THE EFFICACY OF TOLVAPTAN IN SLOWING KIDNEY FUNCTION DECLINE IN ADULTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Bibliographic record
Abstract
THE EFFICACY OF TOLVAPTAN IN SLOWING KIDNEY FUNCTION DECLINE IN ADULTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS Dr. Shehneela Dar, MD; Pawel Kostyrko, MD; Shanthan Vinala, MDDepartment of Stroke and Neurology, St Michael’s Hospital, Toronto, CanadaCorresponding Author: Shehneela.dar@unityhealth.to DOI: 10.5281/zenodo.17943553 ORCID ID: https://orcid.org/0009-0004-8320-649X Google Scholar ID: https://scholar.google.ca/citations?user=8K0XYrgAAAAJ&hl=en Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder leading to progressive renal failure. Tolvaptan, a vasopressin V2 receptor antagonist, targets underlying cyst pathophysiology. This meta-analysis synthesizes evidence from randomized controlled trials (RCTs) to determine the effect of tolvaptan on the annual rate of estimated glomerular filtration rate (eGFR) decline in adults with ADPKD. A systematic search of PubMed, Embase, and Cochrane Library databases was conducted up to May 2024 for RCTs comparing tolvaptan to placebo in adults with ADPKD, reporting change in eGFR over ≥12 months. Data on study characteristics, patient demographics, and outcomes were extracted independently. A random-effects model was used to calculate the pooled mean difference (MD) in annual eGFR decline with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Seven RCTs involving 3,412 participants were included. The mean age ranged from 37 to 54 years, and baseline eGFR from 44 to 81 mL/min/1.73 m². Tolvaptan dosing varied from 60-120 mg/day over 12-36 months. Tolvaptan treatment was associated with a significantly slower annual eGFR decline compared to placebo (MD: +1.90 mL/min/1.73 m²/year; 95% CI: 1.43 to 2.38; p < 0.001). Heterogeneity was moderate (I² = 32%, p = 0.18). Common adverse effects were aquaretic (polyuria, thirst), while significant liver enzyme elevation was rare (<1%). Tolvaptan significantly attenuates the decline of kidney function in adults with ADPKD with an acceptable safety profile, supporting its role as a disease-modifying therapy. Long-term studies assessing progression to end-stage renal disease are warranted. Keywords: Polycystic Kidney Disease, ADPKD, Tolvaptan, Kidney Function, eGFR, Meta-analysis, Randomized Controlled Trials, Renal Decline
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.036 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.057 |
| Bibliometrics | 0.004 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".