The entire November issue is FREE until November 30th in celebration of Kidney Week

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 2022 issue:

Apixaban Dosing Patterns Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation Receiving Dialysis: A Retrospective Cohort Study by James B. Wetmore et al 

From the authors: Some patients on dialysis who have atrial fibrillation receive apixaban for stroke prevention at a dose below that indicated by the official drug label to reduce adverse bleeding events. Using US Renal Data System data, we compared apixaban dosed according to the label, apixaban dosed below the label, and warfarin to assess each regimen’s association with stroke prevention, major bleeding, and death. We found that apixaban, regardless of dosing strategy, was associated with a lower risk of major bleeding than warfarin. When dosed in accordance with the label, apixaban appears to be associated with a lower risk of death compared with warfarin. There were no differences in stroke prevention among any of the 3 treatment approaches. Apixaban dosed in accordance with the label may provide the most favorable benefit-risk trade-off in dialysis patients with atrial fibrillation.

DOI: 10.1053/j.ajkd.2022.03.007

Editorial: Anticoagulation for Stroke Prevention in Atrial Fibrillation by Nicolas Krepostman and Holly J. Kramer [FREE] 

Efficacy of Potassium Supplementation in Hypokalemic Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial by Watthikorn Pichitporn et al 

From the authors: Hypokalemia, which is commonly found in patients on peritoneal dialysis (PD), is associated with poor out-comes. A multicenter, open-label, prospective, randomized controlled trial was conducted with 167 hypokalemic patients receiving PD. It examined whether a protocol-based correction of hypokalemia to maintain a serum potassium concentration of 4-5 mEq/L (85 participants) could improve PD-related outcomes compared with reactive potassium supplementation administered when serum potassium levels fell below 3.5 mEq/L (82 participants). During the median follow-up time of 401 days, the protocol supplementation appeared safe and significantly reduced the risk of peritonitis.

DOI: 10.1053/j.ajkd.2022.03.013

Editorial: Correction of Hypokalemia in Peritoneal Dialysis Patients May Decrease Peritonitis Risk by Beth M. Piraino [FREE] 

Association Between Ultraprocessed Food Consumption and Risk of Incident CKD: A Prospective Cohort Study by Shotung Du  et al

From the authors: Ultraprocessed foods are industrially processed foods and drinks that contain little to no intact foods and mostly consist of artificial substances and additives. The consumption of ultraprocessed foods has been increasing around the world recently and has been linked with adverse health outcomes. In this study, we aimed to expand the evidence by investigating the relationship between ultraprocessed foods consumption and risk of chronic kidney disease. We found that the higher consumption of ultraprocessed foods is associated with higher risk of chronic kidney disease. Our results provided support to avoid ultraprocessed foods, and further studies should explore the underlying mechanisms by which ultraprocessed foods may be harmful to the kidneys.

DOI: 10.1053/j.ajkd.2022.03.016

Editorial: Nutrition and Kidney Health: Processing Emerging Evidence About Foods by Cheryl A.M. Anderson and Titilayo Ilori [FREE] 

Shared Decision Making Among Older Adults With Advanced CKD by Rebecca Frazier et al [OPEN ACCESS]

From the authors: Older adults with advanced kidney disease face difficult treatment decisions. Dialysis offers uncertain survival benefits but has significant quality of life implications. Shared decision making (SDM) may help patients choose treatment options that best align with their goals and values. We performed a cross-sectional analysis among older adults with advanced kidney disease to examine SDM in nephrology clinics using the 9-item Shared Decision Making Questionnaire. We found that SDM was suboptimal, with a mean questionnaire score of 52 (possible scores of 0-100). Being “well informed” and “very well informed” about kidney treatment options, having higher decisional certainty, and attendance at a kidney treatment options class were associated with greater SDM. Our research highlights the need to improve SDM for older adults facing dialysis decisions.

DOI: 10.1053/j.ajkd.2022.02.017

Black and White Adults With CKD Hospitalized With Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study by Anthony N. Muiru et al 

From the authors: Although much is known about racial disparities in kidney failure, few studies have investigated Black and White racial differences in acute kidney injury (AKI). We examined whether Black participants in the Chronic Renal Insufficiency Cohort (CRIC) Study were at an increased risk of AKI compared with White study participants, after accounting for differences in prehospitalization clinical risk factors, socioeconomic status, and genetic risk factors. We found that Black participants had a greater risk of AKI than White participants, but this elevated risk was modest and was explained by differences in prehospitalization clinical risk factors such as proteinuria, hypertension, diabetes, and heart failure. These findings suggest that targeted screening and aggressive management of these clinical risk factors may reduce the risk of AKI.

DOI: 10.1053/j.ajkd.2022.02.021

Maternal Chronic Disease and Congenital Anomalies of the Kidney and Urinary Tract in Offspring: A Japanese Cohort Study by Kei Nishiyama et al [OPEN ACCESS]

From the authors: Prior studies reported that several maternal chronic diseases are associated with congenital anomalies of the kidney and urinary tract (CAKUT) in offspring without distinguishing isolated cases of CAKUT from those complicated by extrarenal anomalies. By studying the prospective cohort of the Japan Environment and Children’s Study, we were able to examine the association of maternal diseases with isolated and complicated CAKUT. We found that the risk of isolated CAKUT was increased in children of mothers who experienced kidney disease or cancer, whereas complicated CAKUT was more common in children of mothers with diabetes mellitus. These findings provide insights that may inform the management of pregnancy and highlight potential differences in the genesis of isolated and complicated forms of CAKUT.

DOI: 10.1053/j.ajkd.2022.03.003

Preoperative Ionized Magnesium Levels and Risk of Acute Kidney Injury After Cardiac Surgery by Hee Byung Koh et al 

From the authors: Kidney damage that occurs after heart surgery is a serious complication, but preventive measures are limited. In this study investigating large groups of patients from 2 tertiary hospitals, patients with lower blood magnesium levels were more likely to develop kidney damage after heart surgery. In addition, the probability of kidney damage increased in a stepwise manner with decreasing blood magnesium levels before surgery. These relationships were maintained regardless of other factors that could affect kidney health. These results suggest that testing blood magnesium levels before surgery may assist in the identification of patients who are likely to develop kidney damage after heart surgery.

DOI: 10.1053/j.ajkd.2022.03.004

Association of Long-term Ambient Fine Particulate Matter (PM2.5) and Incident CKD: A Prospective Cohort Study in China by Jing-wen Duan et al [OPEN ACCESS]

From the authors: Exposure to a form of air pollution known as fine particulate matter (ie, particulate matter ≤2.5 μm [PM2.5]) has been linked to an increased risk of chronic kidney disease (CKD), but little is known about how PM2.5 affects CKD in regions with extremely high levels of PM2.5 pollution. This longitudinal cohort study in China investigates the effect of PM2.5 on the incidence of CKD and whether temperature or humidity interact with PM2.5. Our findings suggest that long-term expo-sure to high levels of ambient PM2.5 significantly increased the risk of CKD in mainland China, especially in terms of cumulative average PM2.5. The associations of PM2.5 and incident CKD were greater in high-humidity environments. These findings support the recommendation that reducing PM2.5 pollution should be a priority to decrease the burden of associated health risks, including CKD.

DOI: 10.1053/j.ajkd.2022.03.009

Blog Post: Bad Air Day: The Association of Pollution & Kidney Disease by Natasha Dave [FREE]

Association Between Long-term Ambient PM2.5 Exposure and Cardiovascular Outcomes Among US Hemodialysis Patients by Yuzhi Xi et al [OPEN ACCESS]

From the authors: Long-term exposure to air pollution, also called PM2.5, has been linked to adverse cardiovascular outcomes. However, little is known about the association of PM2.5 and outcomes among patients receiving dialysis, who are individuals with high cardiovascular disease burdens. We conducted an epidemiological study to assess the association between the annual PM2.5 exposure and cardiovascular events and death among patients receiving regular outpatient hemodialysis in the United States between 2011 and 2016. We found a higher risk of heart attacks, strokes, and related events in patients exposed to higher levels of air pollution. Stronger associations between air pollution and adverse health events were observed among patients who were older at the start of dialysis, had chronic obstructive pulmonary disease, or were Asian. These findings bolster the evidence base linking air pollution and adverse health outcomes and may inform policy makers and clinicians.

DOI: 10.1053/j.ajkd.2022.04.008

Blog Post: Bad Air Day: The Association of Pollution & Kidney Disease by Natasha Dave [FREE]

Review from the November 2022 Issue:

Aldosterone, Mineralocorticoid Receptor Activation, and CKD: A Review of Evolving Treatment Paradigms by Murray Epstein et al (FREE)

From the authors: Mineralocorticoid receptor (MR) activation is involved in propagating kidney injury, inflammation, and fibrosis and in the progression of chronic kidney disease (CKD). In this review, we consider the basic science and clinical applicability of MR antagonism. Because hyperkalemia constitutes a constraint to implementing evidence-based MR blockade, we review MRA-associated hyperkalemia in the context of finerenone and discuss evolving mitigation strategies to enhance the safety and efficacy of this treatment. Although the FIDELIO-DKD and FIGARO-DKD clinical trials focused solely on patients with type 2 diabetes mellitus, we propose that MR activation and the resulting inflammation and fibrosis act as a substantive pathogenetic mediator not only in people with diabetic CKD but also in those with CKD without diabetes. We close by briefly discussing both recently initiated and future clinical trials that focus on extending the attributes of MR antagonism to a wider array of nondiabetic kidney disorders, such as patients with nonalbuminuric CKD.

DOI: 10.1053/j.ajkd.2022.04.016

Figure 1. Effect of MR activation in distal nephron. In the kidneys, aldosterone activates the MR in the principal cells of the distal nephron which leads to increased Na+ reabsorption and K+ excretion. The aldosterone-MR complex binds to glucocorticoid-responsive elements (GRE) that activate the apical epithelial sodium channel (ENaC) and the basolateral Na+-K+ ATPase by different regulatory pathways. In response to hyperkalemia, the aldosterone-mediated Na reabsorption via ENaC drives K secretion via ROMK. Created with BioRender.com.

Blog Post: How Does Aldosterone Activation Contribute to CKD? by Christopher Naranjo and Efren Chavez Morales [FREE]

Perspective from the November 2022 Issue:

Beyond the Urine Anion Gap: In Support of the Direct Measurement of Urinary Ammonium by Jaime Uribarri et al (FREE)

From the authors:Ammonium is a major urinary buffer that is necessary for the normal excretion of the daily acid load. Its urinary rate of excretion (UNH4) may be increased several fold in the presence of extrarenal metabolic acidosis. Therefore, measurement of UNH4 can provide important clues about causes of metabolic acidosis. In order to advance the field it is necessary for the medical community to become more familiar with UNH4levels in a variety of clinical settings. Herein, we review the literature, searching for available data on UNH4 under normal and various pathological conditions, in an attempt to establish reference values to interpret UNH4 results if and when UNH4measurements become available as a routine clinical test. In addition, we present original data in 2 large populations that provide further evidence that the UAG is not a good predictor of UNH4. Measurement of urine NH4 holds promise to aid clinicians in the care of patients, and we encourage further research to determine its best diagnostic usage.

DOI: 10.1053/j.ajkd.2022.05.009

Urinary rate of ammonium excrection versus urinary anion gap in (A) non–stone formers (n = 1,007; r2 = 0.0005) and in (B) stone formers (n = 23,997; r2 = 0.0056). Figure 1 from Uribarri et al, AJKD © National Kidney Foundation.

Blog Post: The Case for Direct Measurement of Urinary Ammonium: An Interview with Jaime Uribarri and David S. Goldfarb [FREE]

On the Cover: In this NASA satellite photo from late 2013, eastern China, home to the capital city of Beijing, is obscured by a thick, gray haze. During that time, the air pollution levels of PM2.5 (a measurement of fine particulate matter of less than 2.5 microns in width suspended in the air) in Beijing was nearly 20 times higher than the amount recommended by the World Health Organization. In this issue of AJKD, 2 studies demonstrate links between high PM2.5 levels and adverse clinical outcomes. Duan et al show that higher PM2.5 levels are associated with higher risk of incident CKD in China. Xi et al show that higher PM2.5 levels are associated with higher risk of cardiovascular events and death among patients receiving hemodialysis in the United States Measures aimed at reducing air pollution may help improve health outcomes.

The photograph “Haze over eastern China” by NASA/GSFC/Jeff Schmaltz/MODIS Land Rapid Response Team is released on Flickr under the CC BY 2.0 license

Special Collection: Pregnancy and Kidney Disease (FREE until Dec 11, 2022)

This Special Collection features articles on pregnancy and kidney disease published in AJKD over the past four years. These articles highlight the research and advances in knowledge regarding the clinical care for people with kidney disease with the capacity for pregnancy. Kidney disease poses significant risks for both birthing parent and fetus during pregnancy and pregnancy heightens the risk for kidney disease progression and kidney failure. We hope the article collection provides nephrologists relevant information for this timely topic.