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 December 2024 issue:

Cumulative Blood Pressure Load and Incident CKD by Hye-Sun Park et al. [OPEN ACCESS]

From the authors: Although hypertension is a major risk factor for chronic kidney disease (CKD), most studies have focused on single-point blood pressure (BP) measurements. To explore the association between long-term cumulative BP load and the development of CKD, 5,221 Korean adults with normal kidney function were included in this study. Cumulative systolic BP and diastolic BP load both exhibited a significant association with an increased risk of incident CKD. Notably, the association of cumulative BP loads with elevated risk of incident CKD was evident also in individuals who were not taking antihypertensive agents or who had no previous history of hypertension. These findings underscore the importance of managing long-term exposure to high BP, even in individuals with normal BP levels.

DOI:  10.1053/j.ajkd.2024.05.015

EDITORIAL: Blood Pressure Control and the Prevention of Incident CKD: The Disconnect Between Cohort Studies and Randomized Trials by Rajiv Agarwal [FREE]

Causal Relationship Between Kidney Function and Cancer Risk: A Mendelian Randomization Study by Ellen Dobrijevic et al. 

From the authors: Does reduced kidney function cause cancer? Patients with chronic kidney disease have been shown to have an increased risk of cancer and cancer-related death. However, it is not clear whether kidney disease is causally related to cancer or the association is due to other factors such as immune suppression and inflammation or a result of distortion of the analyses from unidentified variables (confounding). We used large, published genetic studies as well a database including 407,329 people in the United Kingdom in a series of Mendelian randomization analysis. Mendelian randomization uses the random assignment of genetic variants at birth to investigate causal relationships without confounding from measured and unmeasured confounders. We found that there is no evidence of a causal relationship between reduced kidney function and cancer.

DOI:  10.1053/j.ajkd.2024.05.016

EDITORIAL: Exploring the Causal Relationship Between Kidney Function and Cancer Risk: Insights and Limitations of Mendelian Randomization by Sehoon Park et al. [FREE]

Symptom Burden and Its Impact on Quality of Life in Patients With Moderate to Severe CKD: The International Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) by Elodie Speyer et al. 

From the authors: Little is known about symptoms in patients with non-dialysis-dependent chronic kidney disease (ND-CKD). In the Chronic Kidney Disease Outcomes and Practice Patterns Study, which enrolled 4,430 patients with CKD stages 3-5 in Brazil, France, and the United States, patients most often reported soreness in muscles, feeling washed out or drained, cramps, shortness of breath, dry skin, altered sex life, and numbness in hands or feet. Cramps, feeling washed out or drained, lack of appetite, and nausea were more often reported at lower levels of kidney function. The overall symptom burden was higher in women than men, in French than in Brazilian or US patients, and in those with severe albuminuria. The higher the symptom burden, the lower were the physical and mental health quality of life scores. The high symptom burden observed in this large cohort of ND-CKD patients across 3 diverse countries and its strong association with poorer health-related quality of life should inform clinical management of and clinical research in CKD.

DOI: 10.1053/j.ajkd.2024.06.011

EDITORIAL: Why Symptom Burden in Non-Dialysis CKD Matters by Meike Shedden-Mora et al. [FREE]

Clinicopathologic Characteristics of Crystalglobulin-Induced Nephropathy: A Case Series by Samih H. Nasr et al.

CIN is a rare cause of nephropathy associated with lymphoplasmacytic disorders (mostly MGRS) and typically presents with severe AKI and extrarenal manifestations. Diagnosis often requires immunofluorescence performed on paraffin-embedded kidney tissue. Prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function.

DOI: 10.1053/j.ajkd.2024.04.019

Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study by Miquel Blasco et al.

From the authors: The cause of kidney disease is unknown for 1 in 5 patients requiring kidney replacement therapy, reflecting possible prior missed treatment opportunities. We assessed the diagnostic utility of genetic testing in children and adults aged≤45 years with either an estimated glomerular filtration rate of<15mL/min/1.73m² or treatment with maintenance dialysis or transplantation. Genetic testing identified the cause of kidney disease in approximately 1 in 4 patients without a previously known cause of kidney disease, suggesting that genetic studies are a potentially useful tool for the evaluation of these patients.

DOI:  10.1053/j.ajkd.2024.04.021

AJKDBlog COMMENTARY: Uncovering the Unknowns in Nephrology by Becky Mingyao Ma [FREE]

Sex and the Relationship Between Cardiometabolic Risk Factors and Estimated GFR Decline: A Population-Based Cohort Study by Michael K. Sullivan et al.

From the authors: Kidney function is known to decline at a faster rate among males than females. This study incorporated blood laboratory test results from the routine care of 1.1 million adults living in the United Kingdom and found that the decline in kidney function associated with risk factors varied by sex. Before and at the age of 73 years, the decline in kidney function was similar between males and females. After age 73, cardiometabolic risk factors were associated with faster decline in kidney function among males than females, specifically heart failure and smoking. Socioeconomic deprivation was also associated with the decline in kidney function for both sexes, but it was a stronger risk factor among females. These findings may inform the management of kidney disease overall and within sex-specific groups.

DOI:  10.1053/j.ajkd.2024.05.007

AJKDBlog COMMENTARY: Y SeX and Gender Differences Matter in CKD: Understanding the Impact on Kidney Function Decline by Jenny Pan [FREE]

Cardiovascular and Kidney Outcomes of Non-Diabetic CKD by Albuminuria Severity: Findings From the CRIC Study by Rachel Shulman et al.

From the authors: Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies of long-term clinical outcomes in CKD largely included patients with diabetes. As well, few studies have evaluated long-term outcomes across different levels of urine albumin among people without diabetes. In this study, we found individuals with nondiabetic CKD and low urine albumin had much slower decline of kidney function but only a modestly lower risk of a cardiovascular events compared with those with high levels of urine albumin. Individuals with low urine albumin were much more likely to have a cardiovascular event than progression of their kidney disease. These findings inform the design of future studies investigating treatments among individuals with lower levels of albuminuria.

DOI:  10.1053/j.ajkd.2024.05.008

Core Curriculum in the November 2024 issue:

Viral Nephropathies: Core Curriculum 2024  by Amy A. Yau et al [FREE]

In this Core Curriculum, the authors review common viruses responsible for kidney disease worldwide, discuss mechanisms of pathogenesis, and highlight specific management principles of viral nephropathies. They also discuss other viruses with high endemicity despite low incidence of kidney disease in the immunocompetent and immunosuppressed host.

DOI: 10.1053/j.ajkd.2024.06.014

AJKDBlog INTERVIEW: Viral Nephropathies: An Interview with Drs. Gaddy, Yau, and Murugapandian [FREE]

On the Cover:

In the 1860s, Gregor Mendel chose the humble pea plant for his breeding experiments that led to his description of the principles of genetic inheritance. Mendelian Randomization (MR) is a statistical framework anchored on Mendel’s concept that genetic variants are randomly inherited from parents to offspring. The MR approach can be used to assess causal effects of a particular exposure on an outcome while mitigating confounding effects. In this issue, Dobrijevic et al used two-sample MR applied to data from the UK Biobank and found no evidence of a causal relation between reduced kidney function and cancer risk.

The photograph “a green pea hanging from a plant with leaves” is by Michelle Tresemer on Unsplash. Special thanks to Editorial Intern George Vazquez Rios curating the cover image and drafting the cover blurb for this issue.

2024 EDITORS’ CHOICE

The editors are delighted to recognize these articles that have been selected to receive the 2024 AJKD Editors’ Choice Award (all articles are freely available until February 1, 2025).