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 March 2023 issue:

Association of Kidney Function Measures With Signs of Neurodegeneration and Small Vessel Disease on Brain Magnetic Resonance Imaging: The Atherosclerosis Risk in Communities (ARIC) Study by Johannes B. Scheppach et al 

From the authors: Cognitive decline is a major public health issue and common in patients with kidney disease. To better understand this condition, we measured kidney function and albuminuria in 1,527 participants from the Atherosclerosis Risk in Communities Study. The participants were also scanned for different types of brain damage using magnetic resonance imaging. We found that low kidney function and albuminuria are associated with various structural brain pathologies, such as brain atrophy, microvascular damage, and white matter defects. These results confirm the connection between kidney function and albuminuria with brain damage and provide new information about its cause and its localization in the brain.

DOI: 10.1053/j.ajkd.2022.07.013

Editorial: Kidney Disease and Brain Health: Current Knowledge and Next Steps by Anne M. Murray et al.

Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients by Aileen X. Wang et al 

From the authors: The treatment options for hypercalcemic hyperparathyroidism after kidney transplantation include cinacalcet and surgical parathyroidectomy, but best practice remains unclear. Using a large database of US kidney transplant recipients, we examined cinacalcet and parathyroidectomy treatment practices, associations, and outcomes in the first 3 years after kidney transplant. We found that 18% of patients used cinacalcet and 1.8% underwent parathyroidectomy after transplant. For patients transplanted in 2007-2013, the rate of parathyroidectomy remained stable. By contrast, cinacalcet use increased during the study period. A longer time on dialysis and cinacalcet use before transplant were strongly associated with both parathyroidectomy and cinacalcet use subsequent to transplant. Hypocalcemia was a common early complication of parathyroidectomy.

DOI: 10.1053/j.ajkd.2022.07.015

Editorial: Persistent Hyperparathyroidism: A Reality Calling for Additional Evidence by Hanne Skou Jørgensen et al.

Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials by David H. Alpers et al. [OPEN ACCESS]

From the authors: In early clinical trials of tolvaptan (TEMPO 3:4 and TEMPO 4:4), liver enzyme level increases in tolvaptan-treated participants indicated risk for drug-induced liver injury. We evaluated data from 2 subsequent large-scale clinical studies (REPRISE and a long-term extension of all 3 trials) that were conducted after monthly liver enzyme testing became required for patients enrolled in tolvaptan trials. No additional liver enzyme level increases meeting the criteria for greatest risk (ie, “Hy’s Law” cases) were reported, and the less severe increases that did occur were seen mainly during the first 18 months of treatment. These results support the conclusion that monthly liver enzyme testing of tolvaptan-treated patients during the first 18 months of therapy enabled timely detection and intervention before severe drug-induced liver injury could occur.

DOI: 10.1053/j.ajkd.2022.08.012

Editorial: Much Ado About Something: The Clinical Pattern of Tolvaptan-Associated Liver Injury in Participants With ADPKD by Merve Postalcioglu et al.

Efficacy and Safety of Belimumab in Patients With Lupus Nephritis: Subgroup Analyses of a Phase 3 Randomized Trial in the East Asian Population by Xueqing Yu et al. [OPEN ACCESS]

From the authors: Lupus nephritis (LN) is a severe complication of the kidneys in patients with the autoimmune disease systemic lupus erythematosus. Belimumab is used in combination with standard therapy for treatment of patients with LN. As data on belimumab treatment of East Asian patients with LN are limited, we assessed the efficacy and safety of belimumab in a subgroup of East Asian patients from the BLISS-LN study. Patients received monthly belimumab or placebo in addition to standard therapy. After 104 weeks, patients who received belimumab showed earlier and more sustained improvements in kidney outcomes compared with patients who received placebo, while no new safety concerns were raised. These results support the use of belimumab treatment for East Asian patients with LN.

DOI: 10.1053/j.ajkd.2022.06.013

Cardiorenal Outcomes Among Patients With Atrial Fibrillation Treated With Oral Anticoagulants by Marco Trevisan et al. [OPEN ACCESS]

From the authors: The relative safety of anticoagulation with direct oral anticoagulants (DOACs) or vitamin K antagonists like warfarin remains inconclusive, particularly with regard to outcomes related to kidney disease on injury. In a cohort of patients with nonvalvular atrial fibrillation from Sweden, we observed that initiation of a DOAC compared with warfarin was associated with a lower risk of the composite of kidney failure and sustained 30% decline in kidney function, as well as a lower risk of occurrence of acute kidney injury. In agreement with trial evidence, DOAC versus warfarin treatment was associated with a lower risk of major bleeding but a similar risk of the composite of stroke, systemic embolism, or death. Collectively, these findings add to the emerging evidence on the safety and effectiveness of DOAC administered for atrial fibrillation.

DOI: 10.1053/j.ajkd.2022.07.017

Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease by Jill R. Krissberg et al. 

From the authors:  Racial and ethnic disparities have been described in many aspects of kidney disease, but little is known about disparities in glomerular disease. This large multinational cohort study of the Cure Glomerulonephropathy Network describes differences in acute care utilization for patients with glomerular disease across racial and ethnic groups and explores potential underlying reasons for any observed differences. We found that Black race was associated with higher rates of acute care utilization, whereas Asian race was associated with lower rates of acute care utilization. These associations may be explained by differences in socioeconomic status and disease severity among these groups. Efforts to improve health equity should consider socioeconomic factors contributing to disease severity or reliance on hospital over ambulatory care.

DOI:10.1053/j.ajkd.2022.08.010

Review from the March 2023 issue:

Intensive Care Unit–Acquired Weakness in Patients With Acute Kidney Injury: A Contemporary Review by J. Pedro Teixeira et al (FREE)

Acute kidney injury (AKI) and intensive care unit–acquired weakness (ICU-AW) are 2 frequent complications of critical illness that, until recently, have been considered unrelated processes. The adverse impact of AKI on ICU mortality is clear, but its relationship with muscle weakness—a major source of ICU morbidity—has not been fully elucidated. Furthermore, improving ICU survival rates have refocused the field of intensive care toward improving long-term functional outcomes of ICU survivors. The authors begin the review with the epidemiology of AKI in the ICU and of ICU-AW, highlighting emerging data suggesting that AKI and AKI treated with kidney replacement therapy (AKI-KRT) may independently contribute to the development of ICU-AW. The authors then delve into human and animal data exploring the pathophysiologic mechanisms linking AKI and acute KRT to muscle wasting, including altered amino acid and protein metabolism, inflammatory signaling, and deleterious removal of micronutrients by KRT. They next discuss the currently available interventions that may mitigate the risk of ICU-AW in patients with AKI and AKI-KRT. They conclude that additional studies are needed to better characterize the epidemiologic and pathophysiologic relationship between AKI, AKI-KRT, and ICU-AW and to prospectively test interventions to improve the long-term functional status and quality of life of AKI survivors.

DOI: 10.1053/j.ajkd.2022.08.028

On the Cover: On March 9, 2023, the 18th annual World Kidney Day (WKD) will raise awareness on the global burden of kidney disease. This year’s theme, “preparing for the unexpected and supporting the vulnerable,” highlights the need for all members of the kidney community to plan ahead for care disruptions that occur during unpredictable times of disaster. Further information on the 2023 WKD campaign is available at www.WorldKidneyDay.org.

Image adapted from the WKD 2023 campaign image, World Kidney Day 2006-2023.