Our faculty research broadens the knowledge of kidney disease.

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Alexander Teumer, Yong Li, Sahar Ghasemi, Bram P. Prins, Matthias Wuttke, Tobias Hermle, Ayush Giri, Karsten B. Sieber, Chengxiang Qiu, Holger Kirsten, Adrienne Tin, Audrey Y. Chu, Nisha Bansal, Mary F. Feitosa, (...), Cristian Pattaro, Anna Köttgen

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension.

Apolipoprotein L1 Testing in African Americans: Involving the Community in Policy Discussions

Young B.A., Blacksher E., Cavanaugh K.L., Freedman B.I., Fullerton S.M., Kopp J.B., Umeukeje E.M., West K.M., Wilson J.G., Burke W.,  APOL1 Stakeholders Project

Apolipoprotein A1 (APOL1) gene variants occurring in people of West African descent contribute to the greater burden of kidney disease among African Americans. These variants are associated with increased risk of nondiabetic nephropathy, more rapid progression of chronic kidney disease, and shorter survival of donor kidneys after transplantation. However, only a minority of people with APOL1-associated risk develops kidney disease and specific clinical measures to address APOL1-associated risk are lacking. Given these uncertainties, we sought to engage members of the African American public in discussions with other stakeholders about the appropriate use of APOL1 testing.

Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice

Tomoaki Miyazaki, Sina A. Gharib, Yun-Wei A. Hsu, Katherine Xu, Pavlo Khodakivskyi, Akio Kobayashi, Jason Paragas, Alexander D. Klose, Kevin P. Francis, Elena Dubikovskaya, Patrick S. Page-McCaw, Jonathan Barasch, Neal Paragas
 

In highly heterogenous organs such as the kidney, associating pathophysiological changes such as generation of reactive oxygen species (ROS) with transcriptional signals at the cell-type level are challenging, if not impossible. Furthermore, monitoring these pathophysiological intercellular changes non-invasively and longitudinally has not been shown in the kidney. Here we present a coupled cell-specific image-guided transcriptomics approach to visualize ROS generation and associate it with gene expression changes in the injured kidney.

Differentiation of human kidney organoids from pluripotent stem cells

Cruz NM, Freedman BS

Organoid technology has great potential for kidney regeneration and has already been proven to be suitable for modeling kidney disease. However, the methodologies that are used for the generation of kidney organoids require expertise and can be daunting for the inexperienced. Here, we describe in detail a well-established and relatively simple method for the generation of human kidney organoids. We include notes on technical and design considerations for these experiments, and highlight key advantages and limitations of the system.

Cardiac Biomarkers and Risk of Atrial Fibrillation in Chronic Kidney Disease: The CRIC Study

Lamprea-Montealegre JA, Zelnick LR, Shlipak MG, Floyd JS, Anderson AH, He J, Christenson R, Seliger SL, Soliman EZ, Deo R, Ky B, Feldman HI, Kusek JW, deFilippi CR, Wolf MS, Shafi T, Go AS, Bansal N; CRIC Study Investigators

We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients.

Family Perceptions of Quality of End-of-Life Care for Veterans with Advanced CKD

Claire A. Richards, Chuan-Fen Liu, Paul L. Hebert, Mary Ersek, Melissa W. Wachterman, Lynn F. Reinke, Leslie L. Taylor, Ann M. O’Hare

Little is known about the quality of end-of-life care for patients with advanced CKD. We describe the relationship between patterns of end-of-life care and dialysis treatment with family-reported quality of end-of-life care in this population. We designed a retrospective observational study among a national cohort of 9993 veterans with advanced CKD who died in Department of Veterans Affairs facilities between 2009 and 2015. We used logistic regression to evaluate associations between patterns of end-of-life care and receipt of dialysis (no dialysis, acute dialysis, maintenance dialysis) with family-reported quality of end-of-life care.

Optimized nonviral gene delivery for primary urinary renal progenitor cells to enhance cell migration

Liu GW, Johnson SL, Jain R, Peeler DJ, Shankland SJ, Pun SH

Progressive loss of glomerular podocytes during kidney disease leads to irreversible kidney failure, and is exacerbated by the fact that podocytes are terminally differentiated epithelial cells and unable to proliferate. Regeneration of lost podocytes must therefore derive from nonpodocyte sources. Human urine-derived renal progenitor cells (uRPCs) are attractive podocyte progenitors for cell therapy applications due to their availability from patient urine and ability to migrate to injured glomeruli and differentiate into de novo podocytes after intravenous administration. Because gene delivery has emerged as an important strategy to augment the functionality and survival of cell therapies prior to injection, in this work we optimized nonviral gene delivery conditions (cell density, DNA dose, % FBS, and transfection material composition) to primary uRPCs.

Characteristics and Outcomes of Patients with Anti-Glomerular Basement Membrane Antibody Disease and Anti-Neutrophil Cytoplasmic Antibodies

 Percy G. Balderia*, Nicole Andeen, Jonathan A. Jefferson

It is unclear whether patients with Anti-Glomerular Basement Membrane (GBM) disease and Anti-Neutrophil Cytoplasmic Antibodies (ANCA), so called “Double-Positive” (DP), have a different clinical presentation and outcome compared to patients with anti-GBM antibody disease alone. This study describes the clinical and histologic characteristics as well as the patient and renal outcomes of DP patients at the University of Washington compared to patients with anti-GBM antibody disease alone.

APOL1 Kidney Risk Variants and Cardiovascular Disease: An Individual Participant Data Meta-Analysis

Morgan E. Grams, Aditya Surapaneni, Shoshana H. Ballew, Lawrence J. Appel, Eric Boerwinkle, L. Ebony Boulware, Teresa K. Chen, Josef Coresh, Mary Cushman, Jasmin Divers, Orlando M. Gutiérrez, Marguerite R. Irvin, Joachim H. Ix, Jeffrey B. Kopp, Lewis H. Kuller, Carl D. Langefeld, Michael S. Lipkowitz, Kenneth J. Mukamal, Solomon K. Musani, Rakhi P. Naik, Nicholas M. Pajewski, Carmen A. Peralta, Adrienne Tin, Christina L. Wassel, James G. Wilson, Cheryl A. Winkler, Bessie A. Young, Neil A. Zakai, Barry I. Freedman

Two variations in the apo L1 gene (APOL1) common in West African and African American populations are strongly associated with development of ESKD. Studies evaluating whether these APOL1 kidney-risk variants increase the risk of cardiovascular disease have had inconsistent results. The authors conducted a two-stage meta-analysis of individual participant data from eight large cohorts with data on APOL1 kidney-risk variants. The analysis included 21,305 blacks and assessed the relationship between APOL1 kidney-risk variants and several types of cardiovascular disease and death.

ANCA-Associated Vasculitis: Core Curriculum 2020

Geetha, D., Jefferson, J.A.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels and the presence of circulating ANCA. This article in AJKD’s Core Curriculum in Nephrology series provides a detailed review of the epidemiology, pathogenesis, diagnosis, and advances in the management of AAV.