Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort.

Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m2), CKD stages 1-2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.

Urinary epidermal growth factor/monocyte chemotactic peptide 1 ratio as non-invasive predictor of Mayo clinic imaging classes in autosomal dominant polycystic kidney disease.

BACKGROUND: Age- and height-adjusted total kidney volume is currently considered the best prognosticator in patients with autosomal dominant polycystic kidney disease. We tested the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for the prediction of the Mayo Clinic Imaging Classes. METHODS: Urinary epidermal growth factor and monocyte chemotactic peptide 1 levels were measured in two independent cohorts (discovery, n = 74 and validation set, n = 177) and healthy controls (n = 59) by immunological assay. Magnetic resonance imaging parameters were used for total kidney volume calculation and the Mayo Clinic Imaging Classification defined slow (1A-1B) and fast progressors (1C-1E). Microarray and quantitative gene expression analysis were used to test epidermal growth factor and monocyte chemotactic peptide 1 gene expression. RESULTS: Baseline ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 correlated with total kidney volume adjusted for height (r = - 0.6, p < 0.001), estimated glomerular filtration rate (r = 0.69 p < 0.001), discriminated between Mayo Clinic Imaging Classes (p < 0.001), and predicted the variation of estimated glomerular filtration rate at 10 years (r = - 0.51, p < 0.001). Conditional Inference Trees identified cut-off levels of the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for slow and fast progressors at > 132 (100% slow) and < 25.76 (89% and 86% fast, according to age), with 94% sensitivity and 66% specificity (p = 6.51E-16). Further, the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 at baseline showed a positive correlation (p = 0.006, r = 0.36) with renal outcome (delta-estimated glomerular filtration rate per year, over a mean follow-up of 4.2 ± 1.2 years). Changes in the urinary epidermal growth factor and monocyte chemotactic peptide 1 were mirrored by gene expression levels in both human kidney cysts (epidermal growth factor: - 5.6-fold, fdr = 0.001; monocyte chemotactic peptide 1: 3.1-fold, fdr = 0.03) and Pkd1 knock-out mouse kidney (Egf: - 14.8-fold, fdr = 2.37E-20, Mcp1: 2.8-fold, fdr = 6.82E-15). CONCLUSION: The ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 is a non-invasive pathophysiological biomarker that can be used for clinical risk stratification in autosomal dominant polycystic kidney disease.

Total Kidney Volume Measurements in ADPKD by 3D and Ellipsoid Ultrasound in Comparison with Magnetic Resonance Imaging.

BACKGROUND AND OBJECTIVES: Total kidney volume is a validated prognostic biomarker for autosomal dominant polycystic kidney disease. Total kidney volume by magnetic resonance imaging (MRI) and manual segmentation is considered the "reference standard," but it is time consuming and not readily accessible. By contrast, three-dimensional (3D) ultrasound provides a promising technology for total kidney volume measurements with unknown potential. Here, we report a comparative study of total kidney volume measurements by 3D ultrasound versus the conventional methods by ultrasound ellipsoid and MRI ellipsoid. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This single-center prospective study included 142 patients who completed a standardized 3D ultrasound and MRI. Total kidney volumes by 3D ultrasound and ultrasound ellipsoid were compared with those by MRI. We assessed the agreement of total kidney volume measurements by Bland-Altman plots and misclassification of the Mayo Clinic imaging classes between the different imaging methods, and we assessed prediction of Mayo Clinic imaging classes 1C-1E by average ultrasound kidney length >16.5 cm. RESULTS: Compared with MRI manual segmentation, MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid underestimated total kidney volume (mean difference: -3%, -9%, and -11%, respectively), with Mayo Clinic imaging classes misclassified in 11%, 21%, and 22% of patients, respectively; most misclassified cases by MRI ellipsoid (11 of 16), 3D ultrasound (23 of 30), and ultrasound ellipsoid (26 of 31) were placed into a lower Mayo Clinic imaging class. Predictions of the high-risk Mayo Clinic imaging classes (1C-1E) by MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid all yielded high positive predictive value (96%, 95%, and 98%, respectively) and specificity (96%, 96%, and 99%, respectively). However, both negative predictive value (90%, 88%, and 95%, respectively) and sensitivity (88%, 85%, and 94%, respectively) were lower for 3D ultrasound and ultrasound ellipsoid compared with MRI ellipsoid. An average ultrasound kidney length >16.5 cm was highly predictive of Mayo Clinic imaging classes 1C-1E only in patients aged ≤45 years. CONCLUSIONS: Total kidney volume measurements in autosomal dominant polycystic kidney disease by 3D ultrasound and ultrasound ellipsoid displayed similar bias and variability and are less accurate than MRI ellipsoid. Prediction of high-risk Mayo Clinic imaging classes (1C-1E) by all three methods provides high positive predictive value, but ultrasound ellipsoid is simpler to use and more readily available.

Quit smoking for life--social marketing strategy for youth: a case for Pakistan.

Smoking is the single most avoidable risk factor for cancers. Majority of smokers know about this fact but it is difficult for them to give it up mainly in the face of widespread smoking advertisements by the tobacco industries. To reduce the prevalence of smoking and its associated cancers, immediate actions are required by public health authorities. Social marketing is an effective strategy to promote healthy attitudes and influence people to make real, sustained health behavior change by transiting through different stages which include precontemplation, contemplation, preparation, action, and maintenance. Social marketing can influence smokers to voluntarily accept, reject, modify, or abandon their smoking behavior. In Pakistan, the smoking prevalence has been increasing, necessitating effective measures. The trend of its usage has been going upwards and, according to the World Health Organization, in Pakistan, the usage of cigarette smoking is increased by 30% compared to 1998 figures. The Pakistan Pediatrics Association has estimated 1,000 to 1,200 school-going children between the ages of 6 and 16 years take up smoking every day. In Pakistan, ex-smokers in the low socioeconomic group reported spending 25% of the total household income on this habit. This paper focuses on the antismoking social marketing strategy in Pakistan with an aim to reduce smoking prevalence, especially among the youth.