Our research broadens the knowledge of kidney disease.

Vitamin D in human serum and adipose tissue after supplementation

Cora M Best, Devon V Riley, Thomas J Laha, Hannah Pflaum, Leila R Zelnick, Simon Hsu, Kenneth E Thummel, Karen E Foster-Schubert, Jessica N Kuzma, Gail Cromer, Ilona Larson, Derek K Hagman, Kelly Heshelman, Mario Kratz, Ian H de Boer, Andrew N Hoofnagle

Vitamin D occurs in 2 main forms, vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol), and is an essential precursor to the steroid hormone 1,25-dihydroxyvitamin D [1,25(OH)2D]. Humans produce vitamin D3 in the epidermis upon exposure to UVB light and consume both forms (D3 and D2) in foods, beverages, and dietary supplements. Typical daily input from each of these routes and how this varies between individuals are unknown.

Integrating Patient Priorities with Science by Community Engagement in the Kidney Precision Medicine Project

Katherine R. Tuttle, Richard Knight, Paul S. Appelbaum, Tanima Arora, Shweta Bansal, Jack Bebiak, Keith Brown, Catherine Campbell, Leslie Cooperman, Celia P. Corona-Villalobos, Ashveena Dighe, Ian H. de Boer, Daniel E. Hall, Nichole Jefferson, Stacey Jolly, Asra Kermani, Simon C. Lee, Karla Mehl, Raghavan Murugan, Glenda V. Roberts, Sylvia E. Rosas, Jonathan Himmelfarb, R. Tyler Miller and for the Kidney Precision Medicine Project

The Kidney Precision Medicine Project (KPMP) is a multisite study designed to improve understanding of CKD attributed to diabetes or hypertension and AKI by performing protocol-driven kidney biopsies. Study participants and their kidney tissue samples undergo state-of-the-art deep phenotyping using advanced molecular, imaging, and data analytical methods. Few patients participate in research design or concepts for discovery science. A major goal of the KPMP is to include patients as equal partners to inform the research for clinically relevant benefit. The purpose of this report is to describe patient and community engagement and the value they bring to the KPMP.

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Mathias Gorski, Bettina Jung, Yong Li, Pamela R Matias-Garcia, Matthias Wuttke, Stefan Coassin, Chris H L Thio, Marcus E Kleber, Thomas W Winkler, Veronika Wanner, Jin-Fang Chai, Audrey Y Chu, Massimiliano Cocca, Mary F Feitosa, Sahar Ghasemi, Anselm Hoppmann, Katrin Horn, Man Li, Teresa Nutile, Markus Scholz, Karsten B Sieber, Alexander Teumer, Adrienne Tin, Judy Wang, Bamidele O Tayo, Tarunveer S Ahluwalia, Peter Almgren, Stephan J L Bakker, Bernhard Banas, Nisha Bansal, Mary L Biggs, Eric Boerwinkle, Erwin P Bottinger, Hermann Brenner , Robert J Carroll, et al...

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (“CKDi25”; encompassing 19,901 cases, 175,244 controls).

Prediction of Kidney Drug Clearance: A Comparison of Tubular Secretory Clearance and Glomerular Filtration Rate

Yan Chen, Leila R. Zelnick, Andrew N. Hoofnagle, Catherine K. Yeung, Laura M. Shireman, Brian Phillips, Calder C. Brauchla, Ian de Boer, Linda Manahan, Susan R. Heckbert, Jonathan Himmelfarb, Bryan R. Kestenbaum

Although proximal tubular secretion is the primary mechanism of kidney drug elimination, kidney drug dosing strategies are on the basis of eGFR. In a study of 54 participants with or without CKD, measurements of tubular secretory clearance of endogenous secretory solutes predicted the elimination of avidly secreted medications, furosemide and penciclovir. However, GFR’s predictive accuracy (measured by iohexol clearance) resembled that of the secretory solute clearances for predicting furosemide and penciclovir clearance, and the addition of secretory solute clearances yielded only small improvements in predictive accuracy. These findings demonstrate that secretory clearance measurements predict kidney drug elimination but also suggest a tight linkage between GFR and tubular secretory clearance in stable outpatients. This provides some reassurance that GFR is a useful surrogate for secretory drug clearance for drug dosing in such individuals.

Thematic Analysis of the Health Records of a National Sample of US Veterans With Advanced Kidney Disease Evaluated for Transplant

Catherine R. Butler, Aaron Wightman, Claire A. Richards, Ryan S. Laundry, Janelle S. Taylor, Paul L. Hebert, Chuan-Fen Liu, Ann M. O’Hare

Question: What types of clinical care are involved in the kidney transplant evaluation process in real-world clinical settings? Findings: In this qualitative study of the electronic health records of 211 US veterans with advanced kidney disease who were referred for kidney transplant evaluation, 4 dominant themes were identified describing clinical care during the evaluation process: far-reaching and inflexible medical evaluation, psychosocial valuation, surveillance over compliance, and disempowerment and lack of transparency. Meaning: In this study, clinician documentation in the medical record indicated that, to be considered for a kidney transplant, patients were required to participate in a rigid, demanding, and opaque evaluation process over which they and their local clinicians had little control.

Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients

Michael E. Brier, Jessica R. Gooding, James M. Harrington, Jason P. Burgess, Susan L. McRitchie, Xiaolan Zhang, Brad H. Rovin, Jon B. Klein, Jonathan Himmelfarb, Susan J. Sumner, Michael L. Merchant 

Alterations in hemodialysis patients’ serum trace metals have been documented. Early studies addressing associations levels of serum trace metals with erythropoietic responses and/or hematocrit generated mixed results. These studies were conducted prior to current approaches for erythropoiesis stimulating agent (ESA) drug dosing guidelines or without consideration of inflammation markers (e.g. hepcidin) important for regulation of iron availability. This study sought to determine if the serum trace metal concentrations of incident or chronic hemodialysis patients associated with the observed ESA response variability and with consideration to ESA dose response, hepcidin, and high sensitivity C-reactive protein levels.

Burden and Cost of Caring for US Veterans With CKD: Initial Findings From the VA Renal Information System (VA-REINS)

Saran, R., Pearson, A., Tilea, A., Shahinian, V., Bragg-Gresham, J., Heung, M., Hutton, D.W., Steffick, D., Zheng, K., Morgenstern, H., Gillespie, B.W., Leichtman, A., Young, E., O'Hare, A.M., Fischer, M., Hotchkiss, J., Siew, E., Hynes, D., Fried, L., Balkovetz, D., Sovern, K., Liu, C.-F., Crowley, S., Crowley, Fischer, Hynes, O'Hare, Fried, Hickam, E., Balkovetz, Hotchkiss, Liu, Sovern, Ferguson, R., Rodriguez, R., Cupples, S.,, Daniels, S.M., Loftus, S., Ashei, A., Francis, J., Graham, G., Lowe-Bey, F., Gunnar, W., Varga, J.H., Trautman, T., Brown, J., Rios, F., VA-REINS Steering Committee, VA Advisory Board 

Kidney disease is a common, complex, costly, and life-limiting condition. Most kidney disease registries or information systems have been limited to single institutions or regions. A national US Department of Veterans Affairs (VA) Renal Information System (VA-REINS) was recently developed. We describe its creation and present key initial findings related to chronic kidney disease (CKD) without kidney replacement therapy (KRT). Data from the VA’s Corporate Data Warehouse were processed and linked with national Medicare data for patients with CKD receiving KRT. Operational definitions for VA user, CKD, acute kidney injury, and kidney failure were developed.

Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review

Molly Murton, Danielle Goff-Leggett, Anna Bobrowska, Juan Jose Garcia Sanchez, Glen James, Eric Wittbrodt, Stephen Nolan, Elisabeth Sörstadius, Roberto Pecoits-Filho, Katherine Tuttle 

The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines recommend classifying patients by glomerular filtration rate (GFR) and albuminuria to predict chronic kidney disease (CKD) prognosis. The aim of this systematic review was to explore the epidemiological burden of CKD stratified by the KDIGO 2012 categories. MEDLINE® and Embase were searched for observational studies of patients with CKD with results stratified according to the KDIGO 2012 classification. Investigated outcomes were prevalence, incidence, and risk factors and complications of CKD, including mortality.

Incretin drugs in diabetic kidney disease: biological mechanisms and clinical evidence

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

As the prevalence of diabetes continues to climb, the number of individuals living with diabetic complications will reach an unprecedented magnitude. The emergence of new glucose-lowering agents — sodium–glucose cotransporter 2 inhibitors and incretin therapies — has markedly changed the treatment landscape of type 2 diabetes mellitus. In addition to effectively lowering glucose, incretin drugs, which include glucagon-like peptide 1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, can also reduce blood pressure, body weight, the risk of developing or worsening chronic kidney disease and/or atherosclerotic cardiovascular events, and the risk of death. Although kidney disease events have thus far been secondary outcomes in clinical trials, an ongoing phase III trial in patients with diabetic kidney disease will test the effect of a GLP1R agonist on a primary kidney disease outcome.

Cardio-Renal-Metabolic Care Models: Toward Achieving Effective Interdisciplinary Care

Janani Rangaswami, Katherine Tuttle, Muthiah Vaduganathan

The highly interdependent relationship between the heart and kidneys was described as early as in 1836 by Sir Richard Bright, who identified cardiac structural abnormalities in a series of patients with advanced chronic kidney disease.1 Around the same time in 1835, French chemists isolated phlorizin, a natural, nonselective inhibitor of SGLT1 (sodium glucose co-transporter 1) and SGLT2, as part of early attempts to create an animal model for diabetes. Since then, despite major developments in cardiorenal and metabolic medicine, there has been a relative chasm between availability of new approaches to optimize cardiovascular and kidney outcomes and their implementation in clinical practice. With the advent of the sodium glucose cotransporter 2 inhibitors (SGLT2is) and the glucagon-like receptor-1 agonists and other new cardiorenal protective therapies, the spheres of cardio-nephrology and metabolic medicine have converged in unprecedented ways with the potential for population-level improvements in multidomain health.