Our research broadens the knowledge of kidney disease.

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.

Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review

Karine E Manera, Angela Ju, Amanda Baumgart, Elyssa Hannan, Wenjing Qiao, Martin Howell, Melissa Nataatmadja, Martin Wilkie, Fiona Loud, Daniel Schwartz, Helen Hurst, Sarbjit Vanita Jassal, Ana Figueiredo, Rajnish Mehrotra, Jenny Shen, Rachael L Morton, Thyago Moraes, Rachael Walker, Catherine Cheung, Janine F Farragher, Jonathan Craig, David W Johnson, Allison Tong

Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD.

The challenge of insomnia for patients on haemodialysis

Daniel Cukor, Mark Unruh, Susan M McCurry, Rajnish Mehrotra 

Insomnia is common among patients on maintenance haemodialysis and may be exacerbated by the challenges of the COVID pandemic. However, data on the efficacy of insomnia interventions in this population are limited. Efforts are needed to address this important problem and increase access to insomnia interventions for patients on haemodialysis.

Association of the Estimated Glomerular Filtration Rate With vs Without a Coefficient for Race With Time to Eligibility for Kidney Transplant

Question: Is adjusting for Black race in estimating equations for glomerular filtration rate in patients with chronic kidney disease associated with a delay in kidney transplant eligibility? Findings: In this cohort study of 1658 self-identified Black adults with chronic kidney disease, commonly used estimates of kidney function did not correspond well with directly measured kidney function. Estimating kidney function not including a coefficient for race (vs including a race coefficient) was significantly associated with a shorter time to achieving an estimated glomerular filtration rate less than 20 mL/min/1.73 m2, a key threshold of kidney function for referral and listing for kidney transplant. Meaning: The findings suggest that biases in race-based glomerular filtration rate estimates may be associated with delays in potential kidney transplant eligibility.