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Polycystin-1 (PC-1) and PC-2 form a heteromeric ion channel complex that is abundantly expressed in primary cilia of renal epithelial cells. This complex functions as a non-selective cation channel, and mutations within the polycystin complex cause autosomal dominant polycystic kidney disease (ADPKD). The spatial and temporal regulation of the polycystin complex within the ciliary membrane remains poorly understood. Using both whole-cell and ciliary patch-clamp recordings, we identify a cilia-enriched oxysterol, 7β,27-dihydroxycholesterol (DHC), that serves as a necessary activator of the polycystin complex. We further identify an oxysterol-binding pocket within PC-2 and showed that mutations within this binding pocket disrupt 7β,27-DHC-dependent polycystin activation. Pharmacologic and genetic inhibition of oxysterol synthesis reduces channel activity in primary cilia. In summary, our findings reveal a regulator of the polycystin complex. This oxysterol-binding pocket in PC-2 may provide a specific target for potential ADPKD therapeutics.

In autosomal dominant polycystic kidney disease (ADPKD) with germline mutations in a PKD1 or PKD2 gene, innumerable cysts develop from tubules, and renal function deteriorates. Second-hit somatic mutations and renal tubular epithelial (RTE) cell death are crucial features of cyst initiation and disease progression. Here, we use established RTE lines and primary ADPKD cells with disease-associated PKD1 mutations to investigate genomic instability and DNA damage responses. We found that ADPKD cells suffer severe chromosome breakage, aneuploidy, heightened susceptibility to DNA damage, and delayed checkpoint activation. Immunohistochemical analyses of human kidneys corroborated observations in cultured cells. DNA damage sensors (ATM/ATR) were activated but did not localize at nuclear sites of damaged DNA and did not properly activate downstream transducers (CHK1/CHK2). ADPKD cells also had the ability to transform, as they achieved high saturation density and formed colonies in soft agar. Our studies indicate that defective DNA damage repair pathways and the somatic mutagenesis they cause contribute fundamentally to the pathogenesis of ADPKD. Acquired mutations may alternatively confer proliferative advantages to the clonally expanded cell populations or lead to apoptosis. Further understanding of the molecular details of aberrant DNA damage responses in ADPKD is ongoing and holds promise for targeted therapies.

Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents. There were two aims of the study in polycystic kidney disease (PKD): 1) to determine whether increasing serum uric acid with the uricase inhibitor, oxonic acid, resulted in faster cyst growth and 2) to determine whether treatment with the xanthine oxidase inhibitor, oxypurinol, reduced the cyst growth caused by oxonic acid. Orthologous models of human PKD were used: PCK rats, a polycystic kidney and hepatic disease 1 (Pkhd1) gene model of autosomal recessive PKD (ARPKD) and Pkd1RC/RC mice, a hypomorphic Pkd1 gene model. In PCK rats and Pkd1RC/RC mice, oxonic acid resulted in a significant increase in serum uric acid, kidney weight, and cyst index. Mechanisms of increased cyst growth that were investigated were proinflammatory cytokines, the inflammasome, and crystal deposition in the kidney. Oxonic acid resulted in an increase in proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice. Oxonic acid did not cause activation of the inflammasome or uric acid crystal deposition in the kidney. In Pkd1RC/RC male and female mice analyzed together, oxypurinol decreased the oxonic acid-induced increase in cyst index. In summary, increasing serum uric acid by inhibiting uricase with oxonic acid results in an increase in kidney weight and cyst index in PCK rats and Pkd1RC/RC mice. The effect is independent of inflammasome activation or crystal deposition in the kidney. NEW & NOTEWORTHY: This is the first reported study of uric acid measurements and xanthine oxidase inhibition in polycystic kidney disease (PKD) rodents. Raising serum uric acid with a uricase inhibitor resulted in increased kidney weight and cyst index in Pkd1RC/RC mice and PCK rats, elevated levels of proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice, and no uric acid crystal deposition or activation of the caspase-1 inflammasome in the kidney. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common solid lesion within the kidney and accounts for most kidney malignancies. The primary tumor size primarily determines the risk of metastasis in RCC. Literature rarely describes metastasis in tumors less than 2 cm; in fact, around 1/3 of RCC reported cases had metastatic disease at the time of diagnosis. RCC tends to metastasize to the lung in half of the patients, to the bones or the liver in 1/3 of patients, and the brain in 5% of all cases. RCC can metastasize to almost every organ in the human body. However, their metastases to the ovaries are incredibly uncommon. In this report, we describe a female presented with the smallest RCC (1cm) that metastasized to the ovary in a patient with previously undiagnosed autosomal dominant polycystic kidney disease (ADPKD). This case report aimed to raise physicians’ awareness of the possibility of metastasis in RCC regardless of tumor size and that metastatic RCC could be the first presentation of patients with ADPKD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ketogenic dietary interventions (KDI) have been shown to be effective in animal models of polycystic kidney disease (PKD), but data from clinical trials are lacking. METHODS: Ten autosomal dominant PKD (ADPKD) patients with rapid disease progression were enrolled at visit V1 and initially maintained a carbohydrate-rich diet. At V2, patients entered one of the two KDI arms: a 3-day water fast (WF) or a 14-day ketogenic diet (KD). At V3, they resumed their normal diet for 3-6 weeks until V4. At each visit, magnetic resonance imaging kidney and liver volumetry was performed. Ketone bodies were evaluated to assess metabolic efficacy and questionnaires were used to determine feasibility. RESULTS: All participants [KD n = 5, WF n = 5; age 39.8 ± 11.6 years; estimated glomerular filtration rate 82 ± 23.5 mL/min/1.73 m2; total kidney volume (TKV) 2224 ± 1156 mL] were classified as Mayo Class 1C-1E. Acetone levels in breath and beta-hydroxybutyrate (BHB) blood levels increased in both study arms (V1 to V2 average acetone: 2.7 ± 1.2 p.p.m., V2 to V3: 22.8 ± 11.9 p.p.m., P = .0006; V1 to V2 average BHB: 0.22 ± 0.08 mmol/L, V2 to V3: 1.88 ± 0.93 mmol/L, P = .0008). Nine of 10 patients reached a ketogenic state and 9/10 evaluated KDIs as feasible. TKV did not change during this trial. However, we found a significant impact on total liver volume (ΔTLV V2 to V3: -7.7%, P = .01), mediated by changes in its non-cystic fraction. CONCLUSIONS: RESET-PKD demonstrates that short-term KDIs potently induce ketogenesis and are feasible for ADPKD patients in daily life. While TLV quickly changed upon the onset of ketogenesis, changes in TKV may require longer-term interventions.

Localized cystic kidney disease (LCKD) is a distinct renal disorder characterized by the presence of cysts within specific regions of the kidneys. We present a rare case of a 41-year-old African American man, who presented to our medical center with lower urinary tract symptoms and gross hematuria. The initial assessment culminated in the identification of an uncomplicated urinary tract infection, prompting the prescription of appropriate oral antibiotic therapy. On follow-up after 5 months, the patient presented with gross hematuria. Imaging studies revealed a mixed-density cystic lesion of 2.6 cm situated within the interpolar region of the right kidney. This cystic lesion exhibited intricate septations at the superior pole of the kidney. Robotic-assisted right partial nephrectomy was performed, and pathologic examination was diagnostic for LCKD. This report not only underscores the uniqueness of LCKD but also presents a comprehensive review of the existing literature that pertains to this condition. Particular emphasis is placed upon its inherent benign behavior and its marked divergence from the progressive trajectory commonly associated with other renal diseases. We also explored the incidental findings of the disease, its diverse clinical symptomatology, conceivable etiological underpinnings, and the array of diagnostic modalities used. Finally, similarities in histopathologic findings with polycystic kidney disease and other entities are discussed, underscoring the importance of accurate diagnosis and management.

BackgroundKidney transplant is the gold standard for renal replacement therapy in patients with autosomal dominant polycystic kidney disease (ADPKD), which is the fourth leading cause of kidney failure. Despite the medical and economic benefits of preemptive kidney transplant over dialysis before transplant, only 9-21% of qualifying patients receive preemptive transplants. Given the low rates of preemptive transplant, the aim of this study was to determine perceived facilitators and barriers to preemptive transplant among ADPKD patients using a qualitative approach.MethodsData were collected between July 2021 and January 2022 from virtual individual semi-structured interviews of 16 adult participants with ADPKD. Qualitative analysis of the recorded interviews was conducted to generate themes.ResultsOur findings revealed two themes specific for facilitators to preemptive transplant (social support and patient agency) and three themes specific to barriers for preemptive transplant (inadequate social support, gaps in knowledge, and institutional and systemic policies). The results also include various subthemes and the application of these themes to the social ecological model.ConclusionsThese findings suggest that increasing social support and patient agency, such as through patient navigator programs and encouraging effective communication between health care providers and patients, can facilitate the transplant process. Increasing dissemination of transplant knowledge from institutions and systems to patients through paired kidney exchange education and live donor outreach can also increase timely access to preemptive kidney transplants for patients with ADPKD. Our findings are limited by our single site study in the US, which may not apply to individuals experiencing different social, cultural, and health access conditions.

This review navigates the intricate relationship between gender, hormonal influences, and the progression of autosomal dominant polycystic kidney disease (ADPKD), highlighting the limited literature on this crucial topic. The study explores the impact of female sex hormones on liver and renal manifestations, uncovering gender-specific differences in disease progression. Actually, hormonal therapy in women with ADPKD remains a challenging issue and is a source of concern regarding its potential impact on disease outcomes, particularly at the hepatic level. Notably, women with ADPKD exhibit a slower renal disease progression compared to men, attributed to hormonal dynamics. This review sheds light on the role of estrogen in regulating pathways of the renin–angiotensin–aldosterone system, revealing its complex interplay and implications for cardiovascular and renal health. Therapeutic considerations for fertile women with ADPKD, including contraception options, are discussed, emphasizing the necessity for personalized approaches. In the postmenopausal phase, the review evaluates the role of hormonal replacement therapy, considering its potential benefits and risks in the context of ADPKD. The review concludes by underscoring the imperative need for tailored treatment approaches for ADPKD patients, considering individual risks and benefits. The scarcity of literature underlines the call for further research to enhance our understanding of optimal hormonal therapies in the context of ADPKD, ultimately paving the way for innovative and personalized therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficiency and safety between retroperitoneal laparoscopic nephrectomy and traditional open nephrectomy to treat autosomal-dominant polycystic kidney disease before kidney transplantation. Materials and Methods: A total of 57 patients diagnosed with huge autosomal-dominant polycystic kidney disease between 2000 and 2020 at our center were included in this study. Patients were divided into a retroperitoneal laparoscopic (RL; n=23) group and traditional open (TO; n = 34) group. We retrospectively analyzed and compared preoperative and perioperative variables between the two groups. Results: Patients in the RL group showed a longer operation time (201.09±83.76min) compared to patients in the TO group (113.38 ± 51.84min, p < 0.001). The RL group also showed significantly less intraoperative blood loss (p = 0.025) and less intraoperative blood transfusion volume (p = 0.016) compared to the TO group. Meanwhile, time of gastrointestinal function recovery, bed leave, catheter indwelling and postoperative hospitalization in the RL group were 2.13 ± 0.63, 1.30 ± 1.0, 5.22 ± 2.09, 7.35±2.48 days, respectively, which were significantly shorter than the TO group (p < 0.05). Pain degree of patients during the first 48 hours after operation was similar between the RL and TO groups, but the opioid use percentage in the RL group was 8.70% (2/23) and was lower than the 26.47% (9/34) in the TO group (p = 0.022). Meanwhile, 5 and 23 patients exhibited postoperative complications in the RL and TO groups, respectively (p < 0.001). Conclusion: Both retroperitoneal laparoscopic nephrectomy and traditional open surgery are feasible to treat huge polycystic nephrectomy. However, patients who undergo retroperitoneal laparoscopic nephrectomy experience higher levels of safety and recover more rapidly. [ABSTRACT FROM AUTHOR]

Dialysis disequilibrium syndrome (DDS) is a rare syndrome that can occur in patients with severe azotemia undergoing an initial hemodialysis (HD) session. DDS is associated with a more rapid decrease in urea concentration in the blood than in the brain during dialysis. Although severe DDS is less common, the milder forms of DDS may be missed by doctors. A 53-year-old male patient had the main complaint of severe dizziness in the last 10 months accompanied by a sensation of a wobbling head and tinnitus in his right ear. The patient had previously been diagnosed with polycystic kidney disease in 2018 and underwent regular hemodialysis two times a week since June 2019. In the patient's neurological status, cerebellar examination was positive for left dysmetria, left positive past pointing, Romberg test (open eye) fell to the right, and Romberg test (closed eye) fell to the right. There was no nystagmus on the patient's neuro-ophthalmological examination. Patients with kidney failure are at risk of developing DDS, so that appropriate precautions are needed. Due to the variability of symptoms, DDS often goes undiagnosed. Thus, it is important to be aware of the risk factors for DDS so that preventive steps can be taken appropriately. Continuous case reporting will raise awareness and the opportunity for further research to improve outcome in severe cases of DDS. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) affects more than 500,000 individuals in the United States alone. In most cases, ADPKD is caused by a loss-of-function mutation in the PKD1 gene, which encodes polycystin-1 (PC1). Previous studies reported that PC1 interacts with atypical protein kinase C (aPKC). Here we show that PC1 binds to the ζ isoform of aPKC (PKCζ) and identify two PKCζ phosphorylation sites on PC1's C-terminal tail. PKCζ expression is down-regulated in patients with ADPKD and orthologous and nonorthologous PKD mouse models. We find that the US Food and Drug Administration-approved drug FTY720 restores PKCζ expression in in vitro and in vivo models of polycystic kidney disease (PKD) and this correlates with ameliorated disease progression in multiple PKD mouse models. Importantly, we show that FTY720 treatment is less effective in PKCζ null versions of these PKD mouse models, elucidating a PKCζ-specific mechanism of action that includes inhibiting STAT3 activity and cyst-lining cell proliferation. Taken together, our results reveal that PKCζ down-regulation is a hallmark of PKD and that its stabilization by FTY720 may represent a therapeutic approach to the treat the disease.

This case report discusses the management of a 46-year-old male patient with autosomal dominant polycystic kidney disease and a high body mass index, who underwent a semi-simultaneous procedure involving hand-assisted laparoscopic bilateral nephrectomy to alleviate severe abdominal symptoms and prepare for a kidney transplantation, all using the same incision. This is the first reported occurrence of such a procedure in Saudi Arabia. Post-operatively, the patient made a successful recovery with excellent kidney function and no complications. [ABSTRACT FROM AUTHOR]

Tolvaptan is a highly selective vasopressin receptor 2 antagonist that regulates cyclic adenosine monophosphate levels to inhibit both epithelial cell proliferation and chloride ion excretion, two mechanisms known to induce cyst expansion in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan is currently the preferred treatment of rapidly progressive disease ADPKD in adult patients; however, since cyst formation in ADPKD begins early in life, (frequently in utero), and significant disease progression with cyst expansion occurs in the first decade, tolvaptan may be advantageous as a preemptive treatment in children with ADPKD. Tolvaptan has already been used to successfully treat refractory edema or hyponatremia in children; this literature review provides insight into the biochemical basis of its action to contextualize its use in the pediatric population. [ABSTRACT FROM AUTHOR]

Purpose: Total kidney volume (TKV) measurement is crucial for selecting treatment candidates in autosomal dominant polycystic kidney disease (ADPKD). We developed and investigated the performance of fully-automated 3D-volumetry model and applied it to software as a service (SaaS) for clinical support on tolvaptan prescription in ADPKD patients. Materials and Methods: Computed tomography scans of ADPKD patients taken between January 2000 and June 2022 were acquired from seven institutions. The quality of the images was manually reviewed in advance. The acquired dataset was split into training, validation, and test datasets at a ratio of 8.5:1:0.5. Convolutional, neural network-based automatic segmentation model was trained to obtain 3D segment mask for TKV measurement. The algorithm consisted of three steps: data preprocessing, ADPKD area extraction, and post-processing. After performance validation with the Dice score, 3D-volumetry model was applied to SaaS which is based on Mayo imaging classification for ADPKD. Results: A total of 753 cases with 95,117 slices were included. The differences between the ground-truth ADPKD kidney mask and the predicted ADPKD kidney mask were negligible, with intersection over union >0.95. The post-process filter successfully removed false alarms. The test-set performance was homogeneously equal and the Dice score of the model was 0.971; after post-processing, it improved to 0.979. The SaaS calculated TKV from uploaded Digital Imaging and Communications in Medicine images and classified patients according to height-adjusted TKV for age. Conclusions: Our artificial intelligence-3D volumetry model exhibited effective, feasible, and non-inferior performance compared with that of human experts and successfully predicted the rapid ADPKD progressor.

Abstract Background Xanthogranulomatous pyelonephritis (XGP) is a rare chronic pyelonephritis that often mimics other renal diseases, when combined with autosomal dominant polycystic kidney disease(ADPKD), preoperative diagnosis is exceedingly difficult. It is important for clinicians to be aware of an XGP with ADPKD since a misdiagnosis can lead to unnecessary surgical intervention. Case presentation Here, we report a case of a 66-year-old female with a history of bilateral ADPKD and urinary tract infection admitted to our hospital due to right flank pain, feeble, and low-grade fever. Contrast-enhanced ultrasound revealed a malignant mass of the right kidney suspected to be a cystic renal cell carcinoma with polycystic kidney disease. In addition, contrast-enhanced computed tomography (CT) and fluorine 18 fluorodeoxyglucose PET/CT (18F FDG PET/CT) showed similar results. Subsequently, the patient underwent a right radical nephrectomy, but histopathological examination revealed XGP with ADPKD. On the follow-up, the patient's symptoms were relieved. Conclusions XGP should be kept in mind during the differential diagnosis of renal masses with ADPKD even in the absence of characteristic clinical symptoms and imaging manifestations.

Background: K63-linked polyubiquitination of proteins have nonproteolytic functions and regulate the activity of many signal transduction pathways. USP7, a HIF1α deubiquitinase, undergoes K63-linked polyubiquitination under hypoxia. K63-polyubiquitinated USP7 serves as a scaffold to anchor HIF1α, CREBBP, the mediator complex, and the super elongation complex to enhance HIF1α-induced gene transcription. However, the physiological role of K63-polyubiquitinated USP7 remains unknown. Methods: Using a Usp7K444R point mutation knock-in mouse strain, we performed immunohistochemistry and standard molecular biological methods to examine the organ defects of liver and kidney in this knock-in mouse strain. Mechanistic studies were performed by using deubiquitination, immunoprecipitation, and quantitative immunoprecipitations (qChIP) assays. Results: We observed multiple organ defects, including decreased liver and muscle weight, decreased tibia/fibula length, liver glycogen storage defect, and polycystic kidneys. The underlying mechanisms include the regulation of protein stability and/or modulation of transcriptional activation of several key factors, leading to decreased protein levels of Prr5l, Hnf4α, Cebpα, and Hnf1β. Repression of these crucial factors leads to the organ defects described above. Conclusions: K63-polyubiquitinated Usp7 plays an essential role in the development of multiple organs and illustrates the importance of the process of K63-linked polyubiquitination in regulating critical protein functions.

Polycystic kidney disease (Autosomal Dominant Polycystic Kidney Disease, ADPKD) is the most common genetic disease of the kidney, and the measurement of Total Kidney Volume (TKV) in clinical research of this disease is essential to study the progression of ADPKD. At present, the volume segmentation of polycystic kidneys mainly relies on doctors to manually outline the kidney boundary on the radiological image. This process is time-consuming, labor-intensive, inefficient, subjective, and difficult to guarantee consistency. In the research of this paper, A multi-module hybrid U-shape segmentation method is proposed (HUNet), which introduces wavelet pooling, cascade residual, and efficient multi-head self-attention into the U-shape structure. We use wavelet pooling instead of traditional down-sampling to reduce the loss of detailed features, the use of cascaded residual modules can improve the ability of model feature reuse, and the use of efficient multi-head self-attention modules can effectively capture global multi-scale information. In the decoding process of the U-shape, the corresponding loss value of each decoder will be calculated, and finally, the total loss value of the model will be obtained by weighted average. The method was trained and tested on the polycystic kidney dataset provided by Shanghai Changzheng Hospital. We automatically segmented the ADPKD in MRI images using the proposed method with a remarkably high Dice similarity coefficient relative to the manual segmentation (mean=0.915). The percentage difference between the total kidney volume values using manual and HUNet methods was only 0.4%. The proposed approach enables fast and accurate TKV measurement.

Autosomal recessive polycystic kidney disease (ARPKD) is mainly caused by variants in the PKHD1 gene, encoding fibrocystin (FC), a large transmembrane protein of incompletely understood cellular function. Here, we show that a C-terminal fragment of human FC can suppress a signalling module of the kinase SRC and signal transducer and activator of transcription 3 (STAT3). Consistently, we identified truncating genetic variants specifically affecting the cytoplasmic tail in ARPKD patients, found SRC and the cytoplasmic tail of fibrocystin in a joint dynamic protein complex and observed increased activation of both SRC and STAT3 in cyst-lining renal epithelial cells of ARPKD patients.

This review navigates the intricate relationship between gender, hormonal influences, and the progression of autosomal dominant polycystic kidney disease (ADPKD), highlighting the limited literature on this crucial topic. The study explores the impact of female sex hormones on liver and renal manifestations, uncovering gender-specific differences in disease progression. Actually, hormonal therapy in women with ADPKD remains a challenging issue and is a source of concern regarding its potential impact on disease outcomes, particularly at the hepatic level. Notably, women with ADPKD exhibit a slower renal disease progression compared to men, attributed to hormonal dynamics. This review sheds light on the role of estrogen in regulating pathways of the renin–angiotensin–aldosterone system, revealing its complex interplay and implications for cardiovascular and renal health. Therapeutic considerations for fertile women with ADPKD, including contraception options, are discussed, emphasizing the necessity for personalized approaches. In the postmenopausal phase, the review evaluates the role of hormonal replacement therapy, considering its potential benefits and risks in the context of ADPKD. The review concludes by underscoring the imperative need for tailored treatment approaches for ADPKD patients, considering individual risks and benefits. The scarcity of literature underlines the call for further research to enhance our understanding of optimal hormonal therapies in the context of ADPKD, ultimately paving the way for innovative and personalized therapeutic interventions.

Abstract Metformin (MET) has the potential to activate p‐AMPK and block mTORC1‐induced proliferation of tubular cells in PKD kidneys. The aim of this study was to determine the effects of MET on cyst growth, kidney function, AMPK and mTOR signaling, and lactate levels in male PCK rats, a Pkhd1 gene mutation model of human autosomal recessive polycystic kidney disease (ARPKD). MET 300 mg/kg/day IP from days 28 to 84 of age resulted in a mean serum metformin level that was 10 times the upper limit of therapeutic, no effect on cyst indices, nephrotoxicity, and increased serum lactate. MET 150 mg/kg resulted in a therapeutic serum metformin level but had no effect on kidney weight, cyst indices, kidney function, or mTOR and autophagy proteins. In summary, a standard dose of MET was ineffective in reducing PKD, did not activate p‐AMPK or suppress mTOR and the higher dose resulted in increased lactate levels and nephrotoxicity. In conclusion, the study dampens enthusiasm for human studies of MET in PKD. Doubling the metformin dose resulted in a 10‐fold increase in mean blood levels and toxicity suggesting that the dosage range between therapeutic and toxic is narrow.

Background: Xanthogranulomatous pyelonephritis (XGP) is a rare chronic pyelonephritis that often mimics other renal diseases, when combined with autosomal dominant polycystic kidney disease(ADPKD), preoperative diagnosis is exceedingly difficult. It is important for clinicians to be aware of an XGP with ADPKD since a misdiagnosis can lead to unnecessary surgical intervention. Case presentation: Here, we report a case of a 66-year-old female with a history of bilateral ADPKD and urinary tract infection admitted to our hospital due to right flank pain, feeble, and low-grade fever. Contrast-enhanced ultrasound revealed a malignant mass of the right kidney suspected to be a cystic renal cell carcinoma with polycystic kidney disease. In addition, contrast-enhanced computed tomography (CT) and fluorine 18 fluorodeoxyglucose PET/CT (18F FDG PET/CT) showed similar results. Subsequently, the patient underwent a right radical nephrectomy, but histopathological examination revealed XGP with ADPKD. On the follow-up, the patient's symptoms were relieved. Conclusions: XGP should be kept in mind during the differential diagnosis of renal masses with ADPKD even in the absence of characteristic clinical symptoms and imaging manifestations. [ABSTRACT FROM AUTHOR]

Polycystic kidney disease is a disorder of renal epithelial growth and differentiation. Transcription factor EB (TFEB), a master regulator of lysosome biogenesis and function, was studied for a potential role in this disorder. Nuclear translocation and functional responses to TFEB activation were studied in three murine models of renal cystic disease, including knockouts of folliculin, folliculin interacting proteins 1 and 2, and polycystin-1 (Pkd1) as well as in mouse embryonic fibroblasts lacking Pkd1 and three-dimensional cultures of Madin-Darby canine kidney cells. Nuclear translocation of Tfeb characterized cystic but not noncystic renal tubular epithelia in all three murine models as both an early and sustained response to cyst formation. Epithelia expressed elevated levels of Tfeb-dependent gene products, including cathepsin B and glycoprotein nonmetastatic melanoma protein B. Nuclear Tfeb translocation was observed in mouse embryonic fibroblasts lacking Pkd1 but not wild-type fibroblasts. Pkd1 knockout fibroblasts were characterized by increased Tfeb-dependent transcripts, lysosomal biogenesis and repositioning, and increased autophagy. The growth of Madin-Darby canine kidney cell cysts was markedly increased following exposure to the TFEB agonist compound C1, and nuclear Tfeb translocation was observed in response to both forskolin and compound C1 treatment. Nuclear TFEB also characterized cystic epithelia but not noncystic tubular epithelia in human patients with autosomal dominant polycystic kidney disease. Noncanonical activation of TFEB is characteristic of cystic epithelia in multiple models of renal cystic disease including those associated with loss of Pkd1. Nuclear TFEB translocation is functionally active in these models and may be a component of a general pathway contributing to cystogenesis and growth. [ABSTRACT FROM AUTHOR]

Purpose: Decreased quality of life, anxiety, depression, and other negative psychosocial factors in autosomal dominant polycystic kidney disease (ADPKD) may lead to the patient's attitudes that reduce treatment effectiveness. We aimed to evaluate the relationship between the depression, anxiety, perceived social support, genetic psychosocial risk and quality of life levels, and chronic kidney disease (CKD) stage in ADPKD and to investigate the relationship between these variables/parameters and the dietary compliance that is an essential factor in the course of the disease. Methods: 100 ADPKD patients were enrolled in this cross-sectional study. EuroQol-5D-3L (EQ-5D-3L) health-related quality of life ındex, EuroQol-5D-3L visual analog scale (EQ-5D-3L VAS), multidimensional scale of perceived social support (MSPSS), patient health questionnaire (PHQ)-9, and genetic psychosocial risk ınstrument (GPRI) were applied to the patients. Results: There is a relationship with negative regression coefficient between the CKD stage and the total scores of the EQ-5D-3L and EQ-5D-3L VAS scales (p < 0.000 and β = − 5.355, p < 0.000, and β = − 8.394, respectively). There is a relationship with positive regression coefficient between the CKD stage and MSPSS total score and level (p < 0.000 and β = 0.364, p < 0.000 and β = 0.331, respectively). There is no relationship between the CKD stage and GPRI total score (p = 0.800). In addition, there is a relationship with positive regression coefficient between the dietary compliance and EQ-5D and EQ-5D VAS total scores (p = 0.006 and β = 2.687, p = 0.004 and β = 3.148, respectively). There is a relationship with negative regression coefficient between the dietary adherence and PHQ-9 total score and CKD stage (p = 0.003, p = 0.006, and β = − 0.692, respectively). Conclusion: As the CKD stage increases in the ADPKD patients, the quality of life decreases, whereas the level of anxiety and depression increases. It has been seen that the ADPKD patients with more depressive complaints have less dietary compliance. In this particular patient group, the early detection and treatment of psychosocial difficulties and the work to improve the quality of life that affect the course of the ADPKD may be as important as the medical treatment. To determine the needs of ADPKD patients with multiple physical and psychosocial difficulties and to perform appropriate interventions, we think that there is a necessity for a specific scale that evaluates these effective components together in the ADPKD process. [ABSTRACT FROM AUTHOR]

BackgroundApproximately 30% of Persian cats have a c.10063C > A variant in polycystin 1 (PKD1) homolog causing autosomal dominant polycystic kidney disease (ADPKD). The variant is lethal in utero when in the homozygous state and is the only ADPKD variant known in cats. Affected cats have a wide range of progression and disease severity. However, cats are an overlooked biomedical model and have not been used to test therapeutics and diets that may support human clinical trials. To reinvigorate the cat as a large animal model for ADPKD, the efficacy of imaging modalities was evaluated and estimates of kidney and fractional cystic volumes (FCV) determined.MethodsThree imaging modalities, ultrasonography, computed tomography (CT), and magnetic resonance imaging examined variation in disease presentation and disease progression in 11 felines with ADPKD. Imaging data was compared to well-known biomarkers for chronic kidney disease and glomerular filtration rate. Total kidney volume, total cystic volume, and FCV were determined for the first time in ADPKD cats. Two cats had follow-up examinations to evaluate progression.ResultsFCV measurements were feasible in cats. CT was a rapid and an efficient modality for evaluating therapeutic effects that cause alterations in kidney volume and/or FCV. Biomarkers, including glomerular filtration rate and creatinine, were not predictive for disease progression in feline ADPKD. The wide variation in cystic presentation suggested genetic modifiers likely influence disease progression in cats. All imaging modalities had comparable resolutions to those acquired for humans, and software used for kidney and cystic volume estimates in humans proved useful for cats.ConclusionsRoutine imaging protocols used in veterinary medicine are as robust and efficient for evaluating ADPKD in cats as those used in human medicine. Cats can be identified as fast and slow progressors, thus, could assist with genetic modifier discovery. Software to measure kidney and cystic volume in human ADPKD kidney studies is applicable and efficient in cats. The longer life and larger kidney size span than rodents, similar genetics, disease presentation and progression as humans suggest cats are an efficient biomedical model for evaluation of ADPKD therapeutics.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by gradual cyst growth and expansion, increase in kidney volume with an ultimate decline in kidney function leading to end stage renal disease (ESRD). Given the decades long period of stable kidney function while cyst growth occurs, it is important to identify those patients who will progress to ESRD. Recent data from our and other laboratories have demonstrated that metabolic reprogramming may play a key role in cystic epithelial proliferation resulting in cyst growth in ADPKD. Height corrected total kidney volume (ht-TKV) accurately reflects cyst burden and predicts future loss of kidney function. We hypothesize that specific plasma metabolites will correlate with eGFR and ht-TKV early in ADPKD, both predictors of disease progression, potentially indicative of early physiologic derangements of renal disease severity.MethodsTo investigate the predictive role of plasma metabolites on eGFR and/or ht-TKV, we used a non-targeted GC-TOF/MS-based metabolomics approach on hypertensive ADPKD patients in the early course of their disease. Patient data was obtained from the HALT-A randomized clinical trial at baseline including estimated glomerular filtration rate (eGFR) and measured ht-TKV. To identify individual metabolites whose intensities are significantly correlated with eGFR and ht-TKV, association analyses were performed using linear regression with each metabolite signal level as the primary predictor variable and baseline eGFR and ht-TKV as the continuous outcomes of interest, while adjusting for covariates. Significance was determined by Storey's false discovery rate (FDR) q-values to correct for multiple testing.ResultsTwelve metabolites significantly correlated with eGFR and two triglycerides significantly correlated with baseline ht-TKV at FDR q-value

The rate of disease progression in autosomal-dominant (AD) polycystic kidney disease (PKD) exhibits high intra-familial variability suggesting that environmental factors may play a role. We hypothesized that a prevalent form of renal insult may accelerate cystic progression and investigated tubular crystal deposition. We report that calcium oxalate (CaOx) crystal deposition led to rapid tubule dilation, activation of PKD-associated signaling pathways, and hypertrophy in tubule segments along the affected nephrons. Blocking mTOR signaling blunted this response and inhibited efficient excretion of lodged crystals. This mechanism of "flushing out" crystals by purposefully dilating renal tubules has not previously been recognized. Challenging PKD rat models with CaOx crystal deposition, or inducing calcium phosphate deposition by increasing dietary phosphorous intake, led to increased cystogenesis and disease progression. In a cohort of ADPKD patients, lower levels of urinary excretion of citrate, an endogenous inhibitor of calcium crystal formation, correlated with increased disease severity. These results suggest that PKD progression may be accelerated by commonly occurring renal crystal deposition which could be therapeutically controlled by relatively simple measures.

Oligohydramnios is both a consequence of fetal malformations and of uteroplacental insufficiency. Its existence is associated with a high rate of both antepartum and intrapartum complications. It is vital that its occurrence is detected as early as possible so that we can manage it correctly. The main causes of its occurrence are identified and described in this review. The management of oligohydramnios is most often expectant, the timing of delivery also being determined by Doppler examination and changes in parameters measuring fetal growth and development.

Here we report a case that a young man had early onset myocardial infarction. Coronary angiography showed coronary aneurysm-like dilation and thromboembolism. After stents were implanted, his condition was complicated with repeated stent restenosis. Polycystic kidney, nephrotic syndrome and antiphospholipid antibody syndrome were also present. Antiphospholipid antibody syndrome, a risk factor for recurrent coronary thrombosis, can lead to nephrotic syndrome. Polycystic kidney can be characterized by nephrotic syndrome and may be combined with aneurysmal lesions due to genetic abnormalities. According to the multidisciplinary discussion and follow-up results, the patient was diagnosed as connective tissue diseases and secondary anti-phospholipid antibody syndrome, nephrotic syndrome, and coronary artery lesions. The patient's symptoms improved after treatment for the original disease. The management of this patient broadened our understanding of the etiology of coronary artery disease in young patients and demonstrated the importance of multidisciplinary clinical thinking.

Background: In clinical practice, the possible diagnosis of tuberous sclerosis or polycystic kidney disease is primarily based on clinical criteria, which can later be verified by genetic testing. But in the case of TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1-CGS), the renal appearance of the disease is more serious. Therefore, early genetic analysis is recommended. Methods: Herein we present the report of four children with TSC2/PKD1-CGS, one involving the NTHL1 gene. We aim to emphasize the importance of genetic testing in this rare syndrome. Results: During the follow-up of tuberous sclerosis and polycystic kidney disease patients, it is essential to reappraise the diagnosis if the clinical symptoms' appearance or onset time is unusual. Targeted genetic testing is recommended. However, early tumor formation necessitates the extension of genetic analysis. Conclusions: An appropriate evaluation of the phenotype is the cornerstone of diagnosing the rare TSC2/PKD1-CGS with the help of genetic results. In addition, malignant tumors could draw attention to an infrequent large deletion. [ABSTRACT FROM AUTHOR]

Gillessen‐Kaesbach‐Nishimura syndrome (GIKANIS) is a congenital disease of glycosylation (CDG) linked to the ALG9 gene. GIKANIS is a lethal disorder characterized by atypical facial features, generalized skeletal changes with shortening of the long bones with broad, round metaphyses, round ilia, and deficient ossification of the skull, cervical spine and pubic bones, and visceral abnormalities including polycystic kidneys and congenital cardiac defects. GIKANIS is caused by a homozygous splicing variant (c.1173 + 2 T > A) leading to skipping of exon 10, frameshift, and premature termination codon of the ALG9 gene. To our best knowledge, only two affected families with confirmed molecular analyses have been reported. We present an additional report on two siblings with the same mutation, emphasizing the prenatal ultrasonographic features. Their facial and skeletal manifestations recapitulated those previously reported. Ultrasonography revealed polycystic kidneys and unbalanced atrioventricular septal defect (AVSD) with transposition of the great arteries. [ABSTRACT FROM AUTHOR]

Research into metabolic reprogramming in cancer has become commonplace, yet this area of research has only recently come of age in nephrology. In light of the parallels between cancer and autosomal dominant polycystic kidney disease (ADPKD), the latter is currently being studied as a metabolic disease. In clear cell renal cell carcinoma (RCC), which is now considered a metabolic disease, we and others have shown derangements in the enzyme arginosuccinate synthase 1 (ASS1), resulting in RCC cells becoming auxotrophic for arginine and leading to a new therapeutic paradigm involving reducing extracellular arginine. Based on our earlier finding that glutamine pathways are reprogrammed in ARPKD, and given the connection between arginine and glutamine synthetic pathways via citrulline, we investigated the possibility of arginine reprogramming in ADPKD. We now show that, in a remarkable parallel to RCC, ASS1 expression is reduced in murine and human ADPKD, and arginine depletion results in a dose-dependent compensatory increase in ASS1 levels as well as decreased cystogenesis in vitro and ex vivo with minimal toxicity to normal cells. Nontargeted metabolomics analysis of mouse kidney cell lines grown in arginine-deficient versus arginine-replete media suggests arginine-dependent alterations in the glutamine and proline pathways. Thus, depletion of this conditionally essential amino acid by dietary or pharmacological means, such as with arginine-degrading enzymes, may be a novel treatment for this disease.

Introduction: The purpose of this study was to evaluate the efficacy of polycystic kidney embolization, performed to reduce kidney volume before heterotopic kidney transplantation, as this technique could be an alternative to pretransplant nephrectomy. Materials and Methods: All patients who underwent pretransplant embolization of polycystic kidneys were included in a prospective register from June 2014 to February 2020. All patients underwent computed tomography (CT) scan with volumetric reconstruction (OsiriX, Bernex, Switzerland) before embolization and were then followed up at 3 and 6 months after embolization. Primary outcome was percentage of kidney volume reduction. Secondary outcomes were 30 day mortality and morbidity. Results: Thirty-one embolizations performed on 29 patients (medium age = 55.6; 62.1% male) were included between June 2014 and February 2020. All patients were under dialysis before embolization (9 peritoneal dialysis and 20 hemodialysis). Technical success was observed in 96.8% of cases. Mean procedural time was 65 minutes (range = 35–106 minutes) and mean length of in-hospital stay was 3.8 days (range = 3–6 days). A volume reduction allowing a kidney transplant was obtained for 28 patients (96.5%). The mean volume reduction was 39.9% (range = 6.01–68.2). The main observed complication was postembolization pain in 10 cases (32.2%). One patient needed complementary nephrectomy due to insufficient volume reduction. Twenty-three patients (79.3%) received renal transplant during follow-up with a mean delay of 19.5 month (range = 4–54). Conclusion: Polycystic kidney embolization is an effective and safe minimally invasive technique. It can be proposed as the first-choice technique for kidney transplant recipients as an alternative to pretransplantation nephrectomy. [ABSTRACT FROM AUTHOR]

Oligohydramnios is both a consequence of fetal malformations and of uteroplacental insufficiency. Its existence is associated with a high rate of both antepartum and intrapartum complications. It is vital that its occurrence is detected as early as possible so that we can manage it correctly. The main causes of its occurrence are identified and described in this review. The management of oligohydramnios is most often expectant, the timing of delivery also being determined by Doppler examination and changes in parameters measuring fetal growth and development. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical data of a patient diagnosed as autosomal dominant polycystic kidney disease (ADPKD) complicated with pulmonary embolism (PE), and review reported cases in data base to explore the diagnosis and treatment in the ADPKD patients with venous thromboembolism(VTE). Methods: A 45-year-old male diagnosed as ADPKD [also had polycystic liver disease (PLD)] and pulmonary embolism (PE) was admitted in our hospital, and the clinical manifestations and laboratory results were analyzed. The diagnosis and treatment in the patients with ADPKD complicated with VTE were reviewed through searching PubMed and entire database. Results: The ADPKD patient with PLD, presenting with chest pain and shortness of breath, was diagnosed as PE using pulmonary ventilation perfusion examination and as deep VTE through imaging of deep venous. The MRI enhancement of the upper abdominal organs showed the stenosis lesions in hepatic segment of inferior vena cava, and polycystic liver combined with polycystic kidney. The heterozygous variation of PKD1 gene and PROS1 gene were detected by the whole exon sequencing. A total of 15 ADPKD patients complicated with deep VTE were reviewed. Among them, all cases had inferior vena cava thrombosis (IVCT), 13 cases had PLD, 2 cases had hepatic vein thrombosis, 12 cases had VTE, and 2 cases had PE. The symptoms of 10 ADPKD patients were relieved after anticoagulation treatment with heparin and warfarin, while 5 patients needed hardener or inferior vena cava filter placement or surgical treatment. Conclusions: The polycystic kidney(PKD) and PLD are not considered as the most common causes for VTE, which are easy to be ignored in medical practice. The ADPKD patients usually complicated with PLD, which may cause compression of inferior vena cava and lead to embolism. The primary treatment is anticoagulation, and the adjuvant therapy is relief of cyst compression.

Mutations in PKD1 and PKD2 are the leading cause of autosomal dominant polycystic kidney disease (ADPKD). In this issue of Genes & Development, a report by Cai and colleagues (pp. 781-793) reveals new insight into the molecular basis by which PKD1 deficiency leads to cystic kidney pathogenesis. By using extensive mouse genetic analyses coupled with in vitro cystic assays, the investigators delineate a RhoA-YAP-c-Myc signaling axis as a key downstream from PKD1 deficiency in ADPKD pathogenesis. Their findings provide evidence that the Hippo pathway could be a potential target for treating ADPKD.

BackgroundThe impact of autosomal dominant polycystic kidney disease (ADPKD) on health-related quality of life (HRQoL) is not well understood due to a lack of instruments specific to the condition.Study designContent for a new self-administered patient-reported outcome (PRO) questionnaire to assess ADPKD-related HRQoL was developed through clinical expert and patient focus group discussions. The new PRO instrument was administered to study patients with ADPKD to evaluate its reliability and validity.Setting & participants1,674 adult patients with ADPKD participated in this research: 285 patients in focus groups to generate questionnaire content, 15 patients in debriefing interviews to refine the PRO questionnaire, and 1,374 patients to assess the performance and measurement properties of the PRO questionnaire.OutcomeA new PRO questionnaire.ResultsThe ADPKD Impact Scale (ADPKD-IS), consisting of 14 items representing 3 conceptual domains (physical, emotional, and fatigue) plus 4 additional questions, was developed. The instrument's reliability (regarding internal consistency and test-retest consistency) and validity (content and construct) were supported.LimitationsNeed for more responsiveness testing when more data from clinical use become available over time. Complex concepts such as ADPKD-related pain and impact on a patient's HRQoL need further evaluation.ConclusionsThe ADPKD-IS is a new patient-centric tool that reliably and validly provides a standardized method for assessing HRQoL and overall disease burden in patients with ADPKD.

Head-to-tail polymers of sterile alpha motifs (SAM) can scaffold large macromolecular complexes. Several SAM-domain proteins that bind each other are mutated in patients with cystic kidneys or laterality defects, including the Ankyrin (ANK) and SAM domain-containing proteins ANKS6 and ANKS3, and the RNA-binding protein Bicc1. To address how their interactions are regulated, we first determined a high-resolution crystal structure of a Bicc1-SAM polymer, revealing a canonical SAM polymer with a high degree of flexibility in the subunit interface orientations. We further mapped interactions between full-length and distinct domains of Bicc1, ANKS3, and ANKS6. Neither ANKS3 nor ANKS6 alone formed macroscopic homopolymers in vivo. However, ANKS3 recruited ANKS6 to Bicc1, and the three proteins together cooperatively generated giant macromolecular complexes. Thus, the giant assemblies are shaped by SAM domains, their flanking sequences, and SAM-independent protein-protein and protein-mRNA interactions.

Objective To clarify the pathogenic mutations and provide references for prevention and treatment strategies and prenatal diagnosis by gene detection in 3 pedigrees with autosomal dominant polycystic kidney disease (ADPKD). Methods The family history and clinical data of 3 ADPKD pedigrees who admitted to our department of urology during 2017 and 2020 were collected in this study. The peripheral blood samples of these family members were harvested for DNA extraction. Targeted amplification and high-throughput sequencing was used to screen suspected pathogenic mutations in probands, and then these obtained mutations were verified and analyzed in the probands and their family members by Sanger sequencing. The pathogenicity of these mutations was analyzed with bioinformation analysis and the evaluation criteria of the American Society of Medical Genetics. Results Ultrasound examination showed that all the probands from the 3 families had polycystic kidneys, at the clinical stages of G1, G3a, and G5 respectively. The deletion frameshift mutation c.5933delA (p.Asn1978fs), nonsense heterozygous mutation c.6871C>T (G2291X) and deletion frameshift mutation of c.894_897delCCCT (p.299Sfs*34) in polycystic kidney disease 1 (PKD1) gene were detected in pedigrees 1, 2 and 3, respectively. The above variants in the 3 families were in line with phenotype-genotype separation. Conclusion We identify the pathogenic variants in the 3 pedigrees of hereditary polycystic kidney disease, among which c.5933delA and c.894_897delCCCT are new mutations, and c.6871C>T is a known pathogenic mutation.

A cross-breed female cat was presented with clinical signs of abdominal pain, paralysis of both hind limbs, tachycardia, tachypnea and bilateral absence of the femoral pulse. Necropsy confirmed an aortic thrombus at 2 cm above the adrenal glands, the heart with left atrial dilation and hypertrophied left ventricle, multiple bilateral kidney cysts and ectopic thyroid tissue. Histopathological examination reveals the kidney with multiple cysts, diffuse loss of renal structural details without inflammatory cells, hypertrophic cardiomyopathy, and no ectopic thyroid tissue changes. This communication describes a case of aortic thromboembolism associated with hypertrophic cardiomyopathy due to autosomal dominant polycystic kidney disease and ectopic thyroid tissue. [ABSTRACT FROM AUTHOR]

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common hereditary renal disease with no currently available targeted therapies. Based on the established connection between β-catenin signaling and renal ciliopathies, and on data from our and other laboratories showing striking similarities of this disease and cancer, we evaluated the use of an orally bioavailable small molecule, KPT-9274 (a dual inhibitor of the protein kinase PAK4 and nicotinamide phosphoribosyl transferase), for treatment of ADPKD. Treatment of PKD-derived cells with this compound not only reduces PAK4 steady-state protein levels and regulates β-catenin signaling, but also inhibits nicotinamide phosphoribosyl transferase, the rate-limiting enzyme in a key NAD salvage pathway. KPT-9274 can attenuate cellular proliferation and induce apoptosis associated with a decrease in active (phosphorylated) PAK4 and β-catenin in several Pkd1-null murine cell lines, with a less pronounced effect on the corresponding phenotypically normal cells. Additionally, KPT-9274 shows inhibition of cystogenesis in an ex vivo model of cyclic AMP-induced cystogenesis as well as in the early stage Pkd1flox/flox:Pkhd1-Cre mouse model, the latter showing confirmation of specific anti-proliferative, apoptotic, and on-target effects. NAD biosynthetic attenuation by KPT-9274, while critical for highly proliferative cancer cells, does not appear to be important in the slower growing cystic epithelial cells during cystogenesis. KPT-9274 was not toxic in our ADPKD animal model or in other cancer models. Thus, this small molecule inhibitor could be evaluated in a clinical trial as a viable therapy of ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) with concomitant horseshoe kidney is an extremely rare entity. In this case, we report a 45-year-old male patient with ADPKD and a horseshoe kidney who demonstrated hypertension, urological complications and discomfort symptoms such as pain, breathing difficulties and abdominal meteorism. After preoperative assessment and planning, the patient underwent nephrectomy. Bilateral nephrectomy without dividing the isthmus was performed successfully. The isthmus, which had complicated vasculature and was full of cysts, remained intact avoiding severe bleeding and infection. The postoperative course was uneventful. Keeping the isthmus intact in such cases is a challenge for the surgeon. The rarity of polycystic horseshoe kidney in combination with the altered abdominal anatomy requires the proper preoperative strategy in order to avoid intraoperative complications.

Joubert syndrome (JS), was first discovered by Marie Joubert, which is a rare autosomal recessive inherited disease belonging to ciliopathy with the causative mutation of genes. A 27-years-old woman was referred to our clinic for advanced research over the detection of fetal renal cyst. We observed policycstic kidney in detailed ultrasonographic examination. INPP5E mutation was detected on chorion villus sampling. We were thought may be this findings will be associated with the any syndrome, primarily joubert syndorme (JS), upon detection the vermis hypoplasia, policyctic kidney and molar teeth sign were observed on USG in the 23rd week of pregnancy. The vermis hypoplasia, posterior fossa expansion and bilateral polycystic kidney were seen on MRI and the radiologist has reported as Dandy-Walker depend on this findings. They did not pay attention to the molar tooth finding. We were explained prognosis and suggested termination to the family. The fetus was terminated upon the approval of the family. The most common characteristic brain image of JS is the molar tooth sign(MTS) on the axial plane, cerebellar vermis (CV) hypoplasia, and a deepened interpeduncular fossa. The MTS is the key diagnostic feature for this disease. So far, more than 30 causative genes have been found for the various subtypes of JSRD. One of them is INPP5E. Defects of additional extra-nervous systems involve polycystic kidney disease, retinal degeneration, skeletal defects (such as polydactyly), and liver disorder. Joubert Syndrome can be diagnosed in prenatally period. MTS can be seen easily with usg during prenatal period. The vermian hypoplasia and additional organ anomalies must be brought to mind JS and MTS should be searched and families should be given prenatal counseling. [ABSTRACT FROM AUTHOR]

Myrlene Sanon Aigbogun,1 Robert A Stellhorn,1 Christina S Pao,1 Stephen L Seliger2 1Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 2University of Maryland School of Medicine, Baltimore, MD, USACorrespondence: Stephen L SeligerUniversity of Maryland School of Medicine, 10 N. Greene Street, Baltimore, MD, 21201, USATel +410 605-7000 x5231Fax +410 328-5685Email sseliger@som.umaryland.eduBackground: Progression of autosomal dominant polycystic kidney disease (ADPKD) is highly variable, with some patients progressing rapidly to end-stage renal disease (ESRD). Abdominal imaging is an important modality for verifying diagnosis in patients at risk for rapidly progressing ADPKD, targeting them for early treatment that could slow onset of ESRD. Published literature is limited on the real-world abdominal imaging utilization patterns in ADPKD.Methods: A retrospective healthcare administrative claims analysis examining abdominal imaging scans occurring from January 1, 2014, through June 30, 2017, was conducted using the IBM MarketScan® commercial and Medicare supplemental databases. Patients in the United States who were at least 18 years old and had at least 1 inpatient claim or 2 outpatient claims (with different dates of service) with an ADPKD diagnosis code, as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM codes 753.12 [polycystic kidney, unspecified type] and 753.13 [polycystic kidney, autosomal dominant] and/or Tenth Revision (ICD-10-CM codes Q61.2 [polycystic kidney, adult type] and Q61.3 [polycystic kidney, unspecified]) were included.Results: Of the 4637 patients with ADPKD (mean age, 51.2 years [SD = 15.52]), 59% had ≥ 1 abdominal imaging scan. Of these patients, 46% had ≥ 1 computed tomography (CT) scan, 25% had ≥ 1 ultrasound, 10% had ≥ 1 magnetic resonance imaging scan. Among the 1754 patients (38%) with chronic kidney disease (CKD) stage information, CT imaging was more frequent in later stages (31% stage 1 versus 68% stage 5). The proportion of patients undergoing at least 1 CT or MRI scan increased with disease severity (37% in stage 1, 42% in stage 2, 48% in stage 3, 56% in stage 4, and 71% in stage 5).Conclusion: Results of this analysis support the need for further investigation into abdominal imaging utilization in managing patients with ADPKD. Future research could clarify barriers and increase access to imaging, which has the potential to inform risk stratification, help patients delay dialysis or transplantation associated with ESRD, and help health systems avoid the costs associated with ESRD.Keywords: polycystic kidney, autosomal dominant, kidney diseases, cystic, MRI, CT scan, ultrasound