Our faculty research broadens the knowledge of kidney disease.

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.

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.