal complaints (84%) and disagreed that chiropractic care was beneficial for non-musculoskeletal conditions (77%). The majority agreed that chiropractic care was a useful supplement to conventional care (65%) but most respondents (59%) also indicated that practice diversity among chiropractors presented a barrier to interprofessional collaboration. In our adjusted regression model, attitudes towards chiropractic showed trivial improvement from 2010 to 2019 (0.31 points on the 80-point CAQ; 95%CI 0.001 to 0.62). More negative attitudes were associated with older age (- 1.55 points for each 10-year increment from age 28; 95%CI - 2.67 to - 0.44), belief that adverse events are common with chiropractic care (- 1.41 points; 95% CI - 2.59 to - 0.23) and reported use of the research literature (- 6.04 points; 95% CI - 8.47 to - 3.61) or medical school (- 5.03 points; 95% CI - 7.89 to - 2.18) as sources of knowledge on chiropractic. More positive attitudes were associated with endorsing a relationship with a specific chiropractor (5.24 points; 95% CI 2.85 to 7.64), family and friends (4.06 points; 95% CI 1.53 to 6.60), or personal treatment experience (4.63 points; 95% CI 2.14 to 7.11) as sources of information regarding chiropractic. CONCLUSIONS: Although generally positive, Canadian family physicians' attitudes towards chiropractic are diverse, and most physicians felt that practice diversity among chiropractors was a barrier to interprofessional collaboration.

Disinfection of the Radiologist Workstation and Radiologist Hand Hygiene: A Single Institution Practice Quality Improvement Project.

PURPOSE: The purpose of this study was to evaluate the workstation disinfection rates and hand hygiene of radiologists and trainees at shared departmental workstations and assess the impact of education and reminder placards on daily habits. METHODS: A 10-question survey was administered to all staff radiologists, fellows, and residents at our institution. The questions pertained to workstation disinfection, hand hygiene habits, and accessibility to disinfectant wipes and hand sanitizer stations. Subsequently, a short educational PowerPoint presentation was emailed to the department and small reminder placards were placed at each workstation. A follow-up survey was administered. Chi-square and Wilcoxon signed-rank tests were used to analyse the results. RESULTS: The percentage of participants who disinfect their workstations 1-2 times/week, 3-4 times/week or everyday increased from 53.4% (45 of 84 participants) to 74.3% (55 of 74 participants; P = .01), while the number who disinfect their workstation <1 time/week or never decreased from 46.4% (39 of 84 participants) to 25.7% (19 of 74 participants; P = .01). Hand washing before working at the workstation increased from 41.6% (35 of 84 participants) to 48.7% (36 of 74 participants; P = .76) and hand washing after working at the workstation increased from 50.0% (42 of 84 participants) to 56.8% (42 of 74 participants; P = .49). CONCLUSIONS: At our institution, the implementation of daily reminder placards at each workstation and the administration of an educational PowerPoint presentation improved the rate of radiologist workstation disinfection.

Internal Hernia after Laparoscopic Roux-en-Y Gastric Bypass: Optimal CT Signs for Diagnosis and Clinical Decision Making.

Purpose To evaluate the accuracy of computed tomography (CT) for diagnosis of internal hernia (IH) in patients who have undergone laparoscopic Roux-en-Y gastric bypass and to develop decision tree models to optimize diagnostic accuracy. Materials and Methods This was a retrospective, ethics-approved study of patients who had undergone laparoscopic Roux-en-Y gastric bypass with surgically confirmed IH (n = 76) and without IH (n = 78). Two radiologists independently reviewed each examination for the following previously established CT signs of IH: mesenteric swirl, small-bowel obstruction (SBO), mushroom sign, clustered loops, hurricane eye, small bowel behind the superior mesenteric artery, and right-sided anastomosis. Radiologists also evaluated images for two new signs, superior mesenteric vein (SMV) "beaking" and "criss-cross" of the mesenteric vessels. Overall impressions for diagnosis of IH were recorded. Diagnostic accuracy and interobserver agreement were calculated, and multivariate recursive partitioning was performed to evaluate various decision tree models by using the CT signs. Results Accuracy and interobserver agreement regarding the nine CT signs of IH showed considerable variation. The best signs were mesenteric swirl (sensitivity and specificity, 86%-89% and 86%-90%, respectively; κ = 0.74) and SMV beaking (sensitivity and specificity, 80%-88% and 94%-95%, respectively; κ = 0.83). Overall reader impression yielded the highest sensitivity and specificity (96%-99% and 90%-99%, respectively; κ = 0.79). The decision tree model with the highest overall accuracy and sensitivity included mesenteric swirl and SBO, with a diagnostic odds ratio of 154 (95% confidence interval [CI]: 146, 161), sensitivity of 96% (95% CI: 87%, 99%), and specificity of 87% (95% CI: 75%, 93%). The decision tree with the highest specificity included SMV beaking and SBO, with a diagnostic odds ratio of 105 (95% CI: 101, 109), sensitivity of 90% (95% CI: 79%, 95%), and specificity of 92% (95% CI: 83%, 97%). Conclusion The decision tree with the highest accuracy and sensitivity for diagnosis of IH included mesenteric swirl and SBO, the model with the highest specificity included SMV beaking and SBO, and the remaining signs showed lower accuracy and/or poor to fair interobserver agreement. Overall reader impression yielded the highest accuracy for diagnosis of IH, likely because alternate diagnoses not incorporated in the models were considered. © RSNA, 2016 Online supplemental material is available for this article.

MRI Evaluation of the Urothelial Tract: Pitfalls and Solutions.

OBJECTIVE: MR urography (MRU) can be an alternative to CT urography (CTU) for imaging of the kidneys, urinary bladder, and collecting systems. MRU can be a challenging examination to perform and interpret, which may result in technical and interpretive errors being made. This article highlights the pitfalls associated with MRU and discusses how to recognize and avoid them. CONCLUSION: When performed properly, MRU may provide imaging quality generally comparable to that of CTU, and it enables comprehensive evaluation of the entire urinary tract.

How Well Are We Respecting Patient Privacy in Medical Imaging? Lessons Learnt From a Departmental Audit.

RATIONALE AND OBJECTIVES: Preservation of patient privacy and dignity are basic requirements for all patients visiting a hospital. The purpose of this study was to perform an audit of patients' satisfaction with privacy whilst in the Department of Medical Imaging (MI) at the Civic Campus of the Ottawa Hospital. MATERIALS AND METHODS: Outpatients who underwent magnetic resonance imaging (MRI), computed tomography (CT), ultrasonography (US), and plain film (XR) examinations were provided with a survey on patient privacy. The survey asked participants to rank (on a 6-point scale ranging from 6 = excellent to 1 = no privacy) whether their privacy was respected in 5 key locations within the Department of MI. The survey was conducted over a consecutive 5-day period. RESULTS: A total of 502 surveys were completed. The survey response rate for each imaging modality was: 55% MRI, 42% CT, 45% US, and 47% XR. For each imaging modality, the total percentage of privacy scores greater than or equal to 5 were: 98% MRI, 96% CT, 94% US, and 92% XR. Privacy ratings for the MRI reception and waiting room areas were significantly higher in comparison to the other imaging modalities (P = .0025 and P = .0227, respectively). CONCLUSION: Overall, patient privacy was well respected within the Department of MI.

Is There an Association between STARD Statement Adherence and Citation Rate?

Purpose To determine if adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) is associated with postpublication citation rates. Materials and Methods A comprehensive search of PubMed, EMBASE, and Cochrane Library databases was performed to identify published articles that have evaluated adherence of diagnostic accuracy studies to the STARD statement. These were included if the number of STARD items reported ("STARD result") could be obtained for each evaluated study. The date of publication, journal impact factor, and citation rate (citations per day) were extracted for the diagnostic accuracy studies. Univariate correlations were performed to identify any association between STARD result, impact factor, and citation rate. Multivariate regression analysis was performed to explore the effect of impact factor on postpublication citation rates. Results The authors were able to obtain the STARD results for 1002 "original" diagnostic accuracy studies from eight different "STARD evaluation" articles. The median impact factor was 3.97 (interquartile range [IQR]: 2.32-6.21), the median STARD result was 15 of 25 items (IQR: 12-18), and the median citation rate was 0.007 citations per day (IQR: 0.0032-0.017). The authors identified a weak positive correlation between STARD result and citation rate (r = 0.096; 95% confidence interval [CI]: 0.034, 0.157), a moderate positive correlation between impact factor and citation rate (r = 0.58; 95% CI: 0.535, 0.617), and a weak positive correlation between impact factor and STARD result (r = 0.13; 95% CI: 0.064, 0.186). Multivariate analysis accounting for journal clustering effects revealed that, when impact factor is partialed out, the positive correlation between citation rate and STARD result does not persist (r = 0.029; 95% CI: -0.033, 0.091). Conclusion There is a positive correlation between completeness of reporting, as evaluated with STARD, and citation rate as well as impact factor. When adjusted for impact factor, the positive correlation between completeness of reporting and citation rate does not persist. (©) RSNA, 2016 Online supplemental material is available for this article.

Comparison of Contrast-Enhanced Multiphase Renal Protocol CT Versus MRI for Diagnosis of Papillary Renal Cell Carcinoma.

OBJECTIVE: The objective of this study was to compare contrast-enhanced (CE) CT with MRI for the diagnosis of papillary renal cell carcinoma (pRCC). MATERIALS AND METHODS: Between 2006 and 2013, a total of 27 pRCCs were assessed using CECT or CE-MRI. A blinded radiologist placed ROIs that measured attenuation on unenhanced CT; corticomedullary and nephrographic phase CECT images, with an attenuation difference of 20 HU or more denoting enhancing lesions, 10-19 HU indicating indeterminate findings, and less than 10 HU denoting nonenhancing lesions. MRI enhancement ratios were calculated as follows: (signal intensity on gadolinium-enhanced image minus signal intensity) / (signal intensity on unenhanced image × 100) for phase 1 (acquired at 30 s), phase 2 (acquired at 70 s), and phase 3 (acquired at 180 s), where a difference of 15% or more denoted enhancement. Two additional blinded radiologists qualitatively assessed tumor margin, homogeneity, and calcification with the use of CT, and they also assessed enhancement with the use of subtraction MRI. A fourth radiologist established consensus. Twenty consecutive hemorrhagic/proteinaceous cysts served as a control group. Statistical analyses were performed using a chi-square test and multivariate regression. RESULTS: There was no statistically significant difference in patient age (p = 0.22), patient sex (p = 0.36), or tumor size (p = 0.29), when pRCCs were compared with hemorrhagic/proteinaceous cysts. On unenhanced CT, attenuation of pRCCs (mean ± SD, 35.7 ± 12.9 HU; range, 19-66 HU) was similar to that of hemorrhagic/proteinaceous cysts (mean, 38.9 ± 16.9; range, 8-71 HU) (p = 0.48). A total of 51.9% of pRCCs (14/27) had either absent or indeterminate enhancement on corticomedullary phase CECT images (mean attenuation difference, 23.2 ± 20.3 HU; range, 6-105 HU), and 14.8% of pRCCs (4/27) had indeterminate enhancement on nephrographic phase CECT images (mean attenuation difference, 36.4 ± 24.9; range, 10-128 HU). No pRCC was nonenhancing on nephrographic phase CECT. Qualitatively, pRCCs were more heterogeneous (80% vs 45%; p = 0.02; κ = 0.24), irregular (50% vs 5%; p < 0.001; κ = 0.21), and calcified (25% vs 0%; p = 0.004; κ = 0.67), with overlap existing between hemorrhagic/proteinaceous cysts. On CE-MRI, all pRCCs were quantitatively enhanced by phase 2 (95.4 ± 83.1; percentage change in signal intensity ratio, 16-450%) and qualitatively enhanced after consensus review. No hemorrhagic/proteinaceous cyst enhanced on MRI when quantitative or subjective analysis was performed. CONCLUSION: A small number of pRCCs have indeterminate enhancement when renal protocol CT is used. Heterogeneity, irregular margins, and calcification are suggestive diagnostic features; however, quantitative and qualitative CE-MRI can accurately differentiate hemorrhagic/proteinaceous cysts from pRCC.

MRI evaluation of small (<4cm) solid renal masses: multivariate modeling improves diagnostic accuracy for angiomyolipoma without visible fat compared to univariate analysis.

OBJECTIVE: To assess MRI for diagnosis of angiomyolipoma without visible fat (AMLwvf). MATERIAL AND METHODS: With IRB approval, a retrospective study in consecutive patients with contrast-enhanced (CE)-MRI and <4 cm solid renal masses from 2002-2013 was performed. Ten AMLwvf were compared to 77 RCC; 33 clear cell (cc), 35 papillary (p), 9 chromophobe (ch). A blinded radiologist measured T2W signal-intensity ratio (SIR), chemical-shift (CS) SI-index and area under CE-MRI curve (CE-AUC). Regression modeling and ROC analysis was performed. RESULTS: T2W-SIR was lower in AMLwvf (0.64 ± 0.12) compared to cc-RCC (1.37 ± 0.30, p < 0.001), ch-RCC (0.94 ± 0.19, p = 0.005) but not p-RCC (0.74 ± 0.17, p = 0.2). CS-SI index was higher in AMLwvf (16.1 ± 31.5 %) compared to p-RCC (-5.2 ± 26.1 %, p = 0.02) but not ch-RCC (3.0 ± 12.5 %, p = 0.1) or cc-RCC (7.7 ± 17.9 %,p = 0.1). CE-AUC was higher in AMLwvf (515.7 ± 144.7) compared to p-RCC (154.5 ± 92.8, p < 0.001) but not ch-RCC (341.5 ± 202.7, p = 0.07) or cc-RCC (520.9 ± 276.9, p = 0.95). Univariate ROC-AUC were: T2SIR = 0.86 (CI 0.77-0.96); CE-AUC = 0.76 (CI 0.65-0.87); CS-SI index = 0.66 (CI 0.4.3-0.85). Logistic regression models improved ROC-AUC, A) T2 SIR + CE-AUC = 0.97 (CI 0.93-1.0) and T2 SIR + CS-SI index = 0.92 (CI 0.84-0.99) compared to univariate analyses (p < 0.05). The optimal sensitivity/specificity of T2SIR + CE-AUC and T2SIR + CS-SI index were 100/88.8 % and 60/97.4 %. CONCLUSION: MRI, using multi-variate modelling, is accurate for diagnosis of AMLwvf. KEY POINTS: • AMLwvf are difficult to prospectively diagnose with imaging. • MRI findings associated with AMLwvf overlap with various RCC subtypes. • T2W-SI combined with chemical-shift SI-index is specific for AMLwvf but lacks sensitivity. • T2W-SI combined with AUC CE-MRI is sensitive and specific for AMLwvf. • Models incorporating two or more findings are more accurate than univariate analysis.

Angiomyolipoma (AML) without visible fat: Ultrasound, CT and MR imaging features with pathological correlation.

OBJECTIVE: To compare imaging findings with histopathology in AML without visible fat (AMLwvf). MATERIAL AND METHODS: With IRB approval, we identified 18 AMLwvf that underwent CT between 2002-2014. A radiologist measured NECT-attenuation, corticomedullary (CM) and nephrographic (NG) enhancement, echogenicity relative to renal cortex (RC) (N = 5), T2W (T2AML/T2RC) signal-intensity (SI), and chemical-shift SI ([SIIN-PHASE - SIOPPOSED-PHASE]/SIIN-PHASE) indices (N = 6). A pathologist re-evaluated 15/18 AMLwvf for 1) < or > 25% adipocytes/high-power-field (HPF), 2) "many or few" blood vessels. Comparisons were performed using chi-square and independent t-tests. RESULTS: 73.3%(11/15) of AMLwvf had <25% adipocytes/HPF and 86.7%(13/15) had "many" blood vessels. NECT-attenuation was 41.8(±6.9) HU. 61.1 %(11/18) of AMLwvf were hyper-attenuating and 38.9%(7/18) iso-attenuating; attenuation was associated with %-adipocytes/HPF, (p = 0.01). CM/NG enhancement were 63.3(±20.8)/51.7(±15.5) HU. 72.2%(13/18) of AMLwvf had wash-out enhancement, with no association with amount of blood vessels at pathology, (p = 0.68). No difference in echogenicity was noted by histology (p > 0.05). All AMLwvf were T2-hypointense (SI ratio = 0.61 [±0.1]). 2/6 AMLwvf showed SI drop on chemical-shift MRI; both were iso-attenuating and were associated with >25% adipocytes/HPF (p = 0.04). CONCLUSIONS: AMLwvf are typically T2-hypointense and hyper-attenuating with wash-out enhancement due to abundant smooth muscle and vessels respectively. Iso-attenuating AMLwvf with microscopic fat on MRI contain more adipocytes/HPF. KEY POINTS: • Five percent of AML do not demonstrate detectable fat on imaging • These AML are hyperattenuating and T2-hypointense due to abundant smooth muscle • These AML show washout enhancement without association to vessel count at histopathology • Iso-attenuating AML with microscopic fat on MRI show >25% adipocytes/HPF • The term "AML without visible fat" is proposed to reduce ambiguity.

Solid Renal Cell Carcinoma Measuring Water Attenuation (-10 to 20 HU) on Unenhanced CT.

OBJECTIVE: The objectives of this study were to evaluate the incidence of solid renal cell carcinoma (RCC) with attenuation similar to that of water (-10 to 20 HU) on unenhanced CT and to examine imaging features that can allow RCC to be differentiated from simple cysts. MATERIALS AND METHODS: We performed an enriched quantitative and qualitative retrospective analysis of consecutive patients who underwent unenhanced CT before resection of solid (noncystic and nonnecrotic) renal masses measuring < 5 cm from 2008 to 2013. In all, 93 patients with 96 tumors (55 clear cell, 27 papillary, and 14 chromophobe) were evaluated with unenhanced CT. Attenuation was measured at three standardized levels and compared using the Kruskal-Wallis test. Two radiologists independently assessed calcification, margin (smooth or irregular), and heterogeneity (homogeneous or heterogeneous). Results were compared using the chi-square test with Bonferroni correction. RESULTS: Mean ± SD attenuation values were 31.8 ± 9.6 HU (range, 11-63 HU) overall, 29.9 ± 8.8 HU (range, 11.0-49.0 HU) for clear cell tumors, 34.6 ± 10.3 HU (range, 20.3-63.0 HU) for papillary tumors, and 35.5 ± 9.2 HU (range, 20.7-47 HU) for chromophobe tumors (p = 0.06). Eight clear cell RCCs had attenuation similar to that of water (15.7 ± 2.4 HU; range, 11-18.7 HU). There was no significant difference in calcification or margin among different types of tumors (p = 0.91 and p = 0.55, respectively). Chromophobe tumors were more likely to be homogeneous (p < 0.001). Interobserver agreement was moderate to very good (κ = 0.91 for calcification, κ = 0.55 for margin, and κ = 0.44 for heterogeneity). All eight clear cell RCCs with attenuation similar to that of water were considered heterogeneous by both readers. Irregular margins were identified in three of these eight tumors by reader 1 and four of eight tumors by reader 2. CONCLUSION: A minority of solid RCCs have attenuation similar to that of water on unenhanced CT. In this study, all such tumors were of the clear cell subtype and qualitatively heterogeneous, suggesting they can be distinguished from simple cysts on unenhanced CT.

Podocyte-specific overexpression of human angiotensin-converting enzyme 2 attenuates diabetic nephropathy in mice.

Angiotensin-converting enzyme 2 (ACE2) degrades angiotensin II to angiotensin-(1-7) and is expressed in podocytes. Here we overexpressed ACE2 in podocytes in experimental diabetic nephropathy using transgenic methods where a nephrin promoter drove the expression of human ACE2. Glomeruli from these mice had significantly increased mRNA, protein, and activity of ACE2 compared to wild-type mice. Male mice were treated with streptozotocin to induce diabetes. After 16 weeks, there was no significant difference in plasma glucose levels between wild-type and transgenic diabetic mice. Urinary albumin was significantly increased in wild-type diabetic mice at 4 weeks, whereas albuminuria in transgenic diabetic mice did not differ from wild-type nondiabetic mice. However, this effect was transient and by 16 weeks both transgenic and nontransgenic diabetic mice had similar rates of proteinuria. Compared to wild-type diabetic mice, transgenic diabetic mice had an attenuated increase in mesangial area, decreased glomerular area, and a blunted decrease in nephrin expression. Podocyte numbers decreased in wild-type diabetic mice at 16 weeks, but were unaffected in transgenic diabetic mice. At 8 weeks, kidney cortical expression of transforming growth factor-ß1 was significantly inhibited in transgenic diabetic mice as compared to wild-type diabetic mice. Thus, the podocyte-specific overexpression of human ACE2 transiently attenuates the development of diabetic nephropathy.

Effect of ACE2 and angiotensin-(1-7) in a mouse model of early chronic kidney disease.

Angiotensin-converting enzyme 2 (ACE2) is expressed at high levels in the kidney and converts angiotensin II (ANG II) to ANG-(1-7). We studied the effects of ACE2 inhibition and ANG-(1-7) in the (5/6) nephrectomy ((5/6) Nx) mouse model of chronic kidney disease (CKD). Male FVB mice underwent sham surgery (Sham) or (5/6) Nx and were administered either vehicle, the ACE2 inhibitor MLN-4760 (MLN), the AT(1) receptor antagonist losartan, MLN plus losartan, or ANG-(1-7) for 4 wk. In (5/6) Nx mice with or without MLN, kidney cortical ACE2 protein expression was significantly decreased at 4 wk, compared with Sham. Inhibition of ACE2 caused a decrease in renal cortical ACE2 activity. Kidney cortical ACE expression and activity did not differ between groups of mice. In (5/6) Nx mice treated with MLN, kidney levels of ANG II were significantly increased, compared with Sham. (5/6) Nx induced a mild but insignificant increase in blood pressure (BP), a 50% reduction in FITC-inulin clearance, and a significant increase in urinary albumin excretion. ACE2 inhibition in (5/6) Nx mice did not affect BP or FITC-inulin clearance but significantly increased albuminuria compared with (5/6) Nx alone, an effect reversed by losartan. Treatment of (5/6) Nx mice with ANG-(1-7) increased kidney and plasma levels of ANG-(1-7) but did not alter BP, FITC-inulin clearance, or urinary albumin excretion, and it increased relative mesangial area. These data indicate that kidney ACE2 is downregulated in the early period after (5/6) Nx. Inhibition of ACE2 in (5/6) Nx mice increases albuminuria via an AT(1) receptor-dependent mechanism, independent of BP. In contrast, ANG-(1-7) does not affect albuminuria after (5/6) Nx. We propose that endogenous ACE2 is renoprotective in CKD.

Angiotensin-(1-7) and its effects in the kidney.

Angiotensin-(1-7) (Ang-[1-7]) is a heptapeptide member of the renin-angiotensin system (RAS), and acts as a vasodilator and antagonist of angiotensin II (Ang II) in the vasculature. The role of Ang-(1-7) in regulating kidney function is not well understood. Within the kidneys, Ang-(1-7) is generated by angiotensin-converting enzyme 2 (ACE2)-mediated degradation of Ang II, sequential cleavage of the precursor angiotensin I (Ang I) by ACE2 and ACE, or the actions of brush-border membrane peptidases on Ang I. Ang-(1-7) mediates its effects via binding to kidney Mas receptors, although some actions may occur via Ang II AT1 or AT2 receptors. In vitro studies suggest that Ang-(1-7) is an intrarenal vasodilator. Ang-(1-7) has been reported to induce either natriuresis/diuresis or sodium and water retention, via modulation of sodium transporters in the proximal tubule and loop of Henle, and collecting duct water transport. In the proximal tubule, Ang-(1-7) antagonizes growth-promoting signaling pathways via activation of a protein tyrosine phosphatase, whereas in mesangial cells, Ang-(1-7) stimulates cell growth via activation of mitogen-activated protein kinases. The phenotype of the Mas gene knockout mouse suggests that Ang-(1-7)-signaling events exert cardiovascular protection by regulating blood pressure, and by limiting production of reactive oxygen species and extracellular matrix proteins. Ang-(1-7) also protects against renal injury in the renal wrap hypertension model, independent of effects on blood pressure. In diabetic nephropathy, however, the role of Ang-(1-7) on disease progression remains unclear. In summary, Ang-(1-7) and its receptor Mas have emerged as important components of the intrarenal RAS. The signaling and downstream effects of Ang-(1-7) in the kidney are complex and appear to be cell specific. The body of evidence suggests that Ang-(1-7) is protective against endothelial dysfunction or Ang II-stimulated proximal tubular injury, although the overall effects on glomerular function require further study.