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 September 2023 issue:

Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year Follow-up by Esther N.M. de Rooij et al [OPEN ACCESS]

From the authors: Abnormal potassium blood levels may increase the risk of death or kidney function decline, especially in older people with chronic kidney disease (CKD). We studied 1,714 patients aged ≥65 years with advanced CKD from the European Quality (EQUAL) study and followed them for 8 years. We found that both low and high levels of potassium were associated with an increased risk of death or start of kidney replacement therapy, with the lowest risk observed at a potassium level of 4.9 mmol/L. In patients with CKD, the focus is often on preventing high blood potassium. However, this relatively high optimum potassium level stresses the potential importance of also preventing low potassium levels in older patients with advanced CKD.

DOI: 10.1053/j.ajkd.2023.03.008

EDITORIAL: Outcomes Associated With Potassium Abnormalities in CKD: It Is Time to Move to Clinical Trials by Csaba P. Kovesdy (FREE)

Long-term Visit-to-Visit Variability in Hemoglobin A_1c and Kidney-Related Outcomes in Persons With Diabetes by Yang Xu et al

From the authors: The evidence for current guideline recommendations derives from clinical trials that focus on a single HbA1c as the definitive measure of efficacy of an intervention. However, long-term visit-to-visit fluctuations of HbA_1c may provide additional value in the prediction of future kidney complications. We evaluated the long-term fluctuations in glycemic control in almost 100,000 persons with diabetes undergoing routine care in Stockholm, Sweden. We observed that higher long-term HbA_1c fluctuation is consistently associated with the risks of chronic kidney disease progression, worsening of albuminuria and acute kidney injury. This finding supports a role for long-term glycemic variability in the development of kidney complications and illustrates the potential usefulness of this metric for risk stratification at the bedside beyond a single HbA_1c test.

DOI: 10.1053/j.ajkd.2023.03.007

EDITORIAL: Long-term Glycemic Variability: A Variable Glycemic Metric Entangled With Glycated Hemoglobin by Mengyao Tang and Sahir Kalim (FREE)

Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19 by Steven Menez et al [OPEN ACCESS]

From the authors:  Patients hospitalized with COVID-19 are at increased risk for long-term adverse health outcomes, but not all patients suffer long-term kidney dysfunction. Identification of patients with COVID-19 who are at high risk for adverse kidney events may have important implications in terms of nephrology follow-up and patient counseling. In this study, we found that the plasma biomarkers soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 measured in hospitalized patients with COVID-19 were associated with a greater risk of adverse kidney outcomes. Along with clinical variables previously shown to predict adverse kidney events in patients with COVID-19, both sTNFR1 and sTNFR2 are also strong predictors of adverse kidney outcomes.

DOI: 10.1053/j.ajkd.2023.03.010

Integrated Analysis of Blood and Urine Biomarkers to Identify Acute Kidney Injury Subphenotypes and Associations With Long-term Outcomes by Pavan K. Bhatraju et al

From the authors: Acute kidney injury (AKI) occurs commonly in hospitalized patients and is associated with high morbidity and mortality. The AKI definition lumps many different types of AKI together, but subgroups of AKI may be more tightly linked to the underlying biology and clinical outcomes. We used 29 different clinical, blood, and urinary biomarkers and applied 2 different statistical algorithms to identify AKI subtypes and their association with long-term outcomes. Both clustering algorithms identified 2 AKI subtypes with different risk of chronic kidney disease, independent of the serum creatinine concentrations (the current gold standard to determine severity of AKI). Identification of AKI subtypes may facilitate linking therapies to underlying biology to prevent long-term consequences after AKI.

DOI: 10.1053/j.ajkd.2023.01.449

Metformin Use and Long-term Clinical Outcomes in Kidney Transplant Recipients by Soie Kwon and Yong Chul Kim et al 

From the authors:  This large-scale retrospective cohort study investigated the effect of metformin use in kidney transplant recipients (KTRs) in terms of all-cause mortality, death-censored graft failure (DCGF), biopsy-proven acute rejection (BPAR), and lactic acidosis occurrence. Metformin administration was associated with a reduced risk of DCGF after adjustment for various factors. In the subgroup analysis, insulin users experienced a more significant benefit from metformin usage. Moreover, no case of metformin-associated lactic acidosis (MALA) was identified, and metformin usage was not associated with an increased risk of all-cause lactic acidosis events. Our results suggest that metformin can be a preferred oral antidiabetic agent in KTRs because of its tendency to reduce the risks of DCGF and the absence of MALA events.

DOI: 10.1053/j.ajkd.2023.01.446

Case Report from the September 2023 issue:

Antiviral Treatment Failures After Transplantation of Organs From Donors With Hepatitis C Infection: A Report of 4 Cases by Julie M. Steinbrink et al [OPEN ACCESS]

The transplantation of organs from donors with hepatitis C virus (HCV) infection into uninfected recipients has expanded the available organ donor pool. With the advancement of direct-acting antivirals (DAAs), high rates of cure among transplant recipients are possible. Although DAAs are highly effective, treatment failure can occur following an appropriate 12-week course of a pan-genotypic regimen. Here we describe 4 kidney transplant recipients of organs from donors with HCV infection (3 with genotype 3, 1 genotype 1a) in whom first-line DAA treatment with either glecaprevir-pibrentasvir or sofosbuvir-velpatasvir was unsuccessful, started 22-35 days after the day of transplantation. All ultimately achieved sustained virologic response with second- or third-line therapy. Post-treatment resistance-associated substitutions were tested and noted to be present in 2 cases. Additionally, antiviral levels were assessed in 2 cases and found to be therapeutic in each. This article explores possible reasons for treatment failure, including medication interactions, bariatric surgery, viral dynamics, and drug resistance.

DOI: 10.1053/j.ajkd.2022.12.006

On the Cover: The cover image captures the salt pans of Marsaskala, Malta at sunrise, a testament to the intricate process of sea salt crystallization. This meticulous process, beginning with seawater filling coastal crevices and culminating in evaporation and crystallization in smaller, warmer pans, stands in stark contrast to the pathological retention of salt in the human body. Excessive salt retention, as seen in primary aldosteronism, can lead to hypertension and end-organ damage. In this issue of AJKD, Hernandez and Bhalla summarize the screening and detection of primary aldosteronism, a common yet often underdiagnosed condition, characterized by excessive aldosterone leading to sodium reabsorption and potassium excretion. The review underscores the need for improved screening and diagnostic practices to address this prevalent, consequential, and treatable disease.

The photograph “Salt flats at sunrise” by Giuseppe Milo is released on Flickr under the CC BY 2.0 license.

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

SPECIAL COLLECTION: HIGHLY CITED ARTICLES

This special collection highlights the top cited Original Investigations published in 2020 and 2021 that contributed to AJKD’s 2022 Impact Factor of 13.2, our highest IF yet. The editors would like to thank all the authors and reviewers who helped AJKD achieve this milestone.