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.

Highlights from the September 2024 issue:

Visceral Adiposity and Progression of ADPKD: A Cohort Study of Patients From the TEMPO 3:4 Trial by Kristen L. Nowak et al 

From the authors: We analyzed images from a previous study with the drug tolvaptan conducted in patients with autosomal dominant polycystic kidney disease (ADPKD) to measure the amount of fat tissue surrounding the kidneys (visceral fat). We had previously shown body mass index can predict kidney growth in this population; now we determined whether visceral fat was an important factor associated with kidney growth. Using a machine learning tool to automate measurement of fat in images, we observed that visceral fat was independently associated with kidney growth, that it was a better predictor of faster kidney growth in lean patients than body mass index, and that having more visceral fat made treatment of ADPKD with tolvaptan less effective.

DOI: 10.1053/j.ajkd.2024.02.014

EDITORIAL: Visceral Abdominal Adiposity and ADPKD Progression: One More Step Toward Identifying Useful Biomarkers and Characterizing the Disease Metabolic Links by Elieser Hitoshi Watanabe and Luiz Fernando Onuchic [FREE]

Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study by Petter Bjornstad et al

From the authors: In our study, we explored how a common genetic kidney condition, autosomal dominant polycystic kidney disease (ADPKD), relates to kidney metabolism. ADPKD leads to the growth of numerous cysts in the kidneys, which can impact their ability to work properly. We wanted to understand the kidneys’ ability to process oxygen and blood flow in ADPKD. Our approach involved using advanced imaging techniques to observe kidney metabolism and blood flow in people with ADPKD compared with healthy individuals. We discovered that those with ADPKD had significant changes in kidney oxygen metabolism even when their kidney function was still normal. These findings are crucial as they provide deeper insights into ADPKD, potentially guiding future treatments to target these changes.

DOI: 10.1053/j.ajkd.2024.02.016

EDITORIAL: A Close Look at Metabolic Dysfunction in Autosomal Dominant Polycystic Kidney Disease: From Bench to Imaging by Sol Carriazo and York Pei [FREE]

Peritoneal Dialysis Technique Survival: A Cohort Study by Caroline M. Hsu et al 

From the authors: Peritoneal dialysis (PD) is an important kidney replacement modality with several potential advantages compared with in-center hemodialysis (HD). However, a substantial number of patients transfer to in-center HD early on, without having experienced the quality-of-life and other benefits that come with sustained maintenance of PD. Using retrospective data from a midsize national dialysis provider, we found that initiating dialysis with PD is associated with longer maintenance of PD, compared with initiating dialysis with HD and a later switch to PD. However, many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower small protein removal are other risk factors for PD-to-HD transfer that may be amenable to intervention.

DOI: 10.1053/j.ajkd.2024.03.012

EDITORIAL: Transfers From In-Center Hemodialysis to Peritoneal Dialysis: Better Late Than Never? by Ankur D. Shah and Jeffrey Perl [FREE]

Association of Obesity With Kidney and Cardiac Outcomes Among Patients With Glomerular Disease: Findings From the Cure Glomerulonephropathy Network by Evan M. Zeitler et al 

From the authors:  Obesity is a risk factor for adverse heart and kidney outcomes in patients with chronic kidney disease, but whether it is associated with these outcomes in patients with glomerulonephropathy is not known. This study used existing data from a large sample of adults and children with glomerular diseases to address this question. The findings suggest that obesity increases the risk of cardiovascular but not kidney disease events in adult patients with glomerular disease.

DOI:  10.1053/j.ajkd.2024.03.020

EDITORIAL: The Impact of Obesity on Glomerular Diseases Remains to be Determined by Luis Yu and Niels Olsen Saraiva Câmara [FREE]

Clinical Significance of the Cystic Phenotype in Alport Syndrome by Letizia Zeni et al [OPEN ACCESS]

From the authors: Hematuria is the classic renal presentation of Alport syndrome (AS), a hereditary glomerulopathy caused by pathogenic variants of the COL4A3-5 genes. An atypical kidney cystic phenotype has been rarely reported in individuals with these variants. To determine the prevalence of kidney cysts, we performed abdominal ultrasonography in a large group of patients with AS and a comparison group of patients with another glomerular kidney disease, IgA nephropathy (IgAN). Multiple kidney cysts, usually with normal kidney volume, were found in 38% of patients with AS. A few patients’ kidney volumes were large enough to mimic a different hereditary cystic kidney disease, autosomal dominant polycystic kidney disease. The overall prevalence of kidney cysts in AS was more than double that observed in the well-matched comparison group with IgAN. These findings emphasize the high prevalence of cystic kidney phenotype in AS, suggesting a likely association between the genetic variants that cause this disease and the development of kidney cysts.

DOI: 10.1053/j.ajkd.2024.02.005

Glycated Albumin and Adverse Clinical Outcomes in Patients With CKD: A Prospective Cohort Study by Mengyao Tang et al [OPEN ACCESS]

From the authors: Hemoglobin A_1c (HbA_1c) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown. In this cohort study of 3,110 individuals with non-dialysis-dependent CKD, GA levels were independently associated with risks of end-stage kidney disease, cardiovascular disease (CVD), and mortality. The associations with CVD and mortality appeared to be J-shaped. Among patients with coexisting CKD and diabetes, GA added prognostic value to HbA_1c. Thus, GA may be a valuable complementary test to HbA_1c in patients with CKD.

DOI: 10.1053/j.ajkd.2024.02.006

Glomerular Filtration Rate Estimation Using β2-Microglobulin and β-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study by Verônica T. Costa e Silva et al 

From the authors: The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using β2-microglobulin (B2M) and/or β-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

DOI: 10.1053/j.ajkd.2024.01.532

Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study by Daniel Edmonston et al 

From the authors: Klotho is a protein that is vital to mineral metabolism and aging and may protect against cardiovascular disease. Klotho levels decrease in chronic kidney disease (CKD), but the association between Klotho and clinical outcomes in CKD remains uncertain. In a prospective cohort study of more than 1,000 people with CKD, circulating Klotho levels were not associated with kidney disease progression, cardiovascular outcomes, or mortality. These results suggest that the decrease in circulating Klotho levels in CKD does not play a prominent role in the development of poor clinical outcomes.

DOI: 10.1053/j.ajkd.2024.02.008

Review in the September 2024 issue:

2024 Update on Classification, Etiology, and Typing of Renal Amyloidosis: A Review by Nelson Leung et al

Amyloidosis is a protein folding disease that causes organ injuries and even death. In humans, 42 proteins are now known to cause amyloidosis. Some proteins become amyloidogenic as a result of a pathogenic variant as seen in hereditary amyloidoses. In acquired forms of amyloidosis, the proteins form amyloid in their wild-type state. Four types (serum amyloid A, transthyretin, apolipoprotein A-IV, and β2-macroglobulin) of amyloid can occur either as acquired or as a mutant. Iatrogenic amyloid from injected protein medications have also been reported and AIL1RAP (anakinra) has been recently found to involve the kidney. Finally, the mechanism of how leukocyte cell–derived chemotaxin 2 (ALECT2) forms amyloid remains unknown. This article reviews the amyloids that involve the kidney and how they are typed.

DOI: 10.1053/j.ajkd.2024.01.530

On the Cover:

The unique avian physiologic traits of the mourning dove were highlighted in AJKDBlog’s NephMadness this year. To adapt to the energy requirements for flying, blood glucose levels in mourning doves are substantially higher than mammals, yet these birds generally do not develop diabetes or associated cardiovascular diseases. Differences in amino acid composition between birds and mammals explain the absence of non-enzymatic glycation of proteins with high glucose levels in the mourning dove. In humans, blood levels of glycated proteins reflect the average glucose exposure and can be used as a diagnostic test for diabetes. However, the turnover of some glycated proteins, like hemoglobin A1c (HbA1c), may be affected by chronic kidney disease. In this issue of AJKD, Tang et al report the associations of glycated albumin (independent of HbA1c) and incident end-stage kidney disease, cardiovascular disease, and death among patients with chronic kidney disease.

The photograph “Mourning doves on balcony” by Knoten2010 is is available via Flickr and released into the public domain. Special thanks to Editorial Intern Michael Granda for curating the cover image and drafting the cover blurb for this issue.

SPECIAL COLLECTION: HIGHLY CITED

The articles in this special collection highlight the top cited Original Investigations published in 2021 and 2022 that contributed to AJKD’s 2023 Impact Factor of 9.4.