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Frank S Czerwiec - One of the best experts on this subject based on the ideXlab platform.
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tolvaptan and Kidney Pain in patients with autosomal dominant polycystic Kidney disease secondary analysis from a randomized controlled trial
American Journal of Kidney Diseases, 2017Co-Authors: Niek F Casteleijn, Jaime D Blais, Arlene B Chapman, Frank S Czerwiec, Olivier Devuyst, Eiji Higashihara, Anna M Leliveld, John Ouyang, Ronald D Perrone, Vicente E TorresAbstract:Background Kidney Pain is a common complication in patients with autosomal dominant polycystic Kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on Kidney Pain in this patient group. Because Pain is difficult to measure, the incidence of Kidney Pain leading to objective medical interventions was used in the present study to assess Pain. Study Design Secondary analysis from a randomized controlled trial. Setting & Participants Patients with ADPKD with preserved Kidney function. Intervention Tolvaptan or placebo. Outcomes Kidney Pain events defined by objective medical interventions. Measurements Kidney Pain events were recorded and independently adjudicated. Incidence of a first Kidney Pain event was assessed overall and categorized into 5 subgroups according to severity. Results Of 1,445 participating patients (48.4% women; mean age, 39±7 [SD] years; mean estimated glomerular filtration rate, 81±22mL/min/1.73m 2 ; median total Kidney volume, 1,692 [IQR, 750-7,555] mL), 50.9% reported a history of Kidney Pain at baseline. History of urinary tract infections, Kidney stones, or hematuria (all P P P P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, Kidney stones, and hematuria when compared to placebo. Limitations Trial has specific inclusion criteria for total Kidney volume and Kidney function. Conclusions Tolvaptan decreased the incidence of Kidney Pain events independent of patient characteristics predisposing for Kidney Pain and possibly in part due to reductions in ADPKD-related complications.
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effect of tolvaptan in autosomal dominant polycystic Kidney disease by ckd stage results from the tempo 3 4 trial
Clinical Journal of The American Society of Nephrology, 2016Co-Authors: Vicente E Torres, Jaime D Blais, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Frank S CzerwiecAbstract:Background and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of Kidney growth and eGFR decline in autosomal dominant polycystic Kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline. Design, setting, participants, & measurements In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18–50 years), with total Kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney function decline. Results Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P P =0.17) and eGFR decline by 0.40 in CKD1 ( P =0.23), 1.13 in CKD2 ( P 2 per year in CKD3 ( P P =0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70–0.98; P =0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57–0.89; P =0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85–1.21; P =0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1–3 occurred more frequently than in placebo recipients. Conclusions This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1–3.
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tolvaptan in patients with autosomal dominant polycystic Kidney disease
The New England Journal of Medicine, 2012Co-Authors: Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Holly B Krasa, Frank S CzerwiecAbstract:In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total Kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V 2 -receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total Kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney-function decline. RESULTS Over a 3-year period, the increase in total Kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-up-years, P = 0.01), with lower rates of worsening Kidney function (2 vs. 5 events per 100 person-years of followup, P<0.001) and Kidney Pain (5 vs. 7 events per 100 person-years of follow-up, P = 0.007). Tolvaptan was associated with a slower decline in Kidney function (reciprocal of the serum creatinine level, −2.61 [mg per milliliter] −1 per year vs. −3.81 [mg per milliliter] −1 per year; P<0.001). There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (excretion of electrolyte-free water) and hepatic adverse events unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14% in the placebo group). CONCLUSIONS Tolvaptan, as compared with placebo, slowed the increase in total Kidney volume and the decline in Kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.)
Vicente E Torres - One of the best experts on this subject based on the ideXlab platform.
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tolvaptan and Kidney Pain in patients with autosomal dominant polycystic Kidney disease secondary analysis from a randomized controlled trial
American Journal of Kidney Diseases, 2017Co-Authors: Niek F Casteleijn, Jaime D Blais, Arlene B Chapman, Frank S Czerwiec, Olivier Devuyst, Eiji Higashihara, Anna M Leliveld, John Ouyang, Ronald D Perrone, Vicente E TorresAbstract:Background Kidney Pain is a common complication in patients with autosomal dominant polycystic Kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on Kidney Pain in this patient group. Because Pain is difficult to measure, the incidence of Kidney Pain leading to objective medical interventions was used in the present study to assess Pain. Study Design Secondary analysis from a randomized controlled trial. Setting & Participants Patients with ADPKD with preserved Kidney function. Intervention Tolvaptan or placebo. Outcomes Kidney Pain events defined by objective medical interventions. Measurements Kidney Pain events were recorded and independently adjudicated. Incidence of a first Kidney Pain event was assessed overall and categorized into 5 subgroups according to severity. Results Of 1,445 participating patients (48.4% women; mean age, 39±7 [SD] years; mean estimated glomerular filtration rate, 81±22mL/min/1.73m 2 ; median total Kidney volume, 1,692 [IQR, 750-7,555] mL), 50.9% reported a history of Kidney Pain at baseline. History of urinary tract infections, Kidney stones, or hematuria (all P P P P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, Kidney stones, and hematuria when compared to placebo. Limitations Trial has specific inclusion criteria for total Kidney volume and Kidney function. Conclusions Tolvaptan decreased the incidence of Kidney Pain events independent of patient characteristics predisposing for Kidney Pain and possibly in part due to reductions in ADPKD-related complications.
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effect of tolvaptan in autosomal dominant polycystic Kidney disease by ckd stage results from the tempo 3 4 trial
Clinical Journal of The American Society of Nephrology, 2016Co-Authors: Vicente E Torres, Jaime D Blais, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Frank S CzerwiecAbstract:Background and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of Kidney growth and eGFR decline in autosomal dominant polycystic Kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline. Design, setting, participants, & measurements In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18–50 years), with total Kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney function decline. Results Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P P =0.17) and eGFR decline by 0.40 in CKD1 ( P =0.23), 1.13 in CKD2 ( P 2 per year in CKD3 ( P P =0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70–0.98; P =0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57–0.89; P =0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85–1.21; P =0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1–3 occurred more frequently than in placebo recipients. Conclusions This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1–3.
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tolvaptan in patients with autosomal dominant polycystic Kidney disease
The New England Journal of Medicine, 2012Co-Authors: Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Holly B Krasa, Frank S CzerwiecAbstract:In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total Kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V 2 -receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total Kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney-function decline. RESULTS Over a 3-year period, the increase in total Kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-up-years, P = 0.01), with lower rates of worsening Kidney function (2 vs. 5 events per 100 person-years of followup, P<0.001) and Kidney Pain (5 vs. 7 events per 100 person-years of follow-up, P = 0.007). Tolvaptan was associated with a slower decline in Kidney function (reciprocal of the serum creatinine level, −2.61 [mg per milliliter] −1 per year vs. −3.81 [mg per milliliter] −1 per year; P<0.001). There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (excretion of electrolyte-free water) and hepatic adverse events unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14% in the placebo group). CONCLUSIONS Tolvaptan, as compared with placebo, slowed the increase in total Kidney volume and the decline in Kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.)
Ron T Gansevoort - One of the best experts on this subject based on the ideXlab platform.
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effect of tolvaptan in autosomal dominant polycystic Kidney disease by ckd stage results from the tempo 3 4 trial
Clinical Journal of The American Society of Nephrology, 2016Co-Authors: Vicente E Torres, Jaime D Blais, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Frank S CzerwiecAbstract:Background and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of Kidney growth and eGFR decline in autosomal dominant polycystic Kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline. Design, setting, participants, & measurements In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18–50 years), with total Kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney function decline. Results Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P P =0.17) and eGFR decline by 0.40 in CKD1 ( P =0.23), 1.13 in CKD2 ( P 2 per year in CKD3 ( P P =0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70–0.98; P =0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57–0.89; P =0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85–1.21; P =0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1–3 occurred more frequently than in placebo recipients. Conclusions This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1–3.
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chronic Kidney Pain in autosomal dominant polycystic Kidney disease a case report of successful treatment by catheter based renal denervation
American Journal of Kidney Diseases, 2014Co-Authors: Niek F Casteleijn, Rosa L De Jager, Peer M Neeleman, Peter J Blankestijn, Ron T GansevoortAbstract:Chronic Pain is a common concern in patients with autosomal dominant polycystic Kidney disease (ADPKD). We report what to our knowledge is the first catheter-based renal denervation procedure in a patient with ADPKD resulting in successful management of chronic Pain. The patient was a 43-year-old woman whose chronic Pain could not be controlled by Pain medication or splanchnic nerve blockade. Transluminal radiofrequency renal denervation was performed as an experimental therapeutic option with an excellent result, indicating that this procedure should be considered for chronic Pain management in ADPKD.
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tolvaptan in patients with autosomal dominant polycystic Kidney disease
The New England Journal of Medicine, 2012Co-Authors: Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Holly B Krasa, Frank S CzerwiecAbstract:In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total Kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V 2 -receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total Kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney-function decline. RESULTS Over a 3-year period, the increase in total Kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-up-years, P = 0.01), with lower rates of worsening Kidney function (2 vs. 5 events per 100 person-years of followup, P<0.001) and Kidney Pain (5 vs. 7 events per 100 person-years of follow-up, P = 0.007). Tolvaptan was associated with a slower decline in Kidney function (reciprocal of the serum creatinine level, −2.61 [mg per milliliter] −1 per year vs. −3.81 [mg per milliliter] −1 per year; P<0.001). There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (excretion of electrolyte-free water) and hepatic adverse events unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14% in the placebo group). CONCLUSIONS Tolvaptan, as compared with placebo, slowed the increase in total Kidney volume and the decline in Kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.)
Ronald D Perrone - One of the best experts on this subject based on the ideXlab platform.
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tolvaptan and Kidney Pain in patients with autosomal dominant polycystic Kidney disease secondary analysis from a randomized controlled trial
American Journal of Kidney Diseases, 2017Co-Authors: Niek F Casteleijn, Jaime D Blais, Arlene B Chapman, Frank S Czerwiec, Olivier Devuyst, Eiji Higashihara, Anna M Leliveld, John Ouyang, Ronald D Perrone, Vicente E TorresAbstract:Background Kidney Pain is a common complication in patients with autosomal dominant polycystic Kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on Kidney Pain in this patient group. Because Pain is difficult to measure, the incidence of Kidney Pain leading to objective medical interventions was used in the present study to assess Pain. Study Design Secondary analysis from a randomized controlled trial. Setting & Participants Patients with ADPKD with preserved Kidney function. Intervention Tolvaptan or placebo. Outcomes Kidney Pain events defined by objective medical interventions. Measurements Kidney Pain events were recorded and independently adjudicated. Incidence of a first Kidney Pain event was assessed overall and categorized into 5 subgroups according to severity. Results Of 1,445 participating patients (48.4% women; mean age, 39±7 [SD] years; mean estimated glomerular filtration rate, 81±22mL/min/1.73m 2 ; median total Kidney volume, 1,692 [IQR, 750-7,555] mL), 50.9% reported a history of Kidney Pain at baseline. History of urinary tract infections, Kidney stones, or hematuria (all P P P P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, Kidney stones, and hematuria when compared to placebo. Limitations Trial has specific inclusion criteria for total Kidney volume and Kidney function. Conclusions Tolvaptan decreased the incidence of Kidney Pain events independent of patient characteristics predisposing for Kidney Pain and possibly in part due to reductions in ADPKD-related complications.
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effect of tolvaptan in autosomal dominant polycystic Kidney disease by ckd stage results from the tempo 3 4 trial
Clinical Journal of The American Society of Nephrology, 2016Co-Authors: Vicente E Torres, Jaime D Blais, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Frank S CzerwiecAbstract:Background and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of Kidney growth and eGFR decline in autosomal dominant polycystic Kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline. Design, setting, participants, & measurements In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18–50 years), with total Kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney function decline. Results Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P P =0.17) and eGFR decline by 0.40 in CKD1 ( P =0.23), 1.13 in CKD2 ( P 2 per year in CKD3 ( P P =0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70–0.98; P =0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57–0.89; P =0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85–1.21; P =0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1–3 occurred more frequently than in placebo recipients. Conclusions This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1–3.
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tolvaptan in patients with autosomal dominant polycystic Kidney disease
The New England Journal of Medicine, 2012Co-Authors: Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Holly B Krasa, Frank S CzerwiecAbstract:In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total Kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V 2 -receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total Kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney-function decline. RESULTS Over a 3-year period, the increase in total Kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-up-years, P = 0.01), with lower rates of worsening Kidney function (2 vs. 5 events per 100 person-years of followup, P<0.001) and Kidney Pain (5 vs. 7 events per 100 person-years of follow-up, P = 0.007). Tolvaptan was associated with a slower decline in Kidney function (reciprocal of the serum creatinine level, −2.61 [mg per milliliter] −1 per year vs. −3.81 [mg per milliliter] −1 per year; P<0.001). There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (excretion of electrolyte-free water) and hepatic adverse events unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14% in the placebo group). CONCLUSIONS Tolvaptan, as compared with placebo, slowed the increase in total Kidney volume and the decline in Kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.)
John Ouyang - One of the best experts on this subject based on the ideXlab platform.
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tolvaptan and Kidney Pain in patients with autosomal dominant polycystic Kidney disease secondary analysis from a randomized controlled trial
American Journal of Kidney Diseases, 2017Co-Authors: Niek F Casteleijn, Jaime D Blais, Arlene B Chapman, Frank S Czerwiec, Olivier Devuyst, Eiji Higashihara, Anna M Leliveld, John Ouyang, Ronald D Perrone, Vicente E TorresAbstract:Background Kidney Pain is a common complication in patients with autosomal dominant polycystic Kidney disease (ADPKD), and data from the TEMPO 3:4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on Kidney Pain in this patient group. Because Pain is difficult to measure, the incidence of Kidney Pain leading to objective medical interventions was used in the present study to assess Pain. Study Design Secondary analysis from a randomized controlled trial. Setting & Participants Patients with ADPKD with preserved Kidney function. Intervention Tolvaptan or placebo. Outcomes Kidney Pain events defined by objective medical interventions. Measurements Kidney Pain events were recorded and independently adjudicated. Incidence of a first Kidney Pain event was assessed overall and categorized into 5 subgroups according to severity. Results Of 1,445 participating patients (48.4% women; mean age, 39±7 [SD] years; mean estimated glomerular filtration rate, 81±22mL/min/1.73m 2 ; median total Kidney volume, 1,692 [IQR, 750-7,555] mL), 50.9% reported a history of Kidney Pain at baseline. History of urinary tract infections, Kidney stones, or hematuria (all P P P P for interaction > 0.05). The effect of tolvaptan was explained at least in part by a decrease in incidence of urinary tract infections, Kidney stones, and hematuria when compared to placebo. Limitations Trial has specific inclusion criteria for total Kidney volume and Kidney function. Conclusions Tolvaptan decreased the incidence of Kidney Pain events independent of patient characteristics predisposing for Kidney Pain and possibly in part due to reductions in ADPKD-related complications.
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effect of tolvaptan in autosomal dominant polycystic Kidney disease by ckd stage results from the tempo 3 4 trial
Clinical Journal of The American Society of Nephrology, 2016Co-Authors: Vicente E Torres, Jaime D Blais, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Frank S CzerwiecAbstract:Background and objectives The Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 study demonstrated a significant beneficial effect of the vasopressin V2 receptor antagonist tolvaptan on rates of Kidney growth and eGFR decline in autosomal dominant polycystic Kidney disease (ADPKD). This post hoc analysis was performed to reassess the primary and secondary efficacy endpoints by CKD stage at baseline. Design, setting, participants, & measurements In a phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, 1445 patients with ADPKD (age 18–50 years), with total Kidney volume (TKV) ≥750 ml and estimated creatinine clearance ≥60 ml/min, were randomly assigned 2:1 to split-dose tolvaptan (45/15, 60/30, or 90/30 mg daily as tolerated) or placebo. The primary endpoint was annualized rate of TKV change. Secondary endpoints included a composite endpoint of time to multiple composite ADPKD-related events (worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney function decline. Results Tolvaptan reduced annualized TKV growth by 1.99%, 3.12%, and 2.61% per year (all P P =0.17) and eGFR decline by 0.40 in CKD1 ( P =0.23), 1.13 in CKD2 ( P 2 per year in CKD3 ( P P =0.07) across CKD1, CKD2 and CKD3. ADPKD-related events were less frequent in tolvaptan recipients than in placebo recipients among those with CKD1 (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.70–0.98; P =0.03) and those with CKD 3 (HR, 0.71; 95% CI, 0.57–0.89; P =0.003), but not among those with CKD2 (HR, 1.02; 95% CI, 0.85–1.21; P =0.86). Aquaresis-related adverse events (more frequent in the tolvaptan group) and ADPKD-related adverse events (more frequent in the placebo group) were not associated with CKD stage. Hypernatremia events in tolvaptan-treated patients with CKD3 and plasma aminotransferase elevations in tolvaptan-treated patients across CKD stages 1–3 occurred more frequently than in placebo recipients. Conclusions This post hoc analysis suggests clinically similar beneficial effects of tolvaptan in ADPKD across CKD stages 1–3.
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tolvaptan in patients with autosomal dominant polycystic Kidney disease
The New England Journal of Medicine, 2012Co-Authors: Vicente E Torres, Arlene B Chapman, Olivier Devuyst, Eiji Higashihara, John Ouyang, Ronald D Perrone, Ron T Gansevoort, Jared J Grantham, Holly B Krasa, Frank S CzerwiecAbstract:In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total Kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V 2 -receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total Kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening Kidney function, Kidney Pain, hypertension, and albuminuria) and rate of Kidney-function decline. RESULTS Over a 3-year period, the increase in total Kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P<0.001). The composite end point favored tolvaptan over placebo (44 vs. 50 events per 100 follow-up-years, P = 0.01), with lower rates of worsening Kidney function (2 vs. 5 events per 100 person-years of followup, P<0.001) and Kidney Pain (5 vs. 7 events per 100 person-years of follow-up, P = 0.007). Tolvaptan was associated with a slower decline in Kidney function (reciprocal of the serum creatinine level, −2.61 [mg per milliliter] −1 per year vs. −3.81 [mg per milliliter] −1 per year; P<0.001). There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis (excretion of electrolyte-free water) and hepatic adverse events unrelated to ADPKD, contributing to a higher discontinuation rate (23%, vs. 14% in the placebo group). CONCLUSIONS Tolvaptan, as compared with placebo, slowed the increase in total Kidney volume and the decline in Kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate, owing to adverse events. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; TEMPO 3:4 ClinicalTrials.gov number, NCT00428948.)
