Our faculty research broadens the knowledge of kidney disease.

KTAO: A kidney tissue atlas ontology to support community-based kidney knowledge base development and data integration

He, Y., Steck, B.,  Ong, E.,  Mariani, L.,  Lienczewski, C.,  Balis, U.,  Kretzler, M.,  Himmelfarb, J.,  Bertram, J.F.,  Azeloglu, E.,  Iyengar, R.,  Hoshizaki, D.,  Mooney, S.D

The human kidney has a complex structure and diverse interactions among its cells and cell components, both during homeostasis and in its diseased states. To better understand the kidney, it is critical to systematically classify, represent, and integrate kidney gene activities, cell types, cell states, and interstitial components. Toward this goal, we developed a Kidney Tissue Atlas Ontology (KTAO). KTAO reuses and aligns with existing ontologies such as the Cell Ontology, UBERON, and Human Phenotype Ontology. KTAO also generates new semantic axioms to logically link terms of entities in different domains. As a first study, KTAO represents over 200 known kidney gene markers and their profiles in different cell types in kidney patients. Such a representation supports kidney knowledge base generation, query, and data integration.

Care Practices for Patients With Advanced Kidney Disease Who Forgo Maintenance Dialysis

Susan P. Y. Wong, Lynne V. McFarland, Chuan-Fen Liu, Ryan J. Laundry, Paul L. Hebert, Ann M. O’Hare

The manuscript summarizes the findings of a qualitative study of the medical record of a national cohort of 851 patients with advanced kidney disease in whom there was a decision not to initiate maintenance dialysis. Our findings highlight the need to build a stronger clinical infrastructure to support patients who do wish to pursue dialysis.

Fabricating a Kidney Cortex Extracellular Matrix-Derived Hydrogel

Hiraki HL, Nagao RJ, Himmelfarb J, Zheng Y

Extracellular matrix (ECM) provides important biophysical and biochemical cues to maintain tissue homeostasis. Current synthetic hydrogels offer robust mechanical support for in vitro cell culture but lack the necessary protein and ligand composition to elicit physiological behavior from cells. This manuscript describes a fabrication method for a kidney cortex ECM-derived hydrogel with proper mechanical robustness and supportive biochemical composition.

Human kidney on a chip assessment of polymyxin antibiotic nephrotoxicity

Weber EJ, Lidberg KA, Wang L, Bammler TK, MacDonald JW, Li MJ, Redhair M, Atkins WM, Tran C, Hines KM, Herron J, Xu L, Monteiro MB, Ramm S, Vaidya V, Vaara M, Vaara T, Himmelfarb J, Kelly EJ

Drug-induced kidney injury, largely caused by proximal tubular intoxicants, limits development and clinical use of new and approved drugs. Assessing preclinical nephrotoxicity relies on animal models that are frequently insensitive; thus, potentially novel techniques — including human microphysiological systems, or “organs on chips” — are proposed to accelerate drug development and predict safety. Polymyxins are potent antibiotics against multidrug-resistant microorganisms; however, clinical use remains restricted because of high risk of nephrotoxicity and limited understanding of toxicological mechanisms. To mitigate risks, structural analogs of polymyxins (NAB739 and NAB741) are currently in clinical development.

Blood pressure checks and diagnosing hypertension (BP-CHECK): Design and methods of a randomized controlled diagnostic study comparing clinic, home, kiosk, and 24-hour ambulatory BP monitoring

Green BB, Anderson ML, Campbell J, Cook AJ, Ehrlich K, Evers S, Hall YN, Hsu C, Joseph D, Klasnja P, Margolis KL, McClure JB, Munson SA, Thompson MJ

The US Preventive Services Task Force recommends out-of-office blood pressure (BPs) before making a new diagnosis of hypertension, using 24-h ambulatory (ABPM) or home BP monitoring (HBPM), however this is not common in routine clinical practice. Blood Pressure Checks and Diagnosing Hypertension (BP-CHECK) is a randomized controlled diagnostic study comparing the accuracy and acceptability of clinic, home, and kiosk-based BP monitoring to ABPM for diagnosing hypertension. Stakeholders including patients, providers, policy makers, and researchers informed the study design and protocols.

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.