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 April 2022 issue:

Developing an AKI Consensus Definition for Database Research: Findings From a Scoping Review and Expert Opinion Using a Delphi Process by Greg Guthrie et al

From the authors: The KDIGO definition of acute kidney injury (AKI) is used in both clinical practice and in research. Our scoping review demonstrated that there is wide variation of practice in how this definition is applied and also a lack of transparency about how researchers have applied it. An international panel of experts in AKI was formed in an attempt to achieve consensus on how this definition should be applied. They participated in a Delphi process, and although they were able to agree on some aspects of how the definition should be implemented, there were many areas in which no agreement could be reached. We recommend that researchers clearly state how they applied the KDIGO definition for AKI when conducting studies using routinely collected health care data.

DOI: 10.1053/j.ajkd.2021.05.019

Editorial: Database Research in Acute Kidney Injury: Time to Take Stock? by Chris Laing [FREE] 

Serum Level of Polyubiquitinated PTEN and Loss of Kidney Function in American Indians With Type 2 Diabetes by Helen C. Looker et al

From the authors: A recently identified modified form of the protein PTEN (phosphatase and tensin homolog) has been implicated in kidney fibrosis in animals and in fibrotic mechanisms in human cellular studies. We wanted to see if circulating levels of this form of PTEN were associated with progression of kidney disease in American Indians with type 2 diabetes. We found that the modified form of PTEN was associated with increased risk of decline in kidney function and the onset of kidney failure. In a subgroup of participants, serum levels of modified PTEN were also associated with the severity of lesions in kidney structure, which signify early manifestations of diabetic kidney disease.

DOI: 10.1053/j.ajkd.2021.08.009

Editorial: The Biomarker Promised Land: Are We There Yet? Not Yet by Alexander L. Bullen et al [FREE] 

Risk of Kidney Failure in Patients With Cancer: A South Korean Population-Based Cohort Study by Chang Seong Kim et al [OPEN ACCESS]

From the authors: Previous studies have shown an increased cancer risk within the dialysis and kidney transplant populations compared with the general population. However, it is unclear whether cancer increases the risk of kidney failure. This population-based cohort study was conducted using the Korean National Health Insurance Service database and compared approximately 825,000 patients with cancer versus twice as many patients without cancer but matched on other characteristics. This study found that cancer was associated with an increased risk of kidney failure, even after adjusting for potential confounders and addressing the competing risk of death. Types of cancer that were most significantly associated with kidney failure included multiple myeloma, leukemia, lymphoma, kidney cancer, ovarian cancer, and liver cancer.

DOI: 10.1053/j.ajkd.2021.06.024

Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study by Godela M. Brosnahan et al 

From the authors: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder that leads to kidney failure. Despite decades of research, treatments for ADPKD are limited. Metformin has a track record of safety in patients with type 2 diabetes. The potential benefits of metformin in ADPKD are related to its ability to stimulate AMP kinase, an important enzyme involved in the regulation of cell metabolism. We present the results of a pilot clinical trial to assess the safety and feasibility of using metformin in ADPKD over a 12-month period. Metformin was safe, but only 50% of the participants were able to tolerate the full dose of immediate-release metformin. Future trials should test a better tolerated extended-release formulation for its efficacy to slow the progression of ADPKD.

DOI: 10.1053/j.ajkd.2021.06.026

Mechanism of metformin-uinduced reduction in cyst burden. AMPK activation by metformin inhibits CFTR and mTOR pathways leading to decreased cystic fluid accumulation and cyst cell proliferation.

Blog Post Is Metformin Now in Our Armamentarium for Autosomal Dominant Polycystic Kidney Disease (ADPKD)? by Orhan Efe [FREE] 

Population Epidemiology of Hyperkalemia: Cardiac and Kidney Long-term Health Outcomes by Andrew McLean et al 

From the authors: Severe hyperkalemia is a recognized clinical emergency, but the burden of more moderate hyperkalemia and its clinical implications are not well known. This study describes the burden and health outcomes associated with hyperkalemia episodes in a completely captured population in Scotland over a 3-year period. Hyperkalemia occurred in 1 in 100 persons per year. Hyperkalemia was much more common among the elderly as well as those with advanced chronic kidney disease (CKD) or acute kidney injury. People without CKD who developed hyperkalemia were twice as likely to die, twice as likely to have a cardiac event, and 17 times more likely to develop kidney failure. These findings indicate that hyperkalemia signals diminished kidney function and lasting subsequent risk to kidney health.

DOI: 10.1053/j.ajkd.2021.07.008

Mobility in Older Adults Receiving Maintenance Hemodialysis: A Qualitative Study by Christine K. Liu et al [FREE temporarily] 

From the authors: Mobility, the ability to move from one place to another, enables independence and supports well-being. Yet many older adults receiving hemodialysis need help with walking, and we do not know all the reasons why. We interviewed 31 older adults receiving hemodialysis and 12 of their care partners to ask about the experiences of the older adults with losses in mobility. They described how mobility changed in unpredictable ways, which was emotionally upsetting. To cope, the older adults turned to their church, loved ones, and their own inner will, and remained flexible in their expectations of what they could do. As we develop ways to improve the mobility of older adults receiving hemodialysis, we should consider how mobility changes frequently and incorporate their outlook of adaptability.

DOI: 10.1053/j.ajkd.2021.07.010

Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD by Eric H. Au et al 

From the authors: Past studies have found that people with chronic kidney disease (CKD) may have an increased risk of developing colorectal cancer compared with people in the general population, but little is known of the factors that are associated with the greater risk of colorectal cancer in these patients. This large, international study examined a cohort of 1,706 patients across the spectrum of kidney disease (CKD stages 3-5 not receiving maintenance dialysis, patients receiving maintenance dialysis, and recipients of a kidney transplant) and looked for factors associated with advanced colorectal neoplasia (cancerous and precancerous colorectal polyps). We found that people who were older, male, or taking azathioprine and/or taking erythropoiesis-stimulating medications were more likely to be found to have advanced colorectal neoplasia.

DOI: 10.1053/j.ajkd.2021.07.011

Risk of Acute Kidney Injury After Hypertensive Disorders of Pregnancy: A Population-Based Cohort Study by Joshua Shapiro et al 

From the authors: Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are common complications of pregnancy. Acute kidney injury can be a defining feature of preeclampsia, and we sought to determine whether a history of a hypertensive disorder of pregnancy was associated with a higher risk of subsequent acute kidney injury. We performed a retrospective population-based cohort study to answer this question. We found that a history of preeclampsia was associated with a higher future risk of the development of acute kidney injury. Our findings highlight the importance of considering pregnancy history when evaluating a patient’s susceptibility to future kidney injury and suggest that women with a history of a hypertensive disorder of pregnancy may benefit from monitoring of kidney function.

DOI: 10.1053/j.ajkd.2021.07.017

Blog Post Preeclampsia is not Only a Risk Factor for CKD but Also for Future AKI by Ana Cecilia Farfan Ruiz [FREE] 

KDOQI Commentary

KDOQI US Commentary on the KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD by Amy K. Mottl et al [FREE] 

In October 2020, KDIGO published its first clinical practice guideline directed specifically to the care of patients with diabetes and chronic kidney disease (CKD). This commentary presents the views of the KDOQI work group for diabetes in CKD, convened by the National Kidney Foundation to provide an independent expert perspective on the new guideline. The KDOQI work group believes that the KDIGO guideline takes a major step forward in clarifying glycemic targets and use of specific antihyperglycemic agents in diabetes and CKD. The purpose of this commentary is to carry forward the conversation regarding optimization of care for patients with diabetes and CKD.

DOI: 10.1053/j.ajkd.2021.09.010

On the Cover: In this engraving of a painting from the German painter Johann Geyer (1807-1875), a group of physicians engage in a spirited discussion evocative of modern-day debates on topics such as the classification of AKI. In 2012, KDIGO established a definition and classification for AKI using serum creatinine and urine output, which has become the standard for AKI research. However, there are still significant inconsistencies in the application of this classification scheme in the clinical setting. In this issue of AJKD, Guthrie et al describe an approach to arriving at consensus more sophisticated than is depicted in Geyer’s painting. They conducted a literature review and online surveys of international experts, and then used of a Delphi method to develop recommendations regarding the KDIGO AKI definitions.

“A group of physicians having stormy discussions in an elaborately decorated room” is from the Wellcome Collection and is in the public domain.

Call for Applications: AJKD Editorial Internship ProgramThe AJKD Editorial Internship Program provides editorial experience to early career researchers interested in education, teaching, or medical editing/writing. Applications are due by April 30, 2022. Details on how to apply are provided here.