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Journal of the American Society of... Aug 2021In autosomal dominant polycystic kidney disease (ADPKD), cyst development and enlargement lead to ESKD. Macrophage recruitment and interstitial inflammation promote cyst... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In autosomal dominant polycystic kidney disease (ADPKD), cyst development and enlargement lead to ESKD. Macrophage recruitment and interstitial inflammation promote cyst growth. TWEAK is a TNF superfamily (TNFSF) cytokine that regulates inflammatory responses, cell proliferation, and cell death, and its receptor Fn14 (TNFRSF12a) is expressed in macrophage and nephron epithelia.
METHODS
To evaluate the role of the TWEAK signaling pathway in cystic disease, we evaluated Fn14 expression in human and in an orthologous murine model of ADPKD. We also explored the cystic response to TWEAK signaling pathway activation and inhibition by peritoneal injection.
RESULTS
Meta-analysis of published animal-model data of cystic disease reveals mRNA upregulation of several components of the TWEAK signaling pathway. We also observed that TWEAK and Fn14 were overexpressed in mouse ADPKD kidney cysts, and TWEAK was significantly high in urine and cystic fluid from patients with ADPKD. TWEAK administration induced cystogenesis and increased cystic growth, worsening the phenotype in a murine ADPKD model. Anti-TWEAK antibodies significantly slowed the progression of ADPKD, preserved renal function, and improved survival. Furthermore, the anti-TWEAK cystogenesis reduction is related to decreased cell proliferation-related MAPK signaling, decreased NF-B pathway activation, a slight reduction of fibrosis and apoptosis, and an indirect decrease in macrophage recruitment.
CONCLUSIONS
This study identifies the TWEAK signaling pathway as a new disease mechanism involved in cystogenesis and cystic growth and may lead to a new therapeutic approach in ADPKD.
Topics: Adult; Animals; Antibodies, Neutralizing; Apoptosis; Cell Proliferation; Cysts; Cytokine TWEAK; Disease Models, Animal; Disease Progression; Female; Fibrosis; Gene Expression; Humans; Macrophage Activation; Macrophages; Male; Mice; Middle Aged; NF-kappa B; Polycystic Kidney, Autosomal Dominant; Signal Transduction; TWEAK Receptor
PubMed: 34155062
DOI: 10.1681/ASN.2020071094 -
Physiological Reviews Oct 1998In autosomal dominant polycystic kidney disease (ADPKD), the genetic defect results in the slow growth of a multitude of epithelial cysts within the renal parenchyma.... (Review)
Review
In autosomal dominant polycystic kidney disease (ADPKD), the genetic defect results in the slow growth of a multitude of epithelial cysts within the renal parenchyma. Cysts originate within the glomeruli and all tubular structures, and their growth is the result of proliferation of incompletely differentiated epithelial cells and the accumulation of fluid within the cysts. The majority of cysts disconnect from tubular structures as they grow but still accumulate fluid within the lumen. The fluid accumulation is the result of secretion of fluid driven by active transepithelial Cl- secretion. Proliferation of the cells and fluid secretion are activated by agonists of the cAMP signaling pathway. The transport mechanisms involved include the cystic fibrosis transmembrane conductance regulator (CFTR) present in the apical membrane of the cystic cells and a bumetanide-sensitive transporter located in the basolateral membrane. A lipid factor, called cyst activating factor, has been found in the cystic fluid. Cyst activating factor stimulates cAMP production, proliferation, and fluid secretion by cultured renal epithelial cells and also is a chemotactic agent. Cysts also appear in the intrahepatic biliary tree in ADPKD. Normal ductal cells secrete Cl- and HCO3-. The cystic ductal cell also secretes Cl-, but HCO3- secretion is diminished, probably as the result of a lower population of Cl-/HCO3- exchangers in the apical membrane as compared with the normal cells. Some segments of the normal renal tubule are also capable of utilizing CFTR to secrete Cl-, particularly the inner medullary collecting duct. The ability of Madin-Darby canine kidney cells and normal human kidney cortex cells to form cysts in culture and to secrete fluid and the functional similarities between these incompletely differentiated, proliferative cells and developing cells in the intestinal crypt and in the fetal lung have led us to suggest that Cl- and fluid secretion may be a common property of at least some renal epithelial cells in an intermediate stage of development. The genetic defect in ADPKD may not directly affect membrane transport mechanisms but rather may arrest the development of certain renal epithelial cells in an incompletely differentiated, proliferative stage.
Topics: Animals; Biological Transport; Cysts; Disease Models, Animal; Dogs; Epithelial Cells; Humans; Liver Diseases; Polycystic Kidney, Autosomal Recessive
PubMed: 9790573
DOI: 10.1152/physrev.1998.78.4.1165 -
Journal of Visceral Surgery Dec 2018Polycystic liver disease (PLD) may consist of autosomal dominant PLD or isolated PLD without renal impairment. The natural history of liver cysts is to increase in size... (Review)
Review
Polycystic liver disease (PLD) may consist of autosomal dominant PLD or isolated PLD without renal impairment. The natural history of liver cysts is to increase in size and number, causing progressive disease that can lead to very large and incapacitating hepatomegaly. Only symptomatic hepatomegaly (pain, inability to eat, weight loss, dyspnea) or cystic complications such as infection or intracystic hemorrhage should be treated. The treatment of PLD thus covers a wide range of therapeutic options, ranging from non-intervention to liver transplantation, including needle aspiration evacuation with injection of sclerosant, laparoscopic fenestration and fenestration by laparotomy combined with liver resection. The choice between these different treatments depends on the symptomatology, the intrahepatic extension of the lesions and the patient's general condition. Hepatic resection is commonly chosen since the vast majority of PLD consists of multiple small cysts that are impossible or difficult to fenestrate. Since cysts are inhomogeneously distributed in the hepatic parenchyma with most areas less affected, the preservation of this less-involved territory allows liver regeneration relatively free of cysts. Hepatectomies for PLD are technically difficult because the planes and the vascular and biliary structures are compressed by the cysts. Liver transplantation, whether isolated or associated with renal transplantation, is indicated in cases of severe malnutrition and/or end-stage renal disease or if the volume of remnant parenchyma is insufficient and suggests failure of a partial hepatectomy.
Topics: Ascites; Cysts; Embolization, Therapeutic; Everolimus; Female; Hemorrhage; Hepatectomy; Hepatomegaly; Humans; Liver Diseases; Liver Transplantation; Male; Organ Sparing Treatments; Renal Artery; Sclerosing Solutions; Sex Factors; Somatostatin; Tomography, X-Ray Computed
PubMed: 30145049
DOI: 10.1016/j.jviscsurg.2018.07.004 -
TheScientificWorldJournal Aug 2008Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from...
Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from tubulointerstitial nephropathy. Biopsy findings in patients with lithium-induced chronic tubulointerstitial nephropathy include tubular atrophy and interstitial fibrosis interspersed with tubular cysts and dilatations. Recent studies have shown that cysts are seen in 33-62.5% of the patients undergoing lithium therapy. MR imaging is highly capable of defining renal morphological features and has been demonstrated to be superior to US and CT scan for the visualization of small renal cysts. The microcysts are found in both cortex and medulla, particularly in the regions with extensive atrophy and fibrosis, and can be multiple and bilateral. They tend to be sparse and do not normally exceed 1-2 mm in diameter. The renal microcysts in the image here reported are subtle, but consistent with lithium-induced chronic nephropathy. An MRI of the kidneys provides noninvasive evidence that strengthens the diagnosis of lithium-induced nephropathy.
Topics: Aged; Cysts; Female; Humans; Kidney Diseases; Lithium; Magnetic Resonance Imaging
PubMed: 18758659
DOI: 10.1100/tsw.2008.112 -
BMJ Case Reports Jan 2014A widespread use of ultrasound (US) examination is contributing to an increase in the diagnosis of renal and hepatic cysts. However, the vast majority of these lesions...
A widespread use of ultrasound (US) examination is contributing to an increase in the diagnosis of renal and hepatic cysts. However, the vast majority of these lesions are benign with an indolent course during the patient's lifespan. Adult polycystic kidney disease (APKD) is one of the most common diagnosed entities. APKD is a genetic disease defined by the presence of multiple kidney cysts, occasionally accompanied by hepatic cysts. The presence of hepatic cysts sparing kidneys is very rare and thereby must be assumed as a different clinical entity. This article describes a case of an exuberant hepatomegaly due to the presence of isolated multiple hepatic cysts without renal involvement.
Topics: Cysts; Diagnosis, Differential; Female; Follow-Up Studies; Hepatectomy; Humans; Liver Diseases; Magnetic Resonance Imaging; Middle Aged
PubMed: 24443335
DOI: 10.1136/bcr-2013-202003 -
Journal of Medical Imaging and... Aug 2010Focal incidental renal lesions are commonly encountered on positron emission tomography (PET)/computed tomography (CT) imaging. The vast majority of these lesions are... (Review)
Review
Focal incidental renal lesions are commonly encountered on positron emission tomography (PET)/computed tomography (CT) imaging. The vast majority of these lesions are benign. However, the interpretation of renal lesions can be problematic if the imaging criteria of simple cysts are not met. Limited literature exists on the characterisation of renal masses with metabolic imaging. The purpose of this article is to focus on the imaging features of benign and malignant renal masses with PET/CT. The lesions discussed include renal cyst, angiomyolipoma, oncocytoma, renal cell carcinoma, renal metastases and other infiltrating neoplastic processes affecting the kidney. Both the anatomical and metabolic features which characterise these benign and malignant entities are described. We emphasise the importance of viewing the CT component to identify the typical morphological features and discuss how to best use hybrid imaging for management of renal lesions. Metabolic imaging has a promising role in the imaging of renal lesions and can help prevent unnecessary biopsies and ensure optimal management of suspicious lesions.
Topics: Adenoma, Oxyphilic; Angiomyolipoma; Carcinoma, Renal Cell; Cysts; Fluorodeoxyglucose F18; Humans; Incidental Findings; Kidney; Kidney Diseases; Kidney Neoplasms; Leukemia; Lymphoma; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 20718915
DOI: 10.1111/j.1754-9485.2010.02181.x -
European Radiology Feb 2021The objective was to assess the interobserver agreement rate, progression rates and malignancy rates in the assessment of complex renal cysts (≥ Bosniak IIF) using a...
OBJECTIVE
The objective was to assess the interobserver agreement rate, progression rates and malignancy rates in the assessment of complex renal cysts (≥ Bosniak IIF) using a population-based database.
METHODS
A regional database identified 452 complex renal cysts in 415 patients between 2009 and 2019. Each patient was tracked and followed up using a unique identifier and deterministic linkage methodology. The interobserver agreement rate between radiologists was calculated using a weighted kappa statistic. Progression and malignancy rates of cysts (Bosniak ≥IIF) over the 11-year period were calculated.
RESULTS
The linear-weighted kappa value was 0.69 for all complex cysts. The rate of progression and regression of Bosniak IIF cysts was 4.6% (7/151) and 3.3% (5/151), respectively. All malignant IIF cysts progressed within 16 months of diagnosis. The malignancy rate of surgically resected Bosniak III and IV cysts was 79.3% (23/29) and 84.5% (39/46), respectively. Of all malignant tumours, 73.8% and 93.7% were of low ISUP grade and low stage, respectively.
CONCLUSIONS
This study further confirms that there is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. The progression rate of Bosniak IIF cysts is low, but the malignancy rates of surgically resected Bosniak IIF, III and IV cysts are high. Benign cysts are frequently resected, and a very high proportion of histopathologically confirmed cancers in complex renal cysts are of low grade and stage.
KEY POINTS
• There is a good degree of agreement between radiologists in classifying complex renal masses using the Bosniak classification. • The rate of progression of Bosniak IIF cysts is low, and malignant cysts progress early during surveillance. Although the malignancy rates of resected Bosniak IIF, III and IV cysts are high, the rate of benign cyst resection is significant.
Topics: Cysts; Humans; Kidney Diseases, Cystic; Kidney Neoplasms; Observer Variation; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 32851449
DOI: 10.1007/s00330-020-07186-w -
BMC Nephrology May 2020Abdominal aortic aneurysms (AAA) primarily affect men over 65 years old who often have many other diseases, with similar risk factors and pathobiological mechanisms to...
BACKGROUND
Abdominal aortic aneurysms (AAA) primarily affect men over 65 years old who often have many other diseases, with similar risk factors and pathobiological mechanisms to AAA. The aim of this study was to assess the prevalence of simple renal cysts (SRC), chronic kidney disease (CKD), and other kidney diseases (e.g. nephrolithiasis) among patients presenting with AAA.
METHODS
Two groups of patients (97 AAA and 100 controls), with and without AAA, from the Surgical Clinic Charité, Berlin, Germany, were selected for the study. The control group consisted of patients who were evaluated for a kidney donation (n = 14) and patients who were evaluated for an early detection of a melanoma recurrence (n = 86). The AAA and control groups were matched for age and sex. Medical records were analyzed and computed tomography scans were reviewed for the presence of SRC and nephrolithiasis.
RESULTS
SRC (74% vs. 57%; p<0.016) and CKD (30% vs. 8%; p<0.001) were both more common among AAA than control group patients. On multivariate analysis, CKD, but not SRC, showed a strong association with AAA.
CONCLUSIONS
Knowledge about pathobiological mechanisms and association between CKD and AAA could provide better diagnostic and therapeutic approaches for these patients.
Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Case-Control Studies; Computed Tomography Angiography; Cysts; Female; Germany; Humans; Male; Middle Aged; Nephrolithiasis; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies
PubMed: 32471416
DOI: 10.1186/s12882-020-01841-6 -
Annals of Hepatology 2012Polycystic liver disease rarely occurs in isolation as part of autosomal dominant polycystic liver disease, but more commonly, it exists as an extra-renal manifestation... (Review)
Review
Polycystic liver disease rarely occurs in isolation as part of autosomal dominant polycystic liver disease, but more commonly, it exists as an extra-renal manifestation of autosomal dominant polycystic kidney disease. The pathogenesis of polycystic liver disease involves defects in the primary cilium of the cholangiocyte, with genetic mutations that impair key proteins integral to the complex functioning of cilia. While most patients are asymptomatic and require no intervention aside from reassurance and genetic counseling, in a minority of patients, polycystic liver disease creates a myriad of symptoms from the compressive effects of enlarged cysts, and can even cause malnutrition and liver decompensation in the severest of cases. In patients with symptomatic disease, a variety of interventional radiology or surgical techniques can be considered, including aspiration with sclerotherapy of a dominant cyst, fenestration, segmental hepatic resection, and even liver transplantation. Although there are no curative medical options for polycystic liver disease, somatostatin analogs hold promise and have shown minimal efficacy in human studies. However, further research is needed to develop more efficacious medical treatments.
Topics: Cysts; Genetic Predisposition to Disease; Hepatectomy; Humans; Liver; Liver Diseases; Liver Transplantation; Mutation; Phenotype; Polycystic Kidney, Autosomal Dominant; Protein Kinase Inhibitors; Radiography, Interventional; Sclerotherapy; Somatostatin; TOR Serine-Threonine Kinases; Treatment Outcome
PubMed: 23109444
DOI: No ID Found -
Clinical Nuclear Medicine Apr 2022Cystic renal cell carcinoma (RCC) refers to an indolent version of RCC composed predominantly of cysts, and it is associated with good prognosis. We showed the FDG...
Cystic renal cell carcinoma (RCC) refers to an indolent version of RCC composed predominantly of cysts, and it is associated with good prognosis. We showed the FDG PET/CT findings in a patient with multiple hypermetabolic bone metastases presenting with pain in the left shoulder and upper abdomen, who was later found to have cystic RCC. FDG PET/CT demonstrated hypermetabolic bone lesions and slight thickening of the renal cyst wall with light metabolism. This report indicates the risk of misdiagnosing cystic RCC as a renalcyst.
Topics: Carcinoma, Renal Cell; Cysts; Fluorodeoxyglucose F18; Humans; Kidney Diseases, Cystic; Kidney Neoplasms; Positron Emission Tomography Computed Tomography
PubMed: 35085171
DOI: 10.1097/RLU.0000000000004071