Rationale and Design of the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) 3-4 Study

Background: Reduced kidney function and distorted kidney anatomy in patients with autosomal dominant polycystic kidney disease (ADPKD) may complicate stone interventions more compared with the general population. Objectives: To review studies describing the safety and efficacy of the 3 main stone interventions in adults with ADPKD: shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy (PCNL). Design: Systematic review. Setting: Any country of origin. Patients: Adults with ADPKD who underwent SWL, ureteroscopy, or PCNL. Measurements: Being stone free after the intervention and postoperative complications as reported by each study, which included pain, bleeding, and fever. Methods: Relevant studies published until February 2019 were identified through a comprehensive search of MEDLINE, EMBASE, Web of Science, BIOSIS PREVIEW, and CINAHL. Studies were eligible for review if they reported at least one outcome following SWL, ureteroscopy, and/or PCNL in adults with ADPKD. We then abstracted information on study characteristics, patient characteristics, intervention details, and postintervention outcomes and assessed the methodological quality of each study using a modified Downs and Black checklist. Results: We screened 221 citations from which we identified 24 studies that met our review criteria. We identified an additional article when manually reviewing the reference list of an included article, yielding a total of 25 studies describing 311 patients (32 SWL, 42 ureteroscopy, and 237 PCNL). The percentage of patients who were stone free after 1 session ranged from 0% to 69% after SWL, 73% to 100% after ureteroscopy, and 45% to 100% after PCNL. The percentage of patients with ADPKD that experienced at least one postoperative complication ranged from 0% to 33% for SWL, 0% to 27% for ureteroscopy, and 0% to 100% for PCNL. Limitations: The number and quality of studies published to date are limited. Conclusions: The efficacy and safety of stone interventions in patients with ADPKD remains uncertain, with wide-ranging estimates reported in the literature. Trial Registration: We did not register the protocol of this systematic review.

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EFFICACY AND SAFETY OF SIROLIMUS IN REDUCING CYST VOLUME IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Journal of Evidence Based Medicine and Healthcare ◽

10.18410/jebmh/2016/1096 ◽

2016 ◽

Vol 3 (96) ◽

pp. 5267-5270

Author(s):

Sreelatha Melemadathil ◽

Jayakumar Edathedathe Krishnan ◽

Noushad Thekke Puthiyottil

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Efficacy And Safety ◽

Polycystic Kidney ◽

Cyst Volume ◽

Autosomal Dominant Polycystic Kidney

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Overweight and Obesity and Progression of ADPKD

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.16871020 ◽

2021 ◽

Vol 16 (6) ◽

pp. 908-915 ◽

Cited By ~ 1

Author(s):

Kristen L. Nowak ◽

Cortney Steele ◽

Berenice Gitomer ◽

Wenchyi Wang ◽

John Ouyang ◽

...

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Autosomal Dominant ◽

Normal Weight ◽

Overweight And Obesity ◽

Rapid Progression ◽

Efficacy And Safety ◽

Polycystic Kidney ◽

Annual Percent Change ◽

Autosomal Dominant Polycystic Kidney

Background and objectivesOn the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. More importantly, we also determined whether efficacy of tolvaptan was attenuated in individuals with baseline overweight or obesity.Design, setting, participants, & measurementsA total of 1312 study participants with relatively early-stage autosomal dominant polycystic kidney disease (mean eGFR 78±22 ml/min per 1.73 m2) who were at high risk of rapid progression were categorized by body mass index (BMI; calculated using nonkidney weight) as normal weight (18.5–24.9 kg/m2; n=670), overweight (25.0–29.9 kg/m2; n=429), or obese (≥30 kg/m2; n=213). Linear and multinomial logistic regression models were used to determine the association of baseline overweight and obesity with change in total kidney volume (TKV) over the 3-year study period.ResultsIn fully adjusted models, higher BMI was associated with greater annual percent change in TKV (difference of 1.20 [95% confidence interval (95% CI), 0.85 to 1.55] per five-unit higher BMI). Overweight and obesity were associated with higher odds of annual percent change in TKV of ≥7% versus <5% (overweight: odds ratio, 2.04 [95% CI, 1.45 to 2.87]; obese: odds ratio, 4.31 [95% CI, 2.83 to 6.57] versus normal weight). eGFR decline did not differ according to BMI (fully adjusted difference in decline of −0.95 [95% CI, −2.32 to 0.40] ml/min per 1.73 m2 per year per five-unit higher BMI). The three-way interaction (treatment×time×BMI group) was not statistically significant in linear mixed models with an outcome of TKV (log-transformed estimated coefficient comparing the treatment effect for overweight versus normal weight: 0.56% [95% CI, −0.70% to 1.84%] per year; P=0.38; obese versus normal weight: 0.07% [95% CI, −1.47% to 1.63%] per year; P=0.93) or eGFR (estimated coefficient comparing overweight versus normal weight: −0.07 [95% CI, −0.95 to 0.82] ml/min per 1.73 m2 per year; P=0.88; obese versus normal weight: 0.22 [95% CI, −0.93 to 1.36] ml/min per 1.73 m2 per year; P=0.71).ConclusionsOverweight and particularly obesity are strongly and independently associated with kidney growth, but not eGFR slope, in the TEMPO 3:4 trial, and tolvaptan efficacy is irrespective of BMI categorization.Clinical Trial registry name and registration number:Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4, NCT00428948

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