bims-bicyki Biomed News
on Bicaudal-C1 and interactors in cystic kidney disease
Issue of 2022‒04‒10
24 papers selected by
Céline Gagnieux
École Polytechnique Fédérale de Lausanne (EPFL)
  1. "Tubular cell plasticity - New hope for autosomal dominant polycystic kidney disease?"
  2. Raynaud's phenomenon triggered by the vasopressin V2 receptor antagonist tolvaptan in a patient with autosomal dominant polycystic kidney disease and Sjögren's syndrome.
  3. Autosomal Dominant Polycystic Kidney Disease Does Not Significantly Alter Major COVID-19 Outcomes among Veterans.
  4. Polycystic Kidney Disease-Related Disease Burden in Adolescents With Autosomal Dominant Polycystic Kidney Disease: An International Qualitative Study.
  5. Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease.
  6. Traumatic Kidney in a Patient With Unilateral Renal Cystic Disease.
  7. Delayed Metastasis of Clear Cell Renal Carcinoma to the Colon in the Setting of Benign Kidney Disease.
  8. A Computable Phenotype for Autosomal Dominant Polycystic Kidney Disease.
  9. Mechanisms of Weight Control by Primary Cilia.
  10. Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease.
  11. Organelle Stress and Crosstalk in Kidney Disease.
  12. Pkd1 Mutation Has No Apparent Effects on Peroxisome Structure or Lipid Metabolism.
  13. Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease.
  14. Deployed Deep Learning Kidney Segmentation for Polycystic Kidney Disease MRI.
  15. Total Kidney Volume Measurements in ADPKD by 3D and Ellipsoid Ultrasound in Comparison to Magnetic Resonance Imaging.
  16. Moving Nephrology Genetics into Clinical Care.
  17. mTOR Signaling in Kidney Diseases.
  18. Role of primary cilia and Hedgehog signaling in craniofacial features of Ellis-van Creveld syndrome.
  19. Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients with Polycystic Kidney Disease.
  20. Examining the Role of Novel CKD Therapies for the ADPKD Patient.
  21. Mayo Imaging Classification May Be Useful in Determining the Need for Nephrectomy in ADPKD.
  22. Unexpected Kidney Imaging in a Patient with UTI.
  23. Motile Cilia on Kidney Proximal Tubular Epithelial Cells Are Associated With Tubular Injury and Interstitial Fibrosis.
  24. Cystic Kidneys in a Patient with Craniofacial Abnormalities.
  1. Kidney Int. 2022 Apr 01. pii: S0085-2538(22)00260-5. [Epub ahead of print]
    "Tubular cell plasticity - New hope for autosomal dominant polycystic kidney disease?"
    Marine Berquez, Olivier Devuyst.
      
    DOI:  https://doi.org/10.1016/j.kint.2022.03.015
  2. Clin Kidney J. 2022 Apr;15(4): 827-828
    Raynaud's phenomenon triggered by the vasopressin V2 receptor antagonist tolvaptan in a patient with autosomal dominant polycystic kidney disease and Sjögren's syndrome.
    F J Roca Oporto, Jose L Rocha.
      
    DOI:  https://doi.org/10.1093/ckj/sfab260
  3. Kidney360. 2021 Jun 24. 2(6): 983-988
    Autosomal Dominant Polycystic Kidney Disease Does Not Significantly Alter Major COVID-19 Outcomes among Veterans.
    Xiangqin Cui, Julia W Gallini, Christine L Jasien, Michal Mrug.
      Autosomal dominant polycystic kidney disease (ADPKD) was not a significant, independent risk factor for the four major outcomes studied among veterans with confirmed coronavirus disease 2019 (COVID-19).ADPKD did not significantly increase the risk for newly starting dialysis (after controlling for CKD) among veterans positive for COVID-19.The established risk factors for severe COVID-19 illness had significant effects in this cohort (e.g., type 2 diabetes and Black race).
    Keywords:  COVID-19; ICU admission; SARS-CoV-2; chronic kidney disease; coronavirus disease 2019; cystic kidney disease; hospital admission; kidney failure; mortality; polycystic kidney disease; ventilator; veterans
    DOI:  https://doi.org/10.34067/KID.0007282020
  4. Kidney Med. 2022 Mar;4(3): 100415
    Polycystic Kidney Disease-Related Disease Burden in Adolescents With Autosomal Dominant Polycystic Kidney Disease: An International Qualitative Study.
    Dorothee Oberdhan, Franz Schaefer, Jason C Cole, Andrew C Palsgrove, Ann Dandurand, Lisa Guay-Woodford.
      Rationale & Objective: Little is known about symptoms and disease impacts in adolescents with autosomal dominant polycystic kidney disease (ADPKD). The objective of the study was to explore these issues from the adolescent patient's perspective.Study Design: Observational, qualitative study.
    Setting & Participants: Eligible participants were 12-17 years old and had a diagnosis of ADPKD. Semi-structured interviews were conducted in 18 cities in 13 countries to elicit participant experiences of ADPKD-related symptoms and physical, social, and emotional impacts.
    Analytical Approach: Interviews were recorded, transcribed, and coded. Symptom and impact frequencies from the interviews were calculated, and representative quotes concerning elicited concepts were collated.
    Results: Thirty-three participants (mean age, 14.6 years; 42.4% female) completed interviews. Frequently reported symptoms included urinary urgency (n = 10; 30.3%) and back pain (n = 9; 27.3%). Consistent with previous findings in adults, participants experienced 3 primary types of pain: dull kidney pain, severe or sharp kidney pain, and a feeling of fullness and/or discomfort. Reported disease impacts included avoiding sports and physical activity (n = 10; 30.3%), missing school (n = 6; 18.2%) and social activities (n = 6; 18.2%), and feeling worried (n = 6; 18.2%), sad (n = 4; 12.1%), or frustrated (n = 3; 9.1%) about the disease and their future. Approximately one-fifth of participants (n = 7; 21.2%) reported that they were bothered or impacted by dietary limitations (primarily the need for reduced sodium intake and increased water intake).
    Limitations: The study had a small sample size. The researchers were unable to conduct focus groups with participants because of parental preferences.
    Conclusions: The findings from this exploratory study indicate that a substantial proportion of adolescents with ADPKD experience physical, social, and emotional impacts from their disease.
    Keywords:  Adolescent; PRO; QoL; autosomal dominant; autosomal dominant polycystic kidney disease; cystic; disease burden; patient-reported outcome; pediatric; polycystic kidney; quality of life
    DOI:  https://doi.org/10.1016/j.xkme.2022.100415
  5. Kidney360. 2021 Jul 29. 2(7): 1148-1151
    Dose-Dependent Effect of Tolvaptan on Renal Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease.
    Taro Akihisa, Shun Manabe, Hiroshi Kataoka, Shiho Makabe, Rie Yoshida, Yusuke Ushio, Kentaro Watanabe, Masayo Sato, Ken Tsuchiya, Toshio Mochizuki, Kosaku Nitta.
      This is the first report to describe dose dependency in the effects of tolvaptan treatment for autosomal dominant polycystic kidney disease.The weight-adjusted average daily dose of tolvaptan was found to be a factor that significantly affected the change in eGFR.If a patient shows tolerance, increasing the tolvaptan dose to the maximum should be considered.
    Keywords:  ADPKD; cystic kidney disease; dose-dependent; estimated glomerular filtration rate; prognostic factor; renal prognosis; tolvaptan; total kidney volume
    DOI:  https://doi.org/10.34067/KID.0007342020
  6. J Investig Med High Impact Case Rep. 2022 Jan-Dec;10:10 23247096221089495
    Traumatic Kidney in a Patient With Unilateral Renal Cystic Disease.
    Van Trung Hoang, The Huan Hoang, Thanh Tam Thi Nguyen, Cong Thao Trinh, Vichit Chansomphou, Duc Thanh Hoang.
      Renal trauma occurring in patients with unilateral renal cystic disease (URCD) is extremely rare. Unilateral renal cystic disease is benign, nonprogressive, nonfamilial, nonencapsulated, and unrelated to cysts in other organs. It should be differentiated from autosomal dominant polycystic kidney disease (ADPKD) parenthesis, multicystic dysplastic kidney disease, multiple renal simple cysts, and cystic renal neoplasms. We report a case of a 15-year-old male with URCD admitted to the hospital sustaining blunt trauma to his right flank after a motor vehicle crash. Final diagnosis in this case was renal injury in a URCD patient. The patient was treated conservatively and subsequently discharged. Unilateral renal cystic disease can be diagnosed and followed by a combination of imaging methods and functional studies. The management of URCD is conservative. Although the disease is stable, nephrectomy may occasionally be indicated when there is a strong suspicion for malignancy.
    Keywords:  kidney injury; polycystic kidney disease; renal cystic diseases; renal trauma; unilateral renal cystic disease
    DOI:  https://doi.org/10.1177/23247096221089495
  7. Cureus. 2022 Feb;14(2): e22659
    Delayed Metastasis of Clear Cell Renal Carcinoma to the Colon in the Setting of Benign Kidney Disease.
    Ariana R Tagliaferri, Caitlyn Costanzo.
      Clear cell renal carcinoma (CCRC) is a common variant of renal cell carcinoma (RCC), which presents with unpredictable features. The occurrence of RCC in those with autosomal dominant polycystic kidney disease (ADPKD) is debated. Most studies agree that ADPKD does not increase the risk of RCC; however, it makes diagnosing RCC difficult due to the nature of the disease. RCC frequently metastasizes to the lungs, lymph nodes, bones, liver, adrenal glands, and brain, but rarely metastasizes to the colon. In all previous reports, primary RCC was already diagnosed in the kidneys; thus, metastatic CCRC to the colon has never been described in the current literature in the absence of a primary renal tumor. Here, we report a rare presentation of metastatic CCRC wherein a patient with ADPKD presented with an obstructing sigmoid mass six years after bilateral nephrectomy for pathologically benign cysts. Despite a close follow-up after nephrectomy, our patient's non-specific symptoms were attributed to underlying comorbidities and more likely etiologies of back pain, diarrhea, and anemia, thus delaying and complicating the diagnosis of CCRC which subsequently led to metastases at the time of presentation. Although past literature has described CCRC metastases to other parts of the gastrointestinal tract or even described primary clear cell carcinoma of the colon, this is the first case in which a patient with benign cystic renal disease developed CCRC presenting as metastatic disease of the colon, rectum, liver, and lung. This paper will address the manifestations of ADPKD and postulate mechanisms for the unpredictable nature of this patient's RCC metastasis.
    Keywords:  colonic neoplasms; colorectal surgery; kidney transplantation; polycystic kidney disease; renal cell carcinoma
    DOI:  https://doi.org/10.7759/cureus.22659
  8. Kidney360. 2021 Nov 25. 2(11): 1728-1733
    A Computable Phenotype for Autosomal Dominant Polycystic Kidney Disease.
    Mohamad A Kalot, Abdallah El Alayli, Mohammad Al Khatib, Nedaa Husainat, Kerri McGreal, Diana I Jalal, Alan S L Yu, Reem A Mustafa.
      Background: A computable phenotype is an algorithm used to identify a group of patients within an electronic medical record system. Developing a computable phenotype that can accurately identify patients with autosomal dominant polycystic kidney disease (ADPKD) will assist researchers in defining patients eligible to participate in clinical trials and other studies. Our objective was to assess the accuracy of a computable phenotype using International Classification of Diseases 9th and 10th revision (ICD-9/10) codes to identify patients with ADPKD.Methods: We reviewed four random samples of approximately 250 patients on the basis of ICD-9/10 codes from the EHR from the Kansas University Medical Center database: patients followed in nephrology clinics who had ICD-9/10 codes for ADPKD (Neph+), patients seen in nephrology clinics without ICD codes for ADPKD (Neph-), patients who were not followed in nephrology clinics with ICD codes for ADPKD (No Neph+), and patients not seen in nephrology clinics without ICD codes for ADPKD (No Neph-). We reviewed the charts and determined ADPKD status on the basis of internationally accepted diagnostic criteria for ADPKD.
    Results: The computable phenotype to identify patients with ADPKD who attended nephrology clinics has a sensitivity of 99% (95% confidence interval [95% CI], 96.4 to 99.7) and a specificity of 84% (95% CI, 79.5 to 88.1). For those who did not attend nephrology clinics, the sensitivity was 97% (95% CI, 93.3 to 99.0), and a specificity was 82% (95% CI, 77.4 to 86.1).
    Conclusion: A computable phenotype using the ICD-9/10 codes can correctly identify most patients with ADPKD, and can be utilized by researchers to screen health care records for cohorts of patients with ADPKD with acceptable accuracy.
    Keywords:  ADPKD; ICD code; computable phenotype; cystic kidney disease; diagnosis; polycystic kidney; test accuracy
    DOI:  https://doi.org/10.34067/KID.0000852021
  9. Mol Cells. 2022 Apr 30. 45(4): 169-176
    Mechanisms of Weight Control by Primary Cilia.
    Chan Hee Lee, Gil Myoung Kang, Min-Seon Kim.
      A primary cilium, a hair-like protrusion of the plasma membrane, is a pivotal organelle for sensing external environmental signals and transducing intracellular signaling. An interesting linkage between cilia and obesity has been revealed by studies of the human genetic ciliopathies Bardet-Biedl syndrome and Alström syndrome, in which obesity is a principal manifestation. Mouse models of cell type-specific cilia dysgenesis have subsequently demonstrated that ciliary defects restricted to specific hypothalamic neurons are sufficient to induce obesity and hyperphagia. A potential mechanism underlying hypothalamic neuron cilia-related obesity is impaired ciliary localization of G protein-coupled receptors involved in the regulation of appetite and energy metabolism. A well-studied example of this is melanocortin 4 receptor (MC4R), mutations in which are the most common cause of human monogenic obesity. In the paraventricular hypothalamus neurons, a blockade of ciliary trafficking of MC4R as well as its downstream ciliary signaling leads to hyperphagia and weight gain. Another potential mechanism is reduced leptin signaling in hypothalamic neurons with defective cilia. Leptin receptors traffic to the periciliary area upon leptin stimulation. Moreover, defects in cilia formation hamper leptin signaling and actions in both developing and differentiated hypothalamic neurons. The list of obesity-linked ciliary proteins is expending and this supports a tight association between cilia and obesity. This article provides a brief review on the mechanism of how ciliary defects in hypothalamic neurons facilitate obesity.
    Keywords:  G protein-coupled receptor; ciliopathy; hypothalamus; leptin; obesity; primary cilia
    DOI:  https://doi.org/10.14348/molcells.2022.2046
  10. Kidney360. 2020 08 27. 1(8): 740-745
    Regional Variance of the Early Use of Tolvaptan for Autosomal Dominant Polycystic Kidney Disease.
    Reiko Inoue, Hiroshi Nishi, Daisuke Inoue, Kenjiro Honda, Masaomi Nangaku.
      Background: The development and prompt dissemination of the first drug against a particular disease can contribute to improvements in national health status and medical economy end points and are assumedly affected by socioeconomic factors that have yet to be analyzed. Tolvaptan, a vasopressin receptor 2 antagonist, was developed to treat hyponatremia, congestive heart failure, and cirrhosis ascites, although the approved indications may differ among countries. In Japan, high-dose tolvaptan tablets were approved as the first drug for autosomal dominant polycystic kidney disease (ADPKD) in 2014. This study aimed to better understand the factors that influence the total number of regional prescriptions of tolvaptan for ADPKD since its launch.Methods: The National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data was used as a national claim-based database. In each of the 47 prefectures in Japan, the total prescribed number of 30 mg tolvaptan tablets between 2015 and 2017 was examined. The parameters explaining the prescription variation among regions were then examined by correlation analysis.
    Results: Prescriptions for high-dose tolvaptan increased substantially 2 years after the drug's approval; however, the increase differed by approximately 21-fold between regions. Population density was positively associated with prescribed 30 mg tolvaptan tablets per 1000 population in 2015 (r=0.47, P<0.001). In addition, the increase in prescribed number of tablets per 1000 population was correlated with population density in 2016-2017 (r=0.30, P=0.04).
    Conclusions: This macro perspective analysis revealed an urban-rural inequity in prescriptions for the newly approved drug for ADPKD. Further studies are needed to elucidate the factors affecting the geographic variation.
    Keywords:  Japan; autosomal dominant; cystic kidney disease; polycystic kidney; population density; regional variance; tolvaptan
    DOI:  https://doi.org/10.34067/KID.0002262020
  11. Kidney360. 2020 Oct 29. 1(10): 1157-1164
    Organelle Stress and Crosstalk in Kidney Disease.
    Sho Hasegawa, Reiko Inagi.
      Organelles play important roles in maintaining cellular homeostasis. Organelle stress responses, especially in mitochondria, endoplasmic reticula (ER), and primary cilia, are deeply involved in kidney disease pathophysiology. Mitochondria are the center of energy production in most eukaryotic cells. Renal proximal tubular cells are highly energy demanding and abundant in mitochondria. Mitochondrial dysfunctions in association with energy metabolism alterations produce reactive oxygen species and promote inflammation in proximal tubular cells, resulting in progression of kidney disease. The ER play critical roles in controlling protein quality. Unfolded protein response (UPR) pathways are the adaptive response to ER stress for maintaining protein homeostasis. UPR pathway dysregulation under pathogenic ER stress often occurs in glomerular and tubulointerstitial cells and promotes progression of kidney disease. The primary cilia sense extracellular signals and maintain calcium homeostasis in cells. Dysfunction of the primary cilia in autosomal dominant polycystic kidney disease reduces the calcium concentration in proximal tubular cells, leading to increased cell proliferation and retention of cyst fluid. In recent years, the direct interaction at membrane contact sites has received increased attention in association with the development of imaging technologies. The part of the ER that is directly connected to mitochondria is termed the mitochondria-associated ER membrane (MAM), which regulates calcium homeostasis and phospholipid metabolism in cells. Disruption of MAM integrity collapses cellular homeostasis and leads to diseases such as diabetes and Alzheimer disease. This review summarizes recent research on organelle stress and crosstalk, and their involvement in kidney disease pathophysiology. In addition, potential treatment options that target organelle stress responses are discussed.
    Keywords:  AKI-to-CKD transition; ER stress; acute kidney injury; chronic kidney disease; lipid metabolism; mitochondria; organelle crosstalk; organelle stress; tubular inflammation; unfolded protein response (UPR)
    DOI:  https://doi.org/10.34067/KID.0002442020
  12. Kidney360. 2021 Oct 28. 2(10): 1576-1591
    Pkd1 Mutation Has No Apparent Effects on Peroxisome Structure or Lipid Metabolism.
    Takeshi Terabayashi, Luis F Menezes, Fang Zhou, Hongyi Cai, Peter J Walter, Hugo M Garraffo, Gregory G Germino.
      Background: Multiple studies of tissue and cell samples from patients and preclinical models of autosomal dominant polycystic kidney disease report abnormal mitochondrial function and morphology and suggest metabolic reprogramming is an intrinsic feature of this disease. Peroxisomes interact with mitochondria physically and functionally, and congenital peroxisome biogenesis disorders can cause various phenotypes, including mitochondrial defects, metabolic abnormalities, and renal cysts. We hypothesized that a peroxisomal defect might contribute to the metabolic and mitochondrial impairments observed in autosomal dominant polycystic kidney disease.Methods: Using control and Pkd1-/- kidney epithelial cells, we investigated peroxisome abundance, biogenesis, and morphology by immunoblotting, immunofluorescence, and live cell imaging of peroxisome-related proteins and assayed peroxisomal specific β-oxidation. We further analyzed fatty acid composition by mass spectrometry in kidneys of Pkd1fl/fl;Ksp-Cre mice. We also evaluated peroxisome lipid metabolism in published metabolomics datasets of Pkd1 mutant cells and kidneys. Lastly, we investigated if the C terminus or full-length polycystin-1 colocalize with peroxisome markers by imaging studies.
    Results: Peroxisome abundance, morphology, and peroxisome-related protein expression in Pkd1-/- cells were normal, suggesting preserved peroxisome biogenesis. Peroxisomal β-oxidation was not impaired in Pkd1-/- cells, and there was no obvious accumulation of very-long-chain fatty acids in kidneys of mutant mice. Reanalysis of published datasets provide little evidence of peroxisomal abnormalities in independent sets of Pkd1 mutant cells and cystic kidneys, and provide further evidence of mitochondrial fatty acid oxidation defects. Imaging studies with either full-length polycystin-1 or its C terminus, a fragment previously shown to go to the mitochondria, showed minimal colocalization with peroxisome markers restricted to putative mitochondrion-peroxisome contact sites.
    Conclusions: Our studies showed that loss of Pkd1 does not disrupt peroxisome biogenesis nor peroxisome-dependent fatty acid metabolism.
    Keywords:  ADPKD; basic science; cystic kidney disease; fatty acids; genetic diseases; metabolism; peroxisomes
    DOI:  https://doi.org/10.34067/KID.0000962021
  13. J Formos Med Assoc. 2022 Mar 31. pii: S0929-6646(22)00112-7. [Epub ahead of print]
    Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease.
    Pei-Feng Hsieh, Shih-Yao Liu, Chih-Hao Chen, Pei-Lung Chen, Sung-Chun Tang, Jiann-Shing Jeng.
      Hereditary cerebral cavernous malformations (CCMs) are characterized by clustered dilated capillary-like vessels in the brain. Autosomal dominant polycystic kidney disease (PKD) is characterized by renal cysts and extra-renal abnormalities. We report a Taiwanese family in which the index case exhibited coexisting phenotypes of both CCMs and PKD. The index case was a 55-year-old woman with known PKD who developed an intracerebral hemorrhage (ICH) in the right medulla. Neuroimaging revealed numerous microbleeds in the bilateral cerebrum and cerebellum. Radiological CCMs were suspected given the absence of other imaging markers of small vessel disease. A comprehensive panel of 183 cerebral vascular malformation genes were investigated through genome sequencing. A novel CCM2 frameshift variant (c.607_608delCT, p.Leu203Valfs∗53) causing a pathogenic premature stop codon, and a known PKD2 nonsense variant (c.2407C > T, p.Arg803∗), were found. Segregation analysis revealed that four siblings were affected by either isolated aforementioned PKD2 or CCM2 variant. Notably, radiological CCMs were exclusively found in siblings who had this CCM2 variant, and bilateral internal carotid artery aneurysms were restricted to one sibling who had the PKD2 variant but not the CCM2 variant. Our study expands the genetic spectrum of CCM2 and demonstrates unambiguous cosegregation of CCM2 and PKD2 variants with their respective phenotypes.
    Keywords:  CCM2; Cerebral cavernous malformations; PKD2; Polycystic kidney disease
    DOI:  https://doi.org/10.1016/j.jfma.2022.03.010
  14. Radiol Artif Intell. 2022 Mar;4(2): e210205
    Deployed Deep Learning Kidney Segmentation for Polycystic Kidney Disease MRI.
    Akshay Goel, George Shih, Sadjad Riyahi, Sunil Jeph, Hreedi Dev, Rejoice Hu, Dominick Romano, Kurt Teichman, Jon D Blumenfeld, Irina Barash, Ines Chicos, Hanna Rennert, Martin R Prince.
      This study develops, validates, and deploys deep learning for automated total kidney volume (TKV) measurement (a marker of disease severity) on T2-weighted MRI studies of autosomal dominant polycystic kidney disease (ADPKD). The model was based on the U-Net architecture with an EfficientNet encoder, developed using 213 abdominal MRI studies in 129 patients with ADPKD. Patients were randomly divided into 70% training, 15% validation, and 15% test sets for model development. Model performance was assessed using Dice similarity coefficient (DSC) and Bland-Altman analysis. External validation in 20 patients from outside institutions demonstrated a DSC of 0.98 (IQR, 0.97-0.99) and a Bland-Altman difference of 2.6% (95% CI: 1.0%, 4.1%). Prospective validation in 53 patients demonstrated a DSC of 0.97 (IQR, 0.94-0.98) and a Bland-Altman difference of 3.6% (95% CI: 2.0%, 5.2%). Last, the efficiency of model-assisted annotation was evaluated on the first 50% of prospective cases (n = 28), with a 51% mean reduction in contouring time (P < .001), from 1724 seconds (95% CI: 1373, 2075) to 723 seconds (95% CI: 555, 892). In conclusion, our deployed artificial intelligence pipeline accurately performs automated segmentation for TKV estimation of polycystic kidneys and reduces expert contouring time. Keywords: Convolutional Neural Network (CNN), Segmentation, Kidney ClinicalTrials.gov identification no.: NCT00792155 Supplemental material is available for this article. © RSNA, 2022.
    Keywords:  Convolutional Neural Network (CNN); Kidney; Segmentation
    DOI:  https://doi.org/10.1148/ryai.210205
  15. Clin J Am Soc Nephrol. 2022 Apr 05. pii: CJN.14931121. [Epub ahead of print]
    Total Kidney Volume Measurements in ADPKD by 3D and Ellipsoid Ultrasound in Comparison to Magnetic Resonance Imaging.
    Pedram Akbari, Fatemeh Nasri, Shirley Deng, Saima Khowaja, Seung Lee, William Warnica, Hua Lu, Anand Rattansingh, Mostafa Atri, Korosh Khalili, York Pei.
      Background and Objectives: Total kidney volume (TKV) is a validated prognostic biomarker for autosomal dominant polycystic kidney disease (ADPKD). TKV by magnetic resonance imaging (MRI) and manual segmentation is considered the "reference standard", but is time-consuming and not readily accessible. By contrast, 3-dimensional ultrasound (3D ultrasound) provides a promising technology for TKV measurements with unknown potential. Here, we report a comparative study of TKV measurements by 3D ultrasound vs. the conventional methods by ultrasound ellipsoid and MRI ellipsoid. Design, setting, participants, and measurements: Single-center prospective study of 142 patients who completed a standardized 3D ultrasound and MRI. TKV by 3D ultrasound and ultrasound ellipsoid were compared to those by MRI. We assessed the agreement of TKV measurements by Bland-Altman plots and misclassification of the Mayo Clinic Imaging Classes (MCIC) between the different imaging methods, and prediction of MCIC 1C-1E by average ultrasound kidney length >16.5 cm. Results: Compared to MRI manual segmentation, MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid underestimated TKV (mean difference: -3.2%, -9.1%, and -11.0%) with MCIC misclassified in 11%, 21% and 22% of patients, respectively; most misclassified cases by MRI ellipsoid (11/16), 3D ultrasound (23/30), and ultrasound ellipsoid (26/31) were placed into a lower MCIC. Prediction of the high-risk MCIC (1C-1E) by MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid all yielded high positive predictive value (96%, 95%, 98%), and specificity (96%, 96%, 99%). However, both negative predictive value (90%, 88%, 95%) and sensitivity (88%, 85%, 94%) were lower for 3D ultrasound and ultrasound ellipsoid compared to MRI ellipsoid. An average ultrasound kidney length >16.5 cm was highly predictive of MCIC 1C-1E only in patients aged <45 years. Conclusions: TKV measurements in ADPKD by 3D ultrasound and ultrasound ellipsoid displayed similar bias, variability, and are less accurate than MRI ellipsoid. Prediction of high-risk MCIC (1C-1E) by all three methods provides high positive predictive value, but ultrasound ellipsoid is simpler to use and more readily available.
    DOI:  https://doi.org/10.2215/CJN.14931121
  16. Kidney360. 2020 Oct 29. 1(10): 1040-1041
    Moving Nephrology Genetics into Clinical Care.
    Matthew B Lanktree.
      
    Keywords:  chronic kidney disease; genetic testing; genetics; polycystic kidney disease
    DOI:  https://doi.org/10.34067/KID.0005142020
  17. Kidney360. 2020 Nov 25. 1(11): 1319-1327
    mTOR Signaling in Kidney Diseases.
    Yuan Gui, Chunsun Dai.
      The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, is crucial in regulating cell growth, metabolism, proliferation, and survival. Under physiologic conditions, mTOR signaling maintains podocyte and tubular cell homeostasis. In AKI, activation of mTOR signaling in tubular cells and interstitial fibroblasts promotes renal regeneration and repair. However, constitutive activation of mTOR signaling in kidneys results in the initiation and progression of glomerular hypertrophy, interstitial fibrosis, polycystic kidney disease, and renal cell carcinoma. Here, we summarize the recent studies about mTOR signaling in renal physiology and injury, and discuss the possibility of its use as a therapeutic target for kidney diseases.
    Keywords:  TOR serine-threonine kinases; acute kidney injury; acute kidney injury and ICU nephrology; glomerular hypertrophy; kidney fibrosis; mTOR; polycystic kidney disease; renal cell carcinoma
    DOI:  https://doi.org/10.34067/KID.0003782020
  18. Am J Med Genet C Semin Med Genet. 2022 Apr 08.
    Role of primary cilia and Hedgehog signaling in craniofacial features of Ellis-van Creveld syndrome.
    Davis C Thomas, Janani Dakshina Moorthy, Vaishnavi Prabhakar, Ahana Ajayakumar, Priyanka Kodaganallur Pitchumani.
      Ellis-van Creveld syndrome (EvC) is an autosomal recessive genetic disorder involving pathogenic variants of EVC and EVC2 genes and classified as a ciliopathy. The syndrome is caused by mutations in the EVC gene on chromosome 4p16, and EVC2 gene, located close to the EVC gene, in a head-to-head configuration. Regardless of the affliction of EVC or EVC2, the clinical features of Ellis-van Creveld syndrome are similar. Both these genes are expressed in tissues such as, but not limited to, the heart, liver, skeletal muscle, and placenta, while the predominant expression in the craniofacial tissues is that of EVC2. Biallelic mutations of EVC and EVC2 affect Hedgehog signaling and thereby ciliary function, crucial factors in vertebrate development, culminating in the phenotypical features characteristic of EvC. The clinical features of Ellis-van Creveld syndrome are consistent with significant abnormalities in morphogenesis and differentiation of the affected tissues. The robust role of primary cilia in histodifferentiation and morphodifferentiation of oral, perioral, and craniofacial tissues is becoming more evident in the most recent literature. In this review, we give a summary of the mechanistic role of primary cilia in craniofacial development, taking Ellis-van Creveld syndrome as a representative example.
    Keywords:  Ellis-van Creveld syndrome; Hedgehog signaling; ciliopathies; craniofacial; primary cilia
    DOI:  https://doi.org/10.1002/ajmg.c.31969
  19. Kidney360. 2021 Feb 25. 2(2): 312-324
    Long-Term Outcomes and Prognostic Factors in Kidney Transplant Recipients with Polycystic Kidney Disease.
    Gauri Bhutani, Brad C Astor, Didier A Mandelbrot, Lori Mankowski-Gettle, Timothy Ziemlewicz, Shane A Wells, Leah Frater-Rubsam, Vanessa Horner, Courtney Boyer, Jennifer Laffin, Arjang Djamali.
      Background: Polycystic kidney disease (PKD) accounts for approximately 15% of kidney transplants, but long-term outcomes in patients with PKD who have received a kidney transplant are not well understood.Methods: In primary recipients of kidney transplants at our center (1994-2014), we compared outcomes of underlying PKD (N=619) with other native diseases (non-PKD, N=4312). Potential factors influencing outcomes in PKD were evaluated using Cox proportional-hazards regression and a rigorous multivariable model.
    Results: Patients with PKD were older and were less likely to be sensitized or to experience delayed graft function (DGF). Over a median follow-up of 5.6 years, 1256 of all recipients experienced death-censored graft failure (DCGF; 115 patients with PKD) and 1617 died (154 patients with PKD). After adjustment for demographic, dialysis, comorbid disease, surgical, and immunologic variables, patients with PKD had a lower risk of DCGF (adjusted hazard ratio [aHR], 0.73; 95% CI, 0.57 to 0.93; P=0.01) and death (aHR, 0.62; 95% CI, 0.51 to 0.75; P<0.001). In our multiadjusted model, calcineurin-inhibitor (CNI) use was associated with lower risk of DCGF (aHR, 0.45; 95% CI, 0.26 to 0.76; P=0.003), whereas HLA mismatch of five to six antigens (aHR, 2.1; 95% CI, 1.2 to 3.64; P=0.009) was associated with higher likelihood of DCGF. Notably, both pretransplant coronary artery disease (CAD) and higher BMI were associated with increased risk of death (CAD, aHR, 2.5; 95% CI, 1.69 to 3.71; P<0.001; per 1 kg/m2 higher BMI, aHR, 1.07; 95% CI, 1.04 to 1.11; P<0.001), DCGF, and acute rejection. Nephrectomy at time of transplant and polycystic liver disease were not associated with DCGF/death. Incidence of post-transplant diabetes mellitus was similar between PKD and non-PKD cohorts.
    Conclusions: Recipients with PKD have better long-term graft and patient survival than those with non-PKD. Standard practices of CNI use and promoting HLA match are beneficial in PKD and should continue to be promoted. Further prospective studies investigating the potential benefits of CNI use and medical/surgical interventions to address CAD and the immunologic challenges of obesity are needed.
    Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2021_02_25_KID0001182019.mp3.
    Keywords:  calcineurin inhibitor; coronary artery disease; death; graft survival; human leukocyte antigen (HLA); kidney transplant; nephrectomy; obesity; polycystic kidney disease; post-transplant diabetes mellitus; transplantation
    DOI:  https://doi.org/10.34067/KID.0001182019
  20. Kidney360. 2021 Jun 24. 2(6): 1036-1041
    Examining the Role of Novel CKD Therapies for the ADPKD Patient.
    Dipal M Patel, Neera K Dahl.
      
    Keywords:  ADPKD; HIF-PHi; SGLT2i; cystic kidney disease
    DOI:  https://doi.org/10.34067/KID.0007422020
  21. Kidney360. 2021 Feb 25. 2(2): 325-330
    Mayo Imaging Classification May Be Useful in Determining the Need for Nephrectomy in ADPKD.
    Stephanie Rosenberg, Sarthak Virmani, Sharon Klarman, Samantha Santovasi, Feng Dai, Neera K Dahl.
      
    Keywords:  ADPKD; Mayo class; autosomal dominant polycystic kidney; cystic kidney disease; diagnostic imaging; kidney transplantation; nephrectomy
    DOI:  https://doi.org/10.34067/KID.0003902020
  22. Kidney360. 2021 Oct 28. 2(10): 1688-1689
    Unexpected Kidney Imaging in a Patient with UTI.
    Jasmeet Gill, Joris M Schuller, Harold M Szerlip.
      
    Keywords:  ADPKD; cystic kidney disease; unilateral
    DOI:  https://doi.org/10.34067/KID.0003022021
  23. Front Cell Dev Biol. 2022 ;10 765887
    Motile Cilia on Kidney Proximal Tubular Epithelial Cells Are Associated With Tubular Injury and Interstitial Fibrosis.
    Jennifer Eymael, Brigith Willemsen, Joyce Xu, Fieke Mooren, Eric Steenbergen, Jack F Wetzels, Henry Dijkman, Jitske Jansen, Johan Van der Vlag, Bart Smeets.
      It is well established that mammalian kidney epithelial cells contain a single non-motile primary cilium (9 + 0 pattern). However, we noted the presence of multiple motile cilia with a central microtubular pair (9 + 2 pattern) in kidney biopsies of 11 patients with various kidney diseases, using transmission electron microscopy. Immunofluorescence staining revealed the expression of the motile cilia-specific markers Radial Spoke Head Protein 4 homolog A, Forkhead-box-protein J1 and Regulatory factor X3. Multiciliated cells were exclusively observed in proximal tubuli and a relative frequent observation in human kidney tissue: in 16.7% of biopsies with tubular injury and atrophy (3 of 18 tissues), in 17.6% of biopsies from patients with membranous nephropathy (3 of 17 tissues) and in 10% of the human kidney tissues derived from the unaffected pole after tumour nephrectomy (3 of 30 tissues). However, these particular tissues showed marked tubular injury and fibrosis. Further analysis showed a significant relation between the presence of multiciliated cells and an increased expression of alpha-smooth-muscle-actin (p-value < 0.01) and presence of Kidney-injury-molecule-1 (p-value < 0.01). Interestingly, multiciliated cells co-showed staining for the scattered tubular cell markers annexin A2, annexin A3, vimentin and phosphofructokinase platelet but not with cell senescence associated markers, like (p16) and degradation of lamin B. In conclusion, multiciliated proximal tubular cells with motile cilia were frequently observed in kidney biopsies and associated with tubular injury and interstitial fibrosis. These data suggest that proximal tubular cells are able to transdifferentiate into multiciliated cells.
    Keywords:  dedifferentiated; interstitial fibrosis and tubular atrophy; kidney injury and repair; motile cilia; multiciliated cells; multiciliated differentiation; proximal tubular cells
    DOI:  https://doi.org/10.3389/fcell.2022.765887
  24. Kidney360. 2020 Aug 27. 1(8): 882-883
    Cystic Kidneys in a Patient with Craniofacial Abnormalities.
    Allison L Tsao, C John Sperati.
      
    Keywords:  brain; cilia; cystic kidney disease; diagnosis; differential; face; genetic testing; genetics; kidney; mouth; nephromegaly; oro-facial-digital syndrome
    DOI:  https://doi.org/10.34067/KID.0001332020
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