Our faculty research broadens the knowledge of kidney disease.

Organoid single cell profiling identifies a transcriptional signature of glomerular disease

Harder JL, Menon R, Otto EA, Zhou J, Eddy S, Wys NL, O'Connor C, Luo J, Nair V, Cebrian C, Spence JR, Bitzer M, Troyanskaya OG, Hodgin JB, Wiggins RC, Freedman BS, Kretzler M; European Renal cDNA Bank (ERCB); Nephrotic Syndrome Study Network (NEPTUNE).

Podocyte injury is central to many forms of kidney disease, but transcriptional signatures reflecting podocyte injury and compensation mechanisms are challenging to analyze in vivo. Human kidney organoids derived from pluripotent stem cells (PSCs), a potentially new model for disease and regeneration, present an opportunity to explore the transcriptional plasticity of podocytes. Here, transcriptional profiling of more than 12,000 single cells from human PSC-derived kidney organoid cultures was used to identify robust and reproducible cell lineage gene expression signatures shared with developing human kidneys based on trajectory analysis.

Producing Purer Podocytes

Podocytes are highly specialized cells that play a central role in many renal disorders. For many years, podocyte research has been stymied by an inability to culture these cells in a well differentiated state. Recently, this has begun to change - kidney organoids have been generated containing podocytes with differentiated features. The presence of podocytes in organoids has enabled new mechanistic insights into glomerular development and disease processes.

Validity of predictive equations for 24-h urinary potassium excretion based on timing of spot urine collection among adults: the MESA and CARDIA Urinary Sodium Study and NHANES Urinary Sodium Calibration Study

Mercado CI, Cogswell ME, Loria CM, Liu K, Allen N, Gillespie C, Wang CY, de Boer IH, Wright J

24-h urine collections are the suggested method to measure daily urinary potassium excretion (uK) but are costly and burdensome to implement. This study tested how well existing equations with the use of spot urine samples can estimate 24-h uK and if accuracy varies by timing of spot urine collection, age, race, or sex.

Development of an International Standard Set of Value-Based Outcome Measures for Patients With Chronic Kidney Disease

Wouter R.Verberne, Zofia Das-Gupta, Andrew S. Allegretti, Hans A.J.Bart, Wimvan Biesen, Guillermo García-García, Elizabeth Gibbons, Eduardo Parra, Marc H. Hemmelder, Kitty J. Jager, Markus Ketteler, Charlotte Roberts, Muhamed Al Rohani, Matthew J.Salt, Andrea Stopper, TürkanTerkivatan, Katherine R.Tuttle, Chih-Wei Yang, Willem Jan W. Bos

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use.

Better Being Single? Omics Improves Kidney Organoids

Human kidney organoids are complex structures resembling nephron arrays, which can be derived in a variety of ways. Whether all of these differentiation protocols produce qualitatively similar organoid cell types is not yet clear. A comparative analysis of 2 organoid differentiation protocols is recently reported in Cell Stem Cell using single cell RNA sequencing (scRNA-seq) as an analytical tool. This demonstrates that the 2 protocols have much in common, and that neither produces kidney cells in a pure or comprehensive manner.

Preformed Angiotensin II Type-1 Receptor Antibodies Are Associated With Rejection After Kidney Transplantation: A Single-Center, Cohort Study

Kim, D.,  Gimferrer, I.,  Warner, P.,  Nelson, K.,  Sibulesky, L.,  Bakthavatsalam, R.,  Leca, N.

Antibodies against angiotensin II type-1 receptors (AT1R) have been increasingly recognized in association with rejection and poor allograft outcomes. Our goal was to define the prevalence of preformed antibodies against AT1R and evaluate the association with renal allograft outcomes in a consecutive cohort of 150 transplant recipients.

Dietary Phosphorus and Ambulatory Blood Pressure in African Americans: The Jackson Heart Study

Olivo, R.E.,  Hale, S.L.,  Diamantidis, C.J.,  Bhavsar, N.A.,  Tyson, C.C.,  Tucker, K.L.,  Carithers, T.C.,  Kestenbaum, B.,  Muntner, P.,  Tanner, R.M.,  Booth, J.N., 3rd,  Mwasongwe, S.E.,  Pendergast, J.,  Boulware, L.E.,  Scialla, J.J.

 

Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns. Our study included 973 African American adults enrolled in the Jackson Heart Study (2000–2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire.

Editorial: Diuretic use in incident ESKD. Are we out of the loop?

Wang K, Bansal N

Sibbel et al examined the association of loop diuretic continuation with clinical outcomes after maintenance hemodialysis initiation among >11,000 patients with incident ESKD. In this large, observational cohort study, the authors utilized US Renal Data System (USRDS) records to ascertain refill of loop diuretic prescriptions after hemodialysis initiation and within 30 days of exhaustion of prior diuretic supply.

Boronic Acid Copolymers for Direct Loading and Acid-Triggered Release of Bis-T-23 in Cultured Podocytes

Cheng, Y.,  Liu, G.W.,  Jain, R.,  Pippin, J.W.,  Shankland, S.J.,  Pun, S.H.

We report an acid-reversible linker for triggered release of Bis-T-23, an experimental small molecule drug for kidney disease treatment that restores podocyte morphology during disease. Bis-T-23 contains catechols, which form an acid-reversible, covalent boronate ester bond with boronic acids.

Obtaining Dialysis in VA and Non-VA Settings

Virginia Wang, Cynthia J. Coffman, Karen M. Stechuchak, Theodore S.Z. Berkowitz, Paul L. Hebert, David Edelman, Ann M. O’Hare, Susan T. Crowley, Hollis J. Weidenbacher, Matthew L. Maciejewski

Outcomes of veterans with ESRD may differ depending on where they receive dialysis and who finances this care, but little is known about variation in outcomes across different dialysis settings and financial arrangements. We examined survival among 27,241 Veterans Affairs (VA)–enrolled veterans who initiated chronic dialysis in 2008–2011.