Resistant hypertension is associated with higher rates of cardiovascular disease, kidney disease, and death than primary hypertension. Although clinical practice guidelines recommend screening for ...primary aldosteronism among persons with resistant hypertension, rates of screening are unknown. We identified 145 670 persons with hypertension and excluded persons with congestive heart failure or advanced chronic kidney disease. Among this cohort, we studied 4660 persons ages 18 to <90 from the years 2008 to 2014 with resistant hypertension and available laboratory tests within the following 24 months. The screening rate for primary aldosteronism in persons with resistant hypertension was 2.1%. Screened persons were younger (55.9±13.3 versus 65.5±11.6 years;
<0.0001) and had higher systolic (145.1±24.3 versus 139.6±20.5 mm Hg;
=0.04) and diastolic blood pressure (81.8±13.6 versus 74.4±13.8 mm Hg;
<0.0001), lower rates of coronary artery disease (5.2% versus 14.2%;
=0.01), and lower serum potassium concentrations (3.9±0.6 versus 4.1±0.5 mmol/L;
=0.04) than unscreened persons. Screened persons had significantly higher rates of prescription for calcium channel blockers, mixed α/β-adrenergic receptor antagonists, sympatholytics, and vasodilators, and lower rates of prescription for loop, thiazide, and thiazide-type diuretics. The prescription of mineralocorticoid receptor antagonists or other potassium-sparing diuretics was not significantly different between groups (
=0.20). In conclusion, only 2.1% of eligible persons received a screening test within 2 years of meeting criteria for resistant hypertension. Low rates of screening were not due to the prescription of antihypertensive medications that may potentially interfere with interpretation of the screening test. Efforts to highlight guideline-recommended screening and targeted therapy are warranted.
Androgen receptor (AR) is expressed in normal murine and human kidneys of both genders, but its physiologic role is uncertain. Several studies showed loss of AR in renal cell carcinoma (RCC) in ...conjunction with increasing clinical stage and pathological grade, but others found that higher AR expression correlated with worse outcomes. Limited functional studies with renal cell lines suggested tumor-promoting activity of AR. In this study, we queried transcriptomic, proteomic, epigenetic and survival data from The Cancer Genome Atlas (TCGA) to evaluate AR expression and its association with overall survival in three subtypes of RCC (clear cell ccRCC, papillary pRCC, and chromophobe chRCC). We found that although there was no significant difference in AR mRNA expression in ccRCC of males vs. females, AR protein expression in ccRCC was significantly higher in male compared to female patients. More importantly, higher expression of AR at both transcript and protein levels was associated with improved overall survival in both genders with ccRCC, but did not predict survival of either gender with pRCC or chRCC. Genes whose transcript levels were associated with AR mRNA levels significantly overlapped between ccRCC and pRCC, but not with chRCC, suggesting a similar transcriptional program mediated by AR in ccRCC and pRCC. Ingenuity pathway analysis also identified overlapping pathways and upstream regulators enriched in AR-associated genes in ccRCC and pRCC. Hypermethylation of CpG sites located in the promoter and first exon of AR was associated with loss of AR expression and poor overall survival. Our findings support a tumor suppressor role for AR in both genders that might be exploited to decrease the incidence or progression of ccRCC.
Primary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism.
To evaluate testing ...rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension.
Retrospective cohort study.
U.S. Veterans Health Administration.
Veterans with apparent treatment-resistant hypertension (
= 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes.
Rates of primary aldosteronism testing (plasma aldosterone-renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP.
4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio HR, 2.05 95% CI, 1.66 to 2.52) or an endocrinologist (HR, 2.48 CI, 1.69 to 3.63) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 CI, 3.68 to 4.55) and with better BP control over time.
Predominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism.
In a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension.
National Institutes of Health.
Multiparametric magnetic resonance imaging (mpMRI) interpreted by experts is a powerful tool for diagnosing prostate cancer. However, the generalizability of published results across radiologists of ...varying expertise has not been verified.
To assess variability in mpMRI reporting and diagnostic accuracy across radiologists of varying experience in routine clinical care.
Men who underwent mpMRI and MR-fusion biopsy between 2014–2016. Each MRI scan was read by one of nine radiologists using the Prostate Imaging Reporting and Data System (PIRADS) and was not re-read before biopsy. Biopsy histopathology was the reference standard.
Outcomes were the PIRADS score distribution and diagnostic accuracy across nine radiologists. We evaluated the association between age, prostate-specific antigen, PIRADS score, and radiologist in predicting clinically significant cancer (Gleason ≥7) using multivariable logistic regression. We conducted sensitivity analyses for case volume and changes in accuracy over time.
We analyzed data for 409 subjects with 503 MRI lesions. While the number of lesions (mean 1.2 lesions/patient) did not differ across radiologists, substantial variation existed in PIRADS distribution and cancer yield. The significant cancer detection rate was 3–27% for PIRADS 3 lesions, 23–65% for PIRADS 4, and 40–80% for PIRADS 5 across radiologists. Some 13–60% of men with a PIRADS score of <3 on MRI harbored clinically significant cancer. The area under the receiver operating characteristic curve varied from 0.69 to 0.81 for detection of clinically significant cancer. PIRADS score (p<0.0001) and radiologist (p=0.042) were independently associated with cancer in multivariable analysis. Neither individual radiologist volume nor study period impacted the results. MRI scans were not retrospectively re-read by all radiologists, precluding measurement of inter-observer agreement.
We observed considerable variability in PIRADS score assignment and significant cancer yield across radiologists. We advise internal evaluation of mpMRI accuracy before widespread adoption.
We evaluated the interpretation of multiparametric magnetic resonance imaging of the prostate in routine clinical care. Diagnostic accuracy depends on the Prostate Imaging Reporting and Data System score and the radiologist.
In our study, the diagnostic accuracy of multiparametric magnetic resonance imaging (MRI) varied significantly across radiologists. We recommend internal evaluation of results before widespread adoption of MRI at individual medical centers.
Abstract Exposure to ambient air pollution has significant adverse health effects; however, whether air pollution is associated with urological cancer is largely unknown. We conduct a systematic ...review and meta-analysis with epidemiological studies, showing that a 5 μg/m 3 increase in PM 2.5 exposure is associated with a 6%, 7%, and 9%, increased risk of overall urological, bladder, and kidney cancer, respectively; and a 10 μg/m 3 increase in NO 2 is linked to a 3%, 4%, and 4% higher risk of overall urological, bladder, and prostate cancer, respectively. Were these associations to reflect causal relationships, lowering PM 2.5 levels to 5.8 μg/m 3 could reduce the age-standardized rate of urological cancer by 1.5 ~ 27/100,000 across the 15 countries with the highest PM 2.5 level from the top 30 countries with the highest urological cancer burden. Implementing global health policies that can improve air quality could potentially reduce the risk of urologic cancer and alleviate its burden.
Abstract Background External shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PNL) have been the standard of care for the treatment of intrarenal calculi. Objective We sought to ...determine the safety and efficacy of flexible ureteroscopy and holmium laser lithotripsy for the treatment of multiple intrarenal calculi and further stratify the efficacy by stone burden less than and greater than 20 mm. Design, setting, and participants Patients with multiple unilateral renal calculi treated between 2000 and 2006 at a single tertiary academic center were retrospectively evaluated. Intervention All patients underwent retrograde flexible ureteroscopy and holmium laser lithotripsy. Measurements Stone-free status was determined by ureteroscopy 15 d after the last procedure and was defined as the absence of stones in the kidney or residual fragments <1 mm. A renal ultrasound was performed 30 d after the last treatment to confirm the absence of stones and hydronephrosis. Results and Limitations Fifty-one patients were identified for a total of 161 intrarenal calculi with a mean stone size per patient of 6.6 ± 3 mm (range: 2–15). The mean number of stones per patient was 3.1 ± 1 (range: 2–6). The mean number of primary procedures was 1.4 ± 0.6 (range: 1–3). The overall stone-free rates after one and two procedures were 64.7% and 92.2%, respectively. The stone-free rates for patients with a stone burden greater than and less than 20 mm were 85.1% and 100%, respectively. The overall complication rate was 13.6%; 97.6% of cases were performed as outpatient procedures. There are some limitations to this study, however: This is a retrospective review from a single institution, and our results are based on a relatively small sample size. Conclusions For select patients with multiple intrarenal calculi, flexible ureteroscopy with holmium laser lithotripsy may represent an alternative therapy to ESWL or PNL, with acceptable efficacy and low morbidity.
PDF
