Search Results (185)

The endocannabinoid system is a complex regulatory network whose functioning is associated with maintaining homeostasis and regulating immune response. The aim of this study was to evaluate the relationship between endocannabinoid system activity, inflammation, and the progression of chronic kidney disease (CKD) in patients with autosomal dominant polycystic kidney disease (ADPKD). The study included 105 participants: 60 individuals with ADPKD and 45 healthy volunteers. From a single venous blood draw, concentrations of anandamide (AEA), 2-arachidonoylglycerol (2-AG), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) were measured in EDTA plasma. Basic laboratory parameters were also assessed, including complete blood count, iron metabolism indices, electrolyte panel, and azotemia parameters. There were statistically significant differences in the concentrations of both endocannabinoids, with higher mean values observed in the control group (p < 0.001). IL-6 concentrations were significantly higher in the ADPKD group compared with controls (p < 0.001). Although TNF-α concentrations were higher in the ADPKD group than in the control group, these differences did not reach statistical significance. Statistically significant correlations were also identified between inflammatory markers, endocannabinoid concentrations, and indices of renal function. Patients with ADPKD exhibit an altered endocannabinoid profile characterized by reduced AEA and 2-AG concentrations, which correlates with disease progression and poorer kidney function. The endocannabinoid system may modulate inflammation in ADPKD. Full article

Autosomal dominant polycystic kidney disease (ADPKD), with a prevalence of approximately 1 in 1000, is the most common inherited cause of end-stage renal disease (ESRD). It is primarily caused by mutations in the PKD1 or PKD2 genes. Multiple studies have demonstrated that deficiency of polycystin proteins, dysregulation of signaling pathways, and activation of inflammatory factors contribute to the progression of ADPKD. The cAMP-targeting drug tolvaptan is currently the only approved therapy for ADPKD; however, its side effects and high cost have limited its widespread use. Meanwhile, mTOR inhibitors, AMPK-targeting agents, anti-inflammatory agents, and dietary interventions have shown promising results in treating ADPKD. Furthermore, the emergence of novel targets such as Notch3 and AURKA offers new directions for ADPKD therapy. This article aims to review the pathogenesis of ADPKD and current treatment advances, while exploring potential new targets for future research, hoping to provide a scientific theoretical foundation for disease management. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by progressive kidney enlargement by cyst formation. Endothelial dysfunction significantly contributes to chronic kidney disease (CKD). The Mediterranean diet (Med-diet) may reduce endothelial dysfunction in ADPKD patients, but its effect was not investigated in these patients. Our aim was to assess the relationship between Med-diet adherence and endothelial function biomarkers such as nitric oxide (NO) and endothelin-1 (ET-1). We enrolled ADPKD patients aged 18–70 years with CKD stages G2–G4. Adherence to the Med-diet was evaluated using the PREDIMED questionnaire. NO and ET-1 were evaluated at enrolment. Correlations and associations between these markers and Med-diet adherence were analysed. We enrolled 63 patients with ADPKD (mean age was 50.0 ± 11.8 years, 66.7% were female). A low/intermediate adherence to Med-Diet was assessed in 47 (74.6%) patients. When comparing patients with low/intermediate and high adherence, we found a higher NO and lower ET-1 serum concentration (p < 0.001 and p = 0.014, respectively) in patients with high adherence compared with low/intermediate ones. We found a significant correlation between Med-Diet adherence and NO (Spearman’s rs = 0.696, p < 0.001, 95%CI 0.542 to 0.805) and ET-1 serum concentrations (rs = −0.387, p = 0.002, 95%CI −0.579 to −0.154). For the univariable and multivariable linear regression analyses, we found an association between Med-Diet and NO (B: 0.547, 95%CI 0.050 to 0.121, p < 0.001) between Med-Diet and ET-1 (B: −0.327, 95%CI −0.157 to −0.020, p = 0.012). In conclusion, higher Med-Diet adherence seems to be associated with more favourable endothelial function in ADPKD patients. Full article

Background: Patients with chronic kidney disease (CKD), including autosomal dominant polycystic kidney disease (ADPKD), have been reported to be at higher risk for adverse outcomes during the COVID-19 pandemic. We aimed to obtain the characteristics and outcome data obtained in the follow-up of patients with ADPKD who survived COVID-19 and to compare these data with a control group with ADPKD who were COVID-19 naive. Methods: In this national, multicenter observational study, adult ADPKD patients who survived COVID-19 were included, and ADPKD patients without a history of COVID-19 from the same outpatient clinics were selected as a control group. Baseline characteristics and post-COVID-19 first- and third-month data were recorded. Results: In this study, a total of 72 ADPKD patients from 16 centers were included in the study (COVID-19 group, n: 40, non-COVID-19 control group, n: 32). Fourteen (33.3%) patients in the COVID-19 group were hospitalized during active COVID-19. During the first and third months after COVID-19, none of the patients died in either group. Urinary tract infection was significantly higher in the non-COVID-19 group than in the COVID group in the third month (0% vs. 12.5%, p = 0.021). All other follow-up outcomes, including respiratory symptoms and initiation of kidney replacement therapy (KRT), were not different between the groups in the first and third months. The laboratory data of the groups in the first and third months were not significantly different. Hematuria and leukocyturia ratios were also not statistically significantly different between the groups. Conclusions: ADPKD patients who survive COVID-19 have no worse short-term outcomes than non-COVID-19 ADPKD patients, including respiratory symptoms, initiation of KRT, and death. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder primarily known for progressive kidney cysts, and it is the most common hereditary syndrome linked to intracranial aneurysms (IAs). Approximately 5–20% of ADPKD patients have IAs (versus ~3% in the general population). Key risk factors for IAs in ADPKD include a family history of aneurysmal subarachnoid hemorrhage (SAH), early-onset or poorly controlled hypertension, and possibly more severe kidney disease (e.g., large total kidney volume and reduced kidney function). The PKD1 and PKD2 mutations in ADPKD lead to polycystin-1/-2 dysfunction in vascular cells, causing intrinsic vessel wall weakness. This weakness—compounded by chronic hemodynamic stress and inflammation—predisposes ADPKD patients to aneurysm formation. Clinically, most aneurysms in ADPKD are small (<7 mm), asymptomatic, and located in the anterior cerebral circulation. Their growth and rupture risk appears similar to aneurysms in non-ADPKD patients; however, ruptures in ADPKD occur at younger ages, underscoring the need for vigilant management. This narrative review provides a nephrology-oriented overview of intracranial aneurysms in ADPKD, including pathophysiology, epidemiology, and clinical management. Key Messages: -ADPKD carries a higher prevalence of intracranial aneurysms (≈5–20%) than the general population (≈3%). Key risk factors include a family history of aneurysm/SAH, early or poorly controlled hypertension, and possibly advanced renal disease. -Guidelines support targeted rather than universal screening, mainly in patients with family history or prior SAH. -Non-contrast MRA is the preferred modality, usually initiated around age 30 in at-risk individuals. -Most aneurysms are small and asymptomatic; small lesions are monitored with BP control and imaging, while larger or high-risk aneurysms are treated prophylactically. -Broader screening remains debated. Future genetic insights may improve risk stratification, but current practice requires balancing rupture prevention against over screening. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic kidney disease (≈4 cases per 10.000 inhabitants) and a major cause of end-stage kidney disease (ESKD). Beyond progressive cystic enlargement of the kidneys and frequent extrarenal involvement, adults with ADPKD often exhibit a distinctive “body phenotype” with central adiposity and marked abdominal distension due to renal and hepatic organomegaly. In this setting, conventional anthropometric indices such as body mass index (BMI) and crude body weight are of limited value, as they cannot distinguish nutritional tissues (muscle, subcutaneous fat) from non-nutritional mass (cyst fluid, fibrotic tissue, or expanded extracellular water). This review summarizes the current evidence on malnutrition and sarcopenia in adult ADPKD, with a focus on the impact of organomegaly and adiposity. Cross-sectional work using the modified Subjective Global Assessment (SGA) has shown that approximately one-third of ambulatory ADPKD patients are at risk of becoming, or have become, malnourished, and that height-adjusted total kidney and liver volume (htTKLV) is the strongest clinical predictor of malnutrition, whereas eGFR plays a secondary role. Bioelectrical impedance analysis (BIA) further demonstrates a disease-specific body composition phenotype, with increased total and extracellular body water, particularly in the trunk, a reduced phase angle and reduced lean mass, consistent with early malnutrition and sarcopenia. These alterations are present even at relatively preserved kidney function and, in matched analyses, distinguish ADPKD from non-ADPKD CKD. Prospective data from a multicenter cohort indicate that the baseline SGA-defined nutritional status independently predicts short-term eGFR decline in typical ADPKD, supporting malnutrition as a potential modifier of renal trajectory rather than a mere correlate of advanced disease. In parallel, narrative syntheses on adiposity highlight that a higher BMI, waist circumference and visceral fat are associated with larger total kidney volume, faster eGFR loss and greater symptom burden, and raise concern for a sarcopenic obesity phenotype in which excess fat and cystic mass coexist with low muscle mass. Collectively, these findings support a pathophysiological model in which organomegaly-driven mechanical effects (early satiety, gastrointestinal discomfort), systemic inflammation, insulin resistance and cyst-related metabolic reprogramming converge to produce “hidden malnutrition” in ADPKD, masked by apparent overweight. From a clinical perspective, malnutrition and sarcopenia should be regarded as central, disease-modifying components of the ADPKD phenotype. Routine nutritional screening (e.g., SGA/PG-SGA) and BIA-based body composition assessment, particularly in patients with severe organomegaly or symptomatic polycystic liver disease, should be integrated into ADPKD care pathways, and individualized, muscle-preserving nutritional strategies should be tested in future prospective studies. Full article

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 or PKD2, is characterized by progressive and exponential enlargement of renal and hepatic cysts. However, the epithelial dynamics that generate this growth pattern remain incompletely understood. Using Brainbow/Confetti multicolor clonal lineage tracing in developmental and adult-onset ADPKD mouse models, we show that polycystin-deficient epithelial cells initiate clonal expansion at early stages of tubule dilation and continue to expand throughout cyst progression. Concurrently, cyst-lining cells undergo a progressive transition from columnar to flattened morphology, which amplifies luminal enlargement independent of cell number. Integrating these measures, we developed a mathematical model demonstrating that the combination of this clonal expansion and epithelial cell shape remodeling is sufficient to produce the exponential growth trajectory observed in ADPKD. Together, these findings define the core epithelial mechanisms that drive cyst initiation and expansion, and may provide a mathematical framework for the emergent exponential growth of cysts. Full article

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. Full article

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. Full article

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. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder marked by progressive kidney enlargement and cyst formation, often resulting in end-stage renal disease (ESRD). Oxidative stress (OxS) significantly contributes to renal damage in chronic kidney disease (CKD) and ADPKD. While the Mediterranean diet (Med-diet) is known for its antioxidative and anti-inflammatory effects, its impact on OxS in ADPKD remains unclear. This study aimed to assess the relationship between adherence to the Med-diet, OxS levels, and renal function in ADPKD patients. We enrolled 63 ADPKD patients aged 18–70 years with CKD stages G2–G4. Adherence to the Med-diet was evaluated using the PREDIMED questionnaire. OxS markers (NOX2-derived peptide [sNOX2-dp] and hydrogen peroxide [H₂O₂]) were measured via ELISA. Correlations between these markers, Med-diet adherence, serum creatinine, and estimated glomerular filtration rate (eGFR) were analyzed. Higher adherence to the Med-diet was associated with significantly lower OxS markers (sNOX2, p < 0.001; H₂O₂, p = 0.04). Reduced NOX2 and H₂O₂ levels correlated with lower creatinine and higher eGFR (NOX2, p < 0.001; H₂O₂, p < 0.001), suggesting an inverse relationship between OxS and renal function. In conclusion, adherence to the Mediterranean diet appears to be associated with lower levels of oxidative stress and may slow the progression of chronic kidney disease. These findings suggest that dietary interventions could mitigate disease progression by modulating OxS. Further studies are needed to confirm these results and explore the long-term effects of the Med-diet on disease progression. Full article

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by multisystem involvement, including renal cysts, hepatic cysts, intracranial aneurysms, and aortic root dilatation and dissection. Though exceedingly rare, cervical artery dissections (CeAD) have been reported in association with ADPKD. The aim of this retrospective observational study is to investigate clinical features in patients with ADPKD that increase the probability of an associated CeAD diagnosis. Materials and Methods: The National Inpatient Sample from 2016 to 2020 was utilized to compare clinical features for patients with an ICD-10 code diagnosis of ADPKD, CeAD, and both ADPKD and CeAD. The Cochran–Armitage test and Chi-square test were utilized to assess clinical features or trends in ADPKD patients associated with a concurrent CeAD diagnosis. Results: Between 2016 and 2020, there were 224,065 people with ADPKD, 86,135 with CeAD and 155 with both (0.05%). The total cohort had a mean age of 56.74 years, with 47.26% female participants (p = 0.70), and was predominantly white (66.15%, p < 0.001). In patients with ADPKD, comorbid acute ischemic stroke (p < 0.001), transient ischemic attack (p < 0.001), aortic dissection (p < 0.001), coronary artery dissection (p < 0.001), subarachnoid hemorrhage (p < 0.001), coagulation defects (p = 0.002), and hypertension (p < 0.001) are risk factors associated with an increased probability of concomitant CeAD. Conclusions: CeAD in ADPKD patients is rare. In ADPKD patients, acute ischemic stroke, transient ischemic attack, aortic dissection, coronary artery dissection, subarachnoid hemorrhage, coagulation defects, and hypertension are risk factors of concomitant CeAD. Recognizing these factors can aid in the decision to screen for concomitant CeAD in patients with ADPKD. Full article

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in PKD1 or PKD2 genes, encoding polycystin-1 (PC1) or polycystin-2 (PC2), respectively, characterized by excessive cell proliferation and fluid secretion, resulting in renal cyst formation and growth. PC1 and PC2 form a complex localized on the plasma membrane, endoplasmic reticulum, and primary cilia. PC2 is a non-selective cation channel which, in renal epithelial cells, contributes to calcium transport and signaling. It has been previously shown in renal cells that high external calcium increases whole-cell currents likely mediated by PC2. In this study, we explored the possibility that the Calcium Sensing Receptor (CaSR) is involved in the functional regulation of PC2. To test this hypothesis, human conditionally immortalized Proximal Tubular Epithelial cells, isolated from urine sediments, wt or with stably downregulated PKD1 (PC1KD) or PKD2 (PC2KD) were used. Interestingly, CaSR and PC2 co-immunoprecipitated and Proximity Ligation Assay demonstrated a direct physical interaction at endogenous protein levels. Membrane potential measurements demonstrated that selective CaSR activation, elicited by the calcimimetic R568, caused plasma membrane depolarization, consistent with the modulation of PC2-mediated cation currents, which was significantly lower in PC2KD with respect to wt and PC1KD cells. To conclude, this study provides evidence for a functional coupling of CaSR and PC2, which might be relevant for therapeutic strategies to correct dysregulations occurring in ADPKD. Full article

Background/Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder; it is typically diagnosed in adulthood, but occasionally presents antenatally as very-early onset ADPKD. Despite advances in prenatal ultrasonography, knowledge regarding the postnatal course of fetal ADPKD remains limited, restricting reliable prognostic assessment and prenatal counselling. This study aimed to evaluate the prenatal sonographic features of fetal ADPKD and their correlation with postnatal outcomes. Materials and Methods: We retrospectively reviewed 20 cases of prenatally suspected ADPKD diagnosed at a single tertiary referral center between 2006 and 2024. Prenatal ultrasonographic findings including renal size, cortical echogenicity, corticomedullary differentiation (CMD), and cortical cysts were analyzed and correlated with postnatal clinical and genetic outcomes. Postnatal follow-up data, including renal function and progression to chronic kidney disease (CKD), were collected with a median follow-up of 93.6 months. Results: The most consistent prenatal ultrasonographic findings were increased cortical echogenicity (85%), increased CMD (75%), and renal enlargement (35%), with cortical cysts detected in 45% of cases. Amniotic fluid volume was preserved in most cases (80%). Postnatally, most infants maintained normal or near-normal renal function, although two progressed to CKD. Both CKD cases demonstrated absent CMD on prenatal imaging. Sonographic features resembling autosomal recessive polycystic kidney disease (ARPKD) were associated with adverse outcomes. Although CMD severity showed no correlation with short-term neonatal outcomes, loss of CMD may still serve as a potential early indicator of long-term renal dysfunction. Conclusions: Fetal ADPKD was associated with heterogeneous postnatal outcomes. Loss of CMD and ARPKD-like sonographic appearances may be associated with adverse prognosis, whereas most infants maintained preserved renal function. Early recognition of ADPKD is crucial for accurate counselling, appropriate perinatal management, and long-term surveillance. Full article

Objectives: In patients with autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) is the gold standard biomarker for assessing the risk of progression and the need for drug therapy. However, it is a time-consuming process. In this systematic review and meta-analysis, we evaluate the current state of deep learning (DL) algorithms for automatic kidney volume segmentation. Methods: All original research, including the search terms ADPKD, diagnostic imaging, DL, and TKV, was identified in PubMed, Embase, and Ovid MEDLINE databases from January 2000 to 13 October 2024. Articles with insufficient information to assess methodological quality were excluded. Quality was assessed using the “Quality Assessment of Diagnostic Accuracy Studies, Version 2” (QUADAS-2) and Checklist for Artificial Intelligence in Medical Imaging (CLAIM) tools. We focused on the Dice Similarity Coefficient (DSC), bias differences, and time efficiency as outcomes. Results: Nineteen studies were included, with an overall low risk of bias; however, the mean adherence to the CLAIM checklist was 64%. The pooled DSC under the random-effects model was $0.953$ (95% CI: $0.938–0.969$) with relatively low bias for TKV in 5622 ADPKD patients (mean age, 46.1 years; 45% male) and 9180 scans (79% MRI). The average segmentation time was decreased by 75% compared to the ground truth. Performance differences were evident among imaging modalities, MRI sequences, and 3D vs. 2D models, but not among imaging planes. The between-study heterogeneity was low ($I^2=0\%$), and no statistically significant evidence of small-study effects or publication bias was detected. Conclusions: DL models for TKV in ADPKD patients demonstrated high precision compared to manual segmentation in a large, pooled sample with heterogeneous study designs and methods. While clinical implementation is not yet feasible, the current work demonstrates the technical and diagnostic efficacy of image-based DL segmentation models. Full article