多発性嚢胞腎

Congenital abnormalities of the biliary tree are increasingly identified in adulthood as incidental findings on cross-sectional imaging. They range from clinically silent anatomical variants to complex malformations with relevant clinical or surgical implications. This review provides a practical framework for radiologists who encounter these entities in adult patients, organizing them into four categories: congenital cystic biliary dilation, fibropolycystic liver disorders arising from ductal plate malformation, anatomical variants of the biliary tree, and rare developmental anomalies such as ductal duplication, ectopic biliary drainage, and gallbladder agenesis or hypoplasia. Magnetic resonance imaging with cholangiopancreatography (MRCP) is the diagnostic cornerstone, allowing non-invasive assessment of ductal communication, morphology, and pancreaticobiliary junction anatomy, while computed tomography (CT) plays a complementary role in evaluating complications. Key diagnostic CT and MRI features are discussed, including the central dot sign of Caroli disease, the diffuse non-communicating cystic pattern of polycystic liver disease, and the abnormally long common channel characteristic of pancreaticobiliary maljunction. The review also addresses the surgical relevance of biliary anatomical variants. A compact diagnostic algorithm and a structured reporting checklist are provided, together with the acquired conditions that most often mimic congenital disease in adults. From a clinical standpoint, malignant potential varies substantially across entities, ranging from negligible in polycystic liver disease to substantially increased in choledochal cysts and pancreaticobiliary maljunction, although the available estimates derive largely from heterogeneous, mostly retrospective rare-disease series and should be interpreted as orders of magnitude rather than precise risks. This variability nonetheless drives surveillance strategy. A systematic diagnostic approach, combined with close collaboration between radiologists, hepatologists, and surgeons, is essential to guide appropriate management and avoid both missed malignancies and unnecessary intervention.

Chronic kidney disease is a global epidemic affecting ≈10% of adults worldwide. Women have a higher prevalence of chronic kidney disease than men yet are less likely to progress to kidney failure, to initiate dialysis, or to receive a kidney transplantation, underscoring the influence of biological sex on chronic kidney disease development, progression, treatment response, and outcomes. Women may also respond differently from men to pharmacological therapies, but they remain underrepresented in clinical trials, limiting the evidence base for sex-specific kidney care. Preclinical evidence implicates a role for estrogen receptor signaling in renal physiology and pathophysiology. Women with chronic kidney disease are at increased risk for adverse pregnancy outcomes and hypertensive disorders of pregnancy, and pregnancy complications can also increase future chronic kidney disease risk. Menopause and aging accelerate chronic kidney disease progression in women as a result of declining estradiol and shifts in kidney estrogen receptor profiles. Endocrine and metabolic disorders such as polycystic ovary syndrome increase susceptibility to chronic kidney disease. Family planning, prepregnancy counseling, and antenatal care are essential to support reproductive health in women with chronic kidney disease. Because chronic kidney disease and cardiovascular disease are tightly intertwined, chronic kidney disease is also a leading contributor to cardiovascular mortality in women. Advancing precision kidney medicine for women requires equitable access to kidney care, embedding assessment of reproductive health in chronic care, trial design with adequate power that includes both women and men, and mechanistic studies linking reproductive health to long-term cardiovascular disease and chronic kidney disease development and progression.

BACKGROUND: Native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) undergoing kidney transplantation remains controversial, particularly regarding indications, timing, and laterality. This study evaluated surgical strategies and outcomes of native nephrectomy in ADPKD kidney transplant candidates. METHODS: We retrospectively analyzed adult patients with ADPKD who underwent kidney transplantation at a single center between 1999 and 2021. Demographic, transplant-related, nephrectomy-related, surgical, complication, and histopathological data were compared between patients who underwent native nephrectomy and those managed without nephrectomy. RESULTS: Among 109 patients with ADPKD, 79 (72%) underwent native nephrectomy and 30 (28%) did not. Patients undergoing nephrectomy had significantly higher body weight and were more frequently on dialysis before transplantation. Most nephrectomies were performed before transplantation, predominantly as bilateral procedures. The leading indication was lack of intra-abdominal space for graft implantation, followed by cyst infection, chronic pain, and hemorrhagic cysts. Post-transplant nephrectomy was uncommon and mainly performed for persistent or delayed native kidney-related complications. Postoperative complications, including bleeding requiring transfusion, fluid collections, incisional hernias, and surgical reinterventions, with no statistically significant differences in complication rates between nephrectomy strategies. No malignancy was identified in the available histopathological specimens. CONCLUSIONS: Native nephrectomy was frequently performed in ADPKD kidney transplant candidates, most often before transplantation and primarily to create sufficient space for graft implantation. Bilateral pre-transplant nephrectomy was the predominant strategy but was associated with most postoperative complications. These findings highlight the variability of current practice and support individualized, anatomy- and symptom-based decision-making.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive kidney disorder with limited therapeutic options, highlighting an urgent need for safer, long-term treatments. This study presents a multi-step computational and experimental approach to identify and assess target-based hypotheses for mechanisms underlying the cAMP-dependent cyst swelling. We analyzed phenotypic screening data from a 3D mIMCD3-Pkd1-/- forskolin-induced, cAMP-driven cyst swelling (CS) assay, classifying compounds based on their CS activity. These compounds were cross-referenced with the Papyrus database to identify known biological targets, which were then prioritized by considering their expression in the screened cell model and by deprioritizing targets associated with antineoplastic activity. Four prioritized targets, P2X purinoceptor 7 (P2RX7), Glucose Transporter 1 (GLUT1), Mineralocorticoid Receptor (MR), and Adenosine A1 Receptor (A1AR), were experimentally evaluated by testing known ligands in the phenotypic assay. While P2RX7 modulation showed no effect, GLUT1 inhibitors significantly reduced cyst swelling. For A1AR, known agonists reduced CS while the inverse agonist DPCPX enhanced it. In contrast, MR modulation showed compound-specific effects, with the antagonist Esaxerenone uniquely reducing CS among tested MR antagonists. Quantitative structure-activity relationship (QSAR) models for A1AR and MR were used to select structural analogues of known active compounds within chemical vendor catalogues to further confirm identified target-ADPKD activity space. Radioligand displacement assays were conducted to confirm the QSAR-predicted A1AR binding affinities and selectivity among adenosine receptor subtypes. A1AR affinity and subtype selectivity was a common denominator among ligands with CS-reducing activity, with the A1AR positive allosteric modulator MIPS521 showing the strongest effect. The workflow therefore generated a coherent A1AR-linked hypothesis and identified Esaxerenone as a compound-specific phenotypic hit; both require mechanistic confirmation and evaluation in additional disease models.

Autosomal dominant polycystic kidney disease (ADPKD), mainly driven by pathogenic variants in PKD1 and PKD2, is the most common inherited cause of kidney failure. Details of ADPKD pathogenesis are incompletely resolved, but primary cilia are an integral component. There is also evidence for changes to the tubular basement membrane (TBM) in early disease. In this issue of the JCI, Mazloum and colleagues link cilia-dependent, PKD1-mediated regulation of the TBM to ADPKD pathogenesis. Using in vivo, ex vivo, tubule-on-chip, and cellular models of ADPKD, they connect cilia-dependent tubule dilation and TBM thinning to early-stage cystogenesis. Moreover, they identify a cilia-dependent TBM remodeling expression signature in affected tubules and suggest that PC1 loss compromises TBM stiffness. By integrating roles for cilia at the apical membrane and extracellular matrix at the basolateral membrane in cystogenesis, this work highlights the TBM as an additional area for investigation of therapeutic and biomarker discovery in ADPKD.