Our faculty research broadens the knowledge of kidney disease.

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).

Effects of diet and exercise on adipocytokine levels in patients with moderate to severe chronic kidney disease

Nihal Aydemira, Mindy M. Pike, Aseel Alsouqi, Samuel A. E. Headley, Katherine Tuttle, Elizabeth E. Evans, Charles M. Milch, Kelsey A. Moody, Michael Germain, Loren Lipworth, Jonathan Himmelfarb, T. A .Ikizler, Cassianne Robinson-Cohen

Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD.

From Local Explanations to Global Understanding With Explainable AI for Trees

Scott M Lundberg, Gabriel Erion, Hugh Chen, Alex DeGrave, Jordan M Prutkin, Bala Nair, Ronit Katz, Jonathan Himmelfarb, Nisha Bansal, Su-In Lee

These tools enable us to i) identify high magnitude but low frequency non-linear mortality risk factors in the US population, ii) highlight distinct population sub-groups with shared risk characteristics, iii) identify non-linear interaction effects among risk factors for chronic kidney disease, and iv) monitor a machine learning model deployed in a hospital by identifying which features are degrading the model's performance over time. Given the popularity of tree-based machine learning models, these improvements to their interpretability have implications across a broad set of domains.

Association of Cardiac Biomarkers With the Kansas City Cardiomyopathy Questionnaire in Patients With Chronic Kidney Disease Without Heart Failure

Sri Lekha Tummalapalli, Leila R. Zelnick, Amanda H. Andersen, Robert H. Christenson, Christopher R. deFilippi, Rajat Deo, Alan S. Go, Jiang He, Bonnie Ky, James P. Lash, Stephen L. Seliger, Elsayed Z. Soliman, Michael G. Shlipak, Nisha Bansal and the CRIC Study Investigators

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF‐15 (growth differentiation factor‐15), galectin‐3, sST2 (soluble suppression of tumorigenesis‐2), hsTnT (high‐sensitivity troponin T), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known.

Induced Pluripotent Stem Cells Provide Mega Insights Into Kidney Disease

Alessandro Luciani, Benjamin S Freedman

Rare mutations in the LRP2 gene encoding for the endocytic receptor megalin cause developmental abnormalities and kidney disease. However, the mechanisms governing the dysfunction of mutant megalin remain unclear. A new study utilizing patient-derived induced pluripotent stem cells is now putting the endolysosomal system into the spotlight, as it is proposed to play a central role in the regulation of megalin in health and disease.