Our research broadens the knowledge of kidney disease.

Innovating and invigorating the clinical trial infrastructure for glomerular diseases

Laura Barisoni, Jonathan Barratt, Kirk Campbell, Lauren Eva, Barbara S. Gillespie, Debbie Gipson, Tobias Huber, Meg Jardine, Elaine Kamil, Matthias Kretzler, Lauren Lee, Elena Levtchenk, Ali Poyan Mehr, Patrick H. Nachman, Jun Oh, Moin Saleem, Stuart J. Shankland, Kimberly Smith, Irv Smokler, William Smoyer, Josh Tarnoff, Aliza Thompson, Howard Trachtman, Suneel Udani, Marina Vivarelli, Patrick Walker, Melissa West, Brad H. Rovin

The current treatment of glomerular diseases is based largely on expert opinion, and small clinical studies from many years ago. Thankfully, there has been recent intense interest from the pharmaceutical industry in bringing drugs for glomerular diseases to trial, despite past failures. This is due, in part, to research efforts that have increasingly revealed molecular mechanisms of disease, facilitating the development of targeted therapeutics, as well as work undertaken by the larger nephrology community to support the use of surrogate end points, such as proteinuria, as efficacy end points in clinical trials of glomerular disease. Such efforts highlight how effective data sharing can greatly facilitate drug development for rare diseases.

Patient perspectives and involvement in precision medicine research

Katherine R. Tuttle, Jack Bebiak, Keith Brown, Catherine Campbell, Ashveena Dighe, Lynda Hyashi, Nichole Jefferson, Glenda V. Roberts, Christy Stutzke, Richard Knight, for the Kidney Precision Medicine Project, including  Asheveena Dighe, Ian de Boer, Jonathan Himmelfarb, Stuart Shankland

A lack of patient perspectives and involvement in the development of scientific inquiries at the discovery phase has been a major barrier to clinical translation of knowledge that advances patient care. Although patient partners have recently become involved in the clinical phase of nephrology research, they were largely absent in the discovery phase until KPMP. To conduct scientific inquiry guided toward clinically meaningful benefit and build public trust, a major goal of the KPMP from its inception has been inclusion of patients as equal partners for priority setting, study design and conduct, and dissemination of findings.

Clinical Evidence and Proposed Mechanisms for Cardiovascular and Kidney Benefits from Glucagon-like Peptide-1 Receptor Agonists

Emily J Cox, Radica Z Alicic, Joshua J Neumiller, Katherine R Tuttle

Coincident with the diabetes pandemic, diabetic complications—especially kidney disease and cardiovascular disease—have become large-scale public health problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, a newer class of anti-hyperglycemic therapies, represent a major advance in the treatment of these complications in type 2 diabetes. In addition to effectively treating hyperglycemia, they have a low intrinsic risk of hypoglycemia and promote reductions in blood pressure and body weight. Furthermore, in clinical trials of GLP-1 receptor agonists, the risks of cardiovascular events and new or worsening diabetic kidney disease (DKD) were reduced. As a result, guidelines from major professional organizations now recommend GLP-1 receptor agonists for patients with type 2 diabetes, to reduce the risk of atherosclerotic cardiovascular disease or DKD.

Facility-Level Variation in Dialysis Use and Mortality Among Older Veterans With Incident Kidney Failure

Christina Bradshaw, I-Chun Thomas, Maria E. Montez-Rath, Karl A. Lorenz, Steven M. Asch, John T. Leppert, Virginia Wang, Ann M. O’Hare, Manjula Kurella Tamura

Question - To what extent do dialysis use and mortality vary among older adults with incident kidney failure, and are these variations associated with patient or facility factors? Findings - In this cohort study of 8695 older adults with incident kidney failure, dialysis use varied widely across Veterans Affairs facilities with minimal variation in mortality. Most of the variation was associated with patient characteristics, and no correlation was found between the facility-level rate of dialysis use and mortality. Meaning - Results of this study suggest that there is marked variation in dialysis use practices for older adults across Veterans Affairs facilities.

Social Determinants of Health and Race Disparities in Kidney Transplant

Hannah Wesselman, Christopher Graham Ford, Yuridia Leyva, Xingyuan Li, Chung-Chou H Chang, Mary Amanda Dew, Kellee Kendall, Emilee Croswell, John R Pleis, Yue Harn Ng, Mark L Unruh, Ron Shapiro, Larissa Myaskovsky

Black patients have a higher incidence of kidney failure but lower rate of deceased- and living-donor kidney transplantation compared with White patients, even after taking differences in comorbidities into account. We assessed whether social determinants of health (e.g., demographics, cultural, psychosocial, knowledge factors) could account for race differences in receiving deceased- and living-donor kidney transplantation.

ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention

Johann Morelle, Joanna Stachowska-Pietka, Carl Öberg, Liliana Gadola, Vincenzo La Milia, Zanzhe Yu, Mark Lambie, Rajnish Mehrotra, Javier de Arteaga, Simon Davies 

Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function.

Multiphoton-Guided Creation of Complex Organ-Specific Microvasculature.

Samuel G. Rayner, Caitlin C. Howard, Christian J. Mandrycky, Stefan Stamenkovic, Jonathan Himmelfarb, Andy Y. Shih, Ying Zheng

Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of the native microvasculature. Multiphoton ablation has emerged as a promising technique for fabrication of microvascular structures with high resolution and full 3D control, but cellularization and perfusion of complex capillary‐scale structures has remained challenging. Here, multiphoton ablation combined with guided endothelial cell growth from pre‐formed microvessels is used to successfully create perfusable and cellularized organ‐specific microvascular structures at anatomic scale within collagen hydrogels.

The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study

Ian H. de Boer, David K. Prince, Kayleen Williams, Norrina B. Allen, Gregory L. Burke, Andrew N. Hoofnagle, Simon Hsu, Xiaohui Li, Kiang J. Liu, Robyn L. McClelland, Erin D. Michos, Bruce M. Psaty, Steven J. Shea, Kenneth M. Rice. Jerome I. Rotter, David S. Siscovick, Russell P. Tracy, Karol E. Watson, Bryan R. Kestenbaum

The INdividual response to VITamin D (INVITe) trial was a randomized, placebo-controlled, parallel group trial of vitamin D3 supplementation (2000 IU daily) designed to determine clinical and genetic characteristics that modify the response to vitamin D supplementation. To enhance internal and external validity and reduce cost, the INVITe trial was nested within the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective observational cohort study. The INVITe trial enrolled a community-based population of 666 racially and ethnically diverse participants from January 2017 to April 2019. This represents 30% of 2210 MESA participants approached for screening, and 96% of those found to be eligible.

Biomarkers of inflammation and repair in kidney disease progression

Jeremy Puthumana, Heather Thiessen-Philbrook, Leyuan Xu, Steven G Coca, Amit X Garg, Jonathan Himmelfarb, Pavan K Bhatraju, T Alp Ikizler, Edward D Siew, Lorraine B Ware, Kathleen D Liu, Alan S Go , James S Kaufman, Paul L Kimmel, Vernon M Chinchilli, Lloyd G Cantley, Chirag R Parikh

Acute kidney injury and chronic kidney disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term progression to kidney failure is required. We enrolled 1538 hospitalized patients in a multicenter, prospective cohort study. Monocyte chemoattractant protein 1 (MCP-1/CCL2), uromodulin (UMOD), and YKL-40 (CHI3L1) were measured in urine samples collected during outpatient follow-up at 3 months. We followed patients for a median of 4.3 years and assessed the relationship between biomarker levels and changes in estimated glomerular filtration rate (eGFR) over time and the development of a composite kidney outcome (CKD incidence, CKD progression, or end-stage renal disease). We paired these clinical studies with investigations in mouse models of renal atrophy and renal repair to further understand the molecular basis of these markers in kidney disease progression.

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction

Jasleen Ghuman, Xuan Cai, Ravi B Patel, Sadiya S Khan, Jonathan Hecktman, Margaret M Redfield, Gregory Lewis, Sanjiv J Shah, Myles Wolf, Tamara Isakova, Rupal Mehta

Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.