Background: The mechanisms contributing to progressive kidney damage in autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Renal microvascular (MV) rarefaction plays an important role in kidney disease, but its natural history, underlying mechanisms, and contributions to renal disease progression in ADPKD remain unknown. We hypothesized that intrarenal MV rarefaction is present early on and is preceded by vascular transcriptional and metabolic changes. Methods: Pkd1RC/RC and WT mice (n=16 each) were studied at 1, 6, and 12 months. Total kidney volume (TKV) was measured in vivo (MRI), whereas renal MV architecture (3D-micro-CT), capillary density, perivascular fibrosis, and histomorphometric parameters were assessed ex vivo. In randomly selected Pkd1RC/RC and WT kidneys (n=5, each/time point), mRNA-sequencing was performed to identify differentially expressed vasculature-related genes (DEGs). Next, in young humans with ADPKD and matched controls (n=10 each), plasma cellular energy metabolites were determined (LC-MS/MS), validated in an extended cohort (n=32 and n=16, respectively), and correlated with markers of disease severity and progression. Gene-metabolite interaction networks were generated to integrate DEGs in Pkd1RC/RC at 1 month with metabolites dysregulated in individuals with ADPKD, which were further quantified in WT and Pkd1RC/RC kidneys. Results: Renal MV density was preserved at 1 month but progressively decreased at 6 and 12 months, associated with capillary loss and perivascular fibrosis. A total of 110, 48, and 201 DEGs were identified at 1, 6, and 12 months, respectively. Plasma gamma-aminobutyric acid (GABA), homocysteine (Hcy) and asymmetric dimethyl arginine (ADMA) levels were higher in humans with ADPKD versus controls, interacted with DEGs implicated in inflammatory and innate immune response and Hcy metabolism, and correlated with TKV and renal blood flow. Conclusions: Our data demonstrate that intrarenal MV abnormalities present early in ADPKD and are preceded by vascular transcriptional and metabolic changes. The renal microcirculation may constitute an important therapeutic target in ADPKD, and its underlying biomarkers may serve to monitor its progression.

Autosomal dominant polycystic kidney disease (ADPKD) affects approximately 12.5 million individuals globally and is one of the most common causes of end-stage renal disease. It is typically associated with a gradual increase in the volume of numerous cysts in both kidneys. Recent studies have highlighted the critical role of signal transducer and activator of transcription 3 (STAT3) in ADPKD pathogenesis, as it is highly expressed and persistently activated in ADPKD kidneys. Through screening of our in-house compound library, we identified compound WR-S-647 (4e) as a potent and specific inhibitor of STAT3 with a binding affinity of 34nM to STAT3. WR-S-647 suppressed the phosphorylation activation and nuclear localization of STAT3. In vitro, WR-S-647 remarkably suppressed cyst formation and expansion in a Madin-Darby canine kidney (MDCK) cyst model. Meanwhile, it effectively diminished cyst growth in an ex vivo embryonal renal cyst model and an in vivo Pkd1 knockout ADPKD mouse model. Our study identifies WR-S-647 as a potent STAT3-mediated inhibitor and provides preclinical proof-of-concept for its efficacy in reducing cyst growth in ADPKD models.

Optimizing Next Generation Sequencing for Genetic Diagnosis in Autosomal Dominant Polycystic Kidney Disease.

The impact of reproductive steroids on autosomal dominant polycystic kidney disease progression in women.

The many faces of cholesterol in autosomal dominant polycystic kidney disease.

De novo PKD1 splicing and missense variants in two familial ADPKD: Molecular characterization and genetic counseling implications.

Authors' Reply: Deciphering the Cell-Specific Specificity of the α-Klotho-Cellular Inhibitor of Apoptosis Protein 1 Axis in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder leading to kidney failure. Recent advancements in artificial intelligence (AI) are transforming the diagnosis, risk stratification, management, and prognostication in ADPKD by enabling more accurate assessments and individualized care. AI-powered imaging tools enhance the measurement of total kidney volume (TKV), improving the precision and efficiency of monitoring disease progression and more reliable assessment of therapeutic response. Machine learning (ML) algorithms can integrate genetic, imaging, and clinical data to predict kidney function decline, facilitating personalized treatment strategies. In addition, AI is being used to identify genetic variants and to refine genotype-phenotype relationships, offering deeper insights into disease variability. AI-enabled monitoring technologies can support longitudinal tracking of TKV measurements obtained through MRI or CT, thereby improving clinical decision-making and management. Furthermore, AI can optimize clinical trial design by improving patient selection, prediction of treatment responses, and safety monitoring. Despite these promising developments, integrating AI into the clinical practice remains controversial and may pose several challenges. This review highlights the emerging clinical applications of AI in ADPKD, emphasizing its potential to advance precision medicine and improve patient outcomes.

Drainage failure during peritoneal dialysis is most commonly due to mechanical complications, such as catheter migration and obstruction. However, intraperitoneal catheter rupture is extremely rare. We report the case of a 48-year-old man with autosomal dominant polycystic kidney disease (ADPKD) who developed intraperitoneal catheter rupture. Despite a thorough analysis of the removed catheter, the definitive cause of rupture could not be determined. Chronic mechanical stress, exacerbated by obesity (body mass index 40.74kg/m2), was thought to induce catheter rupture. Additionally, the peritoneal wall anchor technique may be associated with mechanical stress. Patients with obesity and ADPKD are at a high risk of catheter rupture. Therefore, intraperitoneal catheter rupture should be considered a differential diagnosis when investigating the cause of poor drainage in patients undergoing peritoneal dialysis.

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease (ESRD). Progressive renal cyst growth in ADPKD can exert mass effects, including compression of the inferior vena cava (IVC), a rare but clinically significant complication with implications for hemodynamic stability and renal outcomes. This study evaluated the prevalence of IVC compression in ADPKD and its impact on progression to ESRD, mortality, and overall survival. We aimed to provide quantitative measures to elucidate its prognostic significance. Materials and Methods: Using the TriNetX database, we conducted a retrospective cohort study of 658 ADPKD patients with IVC compression, comparing them to unmatched controls without compression. Outcomes included ESRD incidence, mortality, and survival. Kaplan–Meier curves and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for analysis. Results: ESRD Risk: IVC compression was associated with a higher risk of ESRD (77.4% vs. 29.7%, RR: 2.61, 95% CI: 2.49–2.73, p < 0.001). Survival Probability: 5-year Survival was significantly reduced in patients with IVC compression (42.6%) compared to controls (61.7%) (HR: 4.00, 95% CI: 3.45–4.63, p = 0.002). Mortality: Mortality was higher in the compression group (29.2% vs. 9.1%). Combined Impact: ESRD patients with IVC compression had a lower survival rate (11.9%) than ESRD patients without compression (28.5%) (HR: 5.60, 95% CI: 5.12–6.13, p < 0.001). Conclusions: IVC compression in ADPKD is associated with significantly worse outcomes, including increased ESRD risk, higher mortality, and reduced survival. These findings underscore the importance of early diagnosis and targeted management strategies.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, with cyst formation and structural kidney changes present during childhood or before birth. The 2025 KDIGO guidelines build on earlier frameworks to improve screening, monitoring, and treatment methodology for pediatric ADPKD patients. This executive summary synthesizes the updated 2025 KDIGO recommendations and supporting evidence to outline advancements in diagnosis, blood pressure and proteinuria management, follow-up, and transition planning. The guidelines introduce more precise definitions of disease subtypes, tighter blood pressure targets, and expanded recommendations for genetic testing, ultrasound screening, and symptom-driven follow-up. KDIGO emphasizes ambulatory blood pressure monitoring from age five, renin-angiotensin system inhibitors as first-line therapy, and structured transition planning during adolescence. The 2025 KDIGO pediatric ADPKD guidelines provide a practical, family-centered framework for individualized care and improved transition to adult services, promoting early detection, proactive management, and shared decision making to support long-term outcomes.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder caused by mutations in genes encoding ciliary proteins. Increasing evidence suggests that immune cell infiltration, chronic inflammation, and dysregulated immune signalling pathways contribute to cyst growth, fibrosis, and progressive kidney function decline. Notably, features of chronic inflammation are already detectable in early stages of the disease, including infiltration by immune cells, elevated levels of pro-inflammatory cytokines, and immunological crosstalk between immune and epithelial cells. These immune responses promote fibroblast activation and excessive extracellular matrix deposition via key signalling pathways such as NF-κB, JAK-STAT, and TGFβ-SMAD, ultimately driving renal fibrosis and functional deterioration. Conversely, components of the adaptive immune system have been implicated in slowing disease progression. CD8+ T cells have been shown to exert a protective effect by limiting cyst expansion and preserving tubular architecture. Remarkably, cyst-lining epithelial cells themselves can regulate immune cell activity, highlighting a complex and dynamic interplay between ADPKD and the immune system at multiple levels. Beyond direct crosstalk, immune mechanisms may also contribute to the genotype-independent interindividual variability observed in ADPKD progression. In this review, we provide a comprehensive overview on the role of immune cells in ADPKD, offering mechanistic insight into the processes underlying cyst initiation and progression. This perspective underscores the increasing recognition that cystic kidneys share fundamental features with tumor-like microenvironments, including chronic inflammation, immune-driven matrix remodelling, and metabolic dysregulation. We further summarize emerging immune-related biomarkers and therapeutic targets, providing a foundation for future translational approaches.

Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease

We report the case of a Japanese man in his 60s undergoing hemodialysis for end-stage renal disease due to autosomal dominant polycystic kidney disease, who had experienced repeated hepatic cyst infections. Despite treatment with oral antibiotics, including minocycline and trimethoprim-sulfamethoxazole, he presented with fever and was admitted to our hospital. Diffusion-weighted magnetic resonance imaging demonstrated a high signal intensity in a large hepatic cyst, and percutaneous transhepatic drainage was performed. Enterococcus faecium was isolated from the cyst fluid. Three intracystic minocycline infusions were administered in combination with intravenous vancomycin after dialysis. The patient achieved clinical improvement and remained free from recurrence until day 253 of illness. Infections in large cysts tend to be refractory, and drainage alone may be insufficient, particularly in immunocompromised patients on hemodialysis. Intracystic sclerotherapy with minocycline offers both antimicrobial and sclerosing effects, with previous reports demonstrating cyst shrinkage and infection control in non-dialysis patients. To our knowledge, this is the first report describing successful intracystic minocycline infusion in a patient undergoing hemodialysis, and no recurrence or significant adverse events were observed. Intracystic minocycline infusion sclerotherapy may be a safe and effective therapeutic option for hepatic cyst infection in this population.

Abstract Background Monogenic causes are increasingly recognized in end-stage kidney disease (ESKD), but the real-world diagnostic efficacy of exome sequencing in unselected dialysis cohorts is still being defined. Methods We conducted a prospective study enrolling 317 adult ESKD patients from a single center in Taiyuan, China, regardless of presumed etiologyWhole-exome sequencing (WES) was performed on peripheral blood DNAVariants were curated and classified per the ACMG/AMP 2015 and ACGS guidelines, with only ‘pathogenic’ or ‘likely pathogenic’ findings considered diagnostic. Results The cohort was 59% male, mean ESKD onset 53.2 ± 14.3 yearsA definitive monogenic diagnosis emerged in 7.3% (23/317) of patients, in line with multicenter and international studiesGenes most frequently implicated were PKD1 (3.5% of cohort; 47.8% of genetically diagnosed) and COL4A3/4/5 (1.9%; 26.1% of diagnosed), reflecting global trends of autosomal dominant polycystic kidney disease (ADPKD) and Alport syndrome as major genetic contributors in adult ESKDNotably, mutations in ACTN4, PAX2, COQ8B or INF2, causing hereditary steroid-resistant nephrotic syndrome (SRNS), led to significantly earlier ESKD onset (mean 31.3 years) compared to PKD1 or COL4-related casesInconclusive genetic findings were present in 7.9% (25/317)Most patients reported no family history of kidney disease, indicating the limitations of clinical suspicion alone. Conclusions In a real-world Chinese dialysis cohort, WES provided a molecular diagnosis in 7.3% of cases, demonstrating clinical utility for risk stratification, family counseling, donor selection, and actionable therapyThese findings underscore the need for routine integration of genetic testing in ESKD care irrespective of family history, especially to clarify ambiguous cases and optimize management.

Robotic-Assisted Simultaneous Bilateral Native Nephrectomy and Living Donor Kidney Transplantation.

Background/Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD), accounting for approximately 5–10% of patients receiving dialysis worldwide. The large and numerous cysts in the liver and kidneys cause abdominal distention and poor appetite. Previous studies showed that renal arterial embolization (RAE) reduces total kidney volume (TKV), increases appetite, and improves quality of life. This article aims to evaluate the efficacy of RAE in increasing psoas muscle (PM) and paraspinal muscle (PS) mass in patients with polycystic kidney disease. Methods: A retrospective study was conducted from May 2016 to December 2020. Thirty-five patients with PKD and ESKD who received RAE were enrolled. The clinical data, including age, sex, body weight, abdominal circumference, and laboratory results, including albumin, creatinine, estimated glomerular filtration rate, and dialysis vintage, were collected. TKV was calculated with the ellipsoid formula method, and muscle mass was measured with bilateral PM and PS areas at the third lumbar level. The associated clinical, laboratory, and imaging data were compared before and after RAE. Results: There were 19 females and 16 males with a mean age of 59.9 for the final analysis. There were significant changes between baseline and 3-month, 6-month, 12-month after RAE, such as a decrease in TKV (4684 ± 3361 vs. 4079 ± 3456, 3675 ± 3401, 2459 ± 1706 mL, all p < 0.001), an increase in the PM area (12.6 ± 5.8 vs. 13.3 ± 5.7, 14.7 ± 6.9, 14.3 ± 7.1 cm2, all p < 0.05), but no difference in body weight, body mass index, albumin, hemoglobin, creatinine, or estimated glomerular filtration rate. The increase in the PM and PS was more obvious in the sarcopenic group than in the non-sarcopenic group in the 12-month follow-up (p = 0.001 and 0.016 vs. p = 0.205 and 0.259). Conclusions: RAE effectively reduces TKV, increases PM and PS mass, and serves as a candidate to reverse muscle loss in patients with PKD.

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease, and the only approved pharmacological therapy shown to slow disease progression is tolvaptan. This study presents a long-term observation of ADPKD patients treated at our center, focusing on changes in eGFR approximately one year before and at least 1 year after the initiation of tolvaptan therapy. Materials and Methods: A retrospective analysis of a cohort of ADPKD patients who have received tolvaptan treatment in our center. Results: In total, 20 patients were enrolled in the analysis. Their median time of observation since tolvaptan introduction was 23.5 months. No statistically significant difference was noted in the median monthly decrease in eGFR between the time prior to tolvaptan introduction and during tolvaptan therapy. Analysis of trajectories of eGFR in particular patients enabled the division of the cohort into three subgroups: beneficiaries (n = 7, 35%), stable (n = 8, 40%), and progressors (n = 5, n = 25%). Conclusions: Despite the low number of patients, together with a relatively short observation period, which are the main limitations of our study, our results suggest that, in real-world settings, the efficacy of tolvaptan may be lower than previously reported. There is an urgent need to identify factors responsible for the suboptimal effect of the medicine. Our findings underscore the need to re-evaluate the current inclusion criteria for tolvaptan, particularly in real-world settings where patient variability is broader than in controlled clinical trials. Tailoring treatment qualification to include more practical and region-specific factors may enhance therapeutic outcomes.

Kidney volume, reflecting cumulative effects of many cysts, is an important prognostic biomarker for autosomal dominant polycystic kidney disease (ADPKD) but fails in many patients. Tracking individual cysts may more directly assess disease progression. Individual cysts (n = 299) from 37 subjects were evaluated retrospectively over ≥ 8 years by serial MRI (mean follow-up = 11 years). Cysts were labeled on every available MRI scan, totaling 1654 contours (median timepoints per cyst = 5). Effects of cyst location, morphology, and growth pattern on kidney function decline were evaluated by univariate and multivariate analyses. Simple, T2-bright cysts follow logistic growth (median cyst growth rate = 11%/year). A subset (94/222, 42%) transitions over time to shrinking, to complex solid-fluid/fluid-fluid cysts, then to homogeneously T1-bright cysts and finally disappearing. By contrast, T1-bright complex cysts have no volume change (median cyst growth rate = 0%/year; p < 0.001). On multivariate analysis, faster kidney function decline is associated with simple cyst diameter > 2 cm on index scan (p = 0.007) and simple cyst transitions (p = 0.02). There is a trend towards faster kidney function decline with higher simple cyst growth rate (p = 0.16). Profiling individual cysts on serial MRI to identify transitions as well as size and growth rate may improve predictions of ADPKD progression and treatment response.

Unrecognized Biases and Validation Gaps in TraceOrg for Automated Autosomal Dominant Polycystic Kidney Disease Volumetry.