Our research broadens the knowledge of kidney disease.

Social Determinants of Health and Race Disparities in Kidney Transplant

Hannah Wesselman, Christopher Graham Ford, Yuridia Leyva, Xingyuan Li, Chung-Chou H Chang, Mary Amanda Dew, Kellee Kendall, Emilee Croswell, John R Pleis, Yue Harn Ng, Mark L Unruh, Ron Shapiro, Larissa Myaskovsky

Black patients have a higher incidence of kidney failure but lower rate of deceased- and living-donor kidney transplantation compared with White patients, even after taking differences in comorbidities into account. We assessed whether social determinants of health (e.g., demographics, cultural, psychosocial, knowledge factors) could account for race differences in receiving deceased- and living-donor kidney transplantation.

ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention

Johann Morelle, Joanna Stachowska-Pietka, Carl Öberg, Liliana Gadola, Vincenzo La Milia, Zanzhe Yu, Mark Lambie, Rajnish Mehrotra, Javier de Arteaga, Simon Davies 

Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function.

Multiphoton-Guided Creation of Complex Organ-Specific Microvasculature.

Samuel G. Rayner, Caitlin C. Howard, Christian J. Mandrycky, Stefan Stamenkovic, Jonathan Himmelfarb, Andy Y. Shih, Ying Zheng

Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of the native microvasculature. Multiphoton ablation has emerged as a promising technique for fabrication of microvascular structures with high resolution and full 3D control, but cellularization and perfusion of complex capillary‐scale structures has remained challenging. Here, multiphoton ablation combined with guided endothelial cell growth from pre‐formed microvessels is used to successfully create perfusable and cellularized organ‐specific microvascular structures at anatomic scale within collagen hydrogels.

The multi-ethnic study of atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study

Ian H. de Boer, David K. Prince, Kayleen Williams, Norrina B. Allen, Gregory L. Burke, Andrew N. Hoofnagle, Simon Hsu, Xiaohui Li, Kiang J. Liu, Robyn L. McClelland, Erin D. Michos, Bruce M. Psaty, Steven J. Shea, Kenneth M. Rice. Jerome I. Rotter, David S. Siscovick, Russell P. Tracy, Karol E. Watson, Bryan R. Kestenbaum

The INdividual response to VITamin D (INVITe) trial was a randomized, placebo-controlled, parallel group trial of vitamin D3 supplementation (2000 IU daily) designed to determine clinical and genetic characteristics that modify the response to vitamin D supplementation. To enhance internal and external validity and reduce cost, the INVITe trial was nested within the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective observational cohort study. The INVITe trial enrolled a community-based population of 666 racially and ethnically diverse participants from January 2017 to April 2019. This represents 30% of 2210 MESA participants approached for screening, and 96% of those found to be eligible.

Biomarkers of inflammation and repair in kidney disease progression

Jeremy Puthumana, Heather Thiessen-Philbrook, Leyuan Xu, Steven G Coca, Amit X Garg, Jonathan Himmelfarb, Pavan K Bhatraju, T Alp Ikizler, Edward D Siew, Lorraine B Ware, Kathleen D Liu, Alan S Go , James S Kaufman, Paul L Kimmel, Vernon M Chinchilli, Lloyd G Cantley, Chirag R Parikh

Acute kidney injury and chronic kidney disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term progression to kidney failure is required. We enrolled 1538 hospitalized patients in a multicenter, prospective cohort study. Monocyte chemoattractant protein 1 (MCP-1/CCL2), uromodulin (UMOD), and YKL-40 (CHI3L1) were measured in urine samples collected during outpatient follow-up at 3 months. We followed patients for a median of 4.3 years and assessed the relationship between biomarker levels and changes in estimated glomerular filtration rate (eGFR) over time and the development of a composite kidney outcome (CKD incidence, CKD progression, or end-stage renal disease). We paired these clinical studies with investigations in mouse models of renal atrophy and renal repair to further understand the molecular basis of these markers in kidney disease progression.

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction

Jasleen Ghuman, Xuan Cai, Ravi B Patel, Sadiya S Khan, Jonathan Hecktman, Margaret M Redfield, Gregory Lewis, Sanjiv J Shah, Myles Wolf, Tamara Isakova, Rupal Mehta

Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.

SGLT2 Inhibitors in Diabetic Kidney Disease

Zoungas S, de Boer IH

Type 2 diabetes, increasing in prevalence globally, is a major cause of CKD and kidney failure. Sodium-glucose transport protein 2 inhibitors (SGLT2i) significantly reduced progression of CKD, major adverse cardiovascular events, heart failure, and all-cause mortality in large clinical trials of people with type 2 diabetes.

Prospective cohort study of renin-angiotensin system blocker usage after hospitalized acute kidney injury

Sandeep Brar, Kathleen D. Liu, Alan S. Go, Raymond K. Hsu, Vernon M. Chinchilli, Steven G. Coca, Amit X. Garg, Jonathan Himmelfarb, T. Alp Ikizler, James Kaufman, Paul L. Kimmel, Chirag R. Parikh, Edward D. Siew, Lorraine B. Ware, Hui Zeng, Chi-yuan Hsu and for the ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) study investigators

Background and objectives:The risk-benefit ratio of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy after AKI may be altered due to concerns regarding recurrent AKI. We evaluated, in a prospective cohort, the association between use (versus nonuse) of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and the subsequent risk of AKI and other adverse outcomes after hospitalizations with and without AKI.

Therapeutic transformation for diabetic kidney disease

Katherine R. Tuttle, David Z.I. Cherney

Risks of kidney failure and heart failure are markedly reduced by inhibition of the sodium glucose cotransporter 2 (SGLT2) in patients with diabetic kidney disease. In a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial, drop-in SGLT2 inhibitor usage during the atrasentan enrichment period led to greater reduction in albuminuria compared with atrasentan alone. These data support the hypothesis of greater longer-term kidney protection by combination SGLT2 inhibition and endothelin A receptor antagonism that could be tested in future clinical trials.

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study

Yan Chen, Leila R Zelnick, Matthew P Huber Ke Wang, Nisha Bansal, Andrew N Hoofnagle, Rajan K Paranji, Susan R Heckbert, Noel S Weiss, Alan S Go, Chi-Yuan Hsu, Harold I Feldman, Sushrut S Waikar, Rupal C Mehta, Anand Srivastava, Stephen L Seliger, James P Lash, Anna C Porter, Dominic S Raj, Bryan R Kestenbaum, CRIC Study Investigators

Rational & Objective: The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.