ASN Kidney Week 2022: Presentations from Yale Nephrology

The American Society of Nephrology (ASN) Kidney Week 2022 Annual Meeting will take place in Orlando, Fla. from November 3-6. The meeting will bring together kidney professionals from around the globe to exchange new research findings, learn about the latest clinical and scientific advances in the field, and engage in exciting discussion with leading international experts.

Faculty members and trainees at Yale School of Medicine (YSM) within the Section of Nephrology will contribute to sessions throughout the week, sharing their medical expertise and novel research findings, which culminates with Mark Perazella, MD, winning the Robert G. Narins Award for his lifetime achievements in education. The Narins Award is the society’s highest honor.

Highlights of Yale Nephrology sessions, abstracts, and poster presentations are listed below. For the program of events, visit the program page. For more information, visit ASN’s Kidney Week 2022 website.

Sessions:

ASN Kidney Week Pre-Meeting: Renal Physiology: Structure and Function in Kidney Health and Disease

Tubule Homeostasis

Lloyd Cantley, MD, speaker

The Renal Interstitium

Dennis G. Moledina, MD, PhD, speaker

ASN Kidney Week Early Program: Critical Care Nephrology: Update 2022

Mark A. Perazella, MD, co-chair

Biomarker for Acute Kidney Injury

Dennis G. Moledina, MD, PhD, speaker

ASN Kidney Week Meeting: Untangling Determinants of AKI Through an -Omics Approach, Including the Robert W. Schrier, MD, Endowed Lectureship: Integrating Analysis of Animal Models and Human Biopsies to Better Understand AKI

Lloyd Cantley, MD, speaker

ASN Kidney Week Meeting: Spatial Analysis of the Kidney: Imaging Mass Cytometry of the Human Kidney

Lloyd Cantley, MD, speaker

ASN Kidney Week Meeting: Clinical Practice Session: Glomerular Diseases and Cancer: Cause or Effect?

Mark A. Perazella, MD, moderator

Posters & Abstracts:

Automated, Medication-Targeted Alerts on AKI Outcomes: A Multi-Center Randomized, Controlled Trial

F. Perry Wilson, YSM; Yu Yamamoto, YSM; Melissa Martin, YSM; Lama Ghazi, YSM; Dennis G. Moledina, YSM; Chirag R. Parikh, Johns Hopkins University, Baltimore, Md.; Sherry Mansour, YSM; Jason H. Greenberg, YSM; Ugochukwu C. Ugwuowo, YSM.

Researchers conducted a pragmatic, open-label, parallel group, randomized controlled trial to determine whether or not prompt detection of acute kidney injury (AKI) with discontinuation of relevant medications improves clinical outcomes. Results will be presented live at the High-Impact Clinical Trials Session at ASN Kidney Week on November 4.

Inhibition of Podocyte Calpain-2 Is Critical for Glomerular Filtration Barrier Maintenance by Stabilizing the Cytoskeleton

Kailin Guo, YSM; Patricia Bunda, YSM; Xuefei Tian, YSM; Gabriel Lerner, YSM; Shuta Ishibe, YSM.

Previous observations of elevated levels of calpain (a calcium-activated protein) activity in tissue and urine samples collected from proteinuric kidney disease patients and the protective effect of the simultaneous inhibition of both calpain-1 and calpain-2 in mouse models have led researchers to seek to determine which calpain (1 or 2) is primarily involved in this phenomenon. Using knockout mice, the study team found that the inhibition of calpain-2 demonstrated mitigation of proteinuria and histological changes upon injection of nephrotoxic serum (NTS) when compared to wild-type mice, indicating the inhibition of calpain-2 may help in stabilizing the cytoskeleton of podocytes (specialized epithelial cells in the kidney) and thus maintaining the glomerular filtration barrier.

Otological Manifestations in ANCA-Negative Pauci-Immune Vasculitis: A Compelling Clue When Serologies Are Negative

Megan L. Baker, YSM; Jeffrey M. Turner, YSM.

The authors outline a challenging case of ANCA-negative pauci-immune vasculitis in which bilateral sensorineural hearing loss was the primary presenting symptom. The rest of the workup at the time of onset was inconclusive, ultimately leading to a delay in recognition and treatment. The case highlights the importance of maintaining a higher suspicion for pauci-immune vasculitis as a diagnosis when evaluating a patient with otological manifestations and acute kidney injury (AKI), even when serologies are negative.

A Novel Role of APOL1 Risk-Alleles in T-Cell Activation and Focal Segmental Glomerulosclerosis

John F. Pell, YSM; Anand Reghuvaran, YSM; Soichiro Nagata, YSM.; Khadija Banu, YSM; Hongmei Shi, YSM; Irene Chernova, YSM; Shuta Ishibe, YSM; Madhav C. Menon, YSM.

Researchers examined the immunological role of apolipoprotein-L1 (APOL1), a gene underlying the disease process of focal segmental glomerulosclerosis (FSGS). The study involved the use of mouse models to determine that activated CD8+ T cells, key parts of the human immune system, may be an important source of IFNγ in G1- and G2 (variants of APOL1) risk-genotype-BAC (bacterial artificial chromosomes)-transgenic mice, causing FSGS. Importantly, the work suggests a novel role for FSGS-associated APOL1 risk alleles (G1 and G2) in T-cell activation.

Collagenofibrotic Glomerulopathy in a Patient With Waldenstrom Macroglobulinemia

Deepthi Gunasekaran, YSM; Gilbert W. Moeckel, YSM; Anushree C. Shirali, YSM.

Researchers presented an unusual case of collagenofibrotic glomerulopathy (CG) in the setting of long-standing diabetes mellitus (DM) and malignancy. The case highlights a patient age outside previously reported cases of the disease and draws attention to the unique sub-nephrotic proteinuria that can accompany the disease.

AA Amyloidosis Presenting With Renal Amyloidoma

Deepthi Gunasekaran, YSM; Gilbert W. Moeckel, YSM; Randy L. Luciano, YSM.

The authors present a unique case of systemic amyloidosis with a renal mass showing biopsy-proven AA amyloidosis. The case highlights the unusual presentation of renal amyloidoma formation by a focal, tumor-like infiltrative process and suggests that radiographic findings can play an important role in the workup of amyloidosis.

Participant Experience in The Kidney Precision Medicine Project

Angela M. Victoria Castro, YSM; Celia P. Corona Villalobos, Johns Hopkins University, Baltimore, Md.; Natalya Sarkisova, University of Washington, Seattle, Wash.; Kristina N. Blank, University of Washington, Seattle, Wash.; Ashveena Dighe, University of Washington, Seattle, Wash.; Glenda V. Roberts, University of Washington, Seattle, Wash.; Alan Y. Xu, Johns Hopkins University, Baltimore, Md.; Victoria Blanc, University of Michigan, Ann Arbor, Mich.; Michael P. Rose, University of Michigan, Ann Arbor, Mich.; Ian H. de Boer, University of Washington, Seattle, Wash.; Jonathan Himmelfarb, University of Washington, Seattle, Wash.; Katherine R. Tuttle, University of Washington, Seattle, Wash.

Researchers studied the patient experience in the Kidney Precision Medicine Project (KPMP), a multi-year project designed to understand and discover new ways to treat chronic kidney disease (CKD) and acute kidney injury (AKI). The study examined motivation for research participation, understanding of informed consent, patient satisfaction, and perception of personal impact. Ultimately results from the 28-day survey indicated patients’ motivation is driven primarily by altruism, and that patients report a positive impact of the study in their daily lives, despite some physical and mental challenges associated with the biopsy procedure.

Urine Proteomic Analysis Identifies Interferon Gamma Downstream Chemokine CXCL-9 as a Biomarker for Diagnosis of Acute Interstitial Nephritis

Dennis G. Moledina, YSM; Wassim Obeid, Johns Hopkins University, Baltimore, Md.; Meghan E. Sise, Massachusetts General Hospital, Boston, Mass.; Ivy A. Rosales, Massachusetts General Hospital, Boston, Mass.; Rex Neal Smith, Massachusetts General Hospital, Boston, Mass.; Robert B. Colvin, Massachusetts General Hospital, Boston, Mass.; Michael Benjamin Kuperman, Arkana Laboratories, Little Rock, Ark.; Michael Kashgarian, YSM; Gilbert W. Moeckel, YSM; F. Perry Wilson, YSM; Chirag R. Parikh, Johns Hopkins University, Baltimore, Md.

A prospective study examined patients who underwent a kidney biopsy for evaluation of acute kidney disease with confirmed histological diagnosis, seeking to identify additional accurate biomarkers for acute interstitial nephritis (AIN). Through urine proteomics analysis, researchers identified CXCL-9 as a novel biomarker for AIN diagnosis, validating the association using immunoassay and kidney tissue expression data.

Safety and Adequacy of Kidney Biopsy Procedure in Patients with Obesity

Long Qian, YSM; Jason Weinstein, YSM; Hannah Melchinger, YSM; David Hu, Johns Hopkins University, Baltimore, Md.; Steven Menez, Johns Hopkins University, Baltimore, Md.; Heather Thiessen-Philbrook, Johns Hopkins University, Baltimore, Md.; Randy Luciano, YSM; Mark A. Perazella, YSM; Melissa M. Shaw, YSM; Chirag R. Parikh, Johns Hopkins University, Baltimore, Md.; F. Perry Wilson, YSM; Dennis G. Moledina, YSM.

The authors conducted a study of participants from the Yale kidney biopsy cohort to compare the safety and adequacy of kidney biopsy procedures between obese and non-obese individuals. Results showed that obese individuals were more likely to have fewer glomeruli available for diagnosis, but did not demonstrate a greater risk of post-biopsy hematocrit drop than those without obesity.

The Ion Transporter Na+-K+-ATPase Enables Pathological B cell Survival in the Kidney Microenvironment of Lupus Nephritis

Irene Chernova, YSM; Joseph Craft, YSM.

Researchers used lupus-prone mouse models to determine the effects of sodium-immune cell interactions on tissue injury in autoimmune disease and the mechanisms used by infiltrating lymphocytes to survive the high sodium environment of the kidney. The work was done by studying the response of B cells to sodium stress in vitro and in vivo though cell culture and water deprivation experiments. The authors ultimately identified the Na+-K+-ATPase ion transporter as a possible target for lupus nephritis therapy, discovering a tissue adaption response to sodium stress by kidney-infiltrating B cells in lupus.

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