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 October 2020 issue:

Exome Sequencing and Identification of Phenocopies in Patients With Clinically Presumed Hereditary Nephropathies by Korbinian M Riedhammer et al

From the authors: Clinicians make tentative diagnoses of a genetic disease based on the patients’ clinical presentations. However, clinical presentations may resemble a specific hereditary disease despite the absence of a causative genetic variant in the gene(s) generally associated with the disease. In these circumstances another diagnosis may be made from broader genetic testing (phenocopy). Exome sequencing is a comprehensive method of genetic testing that can identify causative genetic variants in hereditary kidney diseases independent of the clinical diagnosis. In this study of 174 index patients with clinically presumed hereditary kidney disease, we showed that in nearly 20% of cases, the clinical diagnosis was different than the genetic diagnosis established by exome sequencing. A correct genetic diagnosis is important for clinical management, prognosis, and recurrence risk in offspring.

DOI: 10.1053/j.ajkd.2019.12.008

Editorial: Phenocopies, Phenotypic Expansion, and Coincidental Diagnoses: Time to Abandon Targeted Gene Panels? by Dina F Ahram et al [FREE] 

Acute Kidney Injury Events in Patients With Type 2 Diabetes Using SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs: A Retrospective Cohort Study by Christie Rampersad et al 

From the authors: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are used to treat type 2 diabetes mellitus and have been associated with slower progression of chronic kidney disease. The US Food and Drug Administration has warned that they may lead to increased risk of acute kidney injury (AKI). We retrospectively studied a cohort of patients in Manitoba, Canada, who began treatment with an SGLT2 inhibitor and compared them to patients who were started on another glucose lowering drug. We examined changes in kidney function after drug initiation and did not find the use of SGLT2 inhibitors to be associated with a higher risk of AKI.

DOI: 10.1053/j.ajkd.2020.03.019

Editorial: We Can Finally Stop Worrying About SGLT2 Inhibitors and Acute Kidney Injury by Vikas S Sridhar et al [FREE] 

Blog Post: SGLT2 Inhibitors and AKI: Time to Ditch the Dogma by Krishna Penmatsa [FREE] 

Arteriovenous Fistula Placement, Maturation, and Patency Loss in Older Patients Initiating Hemodialysis by Joyce Z Qian et al

From the authors: The role of age in making clinical recommendations for arteriovenous fistula (AVF) placement is unclear. We assessed the association of age with AVF placement, maturation, and primary and secondary patency loss in a national retrospective cohort of older hemodialysis patients. We found increasing age was significantly associated with a lower probability of fistula placement and maturation. However, in patients with a matured fistula, primary and secondary patency loss did not differ across age groups. The likelihood of fistula maturation is an important consideration for vascular access planning in elderly. Older patients should not be excluded for fistula placement simply because of their age and the decision to place a fistula should be based on an individualized approach.

DOI: 10.1053/j.ajkd.2020.02.449

Editorial: The New Age of Vascular Access: Choosing the Right Access for the Right Reason in Older Hemodialysis Patients by Crystal Farrington and Timmy C Lee [FREE] 

Serologic Detection of SARS-CoV-2 Infections in Hemodialysis Centers: A Multicenter Retrospective Study in Wuhan, China by Hui Tang et al [FREE]

DOI: 10.1053/j.ajkd.2020.06.008

Recurrence of DNAJB9-Positive Fibrillary Glomerulonephritis After Kidney Transplantation: A Case Series by Mireille El Ters et al [FREE]

From the authors: In this case series, we used sequential protocol allograft biopsies and DNAJB9 staining to help characterize the natural history of patients with native kidney FGN who underwent kidney transplantation. DNAJB9 staining was used as a tool to aid in the diagnosis of native fibrillary glomerulonephritis (FGN), specifically to confirm/exclude cases of native FGN where its diagnosis was ambiguous and to detect the earliest stage of recurrent FGN in the allograft. Utilizing DNAJB9 staining on at least the last protocol allograft biopsy, we were able to characterize incident and recurrent FGN. We also reviewed the presence or absence of monoclonal gammopathy to identify potential associations with recurrence.

DOI: 10.1053/j.ajkd.2020.01.018

Metabolomic Markers of Kidney Function Decline in Patients With Diabetes: Evidence From the Chronic Renal Insufficiency Cohort (CRIC) Study by Brian Kwan et al 

From the authors: Individuals with diabetes are at high risk for kidney disease. While clinical factors, e.g., hemoglobin A1c, blood pressure, and proteinuria, are prognostic for diabetic kidney disease (DKD) progression, there is substantial heterogeneity in rates of kidney function decline across patients with similar clinical profiles. Metabolites are small molecules that reflect end-products of cellular function, and thus could offer insights into physiological effects of chronic diseases. In this work we focused on 13 metabolites that reliably characterized patients with DKD vs healthy nondiabetic controls in cross-sectional analysis. Aiming to predict DKD progression, we implemented rigorous multivariate analysis and identified four metabolites that strongly predicted future DKD, after adjusting for clinical factors. Metabolomics may offer new biomarkers and biological insights into DKD.

DOI: 10.1053/j.ajkd.2020.01.019

Risks of Hip and Nonvertebral Fractures in Patients With CKD G3a-G5D: A Systematic Review and Meta-analysis by Tatiane Vilaca et al 

From the authors: Chronic kidney disease (CKD) affects bone health but the effect on fracture risk has not been explored. We conducted a systematic review and meta-analysis on the risks of hip and non-spine fractures in people with CKD. We included results from adults suffering from all stages of CKD. We found a 47% increase in the risk of non-spine fractures and a 2-fold increase in the risk of hip fractures. At the hip, younger age and more severe CKD were associated with greater increase in fracture risk. These findings suggest that fracture prevention should be a consideration in patients with kidney disease at any age.

DOI: 10.1053/j.ajkd.2020.02.450

Developing Consensus-Based Outcome Domains for Trials in Children and Adolescents With CKD: An International Delphi Survey by Charlotte Logeman et al 

From the authors: This study uses an international online Delphi survey to achieve consensus among children with chronic kidney disease (CKD), family members, and health professionals on outcomes that are critically important for trials in children with CKD. Mortality, life participation, kidney function, and blood pressure were consistently highly prioritized by patients, caregivers, and health professionals. Consistent reporting of these critically important outcomes in trials ensures that the evidence is relevant and useful for decision-making and care of children with CKD.

DOI: 10.1053/j.ajkd.2020.03.014

This month’s Policy Forum:

Social Media and Kidney Transplant Donation in the United States: Clinical and Ethical Considerations When Seeking a Living Donor by Macey L Henderson et al [FREE]

A Twitter post showing a man in a sports jersey holding a sign telling of his need for a kidney went “viral.” After the sports team’s official account retweeted the original post, hundreds of thousands of Twitter users engaged with the tweet and many replied to the tweet asking about being a directed living kidney donor for the man pictured.

DOI: 10.1053/j.ajkd.2020.03.027

Blog Post To Post or Not to Post: Ethics of Social Media Use in Living Donation and Kidney Transplantation by Tiffany Truong [FREE]

On the Cover: Every fall, Coloradans look forward to the brilliant autumnal colors of the aspen trees. Miles of hiking trails and scenic drives reveal beautiful landscapes as the green leaves turn to radiant yellow and gold. This same time of year we usually look forward to attending the American Society for Nephrology’s Kidney Week, which this year was to have taken place in Denver, Colorado. The ongoing COVID-19 pandemic has compelled the conversion of this annual in-person conference to a fully virtual event this October. While disappointed to miss out on meeting up with all our AJKD friends, we are pleased to showcase the extraordinary beauty of the Centennial State on this month’s cover, and look forward to joining the virtual conference to learn more about clinical and research innovations in our understanding and management of kidney disease.

The photograph “Aspens1-9” is by Thomas Elliott on Flickr and was released into the public domain.

AJKD Express

Recognizing the efficiency losses to authors and reviewers when a manuscript turned down by a high-profile journal is submitted to a new journal, AJKD is excited to offer a new expedited consideration process for manuscripts that meet the following criteria:

1. The manuscript reports original research within the scope of AJKD and could be reformatted to AJKD style; and
2. The authors supply an unmodified decision letter (including reviews) sent from a high-impact journal within the last 30 days; and
3. The author list excludes any AJKD EIC/Deputy Editor/Education Editor/Associate Editor/International Editor.

In this accelerated manuscript consideration process, the editors aim to provide to authors:

• Notification within 2 business days indicating eligibility for AJKD Express
• Decision letter within a further 5-14 days

Details for AJKD Express are available in this blog post.