99 Greater Effect on Total Kidney Volume (TKV) With Tolvaptan (TOL) Despite Placebo (PBO)-treated Subjects Reaching Similar Spot Urine Osmolality 3(Uosm) Potentially Due to Increased Water Consumption in ADPKD: Post-hoc Analysis of TEMPO 3:4

2021 ◽  
Vol 77 (4) ◽  
pp. 597-598
Author(s):  
Satoru Muto ◽  
Tadashi Okada ◽  
Yoshiyuki Shibasaki ◽  
Tatsuki Ibuki ◽  
Shigeo Horie

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is a progressive condition that eventually leads to end-stage renal disease. A phase 3 trial of tolvaptan (TEMPO 3:4; NCT00428948) and its open-label extension (TEMPO Extension Japan: TEMPO-EXTJ; NCT01280721) were conducted in patients with ADPKD. In this post hoc analysis, effects on renal function and the safety profile of tolvaptan were assessed over a long-term period that included the 3-year TEMPO 3:4 and the approximately 3-year TEMPO-EXTJ trials. Methods Patients from Japanese trial sites who completed TEMPO 3:4 were offered participation in TEMPO-EXTJ. Patients whose efficacy parameters were measured at year 2 in TEMPO-EXTJ for efficacy evaluation were included. The annual slope of the estimated glomerular filtration rate (eGFR) and growth in total kidney volume (TKV) were analyzed. Results In patients who received tolvaptan in TEMPO 3:4 and TEMPO-EXTJ, the annual slope of eGFR (mL/min/1.73 m2) was − 3.480 in TEMPO 3:4 and − 3.417 in TEMPO-EXTJ, with no apparent effect of an approximately 3.6-month off-treatment interval between the two trials. In patients who received a placebo in TEMPO 3:4 before initiating tolvaptan in TEMPO-EXTJ, the slope of eGFR was significantly less steep from TEMPO 3:4 (− 4.287) to TEMPO-EXTJ (− 3.364), a difference of 0.923 (P = 0.0441). Conclusion The TEMPO-EXTJ trial supports a sustained beneficial effect of tolvaptan on eGFR. In patients who received a placebo in TEMPO 3:4, initiation of tolvaptan in TEMPO-EXTJ was associated with a significant slowing of eGFR decline.


2015 ◽  
Vol 41 (3) ◽  
pp. 248-256 ◽  
Author(s):  
Niek F. Casteleijn ◽  
Debbie Zittema ◽  
Stephan J.L. Bakker ◽  
Wendy E. Boertien ◽  
Carlo A. Gaillard ◽  
...  

Background: Vasopressin plays an essential role in osmoregulation, but has deleterious effects in patients with ADPKD. Increased water intake to suppress vasopressin activity has been suggested as a potential renoprotective strategy. This study investigated whether urine and plasma osmolality can be used as reflection of vasopressin activity in ADPKD patients. Methods: We measured urine and plasma osmolality, plasma copeptin concentration, total kidney volume (TKV, by MRI) and GFR (125I-iothalamate). In addition, change in estimated GFR (eGFR) during follow-up was assessed. Results: Ninety-four patients with ADPKD were included (56 males, age 40 ± 10, mGFR 77 ± 32 ml/min/1.73 m2, TKV 1.55 (0.99-2.40) l. Urine osmolality, plasma osmolality and copeptin concentration were 420 ± 195, 289 ± 7 mOsmol/l and 7.3 (3.2-14.6) pmol/l, respectively. Plasma osmolality was associated with copeptin concentration (R = 0.54, p < 0.001), whereas urine osmolality was not (p = 0.4). In addition, urine osmolality was not associated with TKV (p = 0.3), in contrast to plasma osmolality (R = 0.52, p < 0.001) and copeptin concentration (R = 0.61, p < 0.001). Fifty-five patients were followed for 2.8 ± 0.8 years. Baseline plasma and urine osmolality were not associated with change in eGFR (p = 0.6 and p = 0.3, respectively), whereas baseline copeptin concentration did show an association with change in eGFR, in a crude analysis (St. β = -0.41, p = 0.003) and also after adjustment for age, sex and TKV (St. β = -0.23, p = 0.05). Conclusions: These data suggest that neither urine nor plasma osmolality are valid measures to identify ADPKD patients that may benefit from increasing water intake. Copeptin appears a better alternative for this purpose.


2018 ◽  
Vol 24 ◽  
pp. 80-81
Author(s):  
Konstantinos Toulis ◽  
Krishna Gokhale ◽  
G. Neil Thomas ◽  
Wasim Hanif ◽  
Krishnarajah Nirantharakumar ◽  
...  

2018 ◽  
Vol 24 ◽  
pp. 51-52
Author(s):  
Vanita Aroda ◽  
Danny Sugimoto ◽  
David Trachtenbarg ◽  
Mark Warren ◽  
Gurudutt Nayak ◽  
...  

2004 ◽  
Vol 18 (1) ◽  
pp. 13-26 ◽  
Author(s):  
Antoinette R. Miller ◽  
J. Peter Rosenfeld

Abstract University students were screened using items from the Psychopathic Personality Inventory and divided into high (n = 13) and low (n = 11) Psychopathic Personality Trait (PPT) groups. The P300 component of the event-related potential (ERP) was recorded as each group completed a two-block autobiographical oddball task, responding honestly during the first (Phone) block, in which oddball items were participants' home phone numbers, and then feigning amnesia in response to approximately 50% of items in the second (Birthday) block in which oddball items were participants' birthdates. Bootstrapping of peak-to-peak amplitudes correctly identified 100% of low PPT and 92% of high PPT participants as having intact recognition. Both groups demonstrated malingering-related P300 amplitude reduction. For the first time, P300 amplitude and topography differences were observed between honest and deceptive responses to Birthday items. No main between-group P300 effects resulted. Post-hoc analysis revealed between-group differences in a frontally located post-P300 component. Honest responses were associated with late frontal amplitudes larger than deceptive responses at frontal sites in the low PPT group only.


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