Search Results (195)

Both genetics and the environment affect the phenotypes of polycystic kidney diseases (PKD), such as autosomal dominant (AD) PKD, autosomal recessive (AR) PKD and nephronophthisis (NPH). Variable phenotypes, pleiotropy, divergent severity and progression, even in family members who inherited the same disease-causing mutation(s), signal the involvement of networked genes and modifiers. Several PKD-linked genes function in development and renal tubule morphogenesis. Cystic renal tissues feature metabolic remodeling, functional reprogramming and dysregulation of several shared factors and pathways. ADPKD, ARPKD and NPH partially phenocopy each other. Understanding the developmental arc of cystic kidney disease and its complex phenotypes would improve diagnostics and help develop effective personalized treatments. However, this is challenging to study in vertebrate systems due to genetic redundancy, functional overlap, and a dearth of genetic tools. Underused in this context, Drosophila melanogaster offers high genomic and pathway conservation, a wealth of genetic tools, and rapid generation times, making it a reliable and sustainable model for mechanistic, genome-wide, and precision medicine studies. Here, we surveyed ADPKD, ARPKD, and NPH, compared renal and extrarenal phenotypes, and examined the network of shared and unique contributors, their healthy and diseased functions and conservation from the perspective of mechanistic whole-animal modeling. Full article

Vaptans are non-peptide arginine vasopressin (AVP) receptor antagonists essential for modulating water homeostasis. This review evaluates their chemical evolution from peptide analogs to orally bioavailable molecules and summarizes the pharmacokinetic profiles of key agents, including tolvaptan, conivaptan, and mozavaptan. Significant emphasis is placed on the clinical role of tolvaptan as a disease-modifying therapy in autosomal dominant polycystic kidney disease (ADPKD) and its efficacy in syndrome of inappropriate antidiuretic hormone secretion (SIADH). Furthermore, the impact of pharmacogenetic factors, especially CYP3A5 and SVEP1 polymorphisms, is explored as a potential source of inter-individual variability in treatment response. By integrating structural, metabolic, and genetic data, this article highlights the potential for personalized aquaretic therapy and identifies critical safety and monitoring protocols necessary for optimizing clinical outcomes. Full article

Background: Native nephrectomy is frequently required in autosomal-dominant polycystic kidney disease (ADPKD) before or during transplantation, but the optimal minimally invasive approach is unsettled, and it is unclear whether the pattern of post-operative complications tracks with operative technique. We report a retrospective single-centre experience of hand-assisted laparoscopic (HAL) native nephrectomy and, alongside it, a technique-stratified scoping review of complications. Methods: We retrospectively reviewed all consecutive adults undergoing HAL native nephrectomy—with an infra-umbilical midline hand-port and free intraperitoneal cyst rupture—in preparation for transplantation in the period between December 2019 and December 2025. In parallel, we performed a PRISMA-ScR-compliant scoping review (MEDLINE, Embase, Scopus) of minimally invasive ADPKD nephrectomy, with duplicate independent screening and extraction, stratifying complications by operative approach and cyst-decompression method. No quantitative pooling was undertaken. Results: Twenty-three patients (mean age 52.8 ± 9.9 years; 87% dialysis-dependent; 78% for transplant preparation) were included. Median operative time was 102 min (IQR 90–122) with minimal blood loss, one transfusion (4%), and no open conversion. Complications occurred in 8/23 (35%) and were bowel-predominant: one small-bowel perforation, two obstructions, and one ileus—three of Clavien–Dindo grade IIIb, all in right-sided nephrectomies and independent of specimen weight. Peri-operative mortality was 1/23 (4%), from a non-technique-related mycotic aortic dissection. Of 481 records screened, 19 studies met inclusion; the cyst-decompression method was reported in only 7 (37%). Bowel events clustered in series using free intraperitoneal cyst rupture or puncture and were largely absent where decompression was contained, a pattern crossing platform boundaries and that is mechanistically consistent with intraperitoneal spillage of cyst contents. Conclusions: HAL native nephrectomy is a rapid and feasible means of removing massively enlarged polycystic kidneys before transplantation but, in our experience, carries a bowel-predominant morbidity that clustered in right-sided procedures and was independent of specimen weight. The sparse literature is consistent with—but cannot confirm—a relationship to intraperitoneal cyst spillage rather than to the hand-assisted approach itself. Whether contained cyst decompression can preserve operative efficiency while reducing bowel morbidity is a hypothesis warranting prospective study. Full article

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a clinically heterogeneous disorder often leading to end-stage renal disease (ESRD). Prognostication of disease progression remains a major clinical challenge. This study aimed to identify plasma amino acid signatures associated with ADPKD progression and hypertension. Methods: We conducted targeted metabolomic analysis (LC-MS/MS) to quantify 38 plasma amino acids in 203 ADPKD patients, stratified by disease progression (rapid vs. slow) and hypertension status. Support Vector Machine (SVM) models were developed to predict outcomes using clinical data, amino acid profiles, and combined datasets. Results: Our findings revealed that specific amino acid signatures, including valine, glutamic acid, homocitrulline, and methylhistidines, were significantly elevated in both rapid progression and hypertensive groups. Isoleucine and citrulline were elevated only in rapid progressors. Phenylalanine, leucine, asparagine, and arginine were elevated in hypertensive patients. Machine learning analysis showed that integrating clinical and metabolic data modestly improved prediction for progression and hypertension. Proteinuria, glomerular filtration rate (GFR), and uric acid were the top clinical predictors; however, adding arginine, isoleucine, and 3-methylhistidine further enhanced prediction accuracy. Pathway analysis showed shared dysregulation in arginine biosynthesis and branched-chain amino acid (BCAA) metabolism. Specific amino acids were positively correlated with creatinine and uric acid and negatively correlated with GFR, and elevated levels of these metabolites were associated with increased mortality risk in survival analysis. Conclusions: Our results suggest that these plasma amino acid signatures, when combined with clinical markers, may serve as potential biomarkers for early risk stratification and precision prediction of ADPKD progression and hypertension. Full article

Chronic kidney disease (CKD) has become a global health issue, affecting up to 14% of the population worldwide. Between 1990 and 2021, the number of patients grew from 351 million to almost 674 million, with projections warning that CKD may rank as the fifth leading cause of death globally by 2040. Clinically, CKD stems from a complex mix of etiologies, including lifestyle-driven civilization diseases, such as diabetes, hypertension, or obesity, immune-mediated glomerulonephritides (such as IgA, membranous nephropathy or focal segmental glomerulosclerosis), genetic (such as autosomal-dominant polycystic kidney disease, Fabry disease) and tubulointerstitial diseases, or causes of undetermined etiology. Time to diagnosis and the diagnosis of CKD before end-stage organ failure are crucial; therefore, new methods are actively being developed for early detection of kidney disease. Physicians emphasize the need to evaluate markers of kidney dysfunction faster and more accurately. Modern nephrology relies on multi-omics profiling, encompassing genomics, transcriptomics, proteomics, and metabolomics. Applying these technologies to identify molecular drivers of the disease can yield specific signatures that help clinicians stratify patients and decide on a treatment and follow-up plan. Our review addresses a fundamental transformation reshaping nephrology: the transition from a traditional to precision medicine approach. Full article

Treating autosomal dominant polycystic kidney disease (ADPKD) has always been a challenge because the disease is too complex for single-target drugs, which are often held back by side effects. This narrative review explores a different strategy: using plant-derived polyphenols to target multiple disease pathways at the same time. Looking at research from 2005 to 2026, we break down how key compounds like resveratrol, curcumin, naringenin, quercetin, and epigallocatechin-3-gallate (EGCG) actually work. Preclinical studies show these molecules can slow down cyst growth by tackling inflammation, rapid cell division, and tissue scarring all at once, while also resetting the skewed energy metabolism of cystic cells. Some mechanisms are strikingly specific, such as naringenin’s direct interaction with polycystin-2 and quercetin’s ability to clear senescent cells. Yet, the real-world hurdle is poor absorption; a recent clinical trial with standard curcumin fell short simply because the compound could not reach the kidneys in high enough concentrations. Moving forward, the field needs to focus on testing these compounds in realistic animal models, designing smart nanoformulations to improve bioavailability, and exploring combinations that could safely complement current therapies like tolvaptan. Full article

(1) Background: Cardiovascular disease represents the leading cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD), often developing early in the disease course, even in the presence of preserved renal function. We aimed to evaluate circulating heart-type fatty acid–binding protein (H-FABP) as a marker of subclinical cardiac involvement and cardiorenal interaction in ADPKD. (2) Methods: In this single-center observational study, 80 adult patients with ADPKD receiving tolvaptan therapy were evaluated using echocardiography, renal function parameters, and circulating H-FABP levels. Associations between H-FABP and echocardiographic indices of cardiac structure and function, as well as renal parameters, were assessed using linear regression models. In addition, a composite severity score integrating CKD stage and H-FABP levels was constructed to assess the combined cardiorenal burden. (3) Results: Higher H-FABP concentrations were significantly associated with echocardiographic markers suggestive of subclinical cardiac involvement, particularly parameters related to impaired myocardial relaxation, including lower E/A ratio and reduced tissue Doppler e′ velocities. These associations remained significant after adjustment for renal function and relevant clinical covariates. In parallel, H-FABP levels were also associated with markers of renal disease severity, including lower baseline eGFR and greater total kidney volume. The composite severity score showed a graded association with echocardiographic parameters, with a progressive trend toward less favorable diastolic indices as risk categories increased. These findings suggest a potential complementary role for H-FABP in the integrated evaluation of cardiorenal involvement in ADPKD. Given the cross-sectional design and single-centre setting, these results should be considered hypothesis-generating and require prospective validation in larger, independent cohorts. Full article

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

Gender medicine represents a key paradigm for advancing equitable and effective healthcare by systematically integrating sex- and gender-related differences into medical research and clinical practice. Despite regulatory efforts and international guidelines, significant gaps persist in the consideration of sex and gender across medical disciplines, including nephrology. Biological factors—including genetic, hormonal, and metabolic differences—interact with social, cultural, and environmental determinants to influence chronic kidney disease (CKD) susceptibility, clinical presentation, progression, and response to therapy. Insufficient consideration of sex and gender contributes to persistent disparities in CKD progression, cardiovascular outcomes, access to kidney transplantation, adverse drug reactions, dialysis outcomes, and pregnancy-related kidney complications. This narrative review outlines the historical development of gender medicine and critically appraises its relevance and unresolved challenges in kidney disease, with a focus on sex-specific differences in selected conditions, including autosomal dominant polycystic kidney disease, glomerular diseases, acute kidney injury, and pregnancy-associated kidney disorders. Integrating sex- and gender-informed approaches into nephrology is not merely an ethical requirement but a scientific necessity to improve risk stratification, personalize therapeutic strategies, and promote truly equitable and effective kidney care. 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