Our faculty research broadens the knowledge of kidney disease.

An Improved Vascularized, Dual-Channel Microphysiological System Facilitates Modeling of Proximal Tubular Solute Secretion

Alenka Chapron, Brian D. Chapron, Dale W. Hailey, Shih-Yu Chang, Tomoki Imaoka, Kenneth E. Thummel, Edward Kelly, Jonathan Himmelfarb, Danny Shen, Catherine K. Yeung

A vascularized human proximal tubule model in a dual-channel microphysiological system (VPT-MPS) was developed, representing an advance over previous, single-cell-type kidney microphysiological systems. Human proximal tubule epithelial cells (PTECs) and human umbilical vein endothelial cells (HUVECs) were cocultured in side-by-side channels.

The current and future landscape of dialysis

Jonathan Himmelfarb, Raymond Vanholder, Rajnish Mehrotra, Marcello Tonelli 

The development of dialysis by early pioneers such as Willem Kolff and Belding Scribner set in motion several dramatic changes in the epidemiology, economics and ethical frameworks for the treatment of kidney failure. However, despite a rapid expansion in the provision of dialysis — particularly haemodialysis and most notably in high-income countries (HICs) — the rate of true patient-centred innovation has slowed. Current trends are particularly concerning from a global perspective: current costs are not sustainable, even for HICs, and globally, most people who develop kidney failure forego treatment, resulting in millions of deaths every year. Thus, there is an urgent need to develop new approaches and dialysis modalities that are cost-effective, accessible and offer improved patient outcomes. Nephrology researchers are increasingly engaging with patients to determine their priorities for meaningful outcomes that should be used to measure progress. The overarching message from this engagement is that while patients value longevity, reducing symptom burden and achieving maximal functional and social rehabilitation are prioritized more highly. In response, patients, payors, regulators and health-care systems are increasingly demanding improved value, which can only come about through true patient-centred innovation that supports high-quality, high-value care. Substantial efforts are now underway to support requisite transformative changes. These efforts need to be catalysed, promoted and fostered through international collaboration and harmonization.

Impact of the COVID-19 pandemic on clinical research

The COVID-19 pandemic has placed a tremendous strain on sustaining the clinical research enterprise and will also likely affect key study outcomes; these effects must be considered during data analysis and interpretation. Nevertheless, the responses to the pandemic have also introduced innovations that will advance the conduct of clinical research.

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.