1,119 results on '"*AUTOSOMAL recessive polycystic kidney"'
Search Results
102. Pediatric Tubular and Inherited Disorders in Asia: Results of Preliminary Survey of the Asian Pediatric Nephrology Association (AsPNA) Tubular and Inherited Working Group.
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Real Resontoc, Lourdes Paula, Kandai, Nozu, Hooman, Nakisa, Vasudevan, Anil, Jie Ding, and Hee Gyung Kang
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REPORTING of diseases ,BARTTER syndrome ,POLYCYSTIC kidney disease ,BIOCHEMISTRY ,HEALTH services accessibility ,INTERNET ,RESEARCH methodology ,NEPHRITIS ,PHENOMENOLOGICAL biology ,GENETIC testing ,GENETIC disorders ,NEPHROLOGY ,MEDICAL protocols ,DESCRIPTIVE statistics ,INBORN errors of metabolism ,RENAL tubular transport disorders ,PHYSICIANS ,AUTOSOMAL recessive polycystic kidney ,HYPOALDOSTERONISM ,CHILDREN - Abstract
Background and Objective: The registries and guidelines for kidney diseases in children mostly do not include the Asian population and hence, its applicability is questionable. As a first step to address this question, the tubular and inherited disease working group of the Asian Pediatric Nephrology Association aimed to assess the current situation of pediatric tubular and inherited disorders in Asia. Methods: Our group conducted an online survey among the members of AsPNA from September to October 2020. Data collected included demographics, number of patients each physician cares for per year, methods of diagnosis, and access to genetic tests. Descriptive analysis was performed. Results: A total of 299 pediatric nephrologists from 21 countries in Asia participated. Distal renal tubular acidosis, Bartter syndrome, autosomal dominant polycystic kidney disease, autosomal recessive kidney disease, and Alport syndrome were the commonly reported diseases. Around 70% employed clinical history, radiologic imaging, and biochemical tests for diagnosis. More than half (55.4%) of the institutions have access to genetic testing. For future collaborative projects, 88% expressed interest to participate. Conclusions: The results highlight the diversity of disease prevalence, diagnostic practices, capability, and access to genetic tests across Asia. The data gathered from this preliminary survey can be used to address knowledge gaps, and improve management and outcomes. [ABSTRACT FROM AUTHOR]
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- 2022
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103. Choque séptico en paciente con poliquistosis renal y hepática: reporte de un caso.
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Aguayo Moscoso, Santiago, Checa Sánchez, Margarita, Paccha Quizhpe, Viviana, Mosquera Pozo, Ximena, Guzmán Ramírez, Rafael, Puetate Ceballos, Miriam, Chalá Minda, Tatiana, and Vélez Paez, Jorge
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POLYCYSTIC kidney disease ,AUTOSOMAL recessive polycystic kidney ,CYSTIC kidney disease ,SEPTIC shock ,KIDNEY development - Abstract
Copyright of INSPILIP. Revista Ecuatoriana de Ciencia, Tecnología e Innovacion en Salud Pública is the property of Instituto Nacional de Investigacion en Salud Publica (INSPI) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2022
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104. Anthropometric measurements of peri-oral region in a sample of Iraqi thalassemic patients.
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Al-Taee, Riad, Al-Saedi, Aqeel Ibrahim Lazim, and Nahidh, Mohammed
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THALASSEMIA ,AUTOSOMAL recessive polycystic kidney ,BONE marrow ,CONTROL groups ,GENDER differences (Psychology) - Abstract
OBJECTIVES: Thalassemia, one of the most widespread autosomal recessive disorders, is characterized by anomalies in the synthesis of hemoglobin beta chains and is frequently coupled with variable craniofacial characteristics. Thalassemic patients suffer from severe anemia, which triggers several defense mechanisms in the body, such as bone marrow expansion, which forces the bones to expand, resulting in craniofacial bone deformities. This study aims to assess and compare the orofacial dimensions of β-thalassemia patients with those of a control group across similar ages and gender. MATERIALS AND METHODS: Three hundred Iraqi individuals agreed to participate in this study (150 non-thalassemic and 150 thalassemic patients with an equal distribution of genders). A well-trained researcher carried out five anthropometric measurements by using an electronic digital caliper. Gender and group differences were tested using an independent sample t test. RESULTS: Mouth width showed clinical and statistically significant group differences among all measurements in the study group. CONCLUSIONS: All measurements except mouth width showed nonsignificant clinical group differences. [ABSTRACT FROM AUTHOR]
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- 2022
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105. A Rare Case of Pachydermoperisotosis (PDP) and Its Ocular Manifestations.
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Wali, Fariha Sher, Majeed, Adnan Abdul, and Suriho, Sajjad Ali
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AUTOSOMAL recessive polycystic kidney , *HYPERHIDROSIS , *EYELIDS , *MEIBOMIAN glands , *OPACITY (Optics) - Abstract
A case of 56 years old Pakistani male visited OPD with complaint of thickening of both eyelids, ptosis and left lower lid ectropion caused by rare condition named pachydermoperiostosis (PDP). PDP is a rare autosomal dominant condition but autosomal recessive families probably can also occur. It is manifested by clubbing of digits, hyperhidrosis of palm and feet, peri-ostosis, acro-osteolysis and pachydermia. Ocular features include blepharoptosis, floppy eyelids, eyelid and palpebral conjunctival hypertrophy, mechanical ectropion, meibomian gland dysfunction, tear film abnormalities, punctate epithelial erosions and ocular surface disease. Surgical management was given by full-thickness wedge resection leading to horizontal tightening and this was done along with shortening of levator and its advancement. Histopathology demonstrated chronic non-specific inflammation and foreign body giant cell reaction. [ABSTRACT FROM AUTHOR]
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- 2022
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106. Systematic review on outcomes used in clinical research on autosomal recessive polycystic kidney disease—are patient-centered outcomes our blind spot?
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Gimpel, Charlotte, Liebau, Max Christoph, and Schaefer, Franz
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TREATMENT of chronic kidney failure , *PROTEINS , *META-analysis , *GENETICS , *NEUROLOGICAL disorders , *SYSTEMATIC reviews , *CLINICAL medicine research , *PATIENT-centered care , *TREATMENT effectiveness , *HISTOLOGICAL techniques , *DESCRIPTIVE statistics , *AUTOSOMAL recessive polycystic kidney , *CHILDREN - Abstract
Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe hepatorenal disease. Survivors of pulmonary hypoplasia and patients with milder presentations often achieve long-term survival but frequently require kidney and/or liver transplantation. Objective: To examine the use of clinical, surrogate and patient-centered outcomes in studies on ARPKD with special attention to core outcomes of the Standardized Outcomes in NephroloGy project for children with chronic kidney disease (SONG-Kids). Data sources and study eligibility criteria: A systematic MEDLINE literature search identified 367 ARPKD studies published since 1990; however, of these 134 were excluded because they did not report any clinical outcomes (e.g. only histopathological, genetic, protein structure or radiological markers), 19 studies because they only included prenatal patients and 138 because they were case reports with ≤ 3 patients. Study appraisal: Seventy-six eligible studies were examined for study type, size, intervention, and reported outcomes by organ system and type, including all SONG-kids tier 1–3 outcomes. Participants: There were 3231 patient-reports of children and adults with ARPKD. Results: The overwhelming majority of studies reported clinical and surrogate outcomes (75/76 (98%) and 73/76 (96%)), but only 11/76 (14%) examined patient-centered outcomes and only 2/76 (3%) used validated instruments to capture them. Of the SONG-Kids core outcomes, kidney function was reported almost universally (70/76 (92%), infection and survival in three quarters (57/76 (75%), 55/76 (72%)) and measures of life participation (including neurological impairment) only rarely and inconsistently (16/76 (21%)). Limitations: Thirty studies (39%) were of low quality as they were either narrative case reports (n = 14, 18%) and/or patients with ARPKD were an indistinguishable subgroup (n = 18, 24%). Only 28 trials compared interventions, but none were randomized. Conclusions and implications: Studies that reported clinical outcomes in ARPKD usually covered the core outcome domains of kidney function, infections, and survival, but measures of life participation and patient-centered outcomes are distinctly lacking and require more attention in future trials. [ABSTRACT FROM AUTHOR]
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- 2021
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107. Blood pressure in children with renal cysts and diabetes syndrome.
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Seeman, Tomáš, Weigel, Friederike, Blahova, Kveta, Fencl, Filip, Pruhova, Stepanka, Hermes, Katharina, Klaus, Richard, Lange-Sperandio, Bärbel, Grote, Veit, and John-Kroegel, Ulrike
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AUTOSOMAL recessive polycystic kidney , *POLYCYSTIC kidney disease , *CYSTIC kidney disease , *BLOOD pressure , *AMBULATORY blood pressure monitoring , *DIABETIC nephropathies , *KIDNEY diseases - Abstract
Cystic kidney diseases such as autosomal recessive or dominant polycystic kidney disease (ARPKD and ADPKD) are associated with high prevalence of arterial hypertension. On the contrary, studies on hypertension in children with renal cysts and diabetes (RCAD) syndrome caused by abnormalities in the HNF1B gene are rare. Therefore, the primary aim of our study was to investigate the prevalence of high blood pressure in children with RCAD syndrome due to HNF1B gene abnormalities and secondary to search for possible risk factors for development of high blood pressure. Data on all children with genetically proven RCAD syndrome from three pediatric nephrology tertiary centers were retrospectively reviewed (office blood pressure (BP), ambulatory blood pressure monitoring (ABPM), creatinine clearance, renal ultrasound, echocardiography, albuminuria/proteinuria). High blood pressure was defined as BP ≥ 95th percentile of the current ESH 2016 guidelines and/or by the use of antihypertensive drugs. Thirty-two children with RCAD syndrome were investigated. Three children received ACE inhibitors for hypertension and/or proteinuria. High blood pressure was diagnosed using office BP in 22% of the children (n = 7). In the 7 performed ABPM, 1 child (14%) was diagnosed with hypertension and one child with white-coat hypertension. Creatinine clearance, proteinuria, albuminuria, body mass index, enlargement, or hypodysplasia of the kidneys and prevalence of HNF1B-gene deletion or mutation were not significantly different between hypertensive and normotensive children. Conclusion: High blood pressure is present in 22% of children with RCAD syndrome. What is Known: • Arterial hypertension is a common complication in children with polycystic kidney diseases. What is New: • High office blood pressure is present in 22% and ambulatory hypertension in 14% of children with renal cyst and diabetes (RCAD) syndrome. [ABSTRACT FROM AUTHOR]
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- 2021
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108. A digest from evidence-based Clinical Practice Guideline for Polycystic Kidney Disease 2020.
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Nishio, Saori, Tsuchiya, Ken, Nakatani, Shinya, Muto, Satoru, Mochizuki, Toshio, Kawano, Haruna, Hanaoka, Kazushige, Hidaka, Sumi, Ichikawa, Daisuke, Ishikawa, Eiji, Uchiyama, Kiyotaka, Koshi-Ito, Eri, Hayashi, Hiroki, Makabe, Shiho, Ogata, Soshiro, Mitobe, Michihiro, Sekine, Akinari, Suwabe, Tatsuya, Kataoka, Hiroshi, and Kai, Hirayasu
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POLYCYSTIC kidney disease , *INTRACRANIAL aneurysms , *CHOLANGITIS , *AUTOSOMAL recessive polycystic kidney , *SYMPTOMS - Abstract
Autosomal recessive polycystic kidney disease ht Diagnostic criteria for ADPKD as an intractable disease A patient must fulfil either of the following criteria to be diagnosed with ADPKD: Red area of the CKD severity classification heat map. In 2020, the Research for Intractable Renal Diseases of the Ministry of Health, Labour and Welfare of Japan established the Committee of Guideline for Polycystic Kidney Disease, which published (A Digest from Evidence-Based Clinical Practice Guideline for Polycystic Kidney Disease 2020) on the website (jin-shogai.jp/policy/index.html). However, the effect of valvular disease therapy on the prognosis of patients with ADPKD with valvular disease remains unknown. B Prediction of eGFR in patients with class 1 ADPKD Prevalence and prognosis The results of a 1994 epidemiological survey yielded an estimated 31,000 (diagnosed and undiagnosed) patients with ADPKD in Japan, with one in 4033 Japanese citizens estimated to have the disease. [Extracted from the article]
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- 2021
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109. Early childhood height-adjusted total kidney volume as a risk marker of kidney survival in ARPKD.
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Burgmaier, Kathrin, Kilian, Samuel, Arbeiter, Klaus, Atmis, Bahriye, Büscher, Anja, Derichs, Ute, Dursun, Ismail, Duzova, Ali, Eid, Loai Akram, Galiano, Matthias, Gessner, Michaela, Gokce, Ibrahim, Haeffner, Karsten, Hooman, Nakysa, Jankauskiene, Augustina, Körber, Friederike, Longo, Germana, Massella, Laura, Mekahli, Djalila, and Miloševski-Lomić, Gordana
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AUTOSOMAL recessive polycystic kidney , *TUMOR markers , *CHILD patients , *SURVIVAL rate , *MISSENSE mutation , *KIDNEYS , *PROGNOSIS - Abstract
Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic changes resulting in pronounced kidney enlargement. Impairment of kidney function is highly variable and widely available prognostic markers are urgently needed as a base for clinical decision-making and future clinical trials. In this observational study we analyzed the longitudinal development of sonographic kidney measurements in a cohort of 456 ARPKD patients from the international registry study ARegPKD. We furthermore evaluated correlations of sonomorphometric findings and functional kidney disease with the aim to describe the natural disease course and to identify potential prognostic markers. Kidney pole-to-pole (PTP) length and estimated total kidney volume (eTKV) increase with growth throughout childhood and adolescence despite individual variability. Height-adjusted PTP length decreases over time, but such a trend cannot be seen for height-adjusted eTKV (haeTKV) where we even observed a slight mean linear increase of 4.5 ml/m per year during childhood and adolescence for the overall cohort. Patients with two null PKHD1 variants had larger first documented haeTKV values than children with missense variants (median (IQR) haeTKV 793 (450–1098) ml/m in Null/null, 403 (260–538) ml/m in Null/mis, 230 (169–357) ml/m in Mis/mis). In the overall cohort, estimated glomerular filtration rate decreases with increasing haeTKV (median (IQR) haeTKV 210 (150–267) ml/m in CKD stage 1, 472 (266–880) ml/m in stage 5 without kidney replacement therapy). Strikingly, there is a clear correlation between haeTKV in the first eighteen months of life and kidney survival in childhood and adolescence with ten-year kidney survival rates ranging from 20% in patients of the highest to 94% in the lowest quartile. Early childhood haeTKV may become an easily obtainable prognostic marker of kidney disease in ARPKD, e.g. for the identification of patients for clinical studies. [ABSTRACT FROM AUTHOR]
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- 2021
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110. Early clinical management of autosomal recessive polycystic kidney disease.
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Liebau, Max Christoph
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PEDIATRICS , *NEPHROLOGY , *KIDNEY diseases , *AUTOSOMAL recessive polycystic kidney , *SYMPTOMS - Abstract
Autosomal recessive polycystic kidney disease (ARPKD) is a rare but highly relevant disorder in pediatric nephrology. This genetic disease is mainly caused by variants in the PKHD1 gene and is characterized by fibrocystic hepatorenal phenotypes with major clinical variability. ARPKD frequently presents perinatally, and the management of perinatal and early disease symptoms may be challenging. This review discusses aspects of early manifestations in ARPKD and its clincial management with a special focus on kidney disease. [ABSTRACT FROM AUTHOR]
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- 2021
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111. A human multi-lineage hepatic organoid model for liver fibrosis.
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Guan, Yuan, Enejder, Annika, Wang, Meiyue, Fang, Zhuoqing, Cui, Lu, Chen, Shih-Yu, Wang, Jingxiao, Tan, Yalun, Wu, Manhong, Chen, Xinyu, Johansson, Patrik K., Osman, Issra, Kunimoto, Koshi, Russo, Pierre, Heilshorn, Sarah C., and Peltz, Gary
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INTRAHEPATIC bile ducts ,AUTOSOMAL recessive polycystic kidney ,CELLULAR signal transduction ,LIVER ,FIBROSIS - Abstract
To investigate the pathogenesis of a congenital form of hepatic fibrosis, human hepatic organoids were engineered to express the most common causative mutation for Autosomal Recessive Polycystic Kidney Disease (ARPKD). Here we show that these hepatic organoids develop the key features of ARPKD liver pathology (abnormal bile ducts and fibrosis) in only 21 days. The ARPKD mutation increases collagen abundance and thick collagen fiber production in hepatic organoids, which mirrors ARPKD liver tissue pathology. Transcriptomic and other analyses indicate that the ARPKD mutation generates cholangiocytes with increased TGFβ pathway activation, which are actively involved stimulating myofibroblasts to form collagen fibers. There is also an expansion of collagen-producing myofibroblasts with markedly increased PDGFRB protein expression and an activated STAT3 signaling pathway. Moreover, the transcriptome of ARPKD organoid myofibroblasts resemble those present in commonly occurring forms of liver fibrosis. PDGFRB pathway involvement was confirmed by the anti-fibrotic effect observed when ARPKD organoids were treated with PDGFRB inhibitors. Besides providing insight into the pathogenesis of congenital (and possibly acquired) forms of liver fibrosis, ARPKD organoids could also be used to test the anti-fibrotic efficacy of potential anti-fibrotic therapies. Autosomal recessive polycystic kidney disease (ARPKD) is a genetic disorder which is associated with kidney and liver pathology, including liver fibrosis. Here the authors develop and characterize human liver organoids with a ARPKD mutation, and find that they show aspects of the pathology, including fibrosis. [ABSTRACT FROM AUTHOR]
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- 2021
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112. Titinopathy - a rare cause of multiorgan failure.
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URINARY tract infections ,NEUROGENIC bladder ,MULTIPLE organ failure ,AUTOSOMAL recessive polycystic kidney ,PROGNOSIS ,DISEASE risk factors ,NUTCRACKER syndrome - Published
- 2021
113. Two-dimensional (2D) morphologic measurements can quantify the severity of liver disease in children with autosomal recessive polycystic kidney disease (ARPKD).
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Ghosh, Adarsh, Serai, Suraj D., Venkatakrishna, Shyam Sunder B., Dutt, Mohini, and Hartung, Erum A.
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AUTOSOMAL recessive polycystic kidney , *MANN Whitney U Test , *LIVER diseases , *RECEIVER operating characteristic curves - Abstract
Purpose: To evaluate the correlation of 2D shape-based features with magnetic resonance elastography (MRE)-derived liver stiffness and portal hypertension (pHTN) in children with ARPKD-associated congenital hepatic fibrosis. Methods: In a prospective IRB-approved study, 14 children with ARPKD (mean age ± SD = 13.8 ± 5.8 years) and 14 healthy controls (mean age ± SD = 13.7 ± 3.9 years) underwent liver MRE. A 2D region of interest (ROI) outlining the left liver lobe at the level of the abdominal aorta was drawn on sagittal T2-weighted images. Eight shape features (perimeter, major axis length, maximum diameter, perimeter to surface ratio (PSR), elongation, sphericity, minor axis length, and mesh surface) describing the 2D-ROI were calculated. Spearman's correlation was calculated between shape features and MRE-derived liver stiffness (kPa) (n = 28). Shape features were compared between participants with ARPKD with pHTN (splenomegaly and thrombocytopenia), (n = 4) and without pHTN (n = 8) using the Mann Whitney U test. Receiver operating characteristic (ROC) curves were generated to examine the diagnostic accuracy of shape features in identifying cases with liver stiffness > 2.9 kPa. Results: In ARPKD participants and healthy controls, all eight shape features, except elongation, showed moderate to strong correlation with liver stiffness (kPa); the perimeter surface ratio had the strongest correlation (rho = − 0.75, p < 0.001). In ROC analysis, a cut-off of PSR ≤ 0.057 mm−1 gave 100% (95% CI: 59.0–100.0) sensitivity and 100% (95% CI: 83.9–100.0) specificity in identifying ARPKD participants with liver stiffness > 2.9 kPa, with an area under the ROC curve (AUC) of 1.0 (95% CI: 0.88–1.00). Individuals with pHTN had a lower median PSR (mean ± SD = 0.05 ± 0.01) than those without (0.07 ± 0.01; p = 0.027) with an AUC of 0.91 (95% CI: 0.60–0.99) in differentiating the participants with and without pHTN. Conclusion: Shape-based features of the left liver lobe show potential as non-invasive biomarkers of liver fibrosis and portal hypertension in children with ARPKD. [ABSTRACT FROM AUTHOR]
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- 2021
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114. Study Findings on Polycystic Kidney Disease Described by Researchers at Tokyo Women's Medical University (Primary Cilia Elongation in Early-Onset Polycystic Kidney Disease with 2 Hypomorphic PKD1 Alleles: A Case Report).
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AUTOSOMAL recessive polycystic kidney ,POLYCYSTIC kidney disease ,URINARY organ diseases ,CYSTIC kidney disease ,SCHOOL children - Abstract
Researchers at Tokyo Women's Medical University have published a case report on polycystic kidney disease (PKD). The study focused on a child with very early-onset PKD and a history of large, echogenic kidneys in utero. Genetic analysis revealed compound heterozygous variants in the PKD1 gene, which were likely pathogenic. Pathological examination of the patient's kidney showed pronounced elongation of the primary cilia, suggesting that the hypomorphic PKD1 variants expressed in this patient were pathogenic. This research provides valuable insights into the pathology of PKD. [Extracted from the article]
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- 2024
115. Immunoglobulin-G: Lack of efficacy : case report.
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AUTOSOMAL recessive polycystic kidney , *RENAL replacement therapy , *CEREBRAL anoxia-ischemia , *PULMONARY hypoplasia , *DIALYSIS catheters , *CHOLANGITIS - Abstract
This article from Reactions Weekly describes a case report involving a male neonate who experienced a lack of efficacy while being treated with immunoglobulin-G for cholangitis. The neonate was born prematurely and had autosomal recessive polycystic kidney disease. He underwent various medical procedures and developed complications such as peritoneal leakage, fungal peritonitis, catheter-related bloodstream infection, and sepsis. Despite receiving immunoglobulin-G, the neonate developed sepsis secondary to his cholangitis, indicating that the treatment was not effective. He also had severe pulmonary hypoplasia. [Extracted from the article]
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- 2024
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116. Human Gastric Multi-Regional Assembloids Favour Functional Parietal Maturation and Allow Modelling of Antral Foveolar Hyperplasia.
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AUTOSOMAL recessive polycystic kidney ,HYPERPLASIA - Abstract
This article discusses the use of patient-derived human organoids to study the physiological functions of the human stomach. The researchers found that region-specific gastric organoids can self-assemble into complex multi-regional structures called assembloids, which exhibit functional responses to drugs targeting the ATPase H+/K+ pump. These assembloids preserve the regional identity of the stomach and allow for the emergence of parietal cells, which produce gastric acid. The researchers also generated assembloids from patients with a genetic condition associated with antral foveolar hyperplasia and hyperplastic polyposis, providing a model to study these phenomena. Overall, this research offers a promising tool for studying gastric epithelial interactions and disease mechanisms. [Extracted from the article]
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- 2024
117. Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients with Alport Syndrome (COMBINE-ALPORT).
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DIABETIC nephropathies ,DAPAGLIFLOZIN ,SPIRONOLACTONE ,ALBUMINURIA ,AUTOSOMAL recessive polycystic kidney ,POLYCYSTIC kidney disease - Abstract
The article discusses a clinical trial, NCT06499948, that is investigating the use of Dapagliflozin, Spironolactone, and their combination in adult patients with Alport syndrome (AS). AS is a kidney disorder caused by genetic variants, and there is currently no specific treatment for it. The trial aims to evaluate if these drugs, in combination with renin-angiotensin-system inhibitors, can slow the progression of chronic kidney disease. The primary outcome of the trial is the effect on albuminuria, a marker for kidney disease progression. The trial is currently recruiting participants and is expected to be completed by December 2025. [Extracted from the article]
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- 2024
118. New Polycystic Kidney Disease Research Reported from Kuwait University (Genetic landscape and clinical outcomes of autosomal recessive polycystic kidney disease in Kuwait).
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AUTOSOMAL recessive polycystic kidney ,POLYCYSTIC kidney disease ,REPORTING of diseases ,TREATMENT effectiveness - Abstract
A recent study conducted by Kuwait University explored the genetic landscape and clinical outcomes of autosomal recessive polycystic kidney disease (ARPKD) in Kuwait. The study recruited 60 individuals with suspected ARPKD from diverse ethnic backgrounds and collected comprehensive clinical data. The results showed that ARPKD exhibited diverse clinical features, including systematic hypertension, pulmonary hypoplasia, dysmorphic features, cardiac problems, cystic liver, Potter syndrome, developmental delay, and enlarged cystic kidneys. Mutations were identified in various genes, with the majority found in the PKHD1 gene. The study emphasizes the need for personalized approaches to improve ARPKD diagnosis and treatment. [Extracted from the article]
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- 2024
119. Reports on Lung Cancer from Nanjing Medical University Provide New Insights (Pkhd1l1 Blocks the Malignant Behavior of Lung Adenocarcinoma Cells and Restricts Tumor Growth By Regulating Cbx7).
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LUNG cancer ,TUMOR growth ,AUTOSOMAL recessive polycystic kidney ,LUNGS ,ADENOCARCINOMA - Abstract
A study conducted by Nanjing Medical University in Shanghai, China, explores the role of polycystic kidney and hepatic disease 1-like 1 (PKHD1L1) in lung adenocarcinoma (LUAD). The study found that PKHD1L1 is downregulated in LUAD and predicts poor outcomes for patients. Upregulation of PKHD1L1 inhibits the proliferative, invasive, and migrative capabilities of LUAD cells and increases the apoptotic rate. The study also suggests that PKHD1L1 may bind to chromobox protein homolog 7 (CBX7) and positively regulate its expression. The research concludes that PKHD1L1 can hinder LUAD progression by regulating CBX7-mediated Hippo signaling. [Extracted from the article]
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- 2024
120. New Findings from Children's of Alabama in Hypertension Provides New Insights (Survival of Infants With Severe Congenital Kidney Disease After Ecmo and Kidney Support Therapy).
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CONGENITAL disorders ,CHRONICALLY ill ,AUTOSOMAL recessive polycystic kidney ,KIDNEY diseases ,HYPERTENSION - Abstract
A recent study conducted at Children's of Alabama in Birmingham has found that infants with severe congenital kidney disease can survive with the use of extracorporeal membrane oxygenation (ECMO) and kidney support therapy. Previously, ECMO was not used in this population due to the belief that it was not viable. However, the study found that out of 31 neonates with congenital kidney failure, five were placed on ECMO and four survived. The study suggests that meticulous ECMO, respiratory, nutritional, and kidney support therapies can lead to favorable long-term outcomes for these patients. Further research is needed to optimize outcomes in this population. [Extracted from the article]
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- 2024
121. Findings from Johns Hopkins University School of Medicine Provide New Insights into Liver Diseases and Conditions (Ameliorating liver disease in an autosomal recessive polycystic kidney disease mouse model).
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AUTOSOMAL recessive polycystic kidney ,LIVER diseases ,LABORATORY mice ,ANIMAL disease models - Abstract
A recent report from Johns Hopkins University School of Medicine discusses new research on liver diseases and conditions, specifically focusing on autosomal recessive polycystic kidney disease (ARPKD). The study highlights the need for new therapies to treat this genetic disorder, which can cause newborn morbidity and mortality. The researchers found that a CFTR modulator called VX-809 inhibits proliferation and limits bile duct malformation in a mouse model of ARPKD, suggesting a potential therapeutic pathway for treating the disease. [Extracted from the article]
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- 2024
122. Predictors of progression in autosomal dominant and autosomal recessive polycystic kidney disease.
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Benz, Eric G. and Hartung, Erum A.
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POLYCYSTIC kidney disease , *DISEASE progression , *BIOMARKERS , *GENETICS , *DIAGNOSTIC imaging , *AUTOSOMAL recessive polycystic kidney - Abstract
Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are characterized by bilateral cystic kidney disease leading to progressive kidney function decline. These diseases also have distinct liver manifestations. The range of clinical presentation and severity of both ADPKD and ARPKD is much wider than was once recognized. Pediatric and adult nephrologists are likely to care for individuals with both diseases in their lifetimes. This article will review genetic, clinical, and imaging predictors of kidney and liver disease progression in ADPKD and ARPKD and will briefly summarize pharmacologic therapies to prevent progression. [ABSTRACT FROM AUTHOR]
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- 2021
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123. Extreme living donation: A single center simultaneous and sequential living liver-kidney donor experience with long-term outcomes under literature review.
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Yankol, Yücel, Karataş, Cihan, Kanmaz, Turan, Koçak, Burak, Kalayoğlu, Münci, and Acarlı, Koray
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LIVING alone , *AUTOSOMAL recessive polycystic kidney , *KIDNEY diseases , *KIDNEY failure , *LITERATURE reviews - Published
- 2021
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124. Antioxidants as a Therapeutic for San Fillipo Syndrome.
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Pryor, Lauren, Wu, Christina, and Sterling, Felicity
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AUTOSOMAL recessive polycystic kidney , *ANTIOXIDANTS , *MOTOR ability , *GLYCOSAMINOGLYCANS , *CELL death - Abstract
San Fillipo syndrome is a rare pediatric autosomal recessive disorder that affects the brain and spinal cord. Patients are typically born without symptoms and then progressively lose motor function, memory recall, and experience behavioral regressions.This disorder is caused by mutations in four separate genes (SGSH, NAGLU, HGSNAT, and GNS) leading to dysfunction of enzymes involved in the metabolism of glycosaminoglycans (GAGs). As such, GAGs accumulate in lysosomes, thereby inhibiting them. One key lysosomal function that is impaired in San Fillipo Syndrome is mitophagy, which is the clearing of dead mitochondrial fragments. ROS species are often released from mitochondrial fragments, which ultimately results in cell death via apoptosis. We hypothesized that strong antioxidant supplements such as vitamin E, coenzyme Q10, astaxanthin, and vitamin C may mitigate the effects of increased mitochondrial fragments build up in the lysosome. To test our hypothesis, we induced San Fillipo with PuGNAC in COS-7 cells and treated them with vitamin E, coenzyme Q10, astaxanthin, and vitamin C to see changes in mitochondrial activity and cell viability. [ABSTRACT FROM AUTHOR]
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- 2024
125. Molecular genetics of renal ciliopathies.
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Barroso-Gil, Miguel, Olinger, Eric, and Sayer, John A.
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MOLECULAR genetics , *AUTOSOMAL recessive polycystic kidney , *POLYCYSTIC kidney disease , *CILIA & ciliary motion , *CYSTIC kidney disease , *RENAL fibrosis - Abstract
Renal ciliopathies are a heterogenous group of inherited disorders leading to an array of phenotypes that include cystic kidney disease and renal interstitial fibrosis leading to progressive chronic kidney disease and end-stage kidney disease. The renal tubules are lined with epithelial cells that possess primary cilia that project into the lumen and act as sensory and signalling organelles. Mutations in genes encoding ciliary proteins involved in the structure and function of primary cilia cause ciliopathy syndromes and affect many organ systems including the kidney. Recognised disease phenotypes associated with primary ciliopathies that have a strong renal component include autosomal dominant and recessive polycystic kidney disease and their various mimics, including atypical polycystic kidney disease and nephronophthisis. The molecular investigation of inherited renal ciliopathies often allows a precise diagnosis to be reached where renal histology and other investigations have been unhelpful and can help in determining kidney prognosis. With increasing molecular insights, it is now apparent that renal ciliopathies form a continuum of clinical phenotypes with disease entities that have been classically described as dominant or recessive at both extremes of the spectrum. Gene-dosage effects, hypomorphic alleles, modifier genes and digenic inheritance further contribute to the genetic complexity of these disorders. This review will focus on recent molecular genetic advances in the renal ciliopathy field with a focus on cystic kidney disease phenotypes and the genotypes that lead to them. We discuss recent novel insights into underlying disease mechanisms of renal ciliopathies that might be amenable to therapeutic intervention. [ABSTRACT FROM AUTHOR]
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- 2021
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126. Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease.
- Author
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Dorval, Guillaume, Boyer, Olivia, Couderc, Anne, Delbet, Jean-Daniel, Heidet, Laurence, Debray, Dominique, Krug, Pauline, Girard, Muriel, Llanas, Brigitte, Charbit, Marina, Krid, Saoussen, Biebuyck, Nathalie, Fila, Marc, Courivaud, Cécile, Tilley, Frances, Garcelon, Nicolas, Blanc, Thomas, Chardot, Christophe, Salomon, Rémi, and Lacaille, Florence
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KIDNEY physiology , *LIVER physiology , *BLOOD pressure , *FIBROSIS , *HEALTH outcome assessment , *KIDNEY transplantation , *ESOPHAGEAL varices , *RETROSPECTIVE studies , *CYSTIC kidney disease , *AUTOSOMAL recessive polycystic kidney , *PORTAL hypertension , *CHILDREN - Abstract
Background: Autosomal recessive polycystic kidney disease (ARPKD) is a rare ciliopathy characterized by congenital hepatic fibrosis and cystic kidney disease. Lack of data about long-term follow-up makes it difficult to discuss timing and type of organ transplantation. Our objectives were to evaluate long-term evolution and indications for transplantation, from birth to adulthood. Methods: Neonatal survivors and patients diagnosed in postnatal period with ARPKD between 1985 January and 2017 December from 3 French pediatric centers were retrospectively enrolled in the study. Results: Fifty patients with mean follow-up 12.5 ± 1 years were enrolled. ARPKD was diagnosed before birth in 24%, and at mean age 1.8 years in others. Thirty-three patients were < 1 year of age at first symptoms, which were mostly kidney-related. These most often presented high blood pressure during follow-up. Portal hypertension was diagnosed in 29 patients (58%), 4 of them with bleeding from esophageal varices. Eight patients presented cholangitis (> 3 episodes in three children). Liver function was normal in all patients. Nine children received a kidney transplant without liver complications. A 20-year-old patient received a combined liver-kidney transplant (CLKT) for recurrent cholangitis, and a 15-year-old boy an isolated liver transplant for uncontrollable variceal bleeding despite portosystemic shunt. Conclusions: Long-term outcome in patients with ARPKD is heterogeneous, and in this cohort did not depend on age at diagnosis except for blood pressure. Few patients required liver transplantation. Indications for liver or combined liver-kidney transplantation were limited to recurrent cholangitis or uncontrollable portal hypertension. Liver complications after kidney transplantation were not significant. [ABSTRACT FROM AUTHOR]
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- 2021
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127. miRNA-16 as a predictive factor for intracranial aneurysms in autosomal dominant polycystic kidney disease.
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Kulesza, Andrzej, Kulesza, Agnieszka, Fliszkiewicz, Magda, Łabuś, Anna, Pączek, Leszek, and Niemczyk, Mariusz
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POLYCYSTIC kidney disease ,HUMAN chromosome abnormalities ,AUTOSOMAL recessive polycystic kidney ,MICRORNA ,NON-coding RNA - Abstract
Introduction. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder. It leads to multiple extra-renal complications, with intracranial aneurysms (IA) among the most serious. Biological markers could become tools in identifying patients at risk of an IA. MicroRNAs 16 (miR-16) and 25 (miR-25) have been proposed as being markers of IAs in the general population. In the current study, we attempted to discover if they may also be considered markers of IAs in ADPKD. Material and methods. 64 renal transplant recipients with ADPKD were included. After magnetic resonance angiography of the brain, they were divided into a case group (IA+, n = 13) and a control group (IA-, n = 51). Expression of miRNAs in plasma was analysed by qRT-PCR. Material and methods. 64 renal transplant recipients with ADPKD were included. After magnetic resonance angiography of the brain, they were divided into a case group (IA+, n = 13) and a control group (IA-, n = 51). Expression of miRNAs in plasma was analysed by qRT-PCR. Conclusions and clinical implications. MicroRNA-16 is a potential marker of IAs in renal transplant recipients with ADPKD. It may become a tool to identify patients who should undergo screening for an IA. [ABSTRACT FROM AUTHOR]
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- 2021
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128. Imaging manifestations of Caroli disease with autosomal recessive polycystic kidney disease: a case report and literature review.
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Yao, Xiuzhen, Ao, Weiqun, Fang, Jianhua, Mao, Guoqun, Chen, Chuanghua, Yu, Lifang, Cai, Huaijie, and Xu, Chenke
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CAROLI disease , *AUTOSOMAL recessive polycystic kidney , *GENETIC disorders , *POLYCYSTIC kidney disease , *PREGNANCY complications - Abstract
Background: Both Caroli disease (CD) and autosomal recessive polycystic kidney disease (ARPKD) are autosomal recessive disorders, which are more commonly found in infants and children, for whom surviving to adulthood is rare. Early diagnosis and intervention can improve the survival rate to some extent. This study adopted the case of a 26-year-old pregnant woman to explore the clinical and imaging manifestations and progress of CD concomitant with ARPKD to enable a better understanding of the disease.Case Presentation: A 26-year-old pregnant woman was admitted to our hospital for more than 2 months following the discovery of pancytopenia and increased creatinine. Ultrasonography detected an enlarged left liver lobe, widened hepatic portal vein, splenomegaly, and dilated splenic vein. In addition, both kidneys were obviously enlarged and sonolucent areas of varying sizes were visible, but color Doppler flow imaging revealed no abnormal blood flow signals. The gestational age was approximately 25 weeks, which was consistent with the actual fetal age. Polyhydramnios was detected but no other abnormalities were identified. Magnetic resonance imaging revealed that the liver was plump, and polycystic liver disease was observed near the top of the diaphragm. The T1 and T2 weighted images were the low and high signals, respectively. The bile duct was slightly dilated; the portal vein was widened; and the spleen volume was enlarged. Moreover, the volume of both kidneys had increased to an abnormal shape, with multiple, long, roundish T1 and T2 abnormal signals being observed. Magnetic resonance cholangiopancreatography revealed that intrahepatic cystic lesions were connected with intrahepatic bile ducts. The patient underwent a genetic testing, the result showed she carried two heterozygous mutations in PKHD1. The patient was finally diagnosed with CD with concomitant ARPKD. The baby underwent a genetic test three months after birth, the result showed that the patient carried one heterozygous mutations in PKHD1, which indicated the baby was a PKHD1 carrier.Conclusions: This case demonstrates that imaging examinations are of great significance for the diagnosis and evaluation of CD with concomitant ARPKD. [ABSTRACT FROM AUTHOR]- Published
- 2021
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129. PP-08 Meckel Gruber Syndrome a case report.
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Kel, Serem, Kuşcu, Nur, Demir, Süreyya, Duran, Mehmet Nuri, and Demir, Bülent
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AUTOSOMAL recessive polycystic kidney , *GENETIC disorders , *POLYCYSTIC kidney disease , *ENCEPHALOCELE , *ULTRASONIC imaging - Abstract
Objective: Meckel-Gruber Syndrome is a rare fetal anomaly characterized by multiple anomalies that are inherited in an autosomal recessive manner and are incompatible with life. In our clinic, we aimed to present the findings of a fetus with Meckel-Gruber Syndrome, for which we conducted pregnancy termination. Case: A 37-year-old patient with a history of G9P8Y7PPEX1 was referred to our center at 18+2 weeks of gestation due to cranial anomalies identified through a structural anomaly scan. Obstetric ultrasound revealed a single viable fetus consistent with 18+1 weeks of gestation. In intracranial evaluation, the fetus exhibited a single cavity in the lateral ventricles, thalamic fusion, absence of the cavum septum pellucidum, and alobar holoprosencephaly. A cystic hygroma with septations measuring 18x13 mm was observed in the fetal neck. Microcephaly and significant hypertelorism were also present. Ultrasonographic findings were suggestive of Meckel-Gruber Syndrome. Following the decision made by the board and with the consent of the family, the pregnancy termination was carried out. The fetus was aborted vaginally and weighed 110 grams, measuring 18 cm in length. Macroscopic examination of the fetus revealed micrognathia, hypertelorism, flattened nasal bridge, low-set ears, and encephalocele, consistent with female external genitalia. Autopsy examination of the fetus indicated an enlarged liver with absence of the gallbladder, spleen, and pancreas. Other internal organs appeared lithic in appearance. Conclusion: Meckel-Gruber Syndrome is a rare fetal anomaly with an autosomal recessive inheritance pattern, occurring at a frequency of 1 in 13,250 to 140,000 births. It follows a severe and lethal course. While the classic triad includes cystic renal dysplasia, encephalocele, and polydactyly, the syndrome can also manifest with additional anomalies. Differential diagnoses should include Trisomy 13 and Smith-Lemli-Opitz syndrome, given their similar clinical presentations. Careful consideration is necessary in making a differential diagnosis due to the overlapping features with these two conditions. Definitive diagnosis requires autopsy, as karyotype analysis might yield normal results. The recurrence rate is 25%, underscoring the importance of prenatal diagnosis and monitoring. Mortality associated with this syndrome is 100%. Families should be counseled about the risk of mortality in the current pregnancy and the possibility of recurrence in subsequent pregnancies. First-trimester ultrasound evaluation between 11 and 14 weeks is strongly recommended for subsequent pregnancies. [ABSTRACT FROM AUTHOR]
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- 2023
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130. An unusual cause of elevated serum creatinine after kidney transplantation in an adolescent: Questions.
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Leventoğlu, Emre, Büyükkaragöz, Bahar, Gönül, İpek Işık, Fidan, Kibriya, Öğüt, Betül, Söylemezoğlu, Oğuz, Bakkaloğlu, Sevcan A., and Buyan, Necla
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HOMOGRAFTS , *BIOPSY , *KIDNEY failure , *KIDNEY transplantation , *HYPOPHOSPHATEMIA , *AUTOSOMAL recessive polycystic kidney , *HEMODIALYSIS , *IMMUNOSUPPRESSIVE agents , *CREATININE , *ORGAN donors , *PHOSPHATES , *DISEASE complications , *ADOLESCENCE - Abstract
The article presents a case of a 15-year-old girl with kidney failure who was presented to a clinic due to autosomal recessive polycystic kidney disease with combined heterozygous mutation in KPHD1 gene to discuss an unusual cause of elevated serum creatinine following kidney transplantation. She underwent hemodialysis for four months. Also cited are the possible causes of post-transplant hypophosphatemia and the patient's possible diagnosis.
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- 2022
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131. Abstracts ‐ Invited Speaker.
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CALCIUM metabolism ,FRACTURE healing ,FEMORAL epiphysis ,MEDICAL care ,AUTOSOMAL recessive polycystic kidney ,PIGMENT epithelium-derived factor ,MEDICAL personnel - Abstract
FUNDING: NICHD IRP to JCM DISCLOSURES: The author declared no competing interests OC9 Bone cell functions in peptidylprolyl cis-trans isomerase B (PPIB) knock-out mouse model for type IX osteogenesis imperfecta (OI) are distinct from classical dominant OI Ying Liu 1, Theresa Hefferan 2, Nadja Fratzl-Zelman 3, Joan Marini 1 1 Section on Heritable Disorders of Bone and Extracellular Matrix, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States, 2 Biomaterials and Histomorphometry Core Laboratory, Mayo Clinic Rochester, MN., Rochester, United States, 3 Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria Osteogenesis imperfecta (OI) is a genetically heterogeneous bone fragility disorder. DISCLOSURES: The author declared no competing interests P4 Studies of OI patient and murine osteoblasts to investigate phenotypic variability of dominant osteogenesis imperfecta Milena Jovanovic 1, Apratim Mitra 2, Chris Stephan 3, Kenneth Kozloff 3, Ryan K Dale 2, Joan C Marini 1 1 Section on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States, 2 Bioinformatics and Scientific Programming Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States, 3 Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, United States Osteogenesis Imperfecta (OI) is a heterogeneous bone disorder characterized by bone fractures, growth deficiency and skeletal defects. [Extracted from the article]
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- 2021
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132. Anti‐HLA and anti‐SARS‐CoV‐2 antibodies in kidney transplant recipients with COVID‐19.
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Gandolfini, Ilaria, Zanelli, Paola, Palmisano, Alessandra, Salvetti, Daniel, Parmigiani, Alice, Maltzman, Jonathan S., Labate, Claudia, Fiaccadori, Enrico, Cravedi, Paolo, and Maggiore, Umberto
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COVID-19 , *KIDNEY transplantation , *BK virus , *AUTOSOMAL recessive polycystic kidney , *POLYCYSTIC kidney disease - Abstract
One patient (patient 2) had anti-donor antibodies before COVID-19, but neither their MFI nor their HLA specificities increased after COVID-19. 1 TablePatients' characteristics. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its associated illness coronavirus disease 2019 (COVID-19) have severely affected organ transplant recipients, with all-cause mortality rates exceeding 20% [1,2]. Anti-HLA and anti-SARS-CoV-2 antibodies in kidney transplant recipients with COVID-19. [Extracted from the article]
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- 2021
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133. Ultrasound Imaging of Renal Cysts in Children.
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Thomas, Christy Cathreen, Jana, Manisha, Sinha, Aditi, Bagga, Arvind, Ramachandran, Anupama, Sudhakaran, Dipin, and Gupta, Arun Kumar
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CYSTIC kidney disease ,POLYCYSTIC kidney disease ,ULTRASONIC imaging ,AUTOSOMAL recessive polycystic kidney ,GENETIC disorders - Abstract
Renal cysts can be focal or diffuse and unilateral or bilateral. In childhood, most renal cysts are due to hereditary diseases rather than simple cysts or acquired cystic diseases, unlike adults. Inherited cystic diseases can be ciliopathies due to a primary ciliary defect (as in polycystic kidney diseases and nephronophthisis). Acquired causes include obstructive cystic dysplasia, dyselectrolytemia, and acquired cysts in renal replacement therapy. The final diagnosis requires a multispecialty approach, including radiology, pathology, and genetics. Imaging is a very important component in treating patients with cystic renal diseases. This article discusses the ultrasound findings of cystic renal diseases in children, along with a brief discussion of other imaging modalities and a suggested ultrasound reporting format. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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134. Cilia and polycystic kidney disease.
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Ma, Ming
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POLYCYSTIC kidney disease , *AUTOSOMAL recessive polycystic kidney , *CILIA & ciliary motion , *MEMBRANE proteins - Abstract
P olycystic k idney d isease (PKD), comprising a utosomal d ominant p olycystic k idney d isease (ADPKD) and a utosomal r ecessive p olycystic k idney d isease (ARPKD), is characterized by incessant cyst formation in the kidney and liver. ADPKD and ARPKD represent the leading genetic causes of renal disease in adults and children, respectively. ADPKD is caused by mutations in PKD1 encoding polycystin1 (PC1) and PKD2 encoding polycystin 2 (PC2). PC1/2 are multi-pass transmembrane proteins that form a complex localized in the primary cilium. Predominant ARPKD cases are caused by mutations in polycystic kidney and hepatic disease 1 (PKHD1) gene that encodes the Fibrocystin/Polyductin (FPC) protein, whereas a small subset of cases are caused by mutations in DAZ interacting zinc finger protein 1 like (DZIP1L) gene. FPC is a type I transmembrane protein, localizing to the cilium and basal body, in addition to other compartments, and DZIP1L encodes a transition zone/basal body protein. Apparently, PC1/2 and FPC are signaling molecules, while the mechanism that cilia employ to govern renal tubule morphology and prevent cyst formation is unclear. Nonetheless, recent genetic and biochemical studies offer a glimpse of putative physiological malfunctions and the pathomechanisms underlying both disease entities. In this review, I summarize the results of genetic studies that deduced the function of PC1/2 on cilia and of cilia themselves in cyst formation in ADPKD, and I discuss studies regarding regulation of polycystin biogenesis and cilia trafficking. I also summarize the synergistic genetic interactions between Pkd1 and Pkhd1, and the unique tissue patterning event controlled by FPC, but not PC1. Interestingly, while DZIP1L mutations generate compromised PC1/2 cilia expression, FPC deficiency does not affect PC1/2 biogenesis and ciliary localization, indicating that divergent mechanisms could lead to cyst formation in ARPKD. I conclude by outlining promising areas for future PKD research and highlight rationales for potential therapeutic interventions for PKD treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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135. Magnetic resonance elastography to quantify liver disease severity in autosomal recessive polycystic kidney disease.
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Hartung, Erum A., Calle-Toro, Juan S., Lopera, Carolina Maya, Wen, Jessica, Carson, Robert H., Dutt, Mohini, Howarth, Kathryn, Furth, Susan L., Darge, Kassa, and Serai, Suraj D.
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AUTOSOMAL recessive polycystic kidney , *MAGNETIC resonance , *LIVER diseases , *DYSTROPHY , *RECESSIVE genes , *ELASTOGRAPHY - Abstract
Objectives: To evaluate whether liver and spleen magnetic resonance elastography (MRE) can measure the severity of congenital hepatic fibrosis (CHF) and portal hypertension (pHTN) in individuals with autosomal recessive polycystic kidney disease (ARPKD), and to examine correlations between liver MRE and ultrasound (US) elastography. Methods: Cross-sectional study of nine individuals with ARPKD and 14 healthy controls. MRE was performed to measure mean liver and spleen stiffness (kPa); US elastography was performed to measure point shear wave speed (SWS) in both liver lobes. We compared: (1) MRE liver and spleen stiffness between controls vs. ARPKD; and (2) MRE liver stiffness between participants with ARPKD without vs. with pHTN, and examined correlations between MRE liver stiffness, spleen length, platelet counts, and US elastography SWS. Receiver operating characteristic (ROC) analysis was performed to examine diagnostic accuracy of liver MRE. Results: Participants with ARPKD (median age 16.8 [IQR 13.3, 18.9] years) had higher median MRE liver stiffness than controls (median age 14.7 [IQR 9.7, 16.7 years) (2.55 vs. 1.92 kPa, p = 0.008), but MRE spleen stiffness did not differ. ARPKD participants with pHTN had higher median MRE liver stiffness than those without (3.60 kPa vs 2.49 kPa, p = 0.05). Liver MRE and US elastography measurements were strongly correlated. To distinguish ARPKD vs. control groups, liver MRE had 78% sensitivity and 93% specificity at a proposed cut-off of 2.48 kPa [ROC area 0.83 (95% CI 0.63–1.00)]. Conclusion: Liver MRE may be a useful quantitative method to measure the severity of CHF and pHTN in individuals with ARPKD. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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136. Expanded Carrier Screening and the Complexity of Implementation.
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Silver, Julia and Norton, Mary E.
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MEDICAL personnel , *COMPLEX numbers , *PROFESSIONAL ethics , *PROFESSIONAL associations , *GENETIC disorders , *RESEARCH , *ZELLWEGER Syndrome , *RESEARCH methodology , *AUTOIMMUNE diseases , *MEDICAL cooperation , *EVALUATION research , *GENETIC carriers , *CYSTIC fibrosis , *DUCHENNE muscular dystrophy , *COMPARATIVE studies , *AUTOSOMAL recessive polycystic kidney - Abstract
Advances in genetic technology have allowed for the development of multiplex panels that can test for hundreds of genetic disorders at the same time; these large panels are referred to as expanded carrier screening. This process can screen couples for far more conditions than the gene-by-gene approach used with traditional carrier screening; however, although expanded carrier screening has been promoted as an efficient means of detecting many more disorders, the complexities of genetic sequencing raise substantial challenges and concerns. In our practice, we have seen a number of complex cases in which only attention to detail on the part of thorough genetic counselors allowed identification of misclassified variants that could have resulted in significant patient harm. We raise issues that require urgent attention by professional societies, including: whether to endorse testing that uses sequencing compared with genotyping; required components of pretest and posttest counseling; reclassification of variants; whether obstetric health care professionals have a responsibility to assure that patients understand the iterative process of variant interpretation and how it relates to carrier screening results; and the question of rescreening in subsequent pregnancies. Implementation of expanded carrier screening needs to be considered thoughtfully in light of the complexity of genetic sequencing and limited knowledge of genetics of most front-line obstetric health care professionals. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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137. Congenital hepatic fibrosis: case report and review of literature.
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Hasbaoui, Brahim El, Rifai, Zainab, Saghir, Salahiddine, Ayad, Anas, Lamalmi, Najat, Abilkassem, Rachid, and Agadr, Aomar
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AUTOSOMAL recessive polycystic kidney , *POLYCYSTIC kidney disease , *MAGNETIC resonance imaging , *HEPATIC fibrosis , *FIBROSIS , *GASTROINTESTINAL hemorrhage , *SYMPTOMS - Abstract
Congenital hepatic fibrosis (CHF) is a rare autosomal recessive disease derived from biliary dysgenesis secondary to ductal plate malformation; it often coexists with Caroli’s disease, von Meyenburg complexes, autosomal dominant polycystic kidney disease (ADPKD), and autosomal recessive polycystic kidney disease (ARPKD). Although CHF was first named and described in detail by Kerr et al. in 1961. Its pathogenesis still remains unclear. The exact incidence and prevalence are not known, and only a few hundred patients with CHF have been reported in the literature to date. However, with the development of noninvasive diagnostic techniques such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), CHF may now be more frequently detected. Anatomopathological examination of liver biopsy is the gold standard in diagnosis of CHF. Patients with CHF exhibit variable clinical presentations, ranging from no symptoms to severe symptoms such as acute hepatic decompensation and even cirrhosis. The most common presentations in these patients are splenomegaly, esophageal varices, and gastrointestinal bleeding due to portal hypertension. In addition, in younger children, CHF often is accompanied by renal cysts or increased renal echogenicity. Great variability exists among the signs and symptoms of the disease from early childhood to the 5th or 6th decade of life, and in most patients the disorder is diagnosed during adolescence or young adulthood. Here, we present two cases of congenital hepatic fibrosis in 2-years-old girl and 12-year-old male who had been referred for evaluation of an abdominal distension with persistent hyper-transaminasemia and cholestasis, the diagnostic was made according to the results of medical imaging (CT or MRI), a liver biopsy, and genetic testing. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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138. New Liver Diseases and Conditions Study Findings Have Been Published by Researchers at Shahid Beheshti University of Medical Sciences (Clinical manifestation, epidemiology, genetic basis, potential molecular targets, and current treatment of...).
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SYMPTOMS ,LIVER diseases ,DRUG target ,AUTOSOMAL recessive polycystic kidney ,RESEARCH personnel - Abstract
A recent study conducted by researchers at Shahid Beheshti University of Medical Sciences has provided new insights into liver diseases and conditions, specifically focusing on polycystic liver disease (PLD). PLD is a rare condition that is observed in three genetic diseases and typically does not impair liver function. The diagnosis of PLD is primarily based on imaging, and genetic testing is only necessary in complex cases. The study highlights the underlying genetic causes and mechanisms of PLD, as well as current treatment options and potential future research directions. This information can be valuable for researchers and clinicians interested in PLD. [Extracted from the article]
- Published
- 2024
139. Reports Outline Genetics Research from Great Ormond Street Hospital for Children NHS Foundation Trust (Renal Pathology of Ciliopathies).
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GENETICS ,CHILDREN'S hospitals ,AUTOSOMAL recessive polycystic kidney ,PATHOLOGY ,POLYCYSTIC kidney disease - Abstract
A recent report from Great Ormond Street Hospital for Children NHS Foundation Trust in London discusses the research on renal ciliopathies, a group of genetic disorders that affect the function of the primary cilium in the kidney and other organs. The dysfunction of primary cilia leads to various clinical manifestations, including renal failure, cyst formation, and hypertension. The report summarizes the current understanding of the pathophysiological and pathological features of renal ciliopathies in childhood, including different types of kidney diseases. The genetic basis of these disorders has been well-established, with mutations in specific genes being responsible for the majority of cases. The report emphasizes the importance of clinicopathological correlation and genetic testing in understanding the mechanisms of these disorders. [Extracted from the article]
- Published
- 2024
140. University of Zagreb Researcher Discusses Findings in Chronic Kidney Disease (Single-Center Experience of Pediatric Cystic Kidney Disease and Literature Review).
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CYSTIC kidney disease ,CHRONIC kidney failure ,LITERATURE reviews ,AUTOSOMAL recessive polycystic kidney ,RESEARCH personnel ,URINARY tract infections - Abstract
A recent study conducted by researchers at the University of Zagreb in Croatia focused on pediatric cystic kidney disease (CyKD), a condition characterized by renal cysts. The study analyzed data from a 12-year period and found that the most common form of CyKD was multicystic dysplastic kidney disease. The study also identified common symptoms such as abdominal distension, abdominal pain, and oliguria, as well as long-term complications including recurrent urinary tract infections, hypertension, chronic kidney disease (CKD), and end-stage renal disease (ESRD). This study provides valuable insights into the diagnosis and management of CyKD in children. [Extracted from the article]
- Published
- 2024
141. PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure. (Updated March 27, 2024).
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AUTOSOMAL recessive polycystic kidney - Abstract
According to a preprint abstract from biorxiv.org, a study was conducted on mice to investigate the role of the protein PKHD1L1 in hearing function. The study found that PKHD1L1 is required for the maintenance of the stereocilia bundle in sensory hair cells of the cochlea, which is essential for hearing. PKHD1L1-deficient mice displayed disruptions to bundle coherence and developed high-frequency hearing loss that progressed with age. Additionally, these mice were more susceptible to permanent hearing loss from noise exposure compared to wild-type mice. This research suggests that PKHD1L1 plays a crucial role in the development and maintenance of sensory hair bundles, which are necessary for hearing function and resilience to acoustic trauma and aging. [Extracted from the article]
- Published
- 2024
142. The carboxy‐terminus of the human ARPKD protein fibrocystin can control STAT3 signalling by regulating SRC‐activation.
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Dafinger, Claudia, Mandel, Amrei M., Braun, Alina, Göbel, Heike, Burgmaier, Kathrin, Massella, Laura, Mastrangelo, Antonio, Dötsch, Jörg, Benzing, Thomas, Weimbs, Thomas, Schermer, Bernhard, and Liebau, Max C.
- Subjects
AUTOSOMAL recessive polycystic kidney ,MEMBRANE proteins ,POLYCYSTIC kidney disease ,CYSTIC kidney disease - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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143. Mini Orals.
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HOME hemodialysis , *NEPHROLOGISTS , *URETERIC obstruction , *CALCIPHYLAXIS , *MEDICAL personnel , *AUTOSOMAL recessive polycystic kidney , *MEDICAL sciences , *PLASMA cell diseases , *PROGNOSIS - Abstract
B Background: b Patients with chronic kidney disease (CKD) requiring kidney replacement therapy in rural communities are at higher risk of mortality compared with patients in urban areas, and encounter many barriers in accessing care. Changes in plasma metabolites in individuals with diabetes associated chronic kidney disease:... A Lecamwasam 1,2,3, T Mansell 1,4, E I Ekinci 2,5, R Saffery 1,4, K M Dwyer 3 1 Murdoch Children's Research Institute, Epigenetics Research, 2 Austin Health, Department of... B Aim: b We investigated a cross-sectional metabolomic analysis of plasma and urine of patients with early or late diabetes associated chronic kidney disease (CKD), inclusive of stages 1-5 CKD, to identify potential metabolomic profiles between the two groups. Effect of lanthanum carbonate on endogenous calciprotein particles in CKD patients - Results fr... M Tiong 1,2, E R Smith 1,2, N M Lioufas 1,2,3, E Pedagogos 3, E M Pascoe 4, C M Hawley 4... 1 Department of Nephrology, The Royal Melbourne Hospital, 2 Department of Medicine (RMH), Uni... B Aim: b To examine the effect of lanthanum carbonate compared to placebo on calciprotein particles (CPPs) in patients with chronic kidney disease (CKD). Feasibility and acceptability of electronic patient reported outcome measures (e-PROMs) data... E Duncanson 1, P N Bennett 2, A K Viecelli 3, K Dansie 1, L M Greenham 1, A Tong 4, S J... 1 Australia and New Zealand Dialysis and Transplant Registry and SA Health and Medical Resear... B Aim: b To describe the perspectives and experiences of nephrologists, nurses, and patients receiving haemodialysis, about acceptability and feasibility of electronic patient-reported outcome measures (e-PROMs) collection with feedback to clinicians. [Extracted from the article]
- Published
- 2020
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144. Hereditary fructose intolerance: a diagnostic trap in infants?
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Grama, Alina, Sîrbe, Claudia, Mariș, Alexandra, Bulata, Bogdan, Militaru, Mariela, and Pop, Tudor L.
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FRUCTOSE intolerance , *AUTOSOMAL recessive polycystic kidney , *LIVER failure , *INFANT diseases , *INBORN errors of metabolism - Abstract
Introduction. Hereditary fructose intolerance (HFI) is an autosomal recessive disease characterized by the deficiency of aldolase B activity in the liver, kidney and intestine, leading to growth failure, chronic liver or kidney disease. Case report. We present the case of a 6-month-old male with HFI who presented two episodes of acute liver failure (ALF). At the first admission in our hospital, at the age of 7 weeks, the laboratory parameters infirmed an inborn error of metabolism (IEM), the liver injury being correlated with a severe systemic infection with Pseudomonas aeruginosa, with a favorable evolution. Four months later, with the onset of complementary feeding with fruits or juices, the infant presented ALF again. HFI was confirmed by genetic tests, homozygote for A175D mutation in the aldolase B gene. After following a specific diet that consisted in the excluding of fructose, sucrose and sorbitol, the clinical features and the laboratory parameters improved considerably. Conclusions. HFI can be an extremely severe condition, even life-threatening, but with an excellent evolution when the diagnosis is quick and the diet is started as early as possible. This requires a high index of suspicion from the clinician regarding the possibility of an IEM. [ABSTRACT FROM AUTHOR]
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- 2020
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145. Abnormalities of the biliary tract in patients with autosomal recessive polycystic kidney disease (ARPKD).
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Wicher, Dorota, Jurkiewicz, Elżbieta, and Jankowska, Irena
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AUTOSOMAL recessive polycystic kidney ,BILIARY tract ,SERUM ,CHOLANGITIS ,CAROLI disease - Abstract
Introduction: Autosomal recessive polycystic kidney disease (ARPKD) is a ciliopathy with kidney and liver manifestations. Children with ARPKD usually remain only under the care of nephrologist due to silent liver involvement characterized by congenital hepatic fibrosis with or without bile ducts dilatation. The aim of this study is to pay attention on the occurrence of the abnormalities of the biliary tract in ARPKD patients. Material and methods: Data on laboratory (serum total and direct bilirubin concentration, gamma-glutamyltranspeptidase [GGT] activity, serum bile acids concentration) and imaging examinations findings (intrahepatic and extrahepatic bile ducts dilatation, biliary cysts), as well as data on history of cholangitis, were analysed retrospectively in 17 patients (14 male and 3 female, aged from 2.5 to 42 years) with molecularly confirmed diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Results: Increased GGT activity was noticed in 7 patients and slightly increased direct bilirubin in 8 (46.7 and 53.3% respectively). Only one patient had a history of cholangitis. Dilatation of intrahepatic bile ducts and common bile duct on ultrasound examination was described in 10 and 5 patients respectively. There was no close correlation between laboratory and imaging examination findings. Four our patients with dilated bile ducts had normal laboratory results, while two patients had abnormalities only in laboratory tests. Both, laboratory and imaging abnormalities were found in 6 and none of them in 5 patients. Conclusions: In patients with ARPKD abnormalities of the biliary tract can occur even when standard laboratory tests findings stay within normal limits. Detailed biliary tree imaging evaluation should be performed in each patients with increased GGT activity/bile acid concentration, history of cholangitis, before kidney transplantation, as well as in adolescents and young adults due to increased risk of cholangiocarcinoma. [ABSTRACT FROM AUTHOR]
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- 2020
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146. Prospective evaluation of kidney and liver disease in autosomal recessive polycystic kidney disease-congenital hepatic fibrosis.
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Abdul Majeed, Nehna, Font-Montgomery, Esperanza, Lukose, Linda, Bryant, Joy, Veppumthara, Peter, Choyke, Peter L., Turkbey, Ismail B., Heller, Theo, Gahl, William A., and Gunay-Aygun, Meral
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AUTOSOMAL recessive polycystic kidney , *HEPATIC fibrosis , *BONE lengthening (Orthopedics) , *LIVER transplantation , *RECESSIVE genes - Abstract
We have previously published the characteristics of kidney and liver disease in a cohort of 73 individuals with molecularly confirmed autosomal recessive polycystic kidney disease-congenital hepatic fibrosis, based upon cross-sectional data. Here, we present prospective data on the same cohort. Comprehensive biochemical and imaging data on progression of kidney and liver disease in 60 of the 73 patients were prospectively collected at the NIH Clinical Center on multiple visits between 2003 and 2019. Of the 73 patients, 23 received a renal allograft at an average age of 17.5 years and 10 underwent liver transplantation at an average age of 20.3 years. Patients who presented perinatally and those who had corticomedullary disease required kidney transplantation significantly earlier. The mean eGFR slope in patients with corticomedullary disease was −1.6 ml/min/1.73 m2/y, in comparison to −0.6 ml/min/1.73 m2/y in those with medullary disease. Kidney size remained the same over time and normalized to the upper limit of normal by 20–25 years of age. The extent of renal disease on ultrasound remained largely unchanged; no patient progressed from the "medullary" to the "corticomedullary" group. There was no correlation between eGFR slope and kidney size. The synthetic function of the liver remained largely intact even in patients with advanced portal hypertension. Based on spleen length/height ratio, two thirds of patients had portal hypertension which remained stable in 39% and worsened in 61%. Patients with portal hypertension had lower platelet counts and relatively higher levels of AST, GGT, direct bilirubin and ammonia. The progression rates of kidney and liver disease were independent of each other. Patients with bi-allelic non-truncating PKHD1 variants had similar progression of kidney and liver disease in comparison to those who were compound heterozygous for a non-truncating and a truncating variant. [ABSTRACT FROM AUTHOR]
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- 2020
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147. Polycystic kidney disease and other genetic kidney disorders.
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Kerecuk, Larissa
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CYSTIC kidney disease ,KIDNEY diseases ,POLYCYSTIC kidney disease ,KIDNEY failure ,GENOMICS ,AUTOSOMAL recessive polycystic kidney - Abstract
Cystic kidney diseases encompass a range of genetic disorders in which the primary cilia of the cells are affected and thereby cysts form as a result. There are an increasing range of cystic renal diseases recognized due to the advances in genomics. The most common genetic kidney condition is autosomal dominant polycystic kidney disease (ADPKD). ADPKD leads to renal failure in adulthood. In children, hypertension is common and if treated, may slow down renal decline. The most common cystic kidney disease causing renal failure in children is autosomal recessive polycystic kidney disease (ARPKD). ARPKD also affects the liver. These conditions often have extra-renal features which also need to be addressed. Until recently, treatments were mainly supportive but now it is possible to slow down development of cyst formation and renal decline in ADPKD. This raises hope for treatment for other cystic renal conditions as more genes are identified and underlying mechanisms defined. [ABSTRACT FROM AUTHOR]
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- 2020
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148. Clinical and genetic characteristics of autosomal recessive polycystic kidney disease in Oman.
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Al Alawi, Intisar, Molinari, Elisa, Al Salmi, Issa, Al Rahbi, Fatma, Al Mawali, Adhra, and Sayer, John A.
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AUTOSOMAL recessive polycystic kidney ,GENETIC testing ,POLYCYSTIC kidney disease ,HUMAN chromosome abnormality diagnosis ,LUNG abnormalities ,CHRONIC kidney failure ,HYPERTENSION ,RESEARCH ,GENETIC mutation ,RESEARCH methodology ,CIRRHOSIS of the liver ,CELL receptors ,MEDICAL cooperation ,EVALUATION research ,SPLEEN diseases ,INFANT death ,PERINATAL death ,COMPARATIVE studies ,RESEARCH funding ,CONSANGUINITY - Abstract
Background: There is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients.Methods: We studied patients with a clinical diagnosis of ARPKD (n = 40) and their relatives (parents (n = 24) and unaffected siblings (n = 10)) from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 if not previously known was performed using targeted exon PCR of known disease alleles and Sanger sequencing.Results: A clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. Twenty-four patients had documented chronic kidney disease (median age 3 years). Twenty-four out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was known in 18 patients and newly identified in 20 other patients, totalling 38 patients from 30 different families. Two unrelated patients remained genetically unsolved. The different PKHD1 missense pathogenic variants were: c.107C > T, p.(Thr36Met); c.406A > G, p.(Thr136Ala); c.4870C > T, p.(Arg1624Trp) and c.9370C > T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A > G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C > T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C > T; (Thr36Met), which was seen in 24 families.Conclusions: Molecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The limited number of PKHD1 missense variants identified in ARPKD cases suggests these may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman. [ABSTRACT FROM AUTHOR]- Published
- 2020
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149. MITF variants cause nonsyndromic sensorineural hearing loss with autosomal recessive inheritance.
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Thongpradit, Supranee, Jinawath, Natini, Javed, Asif, Noojarern, Saisuda, Khongkraparn, Arthaporn, Tim-Aroon, Thipwimol, Lertsukprasert, Krisna, Suktitipat, Bhoom, Jensen, Laran T., and Wattanasirichaigoon, Duangrurdee
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MICROPHTHALMIA-associated transcription factor , *AUTOSOMAL recessive polycystic kidney , *SENSORINEURAL hearing loss , *EYE abnormalities , *EXOMES - Abstract
MITF is a known gene underlying autosomal dominant hearing loss, Waardenburg syndrome (WS). Biallelic MITF mutations have been found associated with a rare hearing loss syndrome consisting eye abnormalities and albinism; and a more severe type of WS whose heterozygous parents were affected with classic WS in both cases. The aims of this study were to identify a new candidate gene causing autosomal recessive nonsyndromic hearing loss (ARNSHL) and confirm its causation by finding additional families affected with the candidate gene and supporting evidences from functional analyses. By using whole exome sequencing, we identified a homozygous c.1022G>A: p.Arg341His variant of MITF, which co-segregated with the hearing loss in five affected children of a consanguineous hearing couple. Targeted exome sequencing in a cohort of 130 NSHL individuals, using our in-house gene panel revealed a second family with c.1021C>T: p.Arg341Cys MITF variant. Functional studies confirmed that the Arg341His and Arg341Cys alleles yielded a normal sized MITF protein, with aberrant cytosolic localization as supported by the molecular model and the reporter assay. In conclusion, we demonstrate MITF as a new cause of ARNSHL, with heterozygous individuals free of symptoms. MITF should be included in clinical testing for NSHL, though it is rare. [ABSTRACT FROM AUTHOR]
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- 2020
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150. Genetic spectrum of retinal dystrophies in Tunisia.
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Habibi, Imen, Falfoul, Yosra, Turki, Ahmed, Hassairi, Asma, El Matri, Khaled, Chebil, Ahmed, Schorderet, Daniel F., and El Matri, Leila
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RETINAL degeneration , *PHENOTYPES , *AUTOSOMAL recessive polycystic kidney , *USHER'S syndrome - Abstract
We report the molecular basis of the largest Tunisian cohort with inherited retinal dystrophies (IRD) reported to date, identify disease-causing pathogenic variants and describe genotype–phenotype correlations. A subset of 26 families from a cohort of 73 families with clinical diagnosis of autosomal recessive IRD (AR-IRD) excluding Usher syndrome was analyzed by whole exome sequencing and autozygosity mapping. Causative pathogenic variants were identified in 50 families (68.4%), 42% of which were novel. The most prevalent pathogenic variants were observed in ABCA4 (14%) and RPE65, CRB1 and CERKL (8% each). 26 variants (8 novel and 18 known) in 19 genes were identified in 26 families (14 missense substitutions, 5 deletions, 4 nonsense pathogenic variants and 3 splice site variants), with further allelic heterogeneity arising from different pathogenic variants in the same gene. The most common phenotype in our cohort is retinitis pigmentosa (23%) and cone rod dystrophy (23%) followed by Leber congenital amaurosis (19.2%). We report the association of new disease phenotypes. This research was carried out in Tunisian patients with IRD in order to delineate the genetic population architecture. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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