Search Results (109)

Ciliopathies, initially known as fibrocystic liver diseases, encompass a group of inherited disorders characterized by cystic dilatation of intrahepatic bile ducts and portal fibrosis, frequently associated with renal anomalies. These disorders are now recognized as resulting from defects in primary cilia. The hepatic manifestations, such as congenital hepatic fibrosis (CHF), Caroli syndrome, and polycystic liver disease, arise from ductal plate malformation. Recent studies have implicated variants in the TULP3 (Tubby related protein variant 3) gene in a novel monogenic ciliopathy affecting the liver, kidneys, and heart. We report an 8-year-old boy who presented with variceal bleeding and evolved to a progressive phenotype of CHF. Whole exome sequencing revealed a homozygous novel TULP3 mutation. The patient was managed by endotherapy and propranolol prophylaxis. Due to repeated episodes of variceal bleeding and progressive worsening of hepatic synthetic functions, he underwent a living donor liver transplantation at the age of 12 years. 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

The kidney’s intricate physiology relies on finely tuned gene regulatory networks that coordinate cellular responses to metabolic, inflammatory, and fibrotic stress. Beyond protein-coding transcripts, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators of renal biology. By modulating transcriptional, post-transcriptional, and epigenetic pathways, ncRNAs govern podocyte integrity, tubular adaptation, intercellular signaling, and immune activation. Dysregulation of these networks is now recognized as a hallmark of major kidney diseases, ranging from diabetic nephropathy and acute kidney injury to chronic kidney disease, glomerulopathies, and polycystic kidney disease. Mechanistic studies have revealed how pathogenic ncRNAs drive apoptosis, inflammation, fibrosis, and cystic remodeling, while protective ncRNAs mitigate these processes, highlighting their dual roles as both disease mediators and therapeutic targets. The exceptional stability of ncRNAs in urine, plasma, and exosomes further positions them as minimally invasive biomarkers with diagnostic and prognostic value. Translational advances include anti-miR and mimic-based therapies (e.g., lademirsen targeting miR-21, miR-29 mimics, anti-miR-17 oligonucleotides), alongside lncRNA silencing strategies, although challenges in delivery, safety, and redundancy remain significant. This review integrates molecular mechanisms with translational perspectives, providing a comprehensive synthesis of how ncRNAs shape renal pathophysiology. By bridging mechanistic insights with emerging diagnostic and therapeutic applications, we highlight the potential of ncRNAs to transform nephrology, paving the way for biomarker-driven precision medicine and novel interventions aimed at intercepting kidney injury at its regulatory roots. In clinical terms, ncRNA-based biomarkers and therapeutics promise earlier detection, more precise risk stratification, and individualized treatment selection within precision nephrology. Full article

Background: This retrospective case series examines incidental findings (IFs) detected on abdominopelvic CT (APCT) among young Korean soldiers presenting with acute abdominal pain. APCT is a frontline test for acute abdominal pain but frequently reveals incidental findings (IFs) unrelated to the presenting complaint. While many IFs are benign, some require structured follow-up. In military settings with constrained access and frequent personnel transfers, IFs pose challenges for health-system readiness. Methods: We retrospectively reviewed 1062 male Korean soldiers (18–28 years) who underwent APCT for acute abdominal pain at a military emergency department (ED) between January 2021 and December 2022. Two board-certified radiologists independently reassessed all scans to identify IFs and to classify those requiring follow-up based on contemporary guidelines. Results: IFs were identified in 218/1062 (20.5%) patients. Common categories included renal cysts (6.2%) and hepatobiliary IFs (7.5%). Clinically significant lesions comprised Bosniak IIF renal cysts (0.3%), inherited cystic kidney disease (0.2%), IPMN (0.1%), adrenal incidentalomas (0.4%), and appendiceal mucoceles (0.2%). An exploratory analysis suggested co-occurrence clusters (e.g., renal and hepatic cysts). Conclusions: IFs on APCT are prevalent even in a young, ostensibly healthy military cohort, highlighting a gap between detection and effective follow-up. Implementing structured reporting, automated tracking, and cross-institution referral pathways may mitigate long-term risk and support operational readiness in settings with limited subspecialty access and frequent relocations. Full article

The relationship between chronic kidney disease (CKD) and renal cell carcinoma (RCC) is both bidirectional and multifactorial. Several risk factors, including hypertension, diabetes mellitus, obesity, and smoking, have been associated with an increased risk for the development of CKD and RCC. CKD may predispose individuals to RCC through various mechanisms, including renal cystic diseases or induced oxidative stress effects. Conversely, RCC can induce CKD through the direct effects of the tumor, after surgeries for the management of the tumor (either partial or radical nephrectomy), and through perioperative acute kidney injury. Furthermore, medical interventions, including immunotherapy or targeted therapies, may precipitate acute kidney injury, potentially leading to the development of CKD. The expression of several genes in renal tissues has been related to the remodeling of kidneys during end-stage kidney disease and with an increased risk of the development of preneoplastic lesions and tumors. The aim of this review is to update the knowledge of these relationships, highlight the pathophysiologic mechanisms, and identify the genes and molecular expressions involved in this pathway. Full article

Background: In polycystic kidney diseases, increased periostin levels and disease progression are observed. Multicystic dysplastic kidney (MCDK) is characterized by kidney atrophy. The aim of the study is to assess serum periostin activity in children with MCDK and in patients with MCDK and involution of cysts. Methods: We enrolled in the study 64 children aged 1–5 years (mean age 25 +/− 9 months). Serum periostin (sPOSTN) levels were measured using enzyme-linked immunosorbent assay. We divided children into three groups: group A—patients with MCDK and cysts (n = 34); group B—patients with involution of cysts or after nephrectomy (n = 10), and group C—healthy children (n = 20). Results: Blood samples were obtained from 64 children, including 44 children with MCDK (26 boys, 18 girls). sPOSTN levels were significantly higher in group A, 239.1 ± 168.1 [IQR: 62.4, 385.7] ng/mL, compared to group B, 77.7 ± 82.8 [IQR: 31.7, 117.0] ng/mL (p < 0.05). The median level of periostin in patients with MCDK (groups A and B) was 204.4 ± 168.2 [IQR: 34.9, 363.4] ng/mL and 141.1 ± 129.0 [IQR: 30.3, 276.9] ng/mL in group C, respectively. In patients with the renal cysts, the cut-off value of periostin was 133.57 ng/mL. The lowest level of periostin was observed in patients in group B. There were no significant differences in periostin level between groups B and C. Conclusions: The study shows that a high level of sPOSTN was identified in patients with MCDK and cyst presentation in abdominal ultrasonography. The level of sPOSTN could be a promising blood marker of the cyst’s formation in cystic kidney diseases. However, this study remains preliminary; further studies are needed to confirm our findings. Full article

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal cyst development and variable trajectories toward end-stage renal disease (ESRD). Hypertension is both common and prognostically significant in ADPKD. However, the escalating need for antihypertensive agents beyond RAAS inhibition on disease progression remains underexplored. Methods: We conducted a retrospective, single-center cohort study including 133 ADPKD patients followed for a median of 5 years. Baseline clinical, biochemical, and genetic data were collected. The primary outcome was a ≥25% decline in eGFR over 5 years. All patients achieved a blood pressure target range of 110/70 to 130/85 mmHg during follow-up. Univariate and multivariate logistic regression analyses were performed to identify predictors of rapid progression. Results: Patients with hypertension resistant to RAAS (i.e., those requiring additional antihypertensive drugs on top of RAAS inhibitors) had significantly higher odds of rapid eGFR decline (multivariate OR 1.27; 95% CI 1.03–1.57; p = 0.0248). The presence of hypertension resistant to RAAS was interpreted as a potential clinical surrogate for a more aggressive cystic phenotype and intrarenal hemodynamic dysregulation. Conclusions: Hypertension resistant to RAAS is an independent predictor of accelerated renal function decline in ADPKD. Its identification may aid in early risk stratification and prompt consideration of disease-modifying therapies such as tolvaptan. Further validation in larger cohorts is warranted. Full article

P2Y₂ receptors are a subclass of G protein-coupled receptors activated by the extracellular nucleotides ATP and UTP. These receptors are widely expressed in multiple tissues—including the brain, lungs, heart, and kidneys—and play pivotal roles in inflammation, wound healing, and cell migration. Through coupling with various G proteins, P2Y₂ receptors initiate diverse intracellular signaling pathways that mediate calcium mobilization, cytokine release, and cytoskeletal reorganization. Recent studies highlight their dual roles in health and disease. In physiological contexts, P2Y₂ receptors contribute to immune modulation and tissue repair. In pathological conditions, they are implicated in Alzheimer’s disease by promoting non-amyloidogenic processing of amyloid precursor protein and in dry eye disease by enhancing mucin secretion while modulating ocular inflammation. They also influence chloride secretion and mucosal hydration in cystic fibrosis and contribute to inflammatory regulation and epithelial repair in inflammatory bowel disease. Additionally, P2Y₂ receptors modulate breast cancer progression by regulating cell adhesion, migration, and matrix remodeling. Their involvement in blood pressure regulation via epithelial sodium channel modulation and their facilitative role in HIV-1 entry further underscore their clinical significance. These multifaceted functions position P2Y₂ receptors as promising therapeutic targets for diverse diseases, warranting further investigation for translational applications. Full article

As people with cystic fibrosis (PwCF) live longer, kidney disease is emerging as a significant comorbidity that is increasingly linked to cardiovascular complications and progression to end-stage kidney disease. In our recent review, we proposed the unifying term CF-related kidney disease (CFKD) to encompass the spectrum of kidney dysfunction observed in this population. Early detection of kidney injury is critical for improving long-term outcomes, yet remains challenging due to the limited sensitivity of conventional laboratory tests, particularly in individuals with altered muscle mass and unique CF pathophysiology. Emerging approaches, including novel blood and urinary biomarkers, urinary extracellular vesicles, and genetic risk profiling, offer promising avenues for identifying subclinical kidney damage. When integrated with machine learning algorithms, these tools may enable the development of personalized risk stratification models and targeted therapeutic strategies. This precision medicine approach has the potential to transform kidney disease management in PwCF, shifting care from reactive treatment of late-stage disease to proactive monitoring and early intervention. Full article

Background: Senescence, a state of permanent cell cycle arrest, is a complex cellular phenomenon closely affiliated with age-related diseases and pathological fibrosis. Cellular senescence is now recognized as a significant contributor to organ fibrosis, largely driven by transforming growth factor beta (TGF-β) signaling, such as in metabolic dysfunction-associated steatohepatitis (MASH), idiopathic pulmonary fibrosis (IPF), chronic kidney disease (CKD), and myocardial fibrosis, which can lead to heart failure, cystic fibrosis, and fibrosis in pancreatic tumors, to name a few. MASH is a progressive inflammatory and fibrotic liver condition that has reached pandemic proportions, now considered the largest non-viral contributor to the need for liver transplantation. Methods: We previously studied Oxy210, an anti-fibrotic and anti-inflammatory, orally bioavailable, oxysterol-based drug candidate for MASH, using APOE*3-Leiden.CETP mice, a humanized hyperlipidemic mouse model that closely recapitulates the hallmarks of human MASH. In this model, treatment of mice with Oxy210 for 16 weeks caused significant amelioration of the disease, evidenced by reduced hepatic inflammation, lipid deposition, and fibrosis, atherosclerosis and adipose tissue inflammation. Results: Here we demonstrate increased hepatic expression of senescence-associated genes and senescence-associated secretory phenotype (SASP), correlated with the expression of pro-fibrotic and pro-inflammatorygenes in these mice during the development of MASH that are significantly inhibited by Oxy210. Using the HepG2 human hepatocyte cell line, we demonstrate the induced expression of senescent-associated genes and SASP by TGF-β and inhibition by Oxy210. Conclusions: These findings further support the potential therapeutic effects of Oxy210 mediated in part through inhibition of senescence-driven hepatic fibrosis and inflammation in MASH and perhaps in other senescence-associated fibrotic diseases. Full article

Background and Clinical Significance: Spontaneous renal hematoma, also known as Wunderlich syndrome (WS), is a rare disease characterized by the acute onset of spontaneous renal hemorrhage into the subcapsular, perirenal, and/or pararenal spaces without a history of prior trauma. WS can be a life-threatening condition due to hemorrhagic shock; consequently, prompt diagnosis and a therapeutic approach are essential for favorable outcomes. Treatment ranges from conservative management to surgical intervention. The most common etiologies are neoplasms and vascular diseases, but WS can also be observed in patients undergoing hemodialysis. In patients with end-stage renal disease (ESRD), especially those on hemodialysis, acquired cystic kidney disease and renal cell carcinoma are among the primary causes of WS. Although less common, WS can develop in dialysis patients even in the absence of traditional (primary) risk factors. In general, patients with chronic kidney disease (CKD) have a paradoxical hemostatic profile, likely explaining their higher tendency to bleed, so WS can occur without existing predisposing factors. The multifactorial pathogenesis in these patients includes functional platelet abnormalities, intimal arterial fibrosis, chronic inflammation, and oxidative stress associated with ESRD. The use of hemodialysis-related antithrombotic medications could serve as another contributing factor increasing the risk of bleeding. Case Presentation: We present a case report of a 62-year-old male on chronic dialysis who developed sudden right-sided lumbar pain and hematuria during dialysis without evidence of prior trauma. Imaging revealed a large subcapsular hematoma of the right kidney. Further investigations did not reveal additional risk factors in this instance; however, his routinely used hemodialysis-related antithrombotic medications were potentially a contributing factor. Despite conservative treatment, his condition worsened, and the hematoma enlarged, requiring emergency nephrectomy. Postoperatively, his condition gradually improved. Conclusions: This case highlights the importance of considering WS in hemodialysis patients, even without the presence of traditional risk factors, as well as including WS in the differential diagnosis of acute abdominal pain. Full article

Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD), the most common renal genetic disease, leading to the dysregulation of renal tubules and the development of cystic growth that compromises kidney function. Despite significant advances in recent decades, there remains a considerable unmet clinical need, as current therapeutics are not effective at slowing or halting disease progression. Although preclinical animal models have been used extensively, the translatability of such findings is uncertain and human-relevant disease models are urgently needed. The advent of pluripotent stem cells (PSCs) and their ability to more accurately recapitulate organ architecture and function has allowed for the study of renal disease in a more physiological and human-relevant setting. To date, many research groups have studied ADPKD using PSC-derived kidney organoids, identifying many dysregulated pathways and screening drug candidates that may yield effective therapies in the clinic. In this review article, we discuss in detail the development of PSC-derived kidney organoids as ADPKD models and how they have advanced our understanding of the disease’s pathogenesis, as well as their limitations and potential strategies to address them. Full article

Renal cell carcinoma (RCC) is the most prevalent solid organ malignancy among kidney transplant recipients, demonstrating substantially higher incidence rates compared to those in the general population. Although RCC is most commonly diagnosed in native kidneys, its development in transplanted kidneys has an infrequent occurrence. The use of immunosuppressive therapies, pre-existing chronic kidney disease and the unique anatomical characteristics of transplanted kidneys represent considerable therapeutic challenges in managing RCC within this patient cohort. Open radical transplantectomy plays a crucial role in curative treatment for localized RCC, whereas nephron-sparing surgery (NSS), in selected cases, can provide similar oncologic benefits while preserving allograft function. Recently, laparoscopic and robotic surgical procedures have demonstrated favorable outcomes as viable alternatives to conventional open surgery. Furthermore, ablative therapies like radiofrequency ablation and cryoablation can be considered therapeutic alternatives for small renal masses, offering the benefit of preserving allograft function, especially in high-risk surgical candidates. Limited data exist regarding the management of metastatic RCC in transplant recipients. Surgery, withdrawal of immunosuppression and systemic adjuvant therapy could be considered. Management of RCC in transplanted kidneys requires a multidisciplinary approach considering patient-specific characteristics, tumor features and the developing landscape of both surgical and non-surgical options. Further research is needed to refine therapeutic strategies in order to achieve optimal oncological outcomes while preserving allograft function. Full article

Pathogenic variants in type IV collagen genes (COL4A3, COL4A4, COL4A5) are classically associated with Alport syndrome (AS), a hereditary nephropathy primarily affecting the glomerular basement membrane (GBM). Recent findings, however, suggest a broader phenotypic spectrum that includes renal cyst formation, raising questions about overlapping mechanisms with other cystic kidney diseases. Clinically, renal cysts have been increasingly reported in patients with autosomal dominant and X-linked forms of Alport syndrome, particularly in association with glycine missense variants. The most recent studies focusing on the cystic phenotype in Alport syndrome provide growing support for the idea that variants in type IV collagen genes are associated with an increased likelihood of developing renal cysts, likely through mechanisms involving the structural integrity of renal basement membranes. In this review, we explore evidence from murine models and human studies indicating defects in collagen IV and discuss their contribution to cystogenesis. These observations underscore the need for broader genetic screening strategies and further investigation into the molecular mechanisms underlying this emerging phenotype. Full article