Our faculty research broadens the knowledge of kidney disease.

Burden of excess mortality after implementation of the new kidney allocation system may be borne disproportionately by middle-aged recipients

Butler CR, Perkins JD, Johnson CK, Blosser CD, Bakthavatsalam R, Leca N, Sibulesky L

Under the new kidney allocation system (KAS), implemented in 2014, the distribution of the best quality donor kidney grafts shifted between age groups, but it is unclear whether this change translates to meaningful differences in post-transplant outcomes. We conducted a retrospective cohort study of 20,345 deceased donor kidney transplant recipients before and 4,605 recipients after implementation of the KAS using data from the United Network of Organ Sharing

Commentary on "Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in CKD"

Bryan R. Kestenbaum, Stephen L. Seliger

Given the high incidence of both ischemic stroke and major hemorrhage among patients with CKD and atrial fibrillation, treatment decisions regarding oral anaticoagulation can be challenging. The authors note that there is no evidence from randomized trials on the safety or efficacy of these medications in patients with CKD stages 4 and 5.

Patterns of Beverages Consumed and Risk of Incident Kidney Disease

Rebholz, C.M.,  Young, B.A.,  Katz, R.,  Tucker, K.L.,  Carithers, T.C.,  Norwood, A.F.,  Correa, A.

Selected beverages, such as sugar-sweetened beverages, have been reported to influence kidney disease risk, although previous studies have been inconsistent. Further research is necessary to comprehensively evaluate all types of beverages in association with CKD risk to better inform dietary guidelines. We conducted a prospective analysis in the Jackson Heart Study, a cohort of black men and women in Jackson, Mississippi. Beverage intake was assessed using a food frequency questionnaire administered at baseline (2000–2004). Incident CKD was defined as onset of eGFR<60 ml/min per 1.73 m2 and ≥30% eGFR decline at follow-up (2009–13) relative to baseline among those with baseline eGFR ≥60 ml/min per 1.73 m2.

Sodium-Glucose Cotransporter 2 Inhibition and Diabetic Kidney Disease

Alicic, R.Z.,  Neumiller, J.J.,  Johnson, E.J.,  Dieter, B., Tuttle, K.R.

Preclinical studies and clinical trials of SGLT2 inhibitors have consistently demonstrated reduction of albuminuria and preservation of kidney function. In particular, SGLT2 inhibitors lower risk of congestive heart failure, a major cardiovascular complication in DKD. This Perspective summarizes proposed mechanisms of action for SGLT2 inhibitors, integrates these data with results of recent cardiovascular outcomes trials, and discusses clinical applications for patients with DKD.

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.