Our research broadens the knowledge of kidney disease.

Sex Disparities in Organ Donation: Finding an Equitable Donor Pool

Yee E, Hosseini SM, Duarte B, Knapp SM, Carnes M, Young B, Sweitzer NK, Breathett K

Background: The majority of living organ donors are women, but few are deceased organ donors, which increases risks associated with sex mismatched organs. We sought to identify reasons for sex disparities in organ donation and strategies for equity. Methods and Results: Using Amazon's Mechanical Turk, we examined US adults' perceptions regarding donation in a mixed‐methods survey study. Results were compared by sex with Fisher's exact test and T‐tests for quantitative results and qualitative descriptive analyses for write‐in responses. Among 667 participants (55% women), the majority of men (64.8%) and women (63.4%) self‐identified as registered donors. Women's willingness to donate their own organs to family members (P=0.03) or strangers (P=0.03) was significantly higher than men.

Podocyte Aging: Why and How Getting Old Matters

Stuart ShanklandYuliang WangAndrey ShawJoshua VaughanJeffrey PippinOliver Wessely

Abstract: The effects of healthy aging on the kidney, and how these effects intersect with superimposed diseases, are highly relevant in the context of the population's increasing longevity. Age-associated changes to podocytes, which are terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses the molecular and cellular mechanisms underlying podocyte aging, how these mechanisms might be augmented by disease in the aged kidney, and approaches to mitigate progressive damage to podocytes. Furthermore, we address how biologic pathways such as those associated with cellular growth confound aging in humans and rodents.

The Atypical Cyclin-Dependent Kinase 5 (Cdk5) Guards Podocytes from Apoptosis in Glomerular Disease While Being Dispensable for Podocyte Development

Nicole Mangold, Jeffrey Pippin, David Unnersjoe-Jess, Sybille Koehler, Stuart Shankland, Sebastian Brähler, Bernhard Schermer, Thomas Benzing, Paul T. Brinkkoetter, Henning Hagmann

Abstract: Cyclin-dependent kinase 5 (Cdk5) is expressed in terminally differentiated cells, where it drives development, morphogenesis, and survival. Temporal and spatial kinase activity is regulated by specific activators of Cdk5, dependent on the cell type and environmental factors. In the kidney, Cdk5 is exclusively expressed in terminally differentiated glomerular epithelial cells called podocytes. In glomerular disease, signaling mechanisms via Cdk5 have been addressed by single or combined conventional knockout of known specific activators of Cdk5. A protective, anti-apoptotic role has been ascribed to Cdk5 but not a developmental phenotype, as in terminally differentiated neurons. The effector kinase itself has never been addressed in animal models of glomerular disease. In the present study, conditional and inducible knockout models of Cdk5 were analyzed to investigate the role of Cdk5 in podocyte development and glomerular disease. While mice with podocyte-specific knockout of Cdk5 had no developmental defects and regular lifespan, loss of Cdk5 in podocytes increased susceptibility to glomerular damage in the nephrotoxic nephritis model. Glomerular damage was associated with reduced anti-apoptotic signals in Cdk5-deficient mice. In summary, Cdk5 acts primarily as master regulator of podocyte survival during glomerular disease and—in contrast to neurons—does not impact on glomerular development or maintenance.

Identification of persistent and resolving subphenotypes of acute hypoxemic respiratory failure in two independent cohorts

Neha A. Sathe, Leila R. Zelnick, Carmen Mikacenic, Eric D. Morrell, Pavan K. Bhatraju, J. Brennan McNeil, Susanna Kosamo, Catherine L. Hough, W. Conrad Liles, Lorraine B. Ware, Mark M. Wurfel 

Background: Acute hypoxemic respiratory failure (HRF) is associated with high morbidity and mortality, but its heterogeneity challenges the identification of effective therapies. Defining subphenotypes with distinct prognoses or biologic features can improve therapeutic trials, but prior work has focused on ARDS, which excludes many acute HRF patients. We aimed to characterize persistent and resolving subphenotypes in the broader HRF population.

Serum Vitamin D: Correlates of Baseline Concentration and Response to Supplementation in VITAL-DKD

Cora M Best, Leila R Zelnick, Kenneth E Thummel, Simon Hsu, Christine Limonte, Ravi Thadhani, Howard D Sesso, Jo Ann E Manson, Julie E Buring, Samia Mora, I-Min Lee, Nancy R Cook, Georgina Friedenberg, Heike Luttmann-Gibson, Ian H de Boer, Andrew N Hoofnagle

Context: The effect of daily vitamin D supplementation on the serum concentration of vitamin D (the parent compound) may offer insight into vitamin D disposition. Objective: To assess the total serum vitamin D response to vitamin D3 supplementation and whether it varies according to participant characteristics. To compare results with corresponding results for total serum 25-hydroxyvitamin D (25(OH)D), which is used clinically and measured in supplementation trials.

Home Hemodialysis: Core Curriculum 2021

Scott D. Bieber, Bessie A. Young

In the early days of dialysis, because of a lack of existing in-center infrastructure, home hemodialysis (HHD) was frequently used to expand dialysis programs. Recently, HHD has been thrust into the spotlight of kidney care programs once again. Patients and policymakers are demanding more choices for the management of kidney failure while controlling for cost. Perhaps it is not surprising that the kidney community's interest in HHD has been revived, especially during the COVID-19 pandemic. To meet this increased interest and demand, nephrologists and dialysis providers must embrace new technologies and improve their understanding of HHD systems. This installment of AJKD's Core Curriculum in Nephrology seeks to inform the reader about factors that can improve success in the training and retention of HHD patients. Benefits, pitfalls, and challenges of HHD are outlined.

Family Members' Understanding of the End-of-Life Wishes of People Undergoing Maintenance Dialysis

Fahad Saeed, Catherine Butler, Carlyn Clark, Kristen O'Loughlin, Ruth Engelberg, Paul Hebert, Danielle Lavallee, Elizabeth Vig, Manjula Kurella Tamura, J. Randall Curtis, Ann O'Hare

Background: People receiving maintenance dialysis must often rely on family members and other close persons to make critical treatment decisions toward the end of life. Contemporary data on family members' understanding of the end-of-life wishes of members of this population are lacking. Methods: Among 172 family members of people undergoing maintenance dialysis, we ascertained their level of involvement in the patient's care and prior discussions about care preferences. We also compared patient and family member responses to questions about end-of-life care using percent agreement and the kappa statistic.

Bone mineral density and long-term progression of aortic valve and mitral annular calcification: The Multi-Ethnic Study of Atherosclerosis

Daniele Massera, Petra Buzkova, Anna E Bortnick, David S Owens, SongShou Mao, Dong Li, Ian H De Boer, Bryan R Kestenbaum, Matthew J Budoff, Jorge R Kizer

Background and aims: Bone and mineral metabolism has been implicated in the pathophysiology of cardiac valve calcification. Whether bone demineralization, a common aging-related disorder, promotes calcific valve disease remains uncertain. We tested the hypothesis that low bone mineral density (BMD) is associated with greater incidence/progression of cardiac valve calcification in the Multi-Ethnic Study of Atherosclerosis.

A Randomised Controlled Trial Comparing Insulin Degludec U100 and Glargine U100 for the Inpatient Management of Patients with Type 2 Diabetes

Rodolfo J Galindo, Francisco J Pasquel, Priyathama Vellanki, Radica Alicic, David W Lam, Maya Fayfman, Alexandra L Migdal, Georgia M Davis, Saumeth Cardona, Maria A Urrutia, Citlalli Perez-Guzman, Karla Walkiria Zamudio-Coronado, Limin Peng, Katherine R Tuttle, Guillermo E Umpierrez

Aims: Limited data exists about the use of insulin degludec in the hospital. This multicentre, non-inferiority, open-label, prospective randomised trial compared the safety and efficacy of insulin degludec-U100 and glargine-U100 for the management of hospitalized patients with type 2 diabetes. Methods: A total of 180 general medicine and surgery patients with an admission blood glucose (BG) between 7·8 - 22·2 mmol/L, treated with oral agents or insulin prior to hospitalization were randomly allocated (1:1) to a basal bolus regimen using degludec (n=92) or glargine (n=88), as basal and aspart before meals. Insulin dose was adjusted daily to a target BG between 3·9 - 10·0 mmol/L. The primary end point was difference in the mean hospital daily BG between groups.

Patient Activation Measure in Dialysis Dependent Patients in the United States

Daniel Cukor, Leila Zelnick, David Charytan, Amanda Shallcross, Rajnish Mehrotra

The Patient Activation Measure (PAM) is a standardized instrument that assesses an individual's knowledge, ability, skills, and confidence in self-managing chronic medical conditions. A study published in JASN examined whether PAM is a meaningful metric for adults with kidney failure who are on long-term dialysis. These patients are actively involved in multiple domains of their care, such as keeping track of frequent treatments, following specified diets, and taking multiple medications. The study included 175 patients being treated with in-center hemodialysis between August 2020 and January 2021 at 3 sites (2 in New York City and 1 in Seattle). There was no significant relationship between PAM scores and missed dialysis sessions or weight gain between dialysis sessions. Investigators found a strong relationship between lower PAM scores and lower levels of health literacy and higher levels of depression and anxiety, however.