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 July 2019 issue:

Effects of Hydroxychloroquine on Proteinuria in IgAN: A Randomized Controlled Trial by Li-Jun Liu, et al 

From the authors: IgA nephropathy (IgAN) is the most prevalent form of primary glomerular disease. Despite the optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, patients with IgAN may still develop kidney failure, the risk for which is correlated with the level of proteinuria. The effectiveness of treatment with corticosteroids is controversial, and their associated adverse side effects limit their use and make the identification of new therapies compelling. This manuscript describes a randomized placebo-controlled clinical trial focusing on the efficacy and safety of hydroxychloroquine (HCQ) (a drug that modulates the immune system) in patients with IgAN. It showed that HCQ in addition to optimized RAASi treatment significantly reduced proteinuria in patients with IgAN over 6 months without evidence of adverse outcomes. These findings, if confirmed, suggest that HCQ might be a new treatment option for IgAN.

DOI: 10.1053/j.ajkd.2019.01.026

Editorial Antimalarials in IgA Nephropathy: Did Our Supportive Therapy Armamentarium Just Increase? by Jürgen Floege [FREE] 

Cost-effectiveness of Pneumococcal Vaccination Among Patients With CKD in the United States by Junichi Ishigami, et al  [FREE] 

From the authors: Pneumococcal vaccine is recommended for adults aged ≥65 years and <65 years with clinical indications such as diabetes, lung/heart disease, and advanced kidney disease (kidney failure and nephrotic syndrome). In this study, to explore the cost-effectiveness of expanding its indication to adults aged <65 years with less advanced kidney disease, we assessed the costs and benefits of pneumococcal vaccination among adults aged 50-79 years with and without kidney disease. We found that the benefits of pneumococcal vaccination generally outweighed its costs in this population. Among adults aged 50-64 years, pneumococcal vaccine is more cost-effective in those with kidney disease than those without. Thus, the study suggests the cost-effectiveness of expanding its indication to younger adults with less advanced kidney disease.

DOI: 10.1053/j.ajkd.2019.01.025

Editorial A New Indication for Pneumococcal Vaccination? by Michael Z. David [FREE] 

Progressive Decline in Estimated GFR in Patients With Sickle Cell Disease: An Observational Cohort Study by Vimal K. Derebail, et al

From the authors: Sickle cell disease is a group of inherited conditions that lead to distortion of red blood cells and damage to many organs, including the kidneys. We reviewed medical records of over 400 patients with sickle cell disease followed at our medical center. We found that those with more severe inherited forms of the disease had more rapid loss of kidney function over time than that expected for healthy individuals. Among these patients, signs of severe disease in other organs predicted kidney disease at the start of the study. Higher blood counts, suggesting less breakdown of red blood cells, were associated with slower loss of kidney function. These results will help to guide future planned studies of kidney disease in sickle cell patients.

DOI: 10.1053/j.ajkd.2018.12.027

Blog Post Sickle Cell Disease: Peering Behind the Veil… by Ed Gould [FREE] 

An Ex Vivo Test of Complement Activation on Endothelium for Individualized Eculizumab Therapy in Hemolytic Uremic Syndrome by Miriam Galbusera, et al 

From the authors: Primary atypical hemolytic uremic syndrome (aHUS) is a rare condition characterized by anemia, thrombocytopenia and kidney failure. aHUS is associated with genetically-determined dysregulation of the alternative complement pathway, resulting in endothelial injury and microvascular thrombosis. The complement inhibitor eculizumab effectively induces disease remission, but the need for chronic treatment, its high cost, and the risk of infections make individualizing treatment regimens an important goal. By using an ex-vivo test of serum-induced complement deposits on cultured endothelial cells in a series of patients, we detected endothelial-restricted complement activation in aHUS, which normalized under eculizumab. All patients in remission taking eculizumab at extended dosing intervals (3-4 weeks) demonstrated normal serum-induced deposits on endothelium. During eculizumab tapering and after discontinuation, all patients experiencing relapses had elevated complement deposits on unstimulated endothelium. This ex-vivo endothelial assay holds promise to advance our ability to implement personalized eculizumab therapy in aHUS.

DOI: 10.1053/j.ajkd.2018.11.012

Transcriptomics of Human Arteriovenous Fistula Failure: Genes Associated With Nonmaturation by Laisel Martinez, et al 

From the authors: Maturation failure of arteriovenous fistulas (AVF) is the most frequent postsurgical complication in hemodialysis patients. The biological causes of AVFs failing to non-maturation are unknown. This clinical study evaluated whether changes in gene expression in the pre-access vein or in the postoperative AVF tissue are associated with failure to mature. We found that higher expression of five inflammatory genes in smooth muscle cells of pre-access veins was associated with the risk of AVF non-maturation. These findings provide a framework for future confirmatory studies to find therapeutic targets to prevent AVF maturation failure.

DOI: 10.1053/j.ajkd.2018.12.035

Image: Pixabay / qimono

Blog Post Applying Transcriptomics to Fistula Failure – A Novel Approach by Paul Phelan [FREE] 

Identifying Important Outcomes for Young People With CKD and Their Caregivers: A Nominal Group Technique Study by Camilla S. Hanson, et al 

From the authors: This study aimed to determine what outcomes are important to young people with chronic kidney disease (CKD) and their caregivers. We found that the highest ranked outcomes for patients were survival, physical activity/sports participation, fatigue, lifestyle restrictions, and growth, and for caregivers were kidney function, survival, infection, anemia, and growth. Young people with CKD greatly prioritized the outcomes that directly affected their lifestyle and sense of normality or reflected immediate health concerns, while caregiver’s highest priorities concerned the long-term health of their child, as well as their current health problems and the financial and family burdens of caring for a child with CKD. Research that reports outcomes that are important to young people with CKD and their caregivers can better inform shared decision-making.

DOI: 10.1053/j.ajkd.2018.12.040

[Narrative Review] International Variations in Peritoneal Dialysis Utilization and Implications for Practice by Victoria Briggs, et al 

In many countries, the use of peritoneal dialysis (PD) remains low despite arguments that support its greater use, including dialysis treatment away from hospital settings, avoidance of central venous catheters, and potential health economic advantages. This review explores the factors that explain the considerable international variation in the use of PD and presents interventions that can potentially affect them.

DOI: 10.1053/j.ajkd.2018.12.033

Figure 1 from Briggs et al, AJKD © National Kidney Foundation. 

Blog Post Applying Transcriptomics to Fistula Failure – A Novel Approach by Nathaniel Reisinger [FREE] 

On the Cover: This month’s cover, a drawing from the early 20th century by David Louis Ghilchik, a Romanian-British cartoonist, imagines how the newly developed medium of television might revolutionize the practice of medicine. Ghilchik may have been motivated by AT&T’s experimentation with video phones in the 1920s. Forty years later, company’s Picturephone service launched, the precursor of modern video conferencing platforms. Since then, interest in using these developing technologies to promote health has grown, particularly for transforming health care delivery overlarge distances. Marking the maturation of these approaches, by 2010, Accountable Care Organizations often incorporated telehealth programs in efforts to expand access to health care services in the United States. By 2018, the Bipartisan Budget Act extended telehealth access to homedialysis patients, a step that promises to promote patient-centered care. In this month’s Policy Forum, Lew and Sikka discuss these regulatory changes, as well as the technical and operational challenges of implementing telehealth programs.

“A doctor on the telephone (which is linked up to a television screen) to a patient whom he can both observe and talk to from a distance; representing possible technical innovations.” Line block after D.L. Ghilchip, 1932. From the Wellcome Collection, available under CC BY license.

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) from a high-impact journal; 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.