Our faculty research broadens the knowledge of kidney disease.

Tubular Secretory Clearance is Associated with Whole-Body Insulin Clearance

Matthew P Huber, Leila R Zelnick, Kristina M Utzschneider, Steven E Kahn, Ian H de Boer, Bryan R Kestenbaum

The kidneys eliminate insulin via glomerular and peritubular mechanisms; consequently, the kidney contribution to insulin clearance may be underestimated by the glomerular filtration rate (GFR) alone. Objective: To determine associations of tubular secretory clearance with whole-body insulin clearance and sensitivity in a dedicated study of glucose and insulin metabolism.

Continuous Glucose Monitoring and Use of Alternative Markers To Assess Glycemia in Chronic Kidney Disease

Leila R Zelnick, Zona O Batacchi, Iram Ahmad, Ashveena Dighe, Randie R Little, Dace L Trence, Irl B Hirsch, Ian H de Boer

In chronic kidney disease, glycated albumin and fructosamine have been postulated to be better biomarkers of glycemic control than HbA1c. We evaluated the accuracy, variability, and covariate bias of three biomarkers (HbA1c, glycated albumin, and fructosamine) compared with continuous glucose monitoring (CGM)–derived measurement of glycemia across estimated glomerular filtration rate (eGFR) in type 2 diabetes.

Parietal epithelial cell differentiation to a podocyte fate in the aged mouse kidney

Natalya V. Kaverina, Diana G. Eng, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland

Healthy aging is typified by a progressive and absolute loss of podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a podocyte fate with aging, dual reporter PEC-rtTA|LC1|tdTomato|Nphs1-FLPo|FRT-EGFP mice were generated. PECs were inducibly labeled with a tdTomato reporter, and podocytes were constitutively labeled with an EGFP reporter. With advancing age (14 and 24 months) glomeruli in the juxta-medullary cortex (JMC) were more severely injured than those in the outer cortex (OC). In aged mice (24m), injured glomeruli with lower podocyte number (41% decrease), showed more PEC migration and differentiation to a podocyte fate than mildly injured or healthy glomeruli.

Cardiopulmonary Resuscitation Preferences of People Receiving Dialysis

Bernacki, G.M., Engelberg, R.A., Curtis, J.R., Kurella Tamura, M., Brumback, L.C., Lavallee, D.C, Vig, E.K., O'Hare, A.M.

Importance: Whether the cardiopulmonary resuscitation (CPR) preferences of patients receiving dialysis align with their values and other aspects of end-of-life care is not known. Objective: To describe the CPR preferences of patients receiving dialysis and how these preferences are associated with their responses to questions about other aspects of end-of-life care.

Treating Home Versus Predialysis Blood Pressure Among In-Center Hemodialysis Patients: A Pilot Randomized Trial

Nisha Bansal, David V Glidden, Rajnish Mehrotra, Raymond R Townsend, Jordana Cohen, Lori Linke, Farshad Palad, Hannah Larson, Chi-Yuan Hsu

Observational studies have reported a U-shaped association between pre-dialysis blood pressure (BP) and death. In contrast, a linear association between out-of-dialysis unit BP has been reported. Home BP may be a better target for treatment. To test the feasibility of this approach, we conducted a pilot trial of treating home vs. pre-dialysis BP in hemodialysis patients. Study design: A 4-month parallel, randomized controlled trial.

Establishing Core Cardiovascular Outcome Measures for Trials in Hemodialysis: Report of an International Consensus Workshop

O'Lone, E., Viecelli, A.K., Craig, J.C., Tong, A., Sautenet, B., Herrington, W.G., Herzog, C.A., Jafar, T.H., Jardine, M.,, Krane, V., Levin, A., Malyszko, J., Rocco, M.V., Strippoli, G., Tonelli, M., Wang, A.Y.M., Wanner, C., Zannad, F., Winkelmayer, W.C., Wheeler, D.C., Manns, B., Pecoits-Filho, R., Harris, T., Winkelmayer, W., Herzog, C.A., Kleinpeter, M., Ju, A., Cho, Y., Gutman, T., Bernier-Jean, A., James, L., Hamiwka, L., Jardine, A., Bello, A., Stengel, B., Schiller, B., Johnson, D., Bavlovlenkov, E., Caskey, F., Gillespie, B., Block, G., Phan, H.A., Heerspink, H.L., Madero, M., Ruospo, M., Unruh, M., Laville, M., Bansal, N., Mark, P., Blankestijn, P.J., Roy-Chaudhury, P., Perlman, R., Agarwal, R., Mehrotra, R., Seliger, S., Shafi, T., Hiemstra, T., Jassal, V., Perkovic, V., Simplice, A., White, D., Eilers, D., Alexander, H., Landry, Y., Landry, G., Wilkie, C., SONG-HD CVD Consensus Workshop Investigators

Cardiovascular disease (CVD) affects more than two-thirds of patients receiving hemodialysis and is the leading cause of death in this population, yet CVD outcomes are infrequently and inconsistently reported in trials in patients receiving hemodialysis. As part of the Standardised Outcomes in Nephrology-Haemodialysis (SONG-HD) initiative, we convened a consensus workshop to discuss the potential use of myocardial infarction and sudden cardiac death as core outcome measures for CVD for use in all trials in people receiving hemodialysis.

Nephrology Provider Surprise Question Response and Hospitalizations in Older Adults with Advanced CKD

Ramer S.J.Baddour N.A.Siew E.D., Salat H.Bian A.Stewart T.G.Wong S.P.Y.Jhamb M.Abdel-Kader K.

Older adults with advanced non-dialysis-dependent chronic kidney disease (NDD-CKD) face a high risk of hospitalization and related adverse events. This prospective cohort study followed nephrology clinic patients ≥60 years old with NDD-CKD stages 4-5. After an eligible patient’s office visit, study staff asked the patient’s provider to rate the patient’s risk of death within the next year using the surprise question (“Would you be surprised if this patient died in the next 12 months?”) with a 5-point Likert scale response (1, “definitely not surprised” to 5, “very surprised”). We used a statewide database to ascertain hospitalization during follow-up.

Thematic Analysis of Hospice Mentions in the Health Records of Veterans with Advanced Kidney Disease

Ann M. O’Hare, Catherine R. Butler, Janelle S. Taylor, Susan P.Y. Wong, Elizabeth K. Vig, Ryan S. Laundry, Melissa W. Wachterman, Paul L. Hebert, Chuan-Fen Liu, Nilka Rios-Burrows, Claire A. Richards

Little is known regarding how decisions about hospice referral among patients with advanced kidney disease unfold in real-world clinical settings. The authors identified three dominant themes in their qualitative analysis of documentation pertaining to hospice in the electronic medical records of members of a national sample of veterans with advanced kidney disease. First, hospice and usual care seemed to function as conflicting rather than complementary models of care. Second, patients were usually referred to hospice late in the course of illness after all other options had been exhausted. Third, patients’ complex care needs sometimes complicated transitions to hospice, stretched the limits of home hospice, and fostered reliance on the acute medical system. These findings highlight the need to improve hospice transitions for patients with advanced kidney disease.

Advancing Nephrology - Division Leaders Advise ASN

Gregory L. Braden, Arlene Chapman, David H. Ellison, Crystal A. Gadegbeku, Susan B. Gurley, Peter Igarashi, Ellie Kelepouris, Marva M. Moxey-Mims, Mark D. Okusa, Troy J. Plumb, Susan E. Quaggin, David J. Salant, Mark S. Segal, Stuart J. Shankland, Stefan Somlo

New treatments, new understanding, and new approaches to translational research are transforming the outlook for patients with kidney diseases. A number of new initiatives dedicated to advancing the field of nephrology—from value-based care to prize competitions—will further improve outcomes of patients with kidney disease. Because of individual nephrologists and kidney organizations in the United States, we are beginning to gain traction to invigorate nephrology to meet the pandemic of global kidney diseases. Five key issues: (1) asserting the value of nephrology to the health system; (2) productivity and compensation; (3) financial support of faculty’s and divisions’ educational efforts; (4) faculty recruitment, retention, diversity, and inclusion; and (5) ensuring that fellowship programs prepare trainees to provide high-value nephrology care and enhance attraction of trainees to nephrology.

Nanoparticles exhibit greater accumulation in kidney glomeruli during experimental glomerular kidney disease

Gary W. Liu, Jeffrey W. Pippin, Diana G. Eng, Shixian Lv, Stuart J. Shankland, Suzie H. Pun

Loss and dysfunction of glomerular podocytes result in increased macromolecule permeability through the glomerular filtration barrier and nephrotic syndrome. Current therapies can induce and maintain disease remission, but cause serious and chronic complications. Nanoparticle drug carriers could mitigate these side effects by delivering drugs to the kidneys more efficiently than free drug through tailoring of carrier properties. An important extrinsic factor of nanoparticle biodistribution is local pathophysiology, which may drive greater nanoparticle deposition in certain tissues. Here, we hypothesized that a “leakier” filtration barrier during glomerular kidney disease would increase nanoparticle distribution into the kidneys. We examined the effect of nanoparticle size and disease state on kidney accumulation in male BALB/c mice. The effect of size was tested using a panel of fluorescent polystyrene nanoparticles of size 20–200 nm, due to the relevance of this size range for drug delivery applications.