Editor’s Note: We asked authors of Original Investigations to provide short plain-language summaries that would briefly summarize what inspired their study, the basic approach taken, what was learned, and why it matters. We hope our readers will find this valuable in helping them keep up with the latest research in the field of nephrology. From the June 2022 issue:

Patient Preferences for Longer or More Frequent In-Center Hemodialysis Regimens: A Multicenter Discrete Choice Study by James Fotheringham et al [OPEN ACCESS]

From the authors: Longer or 4-times-a-week dialysis has been associated with better outcomes, yet their use is limited, and they are perceived as undesirable to patients. One hundred and eighty-four people on dialysis completed a discrete choice questionnaire that presented the association of these longer and more frequent treatments with longer survival, less hospitalization, better quality of life, and fewer vascular access complications. Presented with available evidence on these associations, 27.1% of patients would choose longer dialysis, and 34.3% would choose 4-times-per-week dialysis, far more than is currently observed in routine practice. Better data on clinical effectiveness to guide patient choice are needed.

DOI: 10.1053/j.ajkd.2021.09.012

Editorial: Dialysis Modality Decisions: Choosing Wisely! by Shira Goldman and Christopher T. Chan [FREE] 

Cost-Effectiveness of Empagliflozin in Patients With Diabetic Kidney Disease in the United States: Findings Based on the EMPA-REG OUTCOME Trial by Odette S. Reifsnider et al [OPEN ACCESS]

From the authors: Kidney injury is a common complication of type 2 diabetes that is associated with increased risk of cardiovascular events and death in this population. Empagliflozin demonstrated slower kidney disease progression and lower kidney event rates than placebo when combined with standard of care in the EMPA-REG OUTCOME trial. A health economic model was used to predict long-term treatment effects and costs for patients with diabetic kidney disease (DKD) at baseline in the EMPA-REG OUTCOME trial. Treatment with empagliflozin combined with standard of care for US patients with DKD may lead to health benefits and be cost-effective versus standard of care alone for commercial insurers and Medicare. These results will help guide patients, clinicians, and decision-makers in selecting a regimen for management of DKD.

DOI: 10.1053/j.ajkd.2021.09.014

Editorial: Time to Invest in the Future: Assessing the Cost-Effectiveness of Empagliflozin in Diabetic Kidney Disease by Annike Khine [FREE] 

Quantification of Glomerular Structural Lesions: Associations With Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome by Jeffrey B. Hodgin et al

From the authors: Focal segmental glomerulosclerosis and minimal change disease are heterogeneous diseases that manifest with a variety of structural changes in the kidney often not captured by conventional classification systems. This study shows that a detailed morphologic analysis and quantification of these changes allow for better representation of the structural abnormalities within each patient and for grouping patients with similar morphologic profiles. The resulting clusters of patients are clinically and biologically relevant because they are associated with kidney disease progression, complete remission of proteinuria, and kidney tissue transcriptomics differences. This study serves as a foundation for eventual subcategorization of nephrotic syndrome to better predict outcomes and select tailored treatments.

DOI: 10.1053/j.ajkd.2021.10.004

Editorial: Outscoring Current Classification Systems for Nephrotic Syndrome by Gentzon Hall and Jennie Lin [FREE] 

Impact of Bioelectrical Impedance–Guided Fluid Management and Vitamin D Supplementation on Left Ventricular Mass in Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial by K. Scott Brimble et al 

From the authors: Patients on peritoneal dialysis have a high risk of cardiovascular events and increased left ventricular mass. They are also at significant risk of fluid overload and vitamin D deficiency, which may have detrimental effects on cardiac structure. We conducted a randomized controlled trial to determine if using bioimpedance analysis, a technology to assess volume status, or vitamin D supplementation reduces left ventricular mass. We found that using bioimpedance analysis and vitamin D supplementation had a potentially beneficial effect on fluid overload and improved vitamin D levels but did not have a beneficial effect on left ventricular mass. These findings do not support the use of bio-impedance analysis or vitamin D supplementation to prevent or reduce left ventricular hypertrophy.

DOI: 10.1053/j.ajkd.2021.08.022

Treatment Effect of Percutaneous Coronary Intervention in Dialysis Patients With ST-Elevation Myocardial Infarction by Akram Kawsara et al 

From the authors: Whether patients who are receiving maintenance dialysis and present with ST-elevation myocardial infarction (STEMI) derive the same benefit from primary percutaneous coronary intervention (pPCI) as patients not on dialysis is unclear. We used the National Inpatient Sample (2016-2018) and research methods to compare the effects of pPCI while adjusting for other clinical differences in patients. We found that pPCI was associated with comparable reductions in short-term mortality in patients regardless of their treatment with dialysis. Our findings may help reduce the treatment gap between patients who are or are not receiving dialysis. Further studies are needed to improve cardiac care in the dialysis population.

DOI: 10.1053/j.ajkd.2021.08.023

CKD Progression From the Time of Estimated GFR-Based Waitlist Eligibility and Racial Disparities in Transplant Access by Chi D. Chu et al 

From the authors: Current US kidney transplant policy requires a glomerular filtration rate (GFR) of ≤20 mL/min/1.73 m2 for activation on the waitlist, but current GFR estimating equations assign a higher value to Black patients compared with non-Black patients for the same age, sex, and creatinine values and may disadvantage Black patients regarding time for preemptive transplantation. We examined chronic kidney disease progression in over 50,000 patients who developed a GFR ≤20 mL/min/1.73 m2 based on a GFR estimation that in-corporates information about race, finding that Black and Hispanic patients progressed to kidney failure more quickly compared with White patients. We observed that classifying all patients as non-Black for the purpose of GFR estimation would allow Black patients to be eligible for earlier waitlisting; however, a large disparity remains in the time available for pre-emptive transplantation due to faster progression to kidney failure compared with White patients. Additionally, faster progression among Hispanic patients would not be remedied by changes in eGFR calculation.

DOI: 10.1053/j.ajkd.2021.08.010

Blog Post Waitlist Eligibility and Disparities in Transplant Access by Adrian Whelan [FREE] 

Associations of Plasma Biomarkers of Inflammation, Fibrosis, and Kidney Tubular Injury With Progression of Diabetic Kidney Disease: A Cohort Study by Orlando M. Gutiérrez et al 

From the authors: Diabetes commonly damages kidney tubules by causing fibrosis and inflammation. However, little is known whether biomarkers of kidney tubule injury, fibrosis, and inflammation are associated with risk of developing kidney failure. We examined whether blood biomarkers of inflammation, fibrosis, and tubular injury were associated with the development of kidney failure in individuals with diabetes and chronic kidney disease. We found that higher concentrations of several of these biomarkers were associated with higher risk of developing kidney failure, particularly kidney injury marker 1 and tumor necrosis factor receptor 1. These data provide important information on factors that cause kidney failure in those with diabetes.

DOI: 10.1053/j.ajkd.2021.09.018

SGLT2 Inhibitors and the Risk of Acute Kidney Injury in Older Adults With Type 2 Diabetes by Min Zhuo et al 

From the authors: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 receptor agonists are 3 newer classes of glucose-lowering medications to treat type 2 diabetes. The beneficial effects of SGLT2 inhibitors extend beyond glycemic control and include reduction in cardiovascular events, kidney disease progression, and mortality. However, there was a concern that SGLT2 inhibitors might increase the risk of acute kidney injury. In this nationwide study using Medicare data, we found that the initiation of an SGLT2 inhibitor was associated with a lower risk of acute kidney injury compared with initiation of a dipeptidyl peptidase inhibitor or a glucagon-like peptide 1 receptor agonist among matched older adults with type 2 diabetes. Our results add to the available evidence on the safety profile of SGLT2 inhibitors in older adults.

DOI: 10.1053/j.ajkd.2021.09.015

Perspective from the June 2022 Issue:

Hypertonic Saline for Hyponatremia: Meeting Goals and Avoiding Harm by Helbert Rondon-Berrios and Richard H. Sterns 

Nearly a century after hypertonic saline was first suggested as a treatment for acute water intoxication, we still don’t know exactly how to use the drug. When is it indicated? How much should be given? At what rate? By what route? How can complications best be avoided? In this perspective we consider these questions, revisiting the various answers that have been proposed over time and the evidence supporting them.

DOI: 10.1053/j.ajkd.2021.07.020

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Blog Post Interview with Drs Rondon-Berrios and Sterns [FREE] 

On the Cover: The hallucinogenic and poisonous properties of the mushroom Amanita muscaria derive from the compounds ibotenic acid, an N-nitrosodimethylamine (NDMA) and glutamate receptor agonist, and muscimol, a potent g-aminobutyric acid (GABA) A agonist. While these mushrooms have been ingested recreationally and ritually, they have also resulted in unintentional poisonings when confused with edible mushrooms. In this issue of AJKD, Mullins and Kraut discuss the role that nephrologists play in the management of intoxications and poisonings. The authors highlight the evidence-based recommendations put forth by the EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup and describe how nephrologists can leverage their extensive knowledge of dialysis and acid-base disorders working alongside toxicologists, emergency physicians, and intensivists in the management of these life-threatening exposures.

The photograph “Amanita muscaria” by Bernard Spragg is available via Flickr and released into the public domain

Special 40th Anniversary Collection: DIALYSIS

AJKD is celebrating its 40th year of publication. In this special collection, the editors highlight landmark papers on dialysis that have been published in the journal over the past four decades.