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 November 2020 issue:   

Impact of ABO-Incompatible Living Donor Kidney Transplantation on Patient Survival by Allan B Massie et al

From the authors: Recipients of ABO-incompatible (ABOi) living donor kidney transplants (LDKT) have a higher risk of graft loss compared to those who receive ABO-compatible (ABOc) LDKT. However, the benefit of ABOi LDKT versus the clinically-relevant comparison, waiting for ABOc LDKT or for a deceased donor kidney transplant (DDKT), remains unknown. Using national registry data, we compared mortality after ABOi LDKT to mortality among a matched control population of patients waitlisted for a kidney transplant who either remained on the waitlist or received an ABOc LDKT or an ABOc DDKT. Compared to conservative therapy, ABOi LDKT was associated with higher mortality risk in the first 30 days post-transplant, but lower mortality risk beyond 180 days post-transplant. Transplant recipients who survive more than 180 days post-transplant receive a survival benefit from undergoing ABOi LDKT versus remaining on the waitlist to receive an ABOc LDKT or an ABOc DDKT.

DOI: 1010.1053/j.ajkd.2020.03.0298

Editorial: Who Benefits From ABO-Incompatible Kidney Transplantation in the Contemporary Era? by Adnan Sharif [FREE] 

Podocyte Antigen Staining to Identify Distinct Phenotypes and Outcomes in Membranous Nephropathy: A Retrospective Multicenter Cohort Study by Nicolas Hanset and Selda Aydin et al 

From the authors: Recent years have brought the identification of M-type phospholipase A2 receptor (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), exostosin (EXT), and neural epidermal growth factor-like1 protein (NELL-1) as established or potential podocyte antigens in membranous nephropathy. In a retrospective multicenter cohort study, we applied the gold-standard method of podocyte antigen immunostaining for 177 consecutive patients with membranous nephropathy unrelated to lupus erythematosus to investigate the prevalence, clinical phenotypes, and outcomes of the different subgroups. PLA2R-positive, THSD7A-positive, and double-negative membranous nephropathy were noted among 66%, 3.5%, and 30.5% of biopsies, respectively. Among biopsies negative for both these markers, EXT and NELL-1 were noted in 8% and 5%, respectively. THSD7A-positive cases had the highest risk for cancer during follow-up. These real-world data support the clinical relevance of a novel classification of membranous nephropathy based on podocyte antigen staining.

DOI: 10.1053/j.ajkd.2020.04.013

Editorial: Antigens in Membranous Nephropathy: Progress Toward Precision by Cynthia C. Nast [FREE] 

Electronic Decision Support for Management of CKD in Primary Care: A Pragmatic Randomized Trial by Carmen A Peralta et al [Open Access]

From the authors: Most adults with chronic kidney disease (CKD) in the U.S. are cared for by primary care providers (PCP). We conducted a clinical trial to evaluate the feasibility and effectiveness of an electronic clinical decision support system (eCDSS) within the electronic health record (EHR) designed to help primary care doctors improve CKD care. We studied 524 adults with CKD, cared for by 80 PCPs in San Francisco. While this study had limited power and did not show significant differences in blood pressure, electronic clinical decision support did increase primary care doctors’ awareness of CKD.

DOI: 10.1053/j.ajkd.2020.05.013

Editorial: CKD Management in Primary Care: Supporting Systems Change by Kathryn Foti and Alex R Chang [FREE] 

Particulate Air Pollution and Progression to Kidney Failure With Replacement Therapy: An Advanced CKD Registry–Based Cohort Study in Taiwan by Yu-Ting Lin et al

From the authors: Fine particulate air pollution is an emerging health risk affecting a wide range of adverse health outcomes. Prior research has identified the potential nephrotoxic effects of PM2.5 in general population. However, the effect of PM2.5 exposure on the progression to end-stage renal disease (ESRD) in patients with chronic kidney disease (CKD) is unclear. Our results suggest that chronic exposure of PM2.5 accelerates progression of CKD to ESRD and that higher concentrations are associated with faster rates of progression. More evidence is required to confirm the generalizability of these findings. If they are reproducible, regulatory actions to improve kidney health by reducing environmental PM2.5 exposure may be warranted.

DOI: 10.1053/j.ajkd.2020.02.447

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study by Seolhye Kim et al [FREE temporarily] 

From the authors: Kidney stones are common worldwide and are closely associated with metabolic syndrome. Since it is unclear whether high levels of blood sugar increase the risk of kidney stones, we evaluated the association between glucose, HbA1C, a long-term measure of glucose levels in the blood, and insulin resistance, with new-onset kidney stones. In this large cohort of Korean adults followed with kidney imaging using ultrasonography, higher levels of glucose, HbA1C, and insulin resistance were associated with an increased risk of kidney stones among men. This elevated risk was apparent during the condition of pre-diabetic when blood sugar levels were higher than normal, but not sufficiently high for the diagnosis of diabetes. These findings suggest that insulin resistance and hyperglycemia, even during the period of prediabetes, may contribute to the development of kidney stones among men

DOI: 10.1053/j.ajkd.2020.03.013

Arteriolar C4d in IgA Nephropathy: A Cohort Study by Bernardo Faria et al

From the authors: IgA Nephropathy is a challenging disease for nephrologists due to its frequency, heterogeneity, and potential to cause kidney failure. Recent studies have demonstrated that glomerular C4d deposition representing activation of the lectin complement pathway can be used to identify a subgroup of patients with poor outcomes. The vascular compartment in IgAN biopsies, however, has not been fully examined for C4d deposition. Consequently, we studied the clinical relevance of arteriolar C4d deposition and found it to be significantly associated with disease progression even after controlling for established predictors and glomerular C4d. These findings suggest that deposition of C4d in the vascular compartment of the kidneys may be a useful prognostic biomarker of IgAN disease progression and enable a more personalized approach to this disease.

DOI: 110.1053/j.ajkd.2020.03.017

Kidney tissue from patients with immunoglobulin A nephropathy (IgAN) was stained for the presence of C4d through immunohistochemistry (IHC). Both glomerular (C4dG) and arteriolar (C4dA) staining was evaluated. (A) Negative C4dA IHC, (B) negative C4dG IHC, (C) positive C4dA IHC, and (D) positive C4dG IHC. Figure 1 from Faria et al, AJKD © National Kidney Foundation

Blog Post: The Serendipitous Complement of IgA Nephropathy: Are We Futuristic Yet? by Priti Meena [FREE]  

COVID-19 Outbreak in an Urban Hemodialysis Unit by Kevin Yau et al [FREE]  

From the authors: The coronavirus disease 2019 (COVID-19) pandemic has presented unique challenges to patients receiving hemodialysis. Dialysis patients who have risk factors for severe infection must visit health care facilities thrice weekly, where physical distancing is challenging. Despite protocols in place to identify and isolate symptomatic individuals, we report a COVID-19 outbreak in a hemodialysis unit in Toronto, Ontario, that prompted the screening of all hemodialysis patients and most staff for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in nasopharyngeal swab specimens, regardless of symptoms. Eleven of 237 (4.6%) hemodialysis patients and 11 of 93 (12%) staff tested positive for COVID-19. Notably, 55% of those with positive test results were asymptomatic at the time of testing. This study demonstrates the importance of universal testing in stopping the spread of COVID-19 during an outbreak.

DOI: 10.1053/j.ajkd.2020.07.001

Blog Post: COVID-19 in ESKD: Managing a Vulnerable Population During a Pandemic by Anthony Valeri [FREE]  

Estimating Shortages in Capacity to Deliver Continuous Kidney Replacement Therapy During the COVID-19 Pandemic in the United States by Yuvaram NV Reddy et al [FREE]  

From the authors: Despite strategic planning, New York encountered continuous kidney replacement therapy (CKRT) shortages during the initial wave of the coronavirus disease 2019 (COVID-19) pandemic. To improve future planning, we developed mathematical models to project CKRT demand and capacity in the United States by state. Shortages were projected in 6 states during the initial wave of the COVID-19 pandemic, with possible shortages in 8 additional states. Currently, these models are based on limited data on CKRT demand and capacity across the United States. This limitation highlights the potential value of collecting national data on dialysis machines, supplies, and personnel using an inpatient kidney replacement therapy national registry and the creation of a federal stockpile of CKRT equipment.

DOI: 10.1053/j.ajkd.2020.07.005

This month’s Policy Forum:

US Organ Procurement Organization Donation Principles, Laws, and Practices by Thomas Mone and Gabriel Danovitch [FREE] 

From the authors: US organ procurement organizations (OPOs) are the world’s donation leaders, with 109 deceased donor transplantations per million population and a 38% increase in donations during the past 5 years. This growth has helped decrease waiting lists by 10% during the past several years despite an increase in the prevalence of kidney failure. During the 2014 to 2019 period, donations have increased in 91% of the 58 OPOs, with those achieving the greatest growth showing increases ≥ 165%. These changes are statistically independent of OPO geographical size, population, death rate, region, race/ethnicity, and leadership tenure. Although OPO population and potential donor demographics differ dramatically, donation growth rates and number of donors are within 1.5 standard deviations of the mean for 90% of OPOs, reflecting that they all share the legal and operational principles and practices described here.

DOI: 10.1053/j.ajkd.2020.05.022

On the Cover: Devastating wildfires in California and the Pacific Northwest have become increasingly common in recent years. The intense smoke generated by these large and fast-moving fires can create an eerie glow in the skies. Many thousands of residents of the West Coast this year and recent prior years have had to contend with air quality during these fires that presents immediate and long-term threats to health. Beyond the devastation from loss of life and property, wildfire smoke widely disperses fine particulate matter (<2.5mm diameter; PM2.5) into the atmosphere that readily enters the lungs and bloodstream. Emerging evidence such as that presented in this issue of AJKD by Lin et al expands upon the set of deleterious effects of air pollution, offering evidence that chronic exposure to PM2.5 accelerates the rate of progression of CKD and the occurrence of ESKD.

The photograph “bad air” is by Eric on Flickr, released under the CC BY 2.0 license.

Special Collection: Acute Kidney Injury

This special collection on AKI includes articles ranging from tools for predicting of AKI, to epidemiologic studies, to biomarkers, among others. Each article in its own way helps to advance the understanding of AKI and improve the care of patients with it. All articles in the collection are freely available until February 1, 2021.