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 2022 issue:

Cancer Risk and Mortality in Patients With Kidney Disease: A Population-Based Cohort Study by Abhijat Kitchlu et al 

From the authors: Patients with kidney disease may have an increased risk of cancer and may be more likely to die of cancer. We used health care databases in Ontario, Canada, to categorize patients according to their kidney function (using blood test data) or records that identify patients receiving dialysis or having received a kidney transplant. We then looked at their risks of being diagnosed with cancer and of dying of cancer. Patients with mild to moderate kidney disease and kidney transplant recipients had a higher risk of cancer than patients with normal kidney function. Patients with kidney disease had a higher risk of dying of cancer than patients with normal kidney function, particularly cancers such as bladder and kidney cancers and multiple myeloma. Our study suggests that improved strategies to detect and treat cancer in patients with kidney disease are needed.

DOI: 10.1053/j.ajkd.2022.02.020

Editorial: Dying of Cancer With Kidney Disease by Jeremy R. Chapman [FREE] 

Cancer Mortality in People Receiving Dialysis for Kidney Failure: An Australian and New Zealand Cohort Study, 1980-2013 by Brenda M. Rosales et al 

From the authors: Cancer survival is improving in the general population because of improved screening and treatments, but it is unclear whether people with kidney failure receiving dialysis, who are more likely to develop cancer, have also benefitted from these trends. We compared the rates of cancer death in people on dialysis with people of their same age and sex in the general population between 1980 and 2013 to see what differences were evident. We found that people on dialysis die from cancer at twice the rate as those of the same age and sex in the general population; while declining, the improvement in cancer deaths has still not kept up with improvements in the general population. An individualized risk-based approach to cancer prevention and treatment is needed in this higher risk population.

DOI: 10.1053/j.ajkd.2022.03.010

Editorial: Dying of Cancer With Kidney Disease by Jeremy R. Chapman [FREE] 

Performance of the 2021 Race-Free CKD-EPI Creatinine- and Cystatin C–Based Estimated GFR Equations Among Kidney Transplant Recipients by Gregory L. Hundemer et al

From the authors: Recently, new kidney function estimating equations were introduced that do not incorporate race information. Nephrology organizations have recommended widespread uptake of these new equations for estimating glomerular filtration rate (GFR), but they have not been well studied among kidney transplant patients. Using measured GFR as the reference, we compared the performance of the new race-free estimated GFR equations versus prior estimated GFR equations among 415 kidney transplant patients. We found that the new race-free estimated GFR equations perform similarly to prior equations. We also found no clear difference in performance between the 2 new race-free equations that used creatinine or both creatinine and cystatin C.

DOI: 10.1053/j.ajkd.2022.03.014

Editorial: Performance of New Estimated GFR Equations in Kidney Transplant Recipients: A Step in the Right Direction by Aimen Liaqat et al [FREE] 

A Clinical Response–Adjusted Steroid Treatment Protocol for Children With Newly Diagnosed Idiopathic Nephrotic Syndrome by Elena Zion et al

From the authors: Thrombosis is a serious complication of dialysis vascular access. There is still controversy regarding the association of aging and comorbidities with worse vascular access outcomes. Frailty is highly prevalent in patients receiving maintenance hemodialysis and is an important contributor of mortality and reduced quality of life. We hypothesized that frail patients would have a higher incidence of dialysis access thrombosis than nonfrail Taiwanese patients. Among 761 patients studied, we found that frailty was significantly associated with dialysis access thrombosis even after adjusting for the influence of age and comorbidities. Our findings suggest that the assessment of frailty may provide important information on risk stratification of vascular access thrombosis beyond clinical information.

DOI: 10.1053/j.ajkd.2022.04.007
Editorial: Prednisone for Steroid-Sensitive Nephrotic Syndrome: Can We Use Lower Doses for the First Presentation in Children? by Elisabeth Hodson et al [FREE] 

Heart-Type Fatty Acid Binding Protein, Cardiovascular Outcomes, and Death: Findings From the German CKD Cohort Study by Markus P. Schneider et al 

From the authors: Heart type-fatty acid binding protein (H-FABP) is released into the bloodstream when blood supply to the heart is inadequately low. We have studied the prognostic value of elevated blood levels of H-FABP in a large cohort of approximately 5,000 patients with chronic kidney disease. We found that elevated H-FABP concentrations are related to greater risks of hospitalization for heart failure, other nonfatal and fatal cardiovascular conditions, and death due to diseases unrelated to the cardiovascular system. After further study, H-FABP may help identify patients with chronic kidney disease who might benefit from preventive health measures.

DOI: 10.1053/j.ajkd.2022.01.424

Association Between Acute Kidney Injury and Dementia in the Atherosclerosis Risk in Communities (ARIC) Study by Sarah Tung et al 

From the authors: Dementia is a major public health concern in the United States. Although there is no known cure, early detection remains one of the most important factors in positive outcomes for both patients and families. Acute kidney injury (AKI) is a common condition that may impair the function of other organs, such as the brain. Using data from a community-based cohort of participants enrolled in the Atherosclerosis Risk in Communities study, we found that participants with hospitalizations for AKI were at higher risk of dementia than those without such hospitalizations.

DOI: 10.1053/j.ajkd.2022.02.015

Association of Uremic Solutes With Cardiovascular Death in Diabetic Kidney Disease by Hima Sapa et al [OPEN ACCESS]

From the authors: For diseases such as chronic kidney disease (CKD), which progress over many years, it would be helpful to identify factors early in the disease course that are associated with complications or disease progression. These biomarkers could ultimately be relevant to the disease pathophysiology or as prediction tools to identify patients who need the most attention. For CKD patients, premature cardiovascular disease is by far the most common cause of death. In this study of diabetic patients with modest CKD, we investigated the association with cardiovascular mortality of 3 biomarkers that are derived from gut bacteria and that have previously been shown to be elevated in patients on dialysis. We found a strong association between 1 of these bio-markers, asymmetric dimethylarginine, and cardiovascular and all-cause mortality.

DOI: 10.1053/j.ajkd.2022.02.016

Special Report from the October 2022 Issue:

Clinical Trial Considerations in Developing Treatments for Early Stages of Common, Chronic Kidney Diseases: A Scientific Workshop Cosponsored by the National Kidney Foundation and the US Food and Drug Administration by Lesley A. Inker et al

From the authors: In the past decade, advances in the validation of surrogate end points for chronic kidney disease (CKD) progression have heightened interest in evaluating therapies in early CKD. In December 2020, the National Kidney Foundation sponsored a scientific workshop in collaboration with the US Food and Drug Administration (FDA) to explore patient, provider, and payor perceptions of the value of treating early CKD. There was consensus among the attendees that there is value to preventing the development and treating the progression of early CKD in people who are at high risk for progression, and that surrogate end points should be used to establish efficacy. Attendees also concluded that cost analyses should be holistic and include aspects beyond direct savings for treatment of kidney failure; and that safety data should be collected outside/beyond the duration of a clinical trial. Successful drug development and implementation of effective therapies will require collaboration across sponsors, patients, patient advocacy organizations, medical community, regulators, and payors.

DOI: 10.1053/j.ajkd.2022.03.011

On the Cover: In 1838, Charles Darwin put forward his theory of natural selection developed from observations of many different species on the Galapagos Islands including giant tortoises, one of the longest-lived vertebrates on earth who can live for more than 100 years. One speculation is that tortoises’ longevity is due to some genetic endowment related to metabolic and immune regulation that make them less susceptible to develop cancer. In this issue of AJKD, Rosales et al report that the relative risk of all-site cancer death in dialysis patients was twice that of the general population. Just as the tortoises’ resilience is likely to result from a complex interplay of genes related to immunity, development, and metabolism, cancer mortality in people on maintenance dialysis is likely the result of multiple interrelated factors. Nonetheless, carefully mapping the extent of the burden is the first step to developing more effective preventive, screening, and therapeutic strategies for this vulnerable patient group.

The photograph “Galapagos Turtle” by kevinofsydney 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.