Our faculty research broadens the knowledge of kidney disease.

Differential effects of phosphate binders on vitamin D metabolism in chronic kidney disease.

C. Ginsberg, L.R. Zelnick, G.A. Block, G.M. Chertow, M.Chonchol, A. Hoofnagle, B. Kestenbaum, I.H. de Boer

 

Phosphate binders are commonly used in the treatment of patients with hyperphosphatemia. While phosphate binders are used to lower phosphate, the effects of specific phosphate binder types on vitamin D metabolism are unknown.

Association of Tubular Solute Clearance with Symptom Burden in Incident Peritoneal Dialysis.

Ke Wang, Michelle Nguyen, Yan Chen, Andrew N. Hoofnagle, Jessica O. Becker, Leila R. Zelnick, John Kundzins, Anne Goodling, Jonathan Himmelfarb, Bryan Kestenmbaum

 

Residual kidney function is important to the health and wellbeing of patients with ESKD. We tested whether the kidney clearances of proximal tubular secretory solutes are associated with burden of uremic and heart failure symptoms among patients on peritoneal dialysis with residual kidney function.

Impaired skeletal muscle mitochondrial bioenergetics and physical performance in chronic kidney disease

B. Kestenmaum, J. Gamboa S. Liu, A.S. Ali, E. Shankland, T. Jue, C. Giulivi, L.R. Smith, J. Himmelfarb, I. de Boer, K. Conley, B. Roshanravan

The maintenance of functional independence is the top priority of patients with chronic kidney disease (CKD). Defects in mitochondrial energetics may compromise physical performance and independence. We investigated associations of the presence and severity of kidney disease with in vivo muscle energetics and the association of muscle energetics with physical performance.

Deregulation of Neuro-Developmental Genes and Primary Cilium Cytoskeleton Anomalies in iPSC Retinal Sheets from Human Syndromic Ciliopathies

Barabino, A., Flamier, A., Hanna, R., Héon, E., Freedman, B.S., Bernier, G.

We describe the generation and molecular characterization of human induced pluripotent stem cell (iPSC)-derived retinal sheets (RSs) from controls, and MKS (TMEM67) and BBS (BBS10) cases. MKS and BBS RSs displayed significant common alterations in the expression of hundreds of developmental genes and members of the WNT and BMP pathways.

High levels of dd-cfDNA identify patients with TCMR 1A and borderline allograft rejection at elevated risk of graft injury

Stites, E., Kumar, D., Olaitan, O., John Swanson, S., Leca, N., Weir, M., Bromberg, J., Melancon, J., Agha, I., Fattah, H., Alhamad, T., Qazi, Y., Wiseman, A., Gupta, G.

The clinical importance of subclinical, early T cell–mediated rejection (Banff TCMR 1A and borderline lesions) remains unclear, due, in part to the fact that histologic lesions used to characterize early TCMR can be nonspecific. Donor‐derived cell‐free DNA (dd‐cfDNA) is an important molecular marker of active graft injury. Over a study period from June 2017 to May 2019, we assessed clinical outcomes in 79 patients diagnosed with TCMR 1A/borderline rejection across 11 US centers with a simultaneous measurement of dd‐cfDNA.

Clinician Engagement in Research as a Path Toward the Learning Health System: A Regional Survey Across the Northwestern United States

Elizabeth L Ciemins, Brenda L Mollis, Jeannine M Brant, Laurie A Hassell, Sandra Albritton, Paul Amoroso, Angela Lloyd, Jodi M Smith, Bethann M Pflugeisen, Katherine R Tuttle, Laura-Mae Baldwin 

Increased research engagement of frontline, community-based clinicians could result in greater research relevancy, increased likelihood of implementation into practice, and improved health care for patients. Establishment of learning health systems within health-care organizations may facilitate this process. In 2016, the U.S. Northwest Participant and Clinical Interactions Network conducted a region-wide survey in four community-based health systems to identify barriers to clinician involvement in research and understand clinician interest and levels of engagement.

Web Exclusive. Annals On Call - The Good, the Bad, and the Ugly-the Sequel: GLP1 Agonists

Robert M Centor, Katherine R Tuttle 

Dr. Centor discusses the role of glucagon-like peptide-1 receptor agonists in the treatment of patients with type 2 diabetes with Dr. Tuttle of Providence Health Care and University of Washington School of Medicine.

Experiences of US Nephrologists in the Delivery of Conservative Care to Patients With Advanced Kidney Disease: A National Qualitative Study

Susan P.Y. Wong, Saritha Boyapati, Ruth A. Engelberg, Bjorg Thorsteinsdottir, Janelle S.Taylor, Ann M.O’Hare

It is relatively unusual for US patients with advanced chronic kidney disease (CKD) to forgo initiation of maintenance dialysis. Our objective was to describe practice approaches of US nephrologists who have provided conservative care for members of this population. A qualitative study using semi-structured interviews.

Glycerol-3-phosphate Is a FGF23 Regulator Derived From the Injured Kidney

Petra Simic, Wondong Kim, Wen Zhou, Kerry A Pierce, Wenhan Chang, David B Sykes, Najihah B Aziz, Sammy Elmariah, Debby Ngo, Paola Divieti Pajevic, Nicolas Govea, Bryan R Kestenbaum, Ian H de Boer, Zhiqiang Cheng, Marta Christov, Jerold Chun, David E Leaf, Sushrut S Waikar, Andrew M Tager, Robert E Gerszten, Ravi I Thadhani, Clary B Clish, Harald Jüppner, Marc N Wein, Eugene P Rhee

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin D3 [1,25(OH)2D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis.

Evidence-based Treatment of Hyperglycemia With Incretin Therapies in Patients With Type 2 Diabetes Mellitus and Advanced Chronic Kidney Disease

Katherine R. Tuttle, Janet B. McGill

Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). The prevalence of CKD is growing in parallel with the rising number of patients with T2DM globally. This review discusses the role of incretin therapies in the management of these patients. Since the presence of advanced CKD in patients with T2DM is associated with a markedly elevated risk of cardiovascular disease (CVD), treatment strategies must include the reduction of both CKD and CVD risks because death, particularly of cardiovascular causes, is more likely than progression to end‐stage kidney disease.