Our faculty research broadens the knowledge of kidney disease.

Medication use, renin–angiotensin system inhibitors, and acute care utilization after hospitalization in patients with chronic kidney disease

Neumiller, J.J., Daratha, K.B., Alicic, R.Z., Short, R.A., Miller, H.M., Gregg, L., Gates, B.J., Corbett, C.F, McPherson, S.M., Tuttle, K.R

The aims of this secondary analysis were to: (a) characterize medication use following hospital discharge for patients with chronic kidney disease (CKD), and (b) investigate relationships of medication use with the primary composite outcome of acute care utilization 90 days after hospitalization.

We Can Finally Stop Worrying About SGLT2 Inhibitors and Acute Kidney Injury

Vikas S. Sridhar, Katherine R. Tuttle, David Z. I. Cherney

Sodium glucose transporter 2 (SGLT2) inhibitors, originally approved solely as antihyperglycemic agents for the treatment of type 2 diabetes mellitus (T2DM), are increasingly recognized for their distinctive kidney and cardiovascular protective properties

Profiling APOL1 Nephropathy Risk Variants in Genome-Edited Kidney Organoids with Single-Cell Transcriptomics

Esther Liu, Behram Radmanesh, Byungha H Chung, Michael D Donnan, Dan Yi, Amal Dadi, Kelly D Smith, Jonathan Himmelfarb, Mingyao Li, Benjamin S Freedman, Jennie Lin

DNA variants in APOL1 associate with kidney disease, but the pathophysiologic mechanisms remain incompletely understood. Model organisms lack the APOL1 gene, limiting the degree to which disease states can be recapitulated. Here we present single-cell RNA sequencing (scRNA-seq) of genome-edited human kidney organoids as a platform for profiling effects of APOL1 risk variants in diverse nephron cell types.

The Difference Between Cystatin C and Creatinine-Based Estimated GFR and Incident Frailty: An Analysis of the Cardiovascular Health Study (CHS)

O Alison Potok, Ronit Katz D Phil, Nisha Bansal, David S Siscovick, Michelle Odden, Joachim H Ix, Michael G Shlipak, Dena E Rifkin 

Glomerular filtration rate is estimated either based on creatinine (eGFRCr), which tends to be high in people with low muscle mass, or cystatin C (eGFRCys), which is not as affected by muscle mass.1 It is not uncommon to see clinic patients with discrepancies between the two. We hypothesized that prognostic information is embedded in the difference in these markers. We propose that older adults with eGFRCys > eGFRCr will have less prevalent frailty, and will be at lower risk for incident frailty and mortality, compared with those having a minimal difference between the two estimates.

Thematic analysis of the medical records of patients evaluated for kidney transplant who did not receive a kidney

Catherine R. Butler, Janelle S. Taylor, Peter P. Reese, Ann M. O’Hare

A potential pitfall of policies intended to promote referral for kidney transplant is that greater numbers of patients may be evaluated for transplant without experiencing the intended benefit of receiving a kidney. Little is known about the potential implications of this experience for patients. We performed a thematic analysis of clinician documentation in the electronic medical records of all adults at a single medical center with advanced kidney disease who were referred to the local transplant coordinator for evaluation between 2008 and 2018 but did not receive a kidney.

Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes

Pavan K. Bhatraju, Max Cohen, Ryan J. Nagao, Eric D. Morrell, Susanna Kosamo, Xin-Ya Chai, Robin Nance, Victoria Dmyterko, Joseph Delaney, Jason D. Christie, Kathleen D. Liu, Carmen Mikacenic, Sina A. Gharib, W. Conrad Liles, Ying Zheng, David C. Christiani, Jonathan Himmelfarb, Mark M. Wurfel

We previously identified two acute kidney injury (AKI) sub-phenotypes (AKI-SP1 and AKI-SP2) with different risk of poor clinical outcomes and response to vasopressor therapy. Plasma biomarkers of endothelial dysfunction (tumor necrosis factor receptor-1, angiopoietin-1 and 2) differentiated the AKI sub-phenotypes. However, it is unknown whether these biomarkers are simply markers or causal mediators in the development of AKI sub-phenotypes.

Relationship Between Chronic Kidney Disease, Glucose Homeostasis, and Plasma Osteocalcin Carboxylation and Fragmentation

Mario Kratz, Leila R. Zelnick, Olgica Trenchevska, Joshua W. Jeffs, Chad R. Borges, Hsin-Hui Tseng, Sarah L. Booth, Bryan R. Kestenbaum, Kristina M. Utzschneider, Ian H. de Boer

Chronic kidney disease (CKD) is associated with reduced insulin sensitivity, through mechanisms that are not well understood. Low vitamin K intake and incomplete carboxylation of the vitamin K-dependent protein osteocalcin may promote insulin resistance. We assessed relationships of osteocalcin concentration, carboxylation, and fragmentation with CKD and glucose homeostasis in a cross-sectional study.

Supervised Exercise Intervention and Overall Activity in CKD

Mindy M. Pike, Aseel Alsouqi, Samuel A. E. Headley, Katherine Tuttle, Elizabeth Elspeth Evans, Charles M. Milch, Kelsey Anne Moody, Michael Germain, G. Stewart, Loren Lipworth, Jonathan Himmelfarb, T. AlpIkizler, Cassianne Robinson-Cohen

Patients are often instructed to engage in multiple weekly sessions of exercise to increase physical activity. We aimed to determine whether assignment to a supervised exercise regimen increases overall weekly activity in individuals with chronic kidney disease (CKD).

Wearable artificial kidney: problems, progress and prospects

Jonathan Himmelfarb, Buddy Ratner

To be truly wearable, a wearable artificial kidney could not weigh more than 8–10 kg and would need a volume of no more than 0.1 m3. A functional, clinically useful, wearable artificial kidney must also meet demanding technical performance and clinical criteria....Despite these obstacles, momentum is steadily growing to support contemporary efforts to emulate, in a wearable format, the superb efficiency of the healthy kidney.

Open microfluidic coculture reveals paracrine signaling from human kidney epithelial cells promotes kidney specificity of endothelial cells

Tianzi Zhang, Daniel Lih, Ryan J. Nagao, Jun Xue, Erwin Berthier, Jonathan Himmelfarb, Ying Zheng, Ashleigh B. Theberge

Outstanding challenges remain to understand and reestablish EC organ specificity for in vitro studies to recapitulate human organ-specific physiology. Here, we designed an open microfluidic platform to study the role of human kidney tubular epithelial cells in supporting EC specificity. The platform consists of two independent cell culture regions segregated with a half wall; culture media are added to connect the two culture regions at a desired time point, and signaling molecules can travel across the half wall (paracrine signaling).