Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy

Tolvaptan, an oral vasopressin V2 receptor antagonist, reduces renal volume expansion and loss of renal function in patients with autosomal dominant polycystic kidney disease (ADPKD). Data for predictive factors indicating patients more likely to benefit from long-term tolvaptan are lacking. Data were retrospectively collected from 55 patients on tolvaptan for 6 years. Changes in renal function, progression of renal dysfunction (estimated glomerular filtration rate [eGFR], 1-year change in eGFR [ΔeGFR/year]), and renal volume (total kidney volume [TKV], percentage 1-year change in TKV [ΔTKV%/year]) were evaluated at 3-years pre-tolvaptan, at baseline, and at 6 years. In 76.4% of patients, ΔeGFR/year improved at 6 years. The average 6-year ΔeGFR/year (range) minus baseline ΔeGFR/year: 3.024 (−8.77–20.58 mL/min/1.73 m2). The increase in TKV was reduced for the first 3 years. A higher BMI was associated with less of an improvement in ΔeGFR (p = 0.027), and family history was associated with more of an improvement in ΔeGFR (p = 0.044). Hypernatremia was generally mild; 3 patients had moderate-to-severe hyponatremia due to prolonged, excessive water intake in response to water diuresis—a side effect of tolvaptan. Family history of ADPKD and baseline BMI were contributing factors for ΔeGFR/year improvement on tolvaptan. Hyponatremia should be monitored with long-term tolvaptan administration

Telmisartan ameliorates fibrocystic liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease.

Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the treatment of fibrocystic liver disease in ARPKD patients

Feasibility of an Ultrasound-Based Method for Measuring Talar Displacement during the Anterior Drawer Stress Test Using a Telos Device : A Preliminary Study

This study was conducted to measured talar displacement using ultrasound during an anterior drawer test (ADT) with a Telos device. Five adults (3 men and 2 women; 8 ankles; mean age: 23.2 y) with a history of ankle sprain and eight adults (5 men and 3 women; 16 ankles; mean age: 22.1 y) without a history of ankle sprain were recruited into a history of ankle sprain (HAS) and a control group, respectively. Talar displacement was observed in response to load forces applied by a Telos device during the ultrasound stress imaging test. The ultrasound probe was placed 5 mm inside from the center of the Achilles tendon on the posterior ankle along the direction of the major axis. The inter-rater reliability for the present method was classified as good and excellent (ICC(2,2) = 0.858 and 0.957 at 120 N and 150 N, respectively) in the control group and excellent (ICC(2,2) = 0.940 and 0.905 at 120 N and 150 N, respectively) in the HAS group, according to specific intraclass correlation coefficient values. We found that talar displacement during the ADT was lower in the HAS group than in the control group. Analysis of the receiver operating characteristic curve revealed that the quantitative ultrasound-based ADT using a Telos device was superior to the X-ray-based test in detecting reduced ankle joint mobility during the ADT (area under the curve of 0.905 and 0.726 at a force of 150 N using ultrasound-based and X-ray-based tests, respectively). Further investigation is needed; nevertheless, this preliminary study suggests that the ultrasound-based quantitative ADT using a Telos device might detect talar displacement more sensitively than the conventional stress X-ray

Validation of Dietary Intake Estimated by Web-Based Dietary Assessment Methods and Usability Using Dietary Records or 24-h Dietary Recalls: A Scoping Review

The goal was to summarize studies comparing the accuracy of web-based dietary assessments with those of conventional face-to-face or paper-based assessments using 24-h dietary recall or dietary record methods in the general population. Using two databases, mean differences and correlation coefficients (CCs) for intakes of energy, macronutrients, sodium, vegetables, and fruits were extracted from each study independently by the authors. We also collected information regarding usability from articles reporting this. From 17 articles included in this review, the mean dietary intake differences in the web-based dietary assessment compared to conventional methods, were −11.5–16.1% for energy, −12.1–14.9% for protein, −16.7–17.6% for fat, −10.8–8.0% for carbohydrates, −11.2–9.6% for sodium, −27.4–3.9% for vegetables, and −5.1–47.6% for fruits. The CC was 0.17–0.88 for energy, protein, fat, carbohydrates, and sodium, and 0.23–0.85 for vegetables and fruits. In three out of four studies reporting usability, more than half of the participants preferred the web-based dietary assessment. In conclusion, % difference and CC of dietary intake were acceptable in both web-based dietary records and 24-h dietary recalls. The findings from this review highlight the possibility of wide-spread application of the web-based dietary assessment in the future

Effect of meniscus repair on pivot-shift during anterior cruciate ligament reconstruction: Objective evaluation using triaxial accelerometer

Background: Some types of meniscus tear, especially lateral meniscus tear, have been reported to be associated with rotatory knee laxity. However, precise information regarding the effect of meniscus repair on rotatory laxity is limited. The purpose of this study was to investigate the effects of lateral and medial meniscus repair on rotatory laxity in anterior cruciate ligament (ACL) injured knees. Methods: Forty-one patients who underwent ACL reconstruction were included in the study. The tibial acceleration during the pivot shift test was measured using a triaxial accelerometer preoperatively under anesthesia and intraoperatively before and after medial and lateral meniscus repair and ACL reconstruction during surgery. Effects of meniscus tear and its repair on rotatory laxity were analyzed. Results: Preoperative measurements revealed that patients with lateral meniscus tear showed significantly higher tibial acceleration compared to the patients without meniscus tear (P = 0.006). Intraoperative measurements revealed that medial and lateral meniscus repair significantly reduced tibial acceleration by 1.46 m/s2 (P = 0.002) and 1.91 m/s2 (P < 0.001), respectively. Conclusion: In ACL injured knees, knees with lateral meniscus tear showed greater rotatory laxity compared to the knees without meniscus tear. In addition, lateral meniscus repair, and to a lesser degree medial meniscus repair, reduced rotatory laxity during ACL reconstruction surgery. Therefore, the meniscus should be repaired as much as possible for its role as a secondary stabilizer of rotatory laxity. Besides, the effect of meniscus repair on rotatory laxity should be considered when the indication of anterolateral augmentation is determined