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 January 2021 issue [FREE temporarily]:   

Treating Home Versus Predialysis Blood Pressure Among In-Center Hemodialysis Patients: A Pilot Randomized Trial by Nisha Bansal et al

From the authors: Home blood pressure may be a better target for treatment compared with blood pressure measured at the time of dialysis in hemodialysis patients. In this pilot clinical trial, we tested the feasibility of measuring and treating home blood pressure (compared with treating blood pressure at the time of hemodialysis) during 4 months in 50 participants at 2 sites. Enrollment rates were high in the trial and nearly all participants completed the study. We observed high rates of adherence to home blood pressure measures and promising safety signals. In conclusion, this trial demonstrates that measurement of home blood pressure is feasible in hemodialysis patients. Larger studies are needed to test the long-term effect and safety of treating home blood pressure in hemodialysis patients.

DOI: 10.1053/j.ajkd.2020.06.014

Editorial: Can We Study Hypertension in Patients on Dialysis? Yes We Can by Panagiotis I Georgianos and Rajiv Agarwal [FREE] 

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program by Brendon L Neuen et al 

From the authors: Canagliflozin reduces the risk for cardiovascular and kidney outcomes in patients with type 2 diabetes. This post hoc analysis of the phase 3 randomized placebo-controlled CANagliflozin cardioVascular Assessment Study (CANVAS) Program (n = 10,142) assessed the effect of canagliflozin on these outcomes in participants with different levels of risk for chronic kidney disease outcomes, defined by the KDIGO (Kidney Disease: Improving Global Outcomes) classification based on estimated glomerular filtration rate and urinary albumin-creatinine ratio. The relative effects of canagliflozin on cardiovascular and kidney outcomes were similar across KDIGO risk categories, but absolute risk reductions were likely greater for individuals within higher-risk KDIGO categories. The KDIGO classification system may be able to be used to identify individuals who would derive greater benefits for end-organ protection from treatment with canagliflozin.

DOI: 10.1053/j.ajkd.2020.06.018

Editorial: What Is the Utility of KDIGO Criteria to Identify High-Risk Populations? by Christoph Wanner and Kai Lopau [FREE] 

Modulation of the Association of Hypobicarbonatemia and Incident Kidney Failure With Replacement Therapy by Venous pH: A Cohort Study by Sachio Kajimoto et al 

From the authors: Metabolic acidosis often occurs in patients with chronic kidney disease (CKD). It is known that lower bicarbonate levels are associated with increased risk for progression for kidney failure requiring replacement therapy (KFRT). However, previous studies did not consider the influence of blood pH. This study assessed how pH measured in venous blood modified the relationship between hypobicarbonatemia and KFRT. We found that nearly 40% of patients with CKD with hypobicarbonatemia did not have associated acidemia (pH < 7.32). In addition, these patients did not have an increased risk for KFRT. In contrast, hypobicarbonatemia was associated with considerable risk for KFRT among patients with acidemia. Therefore, venous pH measurement may be valuable for identifying patients with CKD and hypobicarbonatemia and may inform their treatment.

DOI: 10.1053/j.ajkd.2020.06.019

Editorial: Assessing Acid-Base Status in Patients With CKD: Does Measurement of Blood pH Matter? by Kalani L Raphael and Jeffrey A Kraut [FREE] 

Adiposity, Physical Function, and Their Associations With Insulin Resistance, Inflammation, and Adipokines in CKD by Sankar D Navaneethan et al

From the authors: Obesity as assessed by body mass index is associated with increased risk for heart disease and progression of kidney disease in those with chronic kidney disease (CKD). In this cohort of patients with CKD, we studied whether different obesity measures such as intra-abdominal fat, liver fat, and subcutaneous fat (obtained using magnetic resonance imaging) were associated with known cardiometabolic risk factors. We further assessed whether physical function (measured using a 400-m walk test) was independently associated with the same cardiometabolic risk factors. Our analysis suggests that all measures of higher fat content were associated with an increased level of cardiometabolic risk factors. Although slower walk time was associated with increased levels of cardiometabolic risk factors, it did not modify associations between fat measures and these risk factors. In summary, these data highlight that various abdominal fat measures and lower physical fitness levels are associated with higher cardiovascular risk in those with CKD.

DOI: 10.1053/j.ajkd.2020.05.028

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study by Amanda H Anderson et al [Open Access]

From the authors: The primary goal of this study was to identify independent risk factors for chronic kidney disease (CKD) progression among participants with and without diabetes in a prospective CKD cohort study involving 3,379 participants. Among those with diabetes, CKD progression rates approximately doubled with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro–B-type natriuretic pep-tide (NT-proBNP), and the kidney injury marker urinary neutrophil gelatinase-associated lipocalin (NGAL). Among those without diabetes, rates increased more than 1.5-fold with higher levels of high-sensitivity troponin T, NT-proBNP, and urinary NGAL. The strength of these associations was comparable to that of systolic blood pressure ≥ 140 mm Hg, a well-established risk factor for kidney disease progression. These findings provide insights into potential mechanisms of CKD progression and will guide future research in defining subgroups at highest risk for CKD progression.

DOI: 10.1053/j.ajkd.2020.07.011

Association Between Midlife Physical Activity and Incident Kidney Disease: The Atherosclerosis Risk in Communities (ARIC) Study by Kaushik Parvathaneni et al 

From the authors: In this study, we evaluated the association between physical activity and risk for developing chronic kidney disease (CKD). We conducted a secondary analysis of the Atherosclerosis Risk in Communities Study, which is a community-based prospective multicenter cohort study of 15,792 middle-aged Black and White men and women in the United States. During a median follow-up of 24 years, 33.2% of participants developed CKD. After adjusting for confounding variables, the most physically active group had a statistically significant 11% reduction in risk for CKD when compared with the inactive group. Further research is needed to determine whether increasing physical activity can prevent the onset or progression of CKD.

DOI: 10.1053/j.ajkd.2020.07.020

Multicenter Clinicopathologic Correlation of Kidney Biopsies Performed in COVID-19 Patients Presenting With Acute Kidney Injury or Proteinuria by Shreeram Akilesh et al

From the authors: Acute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19). We undertook a multicenter study to evaluate kidney biopsy findings in living patients to identify different kidney disease pathology in patients with COVID-19. Most patients in this case series developed AKI concurrent with mild COVID-19 symptoms. AKI and proteinuria were the most common indications for biopsy. Both common and rare pathologic processes such as acute tubular injury, collapsing glomerulopathy, and endothelial injury/thrombotic microangiopathy were the most common histologic findings. Two of the 3 transplant recipients developed active antibody-mediated rejection weeks after COVID-19. These data suggest that even symptomatically mild COVID-19 can be associated with AKI and/or heavy proteinuria and may warrant diagnostic kidney biopsy.

DOI: 10.1053/j.ajkd.2020.10.001

This month’s Special Report:

SGLT2 Inhibition for CKD and Cardiovascular Disease in Type 2 Diabetes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation by Katherine R Tuttle et al 

Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels. To clarify and support their role in the treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions to propose therapeutic approaches and delineate future research. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.

DOI: 10.1053/j.ajkd.2020.08.003

This month’s Perspective:

State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies by Julia J. Scialla et al 

This perspective discusses the current state of knowledge and evidence gaps for use of phosphate binders with an emphasis on the choice of phosphate-binding agents in CKD and kidney failure.

DOI: 10.1053/j.ajkd.2020.05.025

Blog Post: Management of Hyperphosphatemia in Patients With CKD Leaves Nephrologists in a Bind by Diana Mahbod [FREE] 

This month’s Narrative Review:

The Evolving Role of Novel Biomarkers in Glomerular Disease: A Review by Corey Cavanaugh and Mark D. Okusa

Although kidney biopsies are considered the gold standard in profiling glomerular diseases, validated novel glomerular biomarkers contribute substantially to the diagnostic and therapeutic approaches through their ability to improve sensitivity, permit dynamic longitudinal monitoring of disease activity, and capture genetic heterogeneity. We describe the value of specific biomarkers in selected glomerular diseases, with the major focus on their clinical applicability.

DOI: 10.1053/j.ajkd.2020.06.016

Blog Post: Glomerular Biomarkers – Peering Into the Future An Interview with Corey Cavanaugh [FREE] 

Intramolecular epitope spreading of the anti–phospholipase A2 receptor antibody (anti-PLA2R) versus baseline multidomain recognition. The reactivity of anti-PLA2R antibodies to a ubiquitous epitope in the cysteine-rich (CysR) domain (left) “spreads” to include subdominant epitopes of the first (center, C-type lectin domain [CTLD1]) and seventh and eighth CTLDs (right, CTLD7 and CTLD8) distinct from the CysR epitope. Disease progression is positively correlated with greater urinary protein excretion and patient age and inversely correlated with the likelihood of remission. An alternative hypothesis is that antibodies to multiple domains are present at the time of diagnosis, and progression of disease is correlated with total anti-PLA2R antibody levels. Abbreviation: FNII, fibronectin type II domain. Figure 1 from Cavanaugh and Okusa, AJKD © National Kidney Foundation

On the Cover: The Rio Tinto arises in the Sierra Morena mountain range of Andalusia in Spain. Its exquisite red hues derive from the high content of dissolved iron salts and sulfides. This mineral content contributes to the river’s extreme acidity which prevents most forms of aquatic life and provides an ideal environment for red and green algae as well as chemo-lithoautotrophic microorganisms whose products of metabolism further acidify the aqueous environment. The adaptation of the Tinto’s biome to extreme acidic conditions is evocative of humans’ ability to adapt to acidification of their internal environments. Hypobicarbonatemia, a hallmark of metabolic acidosis, has been associated with progression of chronic kidney disease in humans but little is known about the effects of acidemia on this association. In this issue of AJKD, Kajimoto et al explore the impact of acidemia on the association between hypobicarbonatemia and CKD progression.

The photograph “Peña del Hierro-Nerva (Huelva) (Spain)” is by Jose A. on Flickr, released under the CC-BY 2.0 license.

2020 Editors’ Choice Award

In 2017, we established an annual celebration of articles that our editorial team designated as “Editors’ Choice” selections. The editors are delighted to recognize five articles that have been selected to receive the 2020 Editors’ Choice Award. These articles will be freely available at AJKD.org until January 15, 2021.