Ciliary ARL13B inhibits developmental kidney cystogenesis in mouse.

ARL13B is a small GTPase enriched in cilia. Deletion of Arl13b in mouse kidney results in renal cysts and an associated absence of primary cilia. Similarly, ablation of cilia leads to kidney cysts. To investigate whether ARL13B functions from within cilia to direct kidney development, we examined kidneys of mice expressing an engineered cilia-excluded ARL13B variant, ARL13BV358A. These mice retained renal cilia and developed cystic kidneys. Because ARL13B functions as a guanine nucleotide exchange factor (GEF) for ARL3, we examined kidneys of mice expressing an ARL13B variant that lacks ARL3 GEF activity, ARL13BR79Q. We found normal kidney development with no evidence of cysts in these mice. Taken together, our results show that ARL13B functions within cilia to inhibit renal cystogenesis during mouse development, and that this function does not depend on its role as a GEF for ARL3.

Renal Pathology of Ciliopathies.

Renal ciliopathies are a group of genetic disorders that affect the function of the primary cilium in the kidney, as well as other organs. Since primary cilia are important for regulation of cell signaling pathways, ciliary dysfunction results in a range of clinical manifestations, including renal failure, cyst formation, and hypertension. We summarize the current understanding of the pathophysiological and pathological features of renal ciliopathies in childhood, including autosomal dominant and recessive polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome, as well as skeletal dysplasia associated renal ciliopathies. The genetic basis of these disorders is now well-established in many cases, with mutations in a large number of cilia-related genes such as PKD1, PKD2, BBS, MKS, and NPHP being responsible for the majority of cases. Renal ciliopathies are broadly characterized by development of interstitial fibrosis and formation of multiple renal cysts which gradually enlarge and replace normal renal tissue, with each condition demonstrating subtle differences in the degree, location, and age-related development of cysts and fibrosis. Presentation varies from prenatal diagnosis of congenital multisystem syndromes to an asymptomatic childhood with development of complications in later adulthood and therefore clinicopathological correlation is important, including increasing use of targeted genetic testing or whole genome sequencing, allowing greater understanding of genetic pathophysiological mechanisms.

Clinical and molecular characteristics of two Italian kindreds with hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome.

PURPOSE: Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome, also known as Barakat syndrome, is a rare autosomal dominant disease characterized by the triad of hypoparathyroidism, deafness, and renal abnormalities. The disorder is caused by the haploinsufficiency of the zinc finger transcription factor GATA3 and exhibits a great clinical variability with an age-dependent penetrance of each feature. We report two unrelated kindreds whose probands were referred to our outpatient clinic for further evaluation of hypoparathyroidism. METHODS: The proband of family 1, a 17-year-old boy, was referred for severe hypocalcemia (5.9 mg/dL) incidentally detected at routine blood tests. Abdomen ultrasound showed bilateral renal cysts. The audiometric evaluation revealed the presence of bilateral moderate hearing loss although the patient could communicate without any problem. Conversely, the proband of family 2, a 19-year-old man, had severe symptomatic hypocalcemia complicated by epileptic seizure at the age of 14 years; his past medical history was remarkable for right nephrectomy at the age of 4 months due to multicystic renal disease and bilateral hearing loss diagnosed at the age of 18 years. RESULTS: Based on clinical, biochemical, and radiologic data, HDR syndrome was suspected and genetic analysis of the GATA3 gene revealed the presence of two pathogenetic variants in exon 3, c.404dupC and c.431dupG, in the proband of family 1 and 2, respectively. CONCLUSION: HDR syndrome is a rare cause of hypoparathyroidism and must be excluded in all patients with apparently idiopathic hypoparathyroidism. A correct diagnosis is of great importance for early detection of other HDR-related features and genetic counseling.

A clinical review of congenital hepatic fibrosis diagnosed in adulthood: presentation, complications, and outcomes.

INTRODUCTION AND OBJECTIVES: Congenital hepatic fibrosis (CHF) is a rare condition characterized by biliary tract changes and a geographic pattern of liver fibrosis. Liver biopsy is essential to confirm its diagnosis. The absence of specific clinical indicators in adults often leads to delays in diagnosis and management, while the natural history has not been well described. We sought to define the presentation and outcomes of adults with biopsy-proven CHF. MATERIALS AND METHODS: A retrospective chart review was conducted of patients diagnosed with CHF by liver biopsy. Continuous variables were summarized with the sample median and range. Categorical variables were summarized with number and percentage of patients. RESULTS: We identified 24 patients evaluated over a 20-year period, with a median age of 51 years (range 22-72 years) at initial presentation; 14 were male. The most common imaging findings were renal cysts (91.3%), splenomegaly (69.6%), and a cirrhotic-appearing liver (60.9%). The most commonly treated liver-related complications were cholangitis (45.8%), varices (45.8%), and hepatic encephalopathy (25%). Two patients died with a median length of follow-up of 2.9 years (range: 0.0-20.0 years). Two patients underwent transjugular intrahepatic portosystemic shunt (TIPS) placement to manage bleeding esophageal varices. Eight patients underwent liver transplantation (LT), the most common indication being decompensated disease (50%). CONCLUSIONS: CHF should be considered when patients present with cholangitis and/or complications of portal hypertension and have a cirrhotic appearing liver and renal cysts on imaging. Depending upon the disease severity, interventions such as TIPS or LT may be required.

Reprogramming of Energy Metabolism in Human PKD1 Polycystic Kidney Disease: A Systems Biology Analysis.

Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. To elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. We found gene expression profiles of PKD1 renal cysts were consistent with the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.

Maturity-onset diabetes of the young type 3 complicated with type 5: A case report and literature review. / é’å°‘å¹´èµ·ç— çš„æˆäººåž‹ç³–å°¿ç— 3型合并5型1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

This report describes a case of maturity-onset diabetes of the young (MODY) type 3 (MODY3) complicated with type 5 (MODY5), including the patient's clinical features, diagnosis, and treatment, and reviews relevant literature. Using next-generation sequencing of MODY (types 1-14) gene exons and Sanger sequencing for verification, the patient and her mother were assessed. Based on the clinical phenotype and genetic test results, the patient was diagnosed as MODY3 combined with MODY5. Treatment included insulin and linagliptin, with monitoring of blood glucose changes. Clinicians should enhance their understanding of MODY clinical phenotypes. In adolescents with diabetes who have congenital pancreatic and renal developmental defects, elevated high-density lipoprotein cholesterol, no spontaneous ketosis, insulin secretion defects, negative pancreatic autoantibodies, no significant insulin resistance, and who are not obese, gene testing should be conducted to screen for MODY. Accurate diagnosis and personalized treatment can aid in achieving glycemic control, improving quality of life, and optimizing reproductive planning.

Ouabain enhances renal cyst growth in a slowly progressive mouse model of autosomal dominant polycystic kidney disease.

Renal cyst progression in autosomal dominant polycystic kidney disease (ADPKD) is highly dependent on agents circulating in blood. We have previously shown, using different in vitro models, that one of these agents is the hormone ouabain. By binding to Na+-K+-ATPase (NKA), ouabain triggers a cascade of signal transduction events that enhance ADPKD cyst progression by stimulating cell proliferation, fluid secretion, and dedifferentiation of the renal tubular epithelial cells. Here, we determined the effects of ouabain in vivo. We show that daily administration of ouabain to Pkd1RC/RC ADPKD mice for 1-5 mo, at physiological levels, augmented kidney cyst area and number compared with saline-injected controls. Also, ouabain favored renal fibrosis; however, renal function was not significantly altered as determined by blood urea nitrogen levels. Ouabain did not have a sex preferential effect, with male and female mice being affected equally. By contrast, ouabain had no significant effect on wild-type mice. In addition, the actions of ouabain on Pkd1RC/RC mice were exacerbated when another mutation that increased the affinity of NKA for ouabain was introduced to the mice (Pkd1RC/RCNKAα1OS/OS mice). Altogether, this work highlights the role of ouabain as a procystogenic factor in the development of ADPKD in vivo, that the ouabain affinity site on NKA is critical for this effect, and that circulating ouabain is an epigenetic factor that worsens the ADPKD phenotype.NEW & NOTEWORTHY This work shows that the hormone ouabain enhances the progression of autosomal dominant polycystic kidney disease (ADPKD) in vivo. Ouabain augments the size and number of renal cysts, the kidney weight to body weight ratio, and kidney fibrosis in an ADPKD mouse model. The Na+-K+-ATPase affinity for ouabain plays a critical role in these effects. In addition, these outcomes are independent of the sex of the mice.

Long-Term Outcomes of Endovascular Treatment for Type B Aortic Dissection with Simple Renal Cysts: A Multicenter Retrospective Study.

Background: Few studies have investigated the characteristics and long-term outcomes of type B aortic dissection (BAD) patients with simple renal cysts (SRC) after thoracic endovascular aortic repair (TEVAR). Methods: A multi-center retrospective cohort study was performed, including 718 BAD patients undergoing TEVAR from 2003 to 2016. The prevalence of SRC was 34.5% (n = 248). After propensity score matching, 214 matched pairs were selected for further analysis. Primary outcomes were long-term aortic-related adverse events (ARAEs). The effects of SRC in each subgroup of interest and their interactions were analyzed. Results: BAD patients with SRC were older and had a greater prevalence of comorbidities, including hypertension, coronary artery disease and chronic occlusive pulmonary disease. In addition, the SRC group presented a greater proportion of pleural effusion and aortic calcification. Compared with the non-SRC group, a significantly higher maximal diameter of ascending aorta was observed in the SRC group. Apart from the timing of the operation, no differences were found in the medication regime or intra-operative parameters. In the matched population, patients with SRC were at a higher risk of ARAEs in the long term. The multivariable Cox model indicated that SRC was an independent predictor of long-term ARAEs (hazard ratio: 1.84, 95% confidence interval: 1.13-3.00). The interaction between SRC and hypertension on rupture after TEVAR was statistically significant (p = 0.023). Conclusions: Compared with the non-SRC group, BAD patients with SRC experienced a higher risk of long-term ARAEs after TEVAR. Among the SRC subgroup, hypertensive patients had the highest risk of rupture after TEVAR.

Renal Lesion Characterization by Dual-Layer Dual-Energy CT: Comparison of Virtual and True Unenhanced Images.

BACKGROUND. Prior studies have provided mixed results for the ability to replace true unenhanced (TUE) images with virtual unenhanced (VUE) images when characterizing renal lesions by dual-energy CT (DECT). Detector-based dual-layer DECT (dlDECT) systems may optimize performance of VUE images for this purpose. OBJECTIVE. The purpose of this article was to compare dual-phase dlDECT examinations evaluated using VUE and TUE images in differentiating cystic and solid renal masses. METHODS. This retrospective study included 110 patients (mean age, 64.3 ± 11.8 years; 46 women, 64 men) who underwent renal-mass protocol dlDECT between July 2018 and February 2022. TUE, VUE, and nephrographic phase image sets were reconstructed. Lesions were diagnosed as solid masses by histopathology or MRI. Lesions were diagnosed as cysts by composite criteria reflecting findings from MRI, ultrasound, and the TUE and nephrographic phase images of the dlDECT examinations. One radiologist measured lesions' attenuation on all dlDECT image sets. Lesion characterization was compared between use of VUE and TUE images, including when considering enhancement of 20 HU or greater to indicate presence of a solid mass. RESULTS. The analysis included 219 lesions (33 solid masses; 186 cysts [132 simple, 20 septate, 34 hyperattenuating]). TUE and VUE attenuation were significantly different for solid masses (33.4 ± 7.1 HU vs 35.4 ± 8.6 HU, p = .002), simple cysts (10.8 ± 5.6 HU vs 7.1 ± 8.1 HU, p < .001), and hyperattenuating cysts (56.3 ± 21.0 HU vs 47.6 ± 16.3 HU, p < .001), but not septate cysts (13.6 ± 8.1 HU vs 14.0 ± 6.8 HU, p = .79). Frequency of enhancement 20 HU or greater when using TUE and VUE images was 90.9% and 90.9% in solid masses, 0.0% and 9.1% in simple cysts, 15.0% and 10.0% in septate cysts, and 11.8% and 38.2% in hyperattenuating cysts. All solid lesions were concordant in terms of enhancement 20 HU or greater when using TUE and VUE images. Twelve simple cysts and nine hyperattenuating cysts showed enhancement of 20 HU or greater when using VUE but not TUE images. CONCLUSION. Use of VUE images reliably detected enhancement in solid masses. However, VUE images underestimated attenuation of simple and hyperattenuating cysts, leading to false-positive findings of enhancement by such lesions. CLINICAL IMPACT. The findings do not support replacement of TUE acquisitions with VUE images when characterizing renal lesions by dlDECT.

AA-amyloidosis in captive northern tree shrews (Tupaia belangeri).

A high prevalence of AA-amyloidosis was identified in a breeding colony of northern tree shrews (Tupaia belangeri) in a retrospective analysis, with amyloid deposits in different organs being found in 26/36 individuals (72%). Amyloid deposits, confirmed by Congo red staining, were detected in kidneys, intestines, skin, and lymph nodes, characteristic of systemic amyloidosis. Immunohistochemically, the deposited amyloid was intensely positive with anti-AA-antibody (clone mc4), suggesting AA-amyloidosis. The kidneys were predominantly affected (80%), where amyloid deposits ranged from mild to severe and was predominantly located in the renal medulla. In addition, many kidneys contained numerous cysts with atrophy of the renal parenchyma. There was no significant association between concurrent neoplastic or inflammatory processes and amyloidosis. The lack of distinctive predisposing factors suggests a general susceptibility of captive T. belangeri to develop amyloidosis. Clinical and laboratory findings of a female individual with pronounced kidney alterations were indicative of renal failure. The observed tissue tropism with pronounced kidney alterations, corresponding renal dysfunction, and an overall high prevalence suggests amyloidosis as an important disease in captive tree shrews.

Burden of Renal Cysts Imaging: A Survey of Patients among the Greater Plains Collaborative.

PURPOSE: Renal cysts are a frequent incidental finding on cross-sectional radiographic imaging. While most cysts are indolent, individuals with such cysts are frequently monitored for interval growth and potential malignant transformation, which is ultimately rare. In this study, we aimed to assess patients' values and preferences (believes and attitudes) about renal cysts. METHODS: We deployed a cross-sectional survey to a random sample of patients with a diagnosis of renal cysts who were identified by billing code and self-identification. We collected data about demographics, insurance status, family history and overall health, and characteristics of patients with renal cysts. We performed a binary regression analysis (adjusted for age, gender, family history of cancer and kidney disease, and treatment plan for renal cysts) to determine anxiety predictors in patients with renal cysts. RESULTS: We included 301 respondents in whom billing code and self-identification corresponded; of these, 138 had renal cysts and 163 did not. In an adjusted regression analysis, there was a suggestion that a clear management plan (OR = 0.49, 95% CI [0.22-1.11]) (p value 0.08) may be associated with less anxiety and a family history of renal disease may be associated with more anxiety (OR = 1.94 [0.76-4.94]) (p value 0.17). Family history of cancer also did not significantly predict anxiety (OR = 0.54 [0.24-1.19]) (p value 0.13). All these results were not statistically significant and had wide confidence intervals of the effect estimates make the results imprecise. CONCLUSION: Findings of this pilot study suggest a clear management plan for the renal cyst(s) management may be associated with a lower level of anxiety, thereby by emphasizing the importance of good communication, patient engagement and evidence-based guidance. More definitive, adequately powered studies are needed to evaluate this finding further. In addition, further studies exploring differences in imaging practices, patient symptomatology and patient engagement by different provider types would be insightful. Ultimately, tools to improve shared decision-making are needed to provide more patient-centered care.

Using Contrast-Enhanced Ultrasound in Addition to Cross-Sectional Imaging for Indeterminate Renal Cysts May Lead to Overclassification in Bosniak III Category: A Case-Control Study.

INTRODUCTION: Indeterminate renal cysts may require several imaging modalities before clinical decision. The aim of this study was to investigate the effect of the imaging modality used to characterize indeterminate renal cysts on the pathological findings after surgical resection. METHODS: From our institutional database, we identified all patients surgically treated for Bosniak III renal masses between January 2008 and January 2018. All complex renal cysts were characterized with a combination of computed tomography (CT) and/or magnetic resonance imaging (MRI), and/or contrast-enhanced ultrasound (CEUS) and discussed during a multidisciplinary tumor board. Potential association between clinical/radiological characteristics and the pathological findings were investigated, using univariate and multivariate analyses. RESULTS: Of the 52 renal cystic lesions surgically removed, with a preoperative diagnosis of Bosniak III renal cyst, 19 (37%) were malignant and 33 (63%) were benign. The proportion of malignant lesions decreased from 47% when the renal cyst was characterized with cross-sectional imaging (CT and/or MRI) to 17% when the diagnosis required CEUS in addition to cross-sectional imaging. In multivariate analysis, prior history of renal cell carcinoma was associated with a higher risk of malignancy (p = 0.016) and diagnosis made with CEUS was associated with a lower risk of malignancy (p = 0.040). CONCLUSION: We found that using CEUS in addition to cross-sectional imaging to characterize indeterminate renal cysts tends to redefine Bosniak III as lesions with a lower risk of malignancy and can lead to overclassification.

[Features of surgical treatment of renal cysts depending on the risk of malignancy].

BACKGROUND: According to national and foreign publications, renal cyst is one of the most common urological diseases with a prevalence up to 20-50%. AIM: To determine the results of surgical treatment of patients with renal cysts, depending on the risk of malignancy. MATERIALS AND METHODS: The analysis of 124 patients with symptomatic renal cysts who were treated in the Department of Urology of Regional Clinical Hospital was carried out. All patients underwent a comprehensive clinical and instrumental evaluation, including contrast-enhanced CT scan of the kidneys. To assess the risk of harboring malignant tumor, the classification of renal cysts of Bosniak (2019) was used. RESULTS: The average age of patients was 56.6+/-12 years. According to CT, Bosniak I, II, IIF and III cysts were diagnosed in 96 (77.4%), 11 (8.9%), 11 (8.9%) and 6 (4.8%) patients, respectively. The morphologic study revealed renal cell cancer in 8 patients (6.4%), four of whom had Bosniak III cysts and other four had Bosniak IIF cysts. DISCUSSION: The prediction of the harboring of malignancy is a fundamental criterion for selection of patients with renal cysts for surgical treatment. CONCLUSION: Surgical treatment of symptomatic renal cysts is a justified treatment method, and in patients with Bosniak class II or higher cysts, it is necessary to exclude the malignant lesion. Based on our data, category IIF and III cysts have a high risk of harboring malignant cells, which is 36.4% and 66.7%, respectively. In our opinion, laparoscopic partial nephrectomy is the most rational treatment method in these categories.

Management of complex renal cysts in Canada: results of a survey study.

BACKGROUND: Bosniak III and IV cysts have a high risk of malignancy and have traditionally been managed surgically. However, growing evidence suggests that many can be managed by active surveillance. The main objective of this study was to characterize the use of surveillance in the management of complex renal cysts. METHODS: A web-based survey was sent to all registered, active members of the Canadian Urological Association (N = 583) in October 2018. RESULTS: The survey response rate was 24.7%. Management of Bosniak III cysts varied considerably. A large proportion of respondents (33.1%) offered active surveillance in > 50% of cases. Only 13.7% of respondents reported never or rarely (< 5% of cases) offering surveillance. In contrast, for Bosniak IV cysts, 60.1% of urologists never or rarely offered surveillance, while only 10.1% offer it in > 50% of cases. A significantly greater proportion of academic urologists, compared to non-academic urologists, viewed surveillance as a management option for patients with a Bosniak III or IV cyst. The most commonly reported barriers to a greater adoption of surveillance were concerns regarding its oncologic safety, the lack of data to support surveillance in this population, and the lack of triggers for discontinuation of active surveillance and intervention. CONCLUSIONS: Despite active surveillance being included as a management option in guidelines, many Canadian urologists are reluctant to offer surveillance to patients with Bosniak III or IV cysts. Practice patterns are heterogeneous among those offering surveillance. High-quality studies are required to better define the benefits and risks of cystic renal mass surveillance.

Aspiration-sclerotherapy versus laparoscopic de-roofing in the treatment of renal cysts: which is better?

BACKGROUND: To compare the clinical efficiency between aspiration-sclerotherapy (AS) and laparoscopic de-roofing (LD) in the management of renal cysts through meta-analysis of comparative studies. METHOD: A comprehensive literature search was performed by PubMed, MEDLINE, Ovid and Web of Science for relevant studies published up to January 2020. The statistical analyses were conducted with Review Manager 5.3.0 and Stata 15.1. The sensitivity analysis was also carried out to confirm the reliability of this Meta-analysis. RESULTS: Our searches of literature generated 6 studies (1547 patients incorporated) comparing AS with LD in the impacts of renal cyst therapy. Of these, 6 studies contained 1106 and 441 patients who were treated with AS and LD, respectively. The outcome of this meta-analysis indicated that LD group was superior in symptomatic successful rate [Odds Ratio (OR): 0.28; 95%Confidence Interval (CI): 0.09 to 0.86; P = 0.03), radiological successful rate (OR: 0.06; 95%CI: 0.02 to 0.15; P < 0.01) and recurrence rate (OR: 6.08; 95%CI: 2.81 to 13.15; p < 0.01). Nevertheless, AS group had shorter treatment time [Mean Difference (MD):-51.10; 95% CI:-73.01 to - 29.20; p < 0.01]. No statistically significant difference was showed in the rate of complications (OR: 3.19; 95% CI: 0.39 to 25.88; P = 0.28). CONCLUSIONS: In our meta-analysis, LD had higher symptomatic successful rate, radiological successful rate as well as lower recurrence rate than AS, while the treatment time was longer.

Cyst Reduction by Melatonin in a Novel Drosophila Model of Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics are needed. Melatonin, a central metabolic regulator conserved across all life kingdoms, exhibits oncostatic and oncoprotective activity and no detected toxicity. Here, we used the Bicaudal C (BicC) Drosophila model of polycystic kidney disease to test the cyst-reducing potential of melatonin. Significant cyst reduction was found in the renal (Malpighian) tubules upon melatonin administration and suggest mechanistic sophistication. Similar to vertebrate PKD, the BicC fly PKD model responds to the antiproliferative drugs rapamycin and mimics of the second mitochondria-derived activator of caspases (Smac). Melatonin appears to be a new cyst-reducing molecule with attractive properties as a potential candidate for PKD treatment.

Contrast-Enhanced Ultrasound (CEUS) for the Evaluation of Bosniak III Complex Renal Cystic Lesions-A 10-Year Specialized European Single-Center Experience with Histopathological Validation.

Background and objectives: The aim of the present retrospective single-center study is to evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for assessing Bosniak III complex renal cystic lesions with histopathological validation. Materials and Methods: 49 patients with CEUS-categorized Bosniak III renal cystic lesions were included in this retrospective study. All patients underwent native B-mode, Color Doppler, contrast-enhanced ultrasound (CEUS) between 2010-2020. Eight and five patients underwent computed tomography (CT) and magnetic resonance imaging (MRI), respectively. Twenty-nine underwent (partial) nephrectomy allowing for histopathological analysis. The applied contrast agent for CEUS was a second-generation blood pool agent. Ultrasonography examinations were performed and interpreted by a single experienced radiologist with more than 15 years of experience (EFSUMB Level 3). Results: CEUS examinations were successfully performed in all included patients without registering any adverse effects. The malignancy rate of CEUS-categorized Bosniak III renal lesions accounted for 66%. Initially, cystic complexity was visualized in native B-mode. In none of the renal lesions hypervascularization was detected in Color Doppler. CEUS allowed for detection of contrast enhancement patterns in all included Bosniak III renal lesions. Delayed wash-out could be detected in 6/29 renal lesions. In two cases of histopathologically confirmed clear-cell RCC, appropriate up-grading from Bosniak IIF to III was achieved by CEUS. Conclusions: CEUS depicts a promising imaging modality for the precise diagnostic workup and stratification of renal cystic lesions according to the Bosniak classification system, thereby helping guidance of adequate clinical management in the future.

[Atypical renal cysts: a clinicopathological and molecular analysis of six cases].

Objective: To investigate the clinicopathological characteristics and molecular genetics of atypical renal cysts. Methods: Six cases of atypical renal cysts were collected from Zhejiang Provincial People's Hospital, Hangzhou, China, between February 2014 and February 2019. The clinicopathological characteristics and disease progression were analyzed. The 3p deletion and trisomy of chromosomes 7 and 17 were detected using fluorescence in situ hybridization (FISH). Results: All of the 6 patients were male, aged 43-63 years (median: 52 years). Preoperative Bosniak classification showed 4 cases of grade Ⅱ, 1 case of grade Ⅰ and 1 of grade Ⅲ. Histologically, atypical renal cysts appeared as unilocular or multilocular cysts, lined by multilayered flattened or cuboidal-shaped clear or eosinophilic cells. They often showed short papillary projections, and lacked solid or nodular growth of the lesional cells within the wall or septa of the cysts. Histologically, these cysts could be classified into three categories: acquired cystic disease-associated renal cell carcinoma (ACKD-RCC)-like (3 cases), clear cell type (2 cases), and eosinophilic papillary type (1 case). Two cases of ACKD-RCC-like atypical renal cysts were accompanied by clear cell renal cell carcinomas. On immunohistochemical staining, ACKD-RCC-like atypical renal cysts were focally CK7+/AMACR+/CD57+, the clear-cell type atypical renal cysts were CK7+/CAⅨ+, and eosinophilic papillary type atypical renal cysts were CK7+/AMACR+. FISH analyses showed that one case of ACKD-RCC-like atypical renal cysts had trisomy 17 and one case of clear cell type had 3p deletion, while no signal abnormality was detected in the other cases. The six patients were followed up for 13 to 70 months (median: 27 months), and no evidence of renal cell carcinoma was noted. Conclusion: Atypical renal cysts are a group of lesions that are heterogeneous in clinical, histological and immunophenotypical and molecular genetic features. FISH analyses suggest that a subset of the cases may be precursors of currently known renal cell carcinomas. Extensively sampling and careful observation of the histological characteristics of the cyst wall are important for distinguishing atypical renal cysts from extensively cystic renal cell carcinomas.

Active Surveillance Versus Nephron-Sparing Surgery for a Bosniak IIF or III Renal Cyst: A Cost-Effectiveness Analysis.

OBJECTIVE: The objective of our study was to evaluate the cost-effectiveness of active surveillance (AS) versus nephron-sparing surgery (NSS) in patients with a Bosniak IIF or III renal cyst. MATERIALS AND METHODS: Markov models were developed to estimate life expectancy and lifetime costs for 60-year-old patients with a Bosniak IIF or III renal cyst (the reference cases) managed by AS versus NSS. The models incorporated the malignancy rates, reclassification rates during follow-up, treatment effectiveness, complications and costs, and short- and long-term outcomes. An incremental cost-effectiveness analysis was performed to identify management preference under an assumed $75,000 per quality-adjusted life-year (QALY) societal willingness-to-pay threshold, using data from studies in the literature and the 2015 Medicare Physician Fee Schedule. The effects of key parameters were addressed in a multiway sensitivity analysis. RESULTS: The prevalence of malignancy for Bosniak IIF and III renal cysts was 26% (25/96) and 52% (542/1046). Under base case assumptions for Bosniak IIF cysts, the incremental cost-effectiveness ratio of NSS relative to AS was $731,309 per QALY for women, exceeding the assumed societal willingness-to-pay threshold, and AS outperformed NSS for both life expectancy and cost for men. For Bosniak III cysts, AS yielded greater life expectancy (24.8 and 19.4 more days) and lower lifetime costs (cost difference of $12,128 and $11,901) than NSS for men and women, indicating dominance of AS over NSS. Superiority of AS held true in sensitivity analyses for men 46 years old or older and women 57 years old or older even when all parameters were set to favor NSS. CONCLUSION: AS is more cost-effective than NSS for patients with a Bosniak IIF or III renal cyst.

Active Surveillance of Small (< 4 cm) Bosniak Category 2F, 3, and 4 Renal Lesions: What Happens on Imaging Follow-Up?

OBJECTIVE. The purpose of this study was to determine the percentage of small (< 4 cm) Bosniak category 2F, 3, and 4 lesions that regress during active surveillance. MATERIALS AND METHODS. In this retrospective study, a hospital database was searched from January 1, 2005, through September 9, 2017, for small (< 4 cm) Bosniak category 2F, 3, and 4 lesions studied with initial and follow-up unenhanced and contrast-enhanced CT or MRI. Prospective Bosniak categories were recorded. Two blinded radiologists retrospectively reassigned Bosniak categories to the initial and last follow-up studies. Interreader variability was analyzed. Rates of stability, regression, and progression were calculated and stratified by size. Logistic regression was used to assess the effects of lesion size, lesion growth, and duration of follow-up on the change in Bosniak categories. RESULTS. The search identified 123 patients (85 men, 38 women) with 138 renal lesions (according to the blinded readings, 83 Bosniak category 2F, 37 category 3, and 18 category 4) and followed for 1-12.3 years (median, 2.7 years). Fifty-one percent (70/138) of the lesions were smaller than 2 cm. Eighty-eight percent (73/83) of category 2F lesions were downgraded or remained stable. Forty-five percent (25/55) of category 3 or 4 lesions were downgraded to 2F or lower. Kappa values were 0.94 between the two readers and 0.72-0.76 between the readers and the prospective Bosniak categories. There was no association between initial size, change in size, or duration of follow-up and change in Bosniak category. CONCLUSION. Approximately one-half of small (< 4 cm) Bosniak category 3 and 4 cystic renal lesions were downgraded, and the majority (88%) of small Bosniak category 2F lesions regressed or remained stable during active surveillance. Therefore, small size should be a consideration for conservative management.