This is the public evidence browser: searchable references, visible evidence tiers, and enough filtering to stop this page from feeling like a dump.
Use search plus tier, year, and study type filters. Visible counts update live and the URL keeps your filter state.
Showing 79 references.
Key claim: Reduced tubule flow and aberrant renal functional reserve, not gross obstruction, tracked with cystogenesis in Pkd2 mutant kidneys
Limitations: Mouse model and fluorescent dextran assay only; no human efficacy or biomarker validation
Open sourceKey claim: Reinforces ultrasound for initial diagnosis, MRI for TKV-based prognostic tracking, and contrast CT/MRI for suspected complications
Limitations: Consensus-guideline methodology may rely on expert opinion when direct evidence is limited; imaging-guidance paper not interventional efficacy trial
Open sourceKey claim: ALDH1A1 inhibition delayed cyst growth in ADPKD mice, and low-dose disulfiram plus anti-PD-L1 showed synergy in mice.
Limitations: Preclinical only; transcriptional mechanism and ADPKD-specific selectivity need confirmation before translation.
Open sourceKey claim: Apelin receptor activation reduced cyst growth, kidney weight, cAMP, and BUN in PKD mice and in 3D cyst assays, nominating apelin signaling as a potential target.
Limitations: Preprint and animal-only evidence; no human efficacy or safety data.
Open sourceKey claim: Hemoglobin (Hb) levels significantly associated with long-term renal prognosis (50% eGFR reduction or RRT initiation) in ADPKD using time-series methodology; identifies anemia as clinically relevant risk-stratification biomarker
Limitations: Observational design with residual confounding potential; iron status and ESA use not fully captured; cross-sectional Hb snapshots vs continuous measurement; does not prove anemia causation or treatment intervention efficacy
Open sourceKey claim: Multivariable-adjusted HR for AD/AA: 1.76 (95% CI 1.13–2.73). Aortic dissection: HR 2.53 (1.13–5.66). Aortic aneurysm: HR 1.56 (0.94–2.60). Risk more pronounced in BMI ≥25 vs <25. ADPKD cohort had lower atherosclerotic burden (DM 7.9%, CAD 2.6%, PAD 5.3%), suggesting ADPKD-specific vascular remodeling mechanism independent of atherosclerosis. Expands ADPKD extrarenal phenotype beyond intracranial aneurysm to aortic disease.
Limitations: ICD-10 code-based diagnosis (no genetic confirmation); potential residual confounding; possible detection bias; single-country population (Japan); unclear generalizability to other ancestry groups. Observational design limits mechanistic causal inference.
Open sourceKey claim: Higher TKV associated with worse physical HRQOL independent of kidney pain and eGFR; kidney pain mediated part of TKV-mental-health link
Limitations: Observational design and regional cohort limits causal inference and global generalizability
Open sourceKey claim: Higher and better-quality skeletal muscle mass (NAMA) was associated with lower all-cause mortality and lower ESKD risk in ADPKD
Limitations: Observational design with potential residual confounding; muscle strength/performance not captured; single-country tertiary-center cohort
Open sourceKey claim: Comprehensive Lancet review summarizing current diagnostic and management approaches; reinforces tolvaptan as strong evidence-base disease-modifying treatment with early use support in high-risk groups; emphasizes risk-stratified management, comprehensive care pathway, and patient-centered shared decision-making. Coverage of genetics, diagnosis, prognosis, treatment (tolvaptan), complications (cyst infection, intracranial aneurysms, PLD management), and emerging therapies in clinical trials.
Limitations: Narrative review format (not systematic; expert-selected evidence); does not quantify new efficacy beyond prior RCTs; concentrates on integrating existing evidence into coherent care narrative
Open sourceKey claim: Australasian commentary on KDIGO 2025 ADPKD guidance highlights real-world implementation barriers, especially subsidy/access constraints for genetic testing and tolvaptan and rural/remoteness equity concerns.
Limitations: Commentary rather than primary outcome data; region-specific health-system framing; supports implementation context, not treatment efficacy ranking changes.
Open sourceKey claim: ADPKD patients undergoing first AVF creation showed comparable primary patency (63.2% vs 60.5%, p=0.81) and assisted primary patency (84.2% vs 73.7%, p=0.26) to non-ADPKD controls at 24 months despite significantly lower atherosclerotic comorbidities (diabetes 7.9% vs 52.6%, CAD 2.6% vs 31.6%, PAD 5.3% vs 23.7%). Suggests ADPKD-specific vascular remodeling (not atherosclerosis-driven) influences vascular access outcomes; distal AVF more common in ADPKD (73.7% vs 57.9%, p=0.147).
Limitations: Retrospective single-center design (n=38 per arm, modest sample). Short follow-up (24 months) may miss longer-term patency divergence. No mechanistic investigation of ADPKD vascular remodeling. Larger prospective studies needed. ADPKD cohort demographics/comorbidity patterns may differ from other centers.
Open sourceKey claim: In untreated children with ADPKD, hypertension/high-normal BP was linked to higher cyst burden and LV remodeling
Limitations: Single-center, cross-sectional design precludes treatment inference and limits generalizability
Open sourceKey claim: Developed and internally validated an ADPKD risk-stratification model predicting ESKD by age 80 in class 1 ADPKD by combining baseline eGFR with exponential estimate of kidney volume growth. Validation showed excellent discrimination (C-index=0.94) and calibration (R²=0.858), comparable to Mayo Clinic Predictive Model (MCPM, C-index=0.95 for Cox). Model supports individualized lifetime ESKD risk prediction to guide targeted therapy initiation and resource allocation.
Limitations: Retrospective single-center cohort (Mexico City); internal validation only (external validation pending). TKV measured by ellipsoid method (not MRI-based Mayo classification imaging). Derivation/validation split limits true prospective external test performance. Applicability to non-Hispanic populations and other Mayo classes (2-5) unclear pending future external prospective validation.
Open sourceKey claim: TKV stabilization: mean change −127 ± 303 mL at 6 mo, −50 ± 325 mL at 12 mo; eGFR decline attenuated (−0.85 ± 1.8 mL/min/1.73m²/yr year 1, −0.87 ± 1.1 mL/min/1.73m²/yr year 2). Dosing range 30–60 mg daily; no transaminase elevation or drug-induced liver injury; aquaretic effects manageable. Cohort spanned CKD stages 1–5.
Limitations: Open-label non-randomized single-center design; potential confounding (hypertension 65.6%, hyperlipidemia 15.6%); small sample limits power; TKV by ultrasound not MRI; 2-year follow-up shorter than TEMPO 3:4. Generalizability to non-Asian populations unclear.
Open sourceKey claim: MQ232 and tolvaptan similarly attenuated PKD in Pkd1RC/RC mice and decoupled disease attenuation from urine-output/cAMP surrogates
Limitations: Mouse model only; no human safety or efficacy data
Open sourceKey claim: GLPG2737 was generally well tolerated but did not reduce htTKV growth or slow eGFR decline versus placebo over 52 weeks in rapidly progressive ADPKD
Limitations: Phase 2a sample size was modest; surrogate endpoints only; open-label extension results do not change the negative double-blind primary readout; results apply to GLPG2737 150 mg once daily and do not exclude other CFTR-inhibition strategies
Open sourceKey claim: Long-term registry data show meaningful discontinuation burden and frequent aquaretic adverse events during tolvaptan care in routine practice
Limitations: Registry is observational/descriptive with limited causal efficacy inference and potential center-selection bias
Open sourceKey claim: Farabursen (miR-17 targeting oligonucleotide, preferential kidney exposure) Phase Ib MAD trial showed promising efficacy and safety in reducing growth of cysts and kidney size, and delaying progression of ADPKD. First-in-class mechanism (miR-17 inhibition) with renal tropism. Completed Phase Ib; Phase II planned. Acquired by Novartis March 2026 ($1.7B, completed June 2025).
Limitations: Preprint/press release only (peer-reviewed publication not yet available). Phase Ib data not yet in peer-reviewed journal; trial details (n, dosing, efficacy metrics [htTKV %, eGFR slope] not yet specified). Mechanism of miR-17 targeting in ADPKD pathophysiology not yet validated in human disease. Phase II outcomes remain key confirmatory test. Novartis acquisition timeline and clinical development continuity should be monitored.
Open sourceKey claim: Successfully generated human-induced pluripotent stem cell (iPSC) line from ADPKD patient carrying PKD1 pathogenic variant (NUMNi003-A); provides cellular model resource for mechanistic studies and drug screening in human genetic ADPKD context. Verifies iPSC generation methodology and variant retention.
Limitations: Resource generation paper (no mechanistic findings or therapeutic efficacy). iPSC line validation for disease modeling still pending (differentiation to kidney cells, phenotypic characterization, drug-response profiling not reported in this resource paper). Cell line availability supports future research infrastructure.
Open sourceKey claim: Genome-wide association identified PKD1L2 (closely related to PKD1) as genetic locus associated with circle of Willis characteristics and intracranial aneurysm (IA) risk. Finding strengthens PKD1-family gene involvement in intracranial vascular phenotypes; note: PKD1 itself is well-established IA risk gene in ADPKD context. PKD1L2 may represent parallel/related vascular developmental pathway.
Limitations: GWAS-derived signal (not mechanistically validated). PKD1L2 functional role in vascular development/IA risk unclear (association does not prove causation). IA screening/management remains clinical standard for ADPKD; PKD1L2 discovery may inform future IA prevention strategies but does not change current practice yet.
Open sourceKey claim: PKD1 knockout in rat kidney epithelial cells (NRK-52E) induces metabolic alterations consistent with enhanced glycolytic metabolism; identifies glycolytic changes as potential biomarkers of PKD1-driven cystogenesis and as possible therapeutic targets. Metabolic profiling methodology developed.
Limitations: Preclinical cell-line study only (no animal models, no human data). NRK-52E cells are established cell line, not patient-derived. Mechanistic relevance to clinical ADPKD progression unclear. Biomarker identification does not imply therapeutic efficacy.
Open sourceKey claim: PubMed-indexed ADPKD-focused medicinal-chemistry work presents GV-001 as an orally available HDAC6 inhibitor candidate.
Limitations: Primary claim is preclinical/candidate generation only; no human efficacy data reviewed in this pass.
Open sourceKey claim: Across published PROM studies, physical health-related quality of life worsened with advancing CKD stage and dialysis burden in ADPKD, while disease-specific instruments appeared more sensitive than generic PROMs.
Limitations: Systematic review of a small underlying literature with heterogeneous PROM tools and no treatment-effect testing; supports symptom-burden measurement and counseling rather than disease-modifying claims.
Open sourceKey claim: HIF-1a promotes Pannexin-1 expression and ATP release into the cyst lumen, driving ATP-dependent cyst expansion; Pannexin-1 inhibitors reduced ATP release and cyst growth in vitro
Limitations: Preclinical human tissue and model-system study only; no patient efficacy or safety data; drug-repurposing implications remain speculative
Open sourceKey claim: Birinapant, bardoxolone methyl, and salicylic acid were identified as repurposing candidates; salicylic acid showed the most promising mechanism profile in preclinical ADPKD models
Limitations: Preclinical only; no human efficacy or safety data; target engagement at clinically relevant concentrations does not establish clinical benefit
Open sourceKey claim: Higher MRI-measured visceral adipose tissue was independently associated with faster eGFR decline over about 31 months in early-stage ADPKD, including despite tolvaptan exposure in some participants.
Limitations: Small single-center observational cohort embedded in a letter format; residual confounding remains possible and the study does not prove that intentional fat loss improves renal outcomes or preserves tolvaptan benefit.
Open sourceKey claim: Autopsy review found portal vein/IVC thrombosis in 4 of 10 ADPKD cases, with larger kidney weight and compression-related venous stasis as plausible contributors, adding a niche advanced-disease complication signal.
Limitations: Tiny single-center autopsy series with substantial selection bias and no prospective incidence estimate; useful for clinician awareness in massively enlarged kidneys, not for broad screening or treatment recommendations.
Open sourceKey claim: PKD2 (polycystin-2) deficiency induces contractile dysfunction via endoplasmic reticulum (ER) stress (elevated BiP, CHOP, impaired Ca2+ handling) and reduced sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. Pharmacological rescue achieved partially via ER-stress alleviators (4-phenylbutyrate/tauroursodeoxycholic acid) or SERCA activators (CDN1163), demonstrating mechanistic targets for PKD2-associated cardiomyopathy intervention.
Limitations: Human cellular model only; no in-vivo animal validation. Partial rescue in vitro; translation to systemic cardiac benefit in ADPKD-PKD2 patients unknown. PKD2 mutations account for ~15% of ADPKD; findings may not generalize to PKD1-dominant ADPKD cardiomyopathies. No patient tissue/iPSC validation. Mechanism of PKD2 loss-of-function in cardiomyocytes vs. kidney epithelial cells differs; ADPKD cardiomyopathy prevalence and clinical significance warrant further investigation.
Open sourceKey claim: Supports selective ICA screening, contrast-free MR angiography, 5-10 year rescreening in high-risk negatives, and attention to thoracic aortic aneurysm risk in ADPKD.
Limitations: Commentary rather than primary outcomes; implementation guidance only, not new efficacy evidence.
Open sourceKey claim: Expert and patient-centered guidance on implementing KDIGO 2025 ADPKD recommendations in U.S. healthcare context; highlights diagnostic, management, treatment, and implementation barriers (imaging access, genetic testing interpretation, multidisciplinary coordination, insurance coverage)
Limitations: Professional commentary format provides expert consensus but not primary efficacy trial; implementation-focused rather than mechanism/intervention efficacy
Open sourceKey claim: Ketogenic-style interventions show metabolic feasibility but renal structural disease-modifying evidence remains uncertain
Limitations: Small heterogeneous short-duration studies; no robust pooled effect on hard renal outcomes
Open sourceKey claim: Higher long-term PM2.5 exposure was associated with steeper eGFR decline in a large adult PKD cohort, suggesting air pollution may act as a disease-progressing environmental modifier.
Limitations: PKD cohort was not genotype-resolved to pure ADPKD; observational design with potential residual confounding; exposure model was ecological rather than personal monitoring; effect size per 1 ug/m3 was modest and does not prove that exposure reduction changes outcomes.
Open sourceKey claim: Tolvaptan group showed slower htTKV growth and better 2-year eGFR trajectory vs untreated controls in this cohort
Limitations: Small non-randomized sample and potential selection bias; country/cohort-specific
Open sourceKey claim: XGBoost ML model (27-feature ensemble) predicted ADPKD dialysis progression with 98.3% accuracy and AUC 0.955 on held-out temporal test set; age 66+, anemia, CHF, AKI were top clinical risk factors
Limitations: Observational/administrative database design with temporal validation; model interpretability limited by ML ensemble black-box; single-country cohort may limit global generalizability
Open sourceKey claim: Developed the TIPS questionnaire and showed tolvaptan-related polyuria meaningfully increases treatment burden and correlates with urinary volume.
Limitations: Small single-center study; symptom burden informs tolerability and shared decision-making but does not change tolvaptan efficacy ranking.
Open sourceKey claim: Mini-CRISPRa vectors improved delivery into mouse renal epithelial cells and drove endogenous Pkd1 upregulation in vitro, addressing a practical delivery bottleneck for activation-based gene therapy.
Limitations: Cell-culture only, no animal or human efficacy; improved transfection does not prove durable kidney correction or clinical safety.
Open sourceKey claim: Human kidney tubuloids can model cAMP-driven cystogenesis and can be genetically modified with AAV, improving human-relevant PKD screening infrastructure.
Limitations: Platform study only; no treatment efficacy or clinical outcome data.
Open sourceKey claim: Targeted NGS panels showed the strongest overall diagnostic yield/cost-effectiveness for ADPKD molecular diagnosis, with MLPA and LR-PCR as useful adjuncts for complex PKD1 or copy-number variants. Strengthens structured genetic-testing workflow, not treatment efficacy.
Limitations: Heterogeneous included cohorts and lab methods; diagnostic yield depends on phenotype selection, sequencing workflow, and variant interpretation. Diagnostic-performance review does not show that broader testing improves renal outcomes by itself.
Open sourceKey claim: Updated Japanese prevalence estimates suggest 1 in 3,055 individuals with ADPKD not receiving KRT and 1 in 2,335 when KRT cases are included, indicating higher burden than previously recognized
Limitations: Survey response rate was 32.9% and KRT-coded cases may not be pure ADPKD; prevalence is an epidemiologic planning estimate, not a treatment or prognosis study
Open sourceKey claim: An ADPKD-tailored ketogenic meal plan could meet macronutrient targets and most micronutrient targets, but iodine was low and iron/zinc may need supplementation in some groups
Limitations: Diet-planning study rather than efficacy trial; no eGFR, htTKV, symptom, adherence, or long-term safety outcomes; cost slightly higher than CKD reference meal plans
Open sourceKey claim: Optimized exome sequencing detected 95.5% of known PKD1 pathogenic variants (100% with higher-depth ES), all PKD2 variants, and solved additional previously unsolved cases
Limitations: Reference-standard cohort design but not therapeutic efficacy evidence; performance depends on pipeline/capture depth and high-quality variant curation
Open sourceKey claim: In non-diabetic adults with early-stage ADPKD and eGFR ≥60, overweight and obesity were independently associated with lower MRI-measured renal blood flow after adjustment for blood pressure, eGFR, and htTKV.
Limitations: Cross-sectional observational design cannot establish causality; BMI was adjusted for organ mass but still remains a crude adiposity surrogate, and the study does not show that weight loss or renal-blood-flow changes improve renal outcomes.
Open sourceKey claim: Patient-derived adult renal organoids reproduced genotype-specific ADPKD cyst biology and identified Rho GTPase inhibition, including ML141, as a cyst-reducing candidate strategy. Strengthens human-model screening infrastructure and Rho/PCP target plausibility, not near-term efficacy.
Limitations: Organoid/drug-screen study only; no animal or human efficacy data. Candidate Rho inhibitors lack ADPKD clinical safety or kidney-delivery validation. Cyst reduction in organoids does not prove kidney-function benefit.
Open sourceKey claim: In a single-center ADPKD cohort, native nephrectomy carried substantial perioperative morbidity, with bilateral nephrectomy showing the highest complication burden; minimally invasive surgery was feasible in selected smaller-kidney cases but did not independently reduce complications after adjustment.
Limitations: Retrospective single-center surgical cohort with episode-level analysis, selection by symptoms/case complexity, and no randomized comparison; useful for specialized surgical planning, not for broad management changes or causal claims about technique superiority.
Open sourceKey claim: Among ADPKD survivors of COVID-19 short-term 1- to 3-month outcomes (KRT initiation/death/lab measures) were not worse than matched ADPKD controls without prior COVID-19
Limitations: Small sample with survivor-only cohort and short follow-up window limits long-term risk inference
Open sourceKey claim: Pravastatin did not reduce annual htTKV growth or slow kidney blood-flow/kidney-function decline versus placebo over 2 years in adults with preserved kidney function
Limitations: Single pharmacologic class/intervention; findings apply to pravastatin regimen tested and do not exclude other pathways
Open sourceKey claim: Self-reported pregnancy history was not associated with eGFR slope, htTKV growth, or composite progression in women with ADPKD across HALT-PKD analyses
Limitations: Self-reported pregnancies and limited in-study pregnancy events constrain causal inference and generalizability
Open sourceKey claim: Human and mouse evidence shows progressive CB1R upregulation and eCB ligand depletion correlated with disease severity, nominating ECS/CB1R as a mechanistic target.
Limitations: Associational mechanistic study; no pharmacologic or genetic modulation in patients; therapeutic benefit remains unproven.
Open sourceKey claim: DCE-MRI intrarenal Ktrans was reproducible with phantom correction, distinguished mild vs severe ADPKD, and correlated with htTKV and eGFR, supporting perfusion biomarker feasibility
Limitations: Small single-center cohort and short repeat-interval imaging design; biomarker validation does not establish treatment efficacy or hard-outcome benefit
Open sourceKey claim: In nondiabetic adults with ADPKD, SGLT2 inhibitor exposure was associated with lower chronic dialysis initiation versus matched controls (19/187 [10.16%] vs 43/187 [22.99%]; HR 0.35, 95% CI 0.21-0.61)
Limitations: Observational database design with residual confounding risk; no TKV or genotype data; medication selection bias and exposure misclassification remain possible; randomized trials still needed before practice change
Open sourceKey claim: RASSF4 enhanced PKD2 channel activity and reduced Pkd2-associated phenotypes in model systems, nominating a PKD2-regulatory complex as a therapeutic target.
Limitations: Animal and cell models only; no human safety or efficacy data.
Open sourceKey claim: Lower baseline renal blood flow independently associated with higher long-term risk of kidney failure and faster progression metrics in early-stage ADPKD
Limitations: Observational/prognostic design and MRI-based RBF measurement may limit generalizability and interventional inference
Open sourceKey claim: In a small single-center ADPKD transplant cohort, simultaneous retroperitoneoscopic nephrectomy appeared safe and less invasive than open nephrectomy, with similar operative time/blood loss and substantially less postoperative abdominal-wall muscle atrophy.
Limitations: Small non-randomized single-center series (RN n=11, ON n=8) with technique-specific expertise and early postoperative focus; useful for specialized transplant planning but not a broad management-changing result.
Open sourceKey claim: PKD1 heterozygous cynomolgus monkeys develop progressive cysts from birth matching human childhood ADPKD trajectory. Remarkably, subset of smaller cysts regressed spontaneously over time, challenging model of relentless progression. PKD1-mosaic monkeys showed similar plasticity. Biallelic PKD1-null monkeys developed severe cystic disease resembling advanced ADPKD. Findings suggest early cystogenesis represents therapeutic window where cyst regression may be promoted; raises mechanistic questions about plasticity of early cysts.
Limitations: Preclinical primate model (not human). Spontaneous regression observed in heterozygous setting (translational relevance to adult humans unknown). Serial ultrasonography methodology (not histologic confirmation). Biallelic animals represent severe phenotype not typical of human ADPKD. Monkey lifespan/disease kinetics differ from humans. Potential therapeutic implications require clinical validation.
Open sourceKey claim: Higher Mediterranean-diet adherence in adults with ADPKD was associated with higher nitric oxide and lower endothelin-1 levels, suggesting more favorable endothelial-function profile as a supportive-care signal.
Limitations: Cross-sectional biomarker study with no htTKV, eGFR-slope, or clinical-event endpoint; small single-country cohort and potential dietary confounding mean this supports general diet-quality counseling, not disease-modifying claims.
Open sourceKey claim: Review synthesizes recent scaffold-diversification work on selective V2 receptor antagonists and highlights that next-generation V2-pathway drug design remains active after setbacks in older lineage programs.
Limitations: Not a primary efficacy study; largely synthesizes preclinical and medicinal-chemistry data; does not provide new human ADPKD outcome evidence or change current treatment rankings.
Open sourceKey claim: Somatostatin analogs were associated with reduced TLV and modest TKV reduction but no eGFR improvement, with higher gallbladder/GI adverse-event burden
Limitations: Population mixes PLD with ADPKD-associated disease and kidney hard-outcome benefit was not demonstrated; low-to-moderate certainty evidence
Open sourceKey claim: A hybrid smartphone diary ('PKD Daily') captured tolvaptan dose timing plus daytime and overnight urinary burden in adults with ADPKD and was judged understandable and relevant for trial and clinical symptom tracking.
Limitations: Content-validation and feasibility study rather than outcome trial; does not prove improved adherence, kidney outcomes, or better dosing decisions in routine practice.
Open sourceKey claim: Higher serum osmolality was associated with substantially higher risk of 40% eGFR decline while urine osmolality showed poor predictive utility
Limitations: Observational cohort design limits causal intervention inference and does not prove that prescribed hydration lowers progression risk
Open sourceKey claim: Association with modest chronic eGFR slope benefit estimate but not statistically significant; high discontinuation rates
Limitations: Observational design with residual confounding and wide confidence intervals; tertiary-centre cohort
Open sourceKey claim: After initiating tolvaptan, nocturnal BP dipping improved and non-dipper prevalence fell; TKV growth and eGFR slope also improved in this small cohort.
Limitations: Small retrospective pre/post cohort with no control arm; BP and renal changes could reflect regression to the mean, selection, or time effects; supportive signal only.
Open sourceKey claim: Integrates guideline recommendations, patient perspective, and real-world data to reinforce risk-stratified multidisciplinary ADPKD care and practical tolvaptan implementation
Limitations: Narrative review without new primary efficacy data; implementation-focused synthesis rather than interventional evidence
Open sourceKey claim: Predicted pathogenic variants in typical ADPKD genes (PKD1/PKD2) present in ~1 in 314 people (PKD1: 1 in 417; PKD2: 1 in 916); atypical ADPKD genes (GANAB/ALG9/DNAJB11/ALG5/IFT140/NEK8) present in ~1 in 283 people. Pathogenic variants more common for atypical than typical ADPKD, particularly ALG9/DNAJB11. NEK8 monoallelic pathogenic-kinase-domain variants not found in gnomAD v.4.1.
Limitations: Computational inference from gnomAD cohort variants and ClinVar-annotated assessments; does not measure clinical penetrance/expressivity or verify all 'pathogenic' predictions in independent cohorts; may overestimate true disease prevalence if penetrance <100%
Open sourceKey claim: Urinary beta2-microglobulin was associated with faster eGFR decline and greater structural severity, while MCP-1, NGAL, and KIM-1 had limited adjusted prognostic utility
Limitations: Single-center cross-sectional study in tolvaptan-treated adults; no causal inference or treatment-effect data; biomarker associations need longitudinal validation
Open sourceKey claim: In adults with ADPKD and baseline eGFR <60 mL/min/1.73 m², adding the Kidney Failure Risk Equation (KFRE) to Mayo Imaging Classification / TKV-based risk assessment improved prediction of kidney replacement therapy initiation or 40% eGFR decline versus imaging classification alone, strengthening combined risk-stratification use rather than changing treatment efficacy rankings.
Limitations: Now PubMed-indexed, which strengthens normalization and abstract-level verification, but this remains a retrospective cohort and does not prove outcome improvement from acting on the combined model. Predictive-performance gains were strongest in the eGFR <60 subgroup, and calibration/sample-detail interpretation still needs full-text review.
Open sourceKey claim: Intrarenal microvascular rarefaction develops early (1–6 mo in Pkd1RC/RC model); preceded by vascular transcriptional dysregulation (110–201 DEGs at 1/6/12 mo). Plasma GABA, homocysteine (Hcy), asymmetric dimethylarginine (ADMA) elevated in ADPKD humans, correlate with TKV and renal blood flow decline; suggest endothelial dysfunction/metabolic dysregulation as early drivers.
Limitations: Mouse model (Pkd1RC/RC) is slowly progressive; human biomarker cohorts small (n=10–32); biomarker validation does not prove therapeutic targeting efficacy; causal pathway requires intervention studies.
Open sourceKey claim: Tolvaptan-treated adults (n=149) showed slower annual eGFR decline vs matched historical controls; eGFR spared by 1.40 mL/min/1.73m² annually in matched set A (p=0.04), trend 1.18 in set B (p=0.10)
Limitations: Real-world observational design; small single-country cohort from 57 nephrologists; historical control era differences; medication adherence not captured
Open sourceKey claim: Supports structured management of extrarenal manifestations and highlights implementation/research gaps
Limitations: Commentary not primary efficacy trial; focus on implementation and hepatopancreatic scope
Open sourceKey claim: Risk-stratified management and evidence-based treatment framework
Limitations: Needs full-text extraction for recommendation-level detail
Open sourceKey claim: Provides full recommendation set for evaluation/risk stratification and treatment of ADPKD
Limitations: No abstract-level efficacy quantification in PubMed listing; full-text extraction needed for recommendation granularity
Open sourceKey claim: Across four RCTs metformin showed no significant benefit on kidney-function decline or htTKV progression and increased gastrointestinal adverse events
Limitations: Small pooled sample and short heterogeneous follow-up intervals with moderate imprecision
Open sourceKey claim: Metformin added to standard care in non-diabetic adults did not improve short-term eGFR trajectory versus control over 6 months
Limitations: Small single-country open-label trial with short follow-up and baseline imbalance in proteinuria; limited power for long-term outcomes
Open sourceKey claim: In tolvaptan-treated ADPKD, 6-month dapagliflozin add-on was associated with attenuated eGFR slope decline and lower TKV growth versus control period
Limitations: Small single-country open-label crossover and short follow-up; surrogate endpoints; needs larger blinded confirmation
Open sourceKey claim: In younger adults (18-35y), tolvaptan reduced eGFR decline rate by 40% (1.69 mL/min/1.73m²/year slower than controls; p<0.001); extrapolated ~11-year delay to kidney failure
Limitations: Pooled analysis with imbalanced follow-up (tolvaptan 4.6y median vs controls 1.7y); linear extrapolation model limitations; younger population-specific finding
Open sourceKey claim: Tolvaptan has clinically relevant liver-injury risk requiring monitoring
Limitations: Generalizability outside trial settings
Open sourceKey claim: CRISPR-based mechanistic editing reduced disease severity in models
Limitations: Preclinical only; no human efficacy
Open sourceKey claim: Prescribed high water intake reduced urine osmolality but did not slow htTKV growth versus ad libitum intake over 3 years
Limitations: Only about half achieved urine-osmolality adherence target and no long-term copeptin reduction was seen; not a no-hydration trial
Open sourceKey claim: Slower eGFR decline than placebo over 1 year
Limitations: Monitoring and tolerability constraints remain
Open sourceKey claim: Slowed TKV growth and kidney function decline vs placebo over 3 years
Limitations: Adverse effects/discontinuation burden; selected population
Open sourceTry clearing one filter, broadening the search term, or switching back to higher-level evidence tiers first.