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 September 2022 issue:

Seroresponse to Inactivated and Recombinant Influenza Vaccines Among Maintenance Hemodialysis Patients by Harold J. Manley et al 

From the authors: There are several influenza vaccines available for use, and studies comparing these vaccines have excluded hemodialysis patients or had conflicting results. Among 254 hemodialysis patients, serologic response was observed over a period of 4 months after administration of high-dose trivalent (in 141 patients), standard-dose quadrivalent (in 36 patients), or recombinant quadrivalent (in 77 patients) influenza vaccines. All patients had a robust initial response to vaccines; however, at months 3 and 4 postvaccination, the durability of seroprotection against influenza A strains was significantly greater with high-dose vaccine. Because sustained seroprotection is associated with protection from influenza, particularly severe influenza during the peak of the influenza season, these results can help guide vaccination strategies for patients receiving maintenance dialysis.

DOI: 10.1053/j.ajkd.2022.01.425

Editorial: Influenza Vaccines in Maintenance Hemodialysis Patients: Does Seroresponse Vary With Different Vaccine Formulations? by Tarek Barbar et al [FREE] 

Transplantation of Patients With Long Dialysis Vintage in the Current Deceased Donor Kidney Allocation System (KAS) by Matthew Kadatz et al 

From the authors: In 2014, the wait-time calculation for the kidney transplant waitlist in the United States was changed from the date when patients were first added to the waitlist to the date of first dialysis treatment. The goal of this policy change was of improve access to transplantation. This study examined the impact of this policy change on the outcomes of receipt of a deceased donor transplant, death, and transplant failure. The results showed that this policy change was not only associated with a greater chance of receiving a transplant, but also a longer duration of survival for patients who had been undergoing dialysis for more than 6.5 years.

DOI: 10.1053/j.ajkd.2022.01.429

Editorial: Kidney Transplantation in the Setting of Prolonged Dialysis Vintage: It’s About Time by Adrian M. Whelan et al [FREE] 

A Cost-effectiveness Analysis of Adherence Promotion Strategies to Improve Rejection Rates in Adolescent Kidney Transplant Recipients by Charles D. Varnell, Jr. et al

From the authors: Among teens with a kidney transplant, taking medication can be challenging, and poor adherence increases the risk of rejection and loss of the transplant. Strategies to help patients take medication exist, but some think these strategies are too costly or insufficiently effective. This study describes a clinical approach to improve adherence called the Medication Adherence Promotion System (MAPS) and evaluates its cost-effectiveness by using the costs and outcomes of a single center. Our findings show that this adherence intervention reduced costs and improved outcomes. Other interventions targeting improved adherence that had costs similar to MAPS can still be cost-effective if they decrease the number of rejection episodes even by a small amount.

DOI: 10.1053/j.ajkd.2021.12.013

Association of Frailty With Thrombosis of Hemodialysis Vascular Access: A Prospective Taiwanese Cohort Study by Chien Ming Luo et al 

From the authors: Thrombosis is a serious complication of dialysis vascular access. There is still controversy regarding the association of aging and comorbidities with worse vascular access outcomes. Frailty is highly prevalent in patients receiving maintenance hemodialysis and is an important contributor of mortality and reduced quality of life. We hypothesized that frail patients would have a higher incidence of dialysis access thrombosis than nonfrail Taiwanese patients. Among 761 patients studied, we found that frailty was significantly associated with dialysis access thrombosis even after adjusting for the influence of age and comorbidities. Our findings suggest that the assessment of frailty may provide important information on risk stratification of vascular access thrombosis beyond clinical information.

DOI: 10.1053/j.ajkd.2021.12.017

Clinicopathological Characteristics and Outcomes of PLA2R-Associated Membranous Nephropathy in Seropositive Patients Without PLA2R Staining on Kidney Biopsy by Jiao Luo et al 

From the authors: Membranous nephropathy (MN) with circulating serum phospholipase A₂ receptor (PLA₂R) autoantibodies but no glomerular deposits of PLA₂R antigen on kidney biopsies has been occasionally reported, but the prognosis of this subtype of MN has been rarely reported or investigated. We performed a retrospective study using data from the Nephrology Department of Nanfang Hospital, Southern Medical University (Guangzhou, China), comparing patients with MN with PLA₂R autoantibodies who did and did not have detectable PLA₂R antigen on kidney biopsies. Lack of detectable PLA₂R in glomerular deposits was associated with more severe clinicopathological features, a worse prognosis, a poor response to treatment, and kidney function deterioration. These findings suggest that seropositive PLA₂R-associated MN without evidence of PLA₂R on kidney biopsy may benefit from reevaluation of currently used therapeutic approaches.

DOI: 10.1053/j.ajkd.2022.01.426

Estimated GFR Slope Across CKD Stages in Primary Hyperoxaluria Type 1 by Prince Singh et al 

From the authors: Primary hyperoxaluria is a genetic disorder characterized by increased hepatic oxalate production. Primary hyperoxaluria type 1 (PH1) accounts for the majority of cases. Approximately half of PH1 patients develop kidney failure by the fourth decade of life. The rate of change in eGFR over time has recently been proposed as a surrogate end point for clinical trials in patients with PH1. Using multivariable statistical analysis, eGFR slope estimates were compared across CKD stages in a PH1 cohort. Results suggest that eGFR decline occurs at a higher rate in more advanced CKD stages, an important consideration in design of clinical trials. Measures to prevent early loss of kidney function in PH1 could be particularly important because eGFR decline accelerates in more advanced stages of CKD.

DOI: 10.1053/j.ajkd.2022.01.428

Core Curriculum from the September 2022 Issue:

Principles of Immunosuppression in the Management of Kidney Disease: Core Curriculum 2022 by Sam Kant et al [FREE] 

The management of immunosuppression utilized in glomerular diseases requires highly nuanced care. Timely recognition and management of these disorders is essential to mitigate the extent of kidney damage. This involves being cognizant of the various classes of immunosuppression, which includes alkylating agents, antimetabolites, calcineurin inhibitors, anti-CD20 therapy, complement inhibitors, corticosteroids, and intravenous immunoglobulin. The mechanisms of action of these drugs, along with associated pharmacokinetics and pharmacodynamics, facets of monitoring, and adverse effects are important aspects with which nephrologists are required to be well versed. The overarching principle of these strategies of immunosuppression is to achieve a balance of disease mitigation without exposure to inadvertent harm.

DOI: 10.1053/j.ajkd.2021.12.011

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

Blog Post Interview with the Authors [FREE] 

On the Cover: This purple Trillium erectum is native to the eastern United States. It has been described as the “stinking Benjamin” due to its odor of carrion but has been used for medicinal purposes and as an aid in childbirth. It is hazardous to humans due to its high concentration of calcium oxalate crystals and elongated needle-shaped crystals called raphides. Oxalate-related diseases can come from high exogenous consumption as well as from inborn errors of metabolism like primary hyperoxaluria type 1 (PH1) that cause increased hepatic oxalate production. In this issue of AJKD, Singh et al analyze predictors of GFR decline in patients with PH1.

The photograph “Purple trillium” by Peter Stevens is released on Flickr under the CC BY 2.0 license

Special Collection: HIGHLY CITED Original Investigations

We are delighted to highlight the top cited Original Investigations published in 2019 and 2020 that contributed to AJKD’s 2021 Impact Factor of 11.072, our highest IF yet. This diverse set of articles includes systematic reviews and qualitative studies, and of course, COVID-19 studies. We would like to thank all the authors and reviewers who helped AJKD achieve this milestone.