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. Highlights from the June 2023 issue:

Identification of Novel Genetic Risk Factors for Focal Segmental Glomerulosclerosis in Children: Results From the Chronic Kidney Disease in Children (CKiD) Cohort by Axelle Durand et al 

From the authors: We assessed the genetic risk factors for primary focal segmental glomerulosclerosis (FSGS) by simultaneously testing over 680,000 genetic markers spread across the genome in 140 children, including 32 with FSGS lesions. Fourteen independent genetic regions were significantly associated with pediatric FSGS, including APOL1 and ALMS1-NAT8, which were previously found to be associated with FSGS and chronic kidney diseases in adults. Novel genes with relevant biological functions were also highlighted, such as GRB2 and FGFR4, which play a role in the kidney filtration barrier and in kidney cell differentiation, respectively. Finally, we revealed the importance of immune regulation in pediatric FSGS through associations involving cell surface proteins presenting antigens to the immune system and interacting with T-cell receptors.

DOI: 10.1053/j.ajkd.2022.11.003

Editorial: Genetics of Focal Segmental Glomerulosclerosis in African American Children by Rebecca Levy et al [FREE]

Associations of Iron Sucrose and Intradialytic Blood Pressure by Anika T. Singh et al 

From the authors: Intradialytic hypotension and intradialytic hypertension are common among patients on hemodialysis, and they are associated with morbidity and mortality. Although many factors may contribute to these risks, medications administered during hemodialysis play an important role. We studied the significance of the intravenous iron sucrose used to treat iron deficiency and the impact it may have on blood pressure during dialysis. In our study of 950 outpatient hemodialysis patients, we observed that administration of iron sucrose was associated with higher systolic blood pressure (during and after hemodialysis sessions) as well as a lower risk of intradialytic hypotension. We also observed that higher doses of iron sucrose are associated with the development of intradialytic hypertension.

Editorial: Iron Sucrose and Blood Pressure Patterns During Hemodialysis by Jingyin Yan [FREE]

DOI: 10.1053/j.ajkd.2022.11.007

Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study by Marieta P. Theodorakopoulou et al

From the authors: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

DOI: 10.1053/j.ajkd.2022.11.013

Editorial: Strengthening the Link Between Cardiovascular Disease and Sarcopenia in CKD by Matthew K. Abramowitz [FREE]

Characteristics of and Outcomes After Dialysis-Treated Acute Kidney Injury, 2009-2018: A Taiwanese Multicenter Study by Cheng-Chia Lee et al (OPEN ACCESS)

From the authors: The current medical management of severe acute kidney injury (AKI) is primarily limited to supportive care and kidney replacement therapy if indicated, leading to perceptions that outcomes among intensive care unit (ICU) patients with dialysis-treated AKI have not improved. In this multicenter retrospective study of ICU patients with dialysis-treated AKI between 2009 and 2018 in Taiwan, patient mortality decreased over time despite increasing comorbidities. Moreover, the decreasing linear trends remained significant even when considering severity of acute illness at dialysis initiation, which was based on physiologic and laboratory measurements seldom evaluated in previous studies. Further research should explore the basis for these improvements.

DOI: 10.1053/j.ajkd.2022.08.022

Early Postoperative Acetaminophen Administration and Severe Acute Kidney Injury After Cardiac Surgery by Chao Xiong et al (OPEN ACCESS)

From the authors: There is uncertainty about whether antioxidant medications such as acetaminophen may protect against kidney injury. Therefore, we evaluated the associations between acetaminophen use and kidney outcomes in adults recovering from cardiac surgery in 2 large clinical registries. Acetaminophen treatment was significantly associated with a 14%-16% lower risk of severe and any-stage acute kidney injury but similar risks of kidney replacement therapy and in-hospital mortality. Our findings suggest that acetaminophen use may protect against kidney injury in adult patients recovering from cardiac surgery.

DOI: 10.1053/j.ajkd.2022.11.009

Subcutaneous C.E.R.A. for the Maintenance Treatment of Anemia in Pediatric Patients With CKD: A Phase 2, Open-Label, Single-Arm, Multicenter Study by Bradley A. Warady et al 

From the authors: Anemia, a complication of chronic kidney disease, is associated with poor quality of life and an increased risk of hospitalization and mortality. The current treatments for anemia include iron therapy and erythropoiesis-stimulating agents (ESAs); however, the relatively short half-lives of the ESAs epoetin alfa/beta or darbepoetin alfa may require more frequent dosing and hospital visits compared with the ESA known as continuous erythropoietin receptor activator (C.E.R.A.). A previous study demonstrated that children aged 5 years or more with anemia associated with chronic kidney disease who were on hemodialysis could be switched to intravenous C.E.R.A. from their existing epoetin alfa/beta or darbepoetin alfa treatment. This study provides evidence that subcutaneous C.E.R.A. can safely and effectively treat anemia in children, including those aged <5 years and regardless of whether they were on dialysis or the type of dialysis they received (peritoneal dialysis or hemodialysis).

DOI: 10.1053/j.ajkd.2022.11.006

Age of Onset and Disease Course in Biopsy-Proven Minimal Change Disease: An Analysis From the Cure Glomerulonephropathy Network by Dhruti P. Chen et al 

From the authors: Minimal change disease is a biopsy diagnosis for nephrotic syndrome. It is diagnosed in childhood, adolescence, or adulthood. Patients and clinicians often have questions about what to expect in the disease course and how to plan therapies. We analyzed a group of patients followed longitudinally as part of the Cure Glomerulonephropathy Network (CureGN) and describe the differences in disease (relapse and remission) based on the age of onset. We also analyzed rituximab response. We found that those with childhood-onset disease had a higher rate of relapse but also have a higher probability of reaching remission when compared with adolescent- or adult-onset disease. Children and all steroid-responsive patients are more likely to achieve remission after rituximab.

DOI: 10.1053/j.ajkd.2022.11.012

Association of Acute Kidney Injury and Cardiovascular Disease Following Percutaneous Coronary Intervention: Assessment of Interactions by Race, Diabetes, and Kidney Function by Joseph Lunyera et al

From the authors: This study examined differences by race, diabetes, or kidney function in the well-known association of AKI with increased risk for cardiovascular outcomes among patients undergoing percutaneous coronary intervention. The authors found that AKI was associated with a greater risk for cardiovascular outcomes, but this risk did not differ by patients’ race, diabetes status, or level of kidney function before the procedure. That said, the risk for cardiovascular outcomes was numerically highest among Black patients compared with White patients or those of other races. These study findings suggest that future efforts to prevent AKI among patients undergoing the procedure could reduce racial disparities in risk for unfavorable cardiovascular outcomes afterward.

DOI: 10.1053/j.ajkd.2022.12.013

Review from the June 2023 issue:

Nutritional Epidemiology and Dietary Assessment for Patients With Kidney Disease: A Primer by Valerie K. Sullivan and Casey M. Rebholz (FREE)

Nutritional epidemiology seeks to understand nutritional determinants of disease in human populations using experimental and observational study designs. This primer offers an overview of nutritional epidemiology, including study designs, exposure definition, traditional and novel diet assessment methods, sources of error, and statistical considerations, to guide researchers and clinicians in interpreting and conducting investigations of diet in CKD.

DOI: 10.1053/j.ajkd.2022.11.014

Figure 1 from Sullivan et al, AJKD © National Kidney Foundation

On the Cover: Before the advent of modern medicine, danewort (Sambucus ebulus), a form of elder plant, was used to treat nephrotic syndrome. Cornelius Roelans described in 1484 a child with “whole body swelling” and recommended to “take the tops of elder plant and danewort, cook in white wine and wrap the child in hot clothes by applying the poultice in whole or in part, and so cure him”. In this issue of AJKD, 2 studies highlight the evolution in our understanding and effective treatment of childhood nephrotic syndrome. Durand et al identify novel genetic risk factors for focal segmental glomerulosclerosis in children. Chen et al show that the disease course of biopsy-proven minimal change disease differs in patients with childhood-onset compared with adolescent- or adult-onset disease.

The photograph “Fla¨der” by Susanne Nilsson is released on Flickr under the CC-BY-SA 2.0 license.

Special thanks to Editorial Intern Jeffrey Ha for curating the cover image and drafting the cover blurb for this issue.

SPECIAL COLLECTION: RESEARCH ACROSS THE WORLD

This special collection highlights kidney disease research from around the world. Articles in this collection will be freely available until July 15, 2023.