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Article: Understanding the Current Landscape of Kidney Disease in Canada to Advance Precision Medicine Guided Personalized Care.

Kitzler, Thomas M / Chun, Justin

Canadian journal of kidney health and disease

2023 Volume 10, Page(s) 20543581231154185

Abstract: Purpose of review: To understand the impact of kidney disease in Canada and the priority areas of kidney research that can benefit from patient-oriented, precision medicine research using novel technologies.: Sources of information: Information was ... ...

Abstract	Purpose of review: To understand the impact of kidney disease in Canada and the priority areas of kidney research that can benefit from patient-oriented, precision medicine research using novel technologies. Sources of information: Information was collected through discussions between health care professionals, researchers, and patient partners. Literature was compiled using search engines (PubMed, PubMed central, Medline, and Google) and data from the Canadian Organ Replacement Register. Methods: We reviewed the impact, prevalence, economic burden, causes of kidney disease, and priority research areas in Canada. After reviewing the priority areas for kidney research, potential avenues for future research that can integrate precision medicine initiatives for patient-oriented research were outlined. Key findings: Chronic kidney disease (CKD) remains among the top causes of morbidity and mortality in the world and exerts a large financial strain on the health care system. Despite the increasing number of people with CKD, funding for basic kidney research continues to trail behind other diseases. Current funding strategies favor existing clinical treatment and patient educational strategies. The identification of genetic factors for various forms of kidney disease in the adult and pediatric populations provides mechanistic insight into disease pathogenesis. Allocation of resources and funding toward existing high-yield personalized research initiatives have the potential to significantly affect patient-oriented research outcomes but will be difficult due to a constant decline of funding for kidney research. Limitations: This is an overview primarily focused on Canadian-specific literature rather than a comprehensive systematic review of the literature. The scope of our findings and conclusions may not be applicable to health care systems in other countries.
Language	English
Publishing date	2023-02-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2765462-X
ISSN	2054-3581
ISSN	2054-3581
DOI	10.1177/20543581231154185
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Article ; Online: Comparative effectiveness of lenalidomide/dexamethasone-based triplet regimens for treatment of relapsed and/or refractory multiple myeloma in the United States: An analysis of real-world electronic health records data.

Ailawadhi, Sikander / Cheng, Mu / Cherepanov, Dasha / DerSarkissian, Maral / Stull, Dawn Marie / Hilts, Annalise / Chun, Justin / Duh, Mei Sheng / Sanchez, Larysa

Current problems in cancer

2024 Volume 50, Page(s) 101078

Abstract: Background: This retrospective longitudinal study compared the effectiveness of dexamethasone+lenalidomide (Rd)-based triplet regimens containing proteasome inhibitors (PIs) ixazomib (IRd), carfilzomib (KRd), and bortezomib (VRd) or monoclonal ... ...

Abstract	Background: This retrospective longitudinal study compared the effectiveness of dexamethasone+lenalidomide (Rd)-based triplet regimens containing proteasome inhibitors (PIs) ixazomib (IRd), carfilzomib (KRd), and bortezomib (VRd) or monoclonal antibodies (MABs) elotuzumab (ERd) and daratumumab (DRd) in patients with relapsed/refractory multiple myeloma (RRMM)-including those with high cytogenetic risk-primarily treated at community oncology clinics in the United States. Methods: Electronic health records of adult RRMM patients in a deidentified real-world database (01/01/2014-09/30/2020) who initiated IRd, KRd, VRd, ERd, or DRd in the second or later line of therapy (LOT) were analyzed. The index date was the date of initiation of each LOT and baseline was the 6-month pre-index period. Duration of therapy (DOT), time to next therapy (TTNT), progression-free survival (PFS), and overall survival (OS) were compared across regimens with multivariable Cox proportional hazards models. Results: Of the 1,185 patients contributing 1,332 LOTs, 985 had standard cytogenetic risk (median age, 71 years) and 180 had high risk (median age, 69 years). Compared with other regimens, DRd was associated with longer DOT overall (adjusted hazard ratio [95 % confidence interval]: 1.84 [1.42, 2.38] vs. KRd, 1.65 [1.20, 2.28] vs. ERd, 1.58 [1.23, 2.04] vs. IRd, and 1.54 [1.18, 2.00] vs. VRd), and longer TTNT and PFS. KRd was associated with shorter OS compared with DRd (1.45 [1.01, 2.08]) and VRd (1.32 [1.01, 1.73]). High-risk patients had similar outcomes with all triplet regimens. Conclusion: Although DRd improved clinical outcomes overall, Rd-based triplet regimens containing a PI or MAB are similarly effective in high-risk RRMM.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	441816-5
ISSN	1535-6345 ; 0147-0272
ISSN (online)	1535-6345
ISSN	0147-0272
DOI	10.1016/j.currproblcancer.2024.101078
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Article: Prospects for Precision Medicine in Glomerulonephritis Treatment.

Liu, Yulu Cherry / Chun, Justin

Canadian journal of kidney health and disease

2018 Volume 5, Page(s) 2054358117753617

Abstract: Background: Glomerulonephritis (GN) consists of a group of kidney diseases that are categorized based on shared histopathological features. The current classifications for GN make it difficult to distinguish the individual variability in presentation, ... ...

Abstract	Background: Glomerulonephritis (GN) consists of a group of kidney diseases that are categorized based on shared histopathological features. The current classifications for GN make it difficult to distinguish the individual variability in presentation, disease progression, and response to treatment. GN is a significant cause of end-stage renal disease (ESRD), and improved therapies are desperately needed because current immunosuppressive therapies sometimes lack efficacy and can lead to significant toxicities. In recent years, the combination of high-throughput genetic approaches and technological advances has identified important regulators contributing to GN. Objectives: In this review, we summarize recent findings in podocyte biology and advances in experimental approaches that have opened the possibility of precision medicine in GN treatment. We provide an integrative basic science and clinical overview of new developments in GN research and the discovery of potential candidates for targeted therapies in GN. Findings: Advances in podocyte biology have identified many candidates for therapeutic targets and potential biomarkers of glomerular disease. The goal of precision medicine in GN is now being pursued with recent technological improvements in genetics, accessibility of biologic and clinical information with tissue biobanks, high-throughput analysis of large-scale data sets, and new human model systems such as kidney organoids. Conclusion: With advances in data collection, technologies, and experimental model systems, we now have vast tools available to pursue precision medicine in GN. We anticipate a growing number of studies integrating data from high-throughput analysis with the development of diagnostic tools and targeted therapies for GN in the near future.
Language	English
Publishing date	2018-02-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2765462-X
ISSN	2054-3581
ISSN	2054-3581
DOI	10.1177/2054358117753617
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Article ; Online: Semi-Supervised Segmentation of Renal Pathology: An Alternative to Manual Segmentation and Input to Deep Learning Training.

Kline, Adrienne / Chung, Hyun Jae / Rahmani, Waleed / Chun, Justin

Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference

2021 Volume 2021, Page(s) 2688–2691

Abstract: Kidney biopsy interpretation is the gold standard for the diagnosis and prognosis for kidney disease. Pathognomonic diagnosis hinges on the correct assessment of different structures within a biopsy that is manually visualized and interpreted by a renal ... ...

Abstract	Kidney biopsy interpretation is the gold standard for the diagnosis and prognosis for kidney disease. Pathognomonic diagnosis hinges on the correct assessment of different structures within a biopsy that is manually visualized and interpreted by a renal pathologist. This laborious undertaking has spurred attempts to automate the process, offloading the consumption of temporal resources. Segmentation of kidney structures, specifically, the glomeruli, tubules, and interstitium, is a precursory step for disease classification problems. Translating renal disease decision making into a deep learning model for diagnostic and prognostic classification also relies on adequate segmentation of structures within the kidney biopsy. This study showcases a semi-automated segmentation technique where the user defines starting points for glomeruli in kidney biopsy images of both healthy normal and diabetic kidney disease stained with Nile Red that are subsequently partitioned into four areas: background, glomeruli, tubules and interstitium. Five of 30 biopsies that were segmented using the semi-automated method were randomly selected and the regions of interest were compared to the manual segmentation of the same images. Dice Similarity Coefficients (DSC) between the methods showed excellent agreement; Healthy (glomeruli: 0.92, tubules: 0.86, intersititium: 0.78) and diabetic nephropathy: (glomeruli: 0.94, tubules: 0.80, intersititium: 0.80). To our knowledge this is the first semi-automated segmentation algorithm performed with human renal biopsies stained with Nile Red. Utility of this methodology includes further image processing within structures across disease states based on biological morphological structures. It can also be used as input into a deep learning network to train semantic segmentation and input into a deep learning algorithm for classification of disease states.
MeSH term(s)	Algorithms ; Biopsy ; Deep Learning ; Humans ; Image Processing, Computer-Assisted ; Kidney/diagnostic imaging
Language	English
Publishing date	2021-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2694-0604
ISSN (online)	2694-0604
DOI	10.1109/EMBC46164.2021.9630248
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Article ; Online: Infecting kidney organoids with a cDNA reporter clone of SARS-CoV-2.

Chung, Hyunjae / Bui-Marinos, Maxwell P / Rahmani, Waleed / Corcoran, Jennifer A / Chun, Justin

STAR protocols

2022 Volume 3, Issue 3, Page(s) 101617

Abstract: Induced pluripotent stem cell (iPSC)-derived kidney organoids can be used for disease modeling and drug testing. Here, we describe a protocol to prepare stocks of an infectious clone of SARS-CoV-2 expressing a stable mNeonGreen reporter (icSARS-CoV-2-mNG) ...

Abstract	Induced pluripotent stem cell (iPSC)-derived kidney organoids can be used for disease modeling and drug testing. Here, we describe a protocol to prepare stocks of an infectious clone of SARS-CoV-2 expressing a stable mNeonGreen reporter (icSARS-CoV-2-mNG). We demonstrate the infection of kidney organoids, primarily at the proximal tubular cells, with icSARS-CoV-2-mNG. Using a TCID50 (tissue culture infectious dose 50) assay and confocal microscopy, we show the quantification of SARS-CoV-2-mNG signal in proximal tubular cells of the kidney organoids. For complete details on the use and execution of this protocol, please refer to Rahmani et al. (2022).
MeSH term(s)	COVID-19 ; Clone Cells ; DNA, Complementary/genetics ; Humans ; Kidney ; Organoids ; SARS-CoV-2/genetics
Chemical Substances	DNA, Complementary
Language	English
Publishing date	2022-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2022.101617
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Article ; Online: Ocular involvement in TEMPI syndrome.

Wu, Jo-Hsuan / Viruni, Narine / Chun, Justin / Shanbhag, Satish / Liu, T Y Alvin

American journal of ophthalmology case reports

2022 Volume 26, Page(s) 101534

Abstract: Purpose: We report the first case of ocular involvement in TEMPI syndrome, a rare disease characterized by telangiectasias, elevated erythropoietin with erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intra-pulmonary shunting.!# ...

Abstract	Purpose: We report the first case of ocular involvement in TEMPI syndrome, a rare disease characterized by telangiectasias, elevated erythropoietin with erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intra-pulmonary shunting. Observations: A 64-year-old Caucasian man with history of TEMPI syndrome presented with subacute bilateral painless vision loss. Ocular examination showed chronic retinal ischemia with microvascular damage, which was likely associated with the chronic systemic hypoxemia, and spontaneous wax and wane of cystoid macular edema, presumedly related to the systemic bortezomib treatment. Conclusions and importance: Our case demonstrates that pathologic retinal vascular changes could be seen in association with TEMPI syndrome and suggests that a comprehensive ophthalmological examination may be beneficial for these patients.
Language	English
Publishing date	2022-04-10
Publishing country	United States
Document type	Case Reports
ISSN	2451-9936
ISSN (online)	2451-9936
DOI	10.1016/j.ajoc.2022.101534
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Article ; Online: Economic burden of early-stage non-small-cell lung cancer: an assessment of healthcare resource utilization and medical costs.

Apple, Jon / DerSarkissian, Maral / Shah, Anne / Chang, Rose / Chen, Yan / He, Xuanhao / Chun, Justin

Journal of comparative effectiveness research

2023 Volume 12, Issue 11, Page(s) e230107

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Humans ; Aged ; United States ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Lung Neoplasms/drug therapy ; Financial Stress ; Neoplasm Staging ; Medicare ; Small Cell Lung Carcinoma ; Patient Acceptance of Health Care ; Chemotherapy, Adjuvant
Language	English
Publishing date	2023-09-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2669725-7
ISSN	2042-6313 ; 2042-6305
ISSN (online)	2042-6313
ISSN	2042-6305
DOI	10.57264/cer-2023-0107
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Article ; Online: Crescentic Glomerulonephritis: Variation in Markers of Kidney Function and Structure.

Chun, Justin / James, Matthew T

American journal of kidney diseases : the official journal of the National Kidney Foundation

2016 Volume 67, Issue 3, Page(s) 355–356

MeSH term(s)	Autoantibodies/blood ; Glomerulonephritis ; Humans ; Kidney/pathology ; Male
Chemical Substances	Autoantibodies
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2015.11.010
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Article ; Online: Attenuation of SARS-CoV-2 infection by losartan in human kidney organoids.

Rahmani, Waleed / Chung, Hyunjae / Sinha, Sarthak / Bui-Marinos, Maxwell P / Arora, Rohit / Jaffer, Arzina / Corcoran, Jennifer A / Biernaskie, Jeff / Chun, Justin

iScience

2022 Volume 25, Issue 2, Page(s) 103818

Abstract: COVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) ... ...

Abstract	COVID-19-associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. The susceptibility of human kidneys to direct SARS-CoV-2 infection and modulation of the renin-angiotensin II signaling (RAS) pathway by viral infection remain poorly characterized. Using induced pluripotent stem cell-derived kidney organoids, SARS-CoV-1, SARS-CoV-2, and MERS-CoV tropism, defined by the paired expression of a host receptor (
Language	English
Publishing date	2022-01-28
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.103818
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Article ; Online: Post-mortem molecular investigations of SARS-CoV-2 in an unexpected death of a recent kidney transplant recipient.

Simms, Emily Lauren / Chung, Hyunjae / Oberding, Lisa / Muruve, Daniel A / McDonald, Braedon / Bromley, Amy / Pillai, Dylan R / Chun, Justin

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2021 Volume 21, Issue 7, Page(s) 2590–2595

Abstract: Solid organ transplant recipients are vulnerable to severe infection during induction therapy. We report a case of a 67-year-old male who died unexpectedly 10 days after receiving a kidney transplant on February 10, 2020. There was no clear cause of ... ...

Abstract	Solid organ transplant recipients are vulnerable to severe infection during induction therapy. We report a case of a 67-year-old male who died unexpectedly 10 days after receiving a kidney transplant on February 10, 2020. There was no clear cause of death, but COVID-19 was considered retrospectively, as the death occurred shortly after the first confirmed case of COVID-19 in Canada. We confirmed the presence of SARS-CoV-2 components in the renal allograft and native lung tissue using immunohistochemistry for SARS-CoV-2 spike protein and RNA scope in situ hybridization for SARS-CoV-2 RNA. Results were reaffirmed with the Food and Drug Administration Emergency Use Authorization approved Bio-Rad SARS-CoV-2 digital droplet PCR for the kidney specimen. Our case highlights the importance of patient autopsies in an unfolding global pandemic and demonstrates the utility of molecular assays to diagnose SARS-CoV-2 post-mortem. SARS-CoV-2 infection during induction therapy may portend a fatal clinical outcome. We also suggest COVID-19 may be transmittable via renal transplant.
MeSH term(s)	Aged ; Autopsy ; COVID-19 ; Canada ; Humans ; Kidney Transplantation/adverse effects ; Male ; RNA, Viral/genetics ; Retrospective Studies ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Transplant Recipients
Chemical Substances	RNA, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-03-15
Publishing country	United States
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1111/ajt.16549
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