Our research broadens the knowledge of kidney disease.

Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review

Karine E Manera, Angela Ju, Amanda Baumgart, Elyssa Hannan, Wenjing Qiao, Martin Howell, Melissa Nataatmadja, Martin Wilkie, Fiona Loud, Daniel Schwartz, Helen Hurst, Sarbjit Vanita Jassal, Ana Figueiredo, Rajnish Mehrotra, Jenny Shen, Rachael L Morton, Thyago Moraes, Rachael Walker, Catherine Cheung, Janine F Farragher, Jonathan Craig, David W Johnson, Allison Tong

Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD.

The challenge of insomnia for patients on haemodialysis

Daniel Cukor, Mark Unruh, Susan M McCurry, Rajnish Mehrotra 

Insomnia is common among patients on maintenance haemodialysis and may be exacerbated by the challenges of the COVID pandemic. However, data on the efficacy of insomnia interventions in this population are limited. Efforts are needed to address this important problem and increase access to insomnia interventions for patients on haemodialysis.

Association of the Estimated Glomerular Filtration Rate With vs Without a Coefficient for Race With Time to Eligibility for Kidney Transplant

Question: Is adjusting for Black race in estimating equations for glomerular filtration rate in patients with chronic kidney disease associated with a delay in kidney transplant eligibility? Findings: In this cohort study of 1658 self-identified Black adults with chronic kidney disease, commonly used estimates of kidney function did not correspond well with directly measured kidney function. Estimating kidney function not including a coefficient for race (vs including a race coefficient) was significantly associated with a shorter time to achieving an estimated glomerular filtration rate less than 20 mL/min/1.73 m2, a key threshold of kidney function for referral and listing for kidney transplant. Meaning: The findings suggest that biases in race-based glomerular filtration rate estimates may be associated with delays in potential kidney transplant eligibility.

KDOQI US Commentary on the 2020 ISPD Practice Recommendations for Prescribing High-Quality Goal-Directed Peritoneal Dialysis

Isaac Teitelbaum, Joel Glickman, Alicia Neu, Joanna Neumann, Matthew B. Rivara, Jenny Shen, Eric Wallace, Suzanne Watnick, Rajnish Mehrotra

The recently published 2020 International Society for Peritoneal Dialysis (ISPD) practice recommendations regarding prescription of high-quality goal-directed peritoneal dialysis differ fundamentally from previous guidelines that focused on “adequacy” of dialysis. The new ISPD publication emphasizes the need for a person-centered approach with shared decision making between the individual performing peritoneal dialysis and the clinical care team while taking a broader view of the various issues faced by that individual. Cognizant of the lack of strong evidence for the recommendations made, they are labeled as “practice points” rather than being graded numerically. This commentary presents the views of a work group convened by the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) to assess these recommendations and assist clinical providers in the United States in interpreting and implementing them. This will require changes to the current clinical paradigm, including greater resource allocation to allow for enhanced services that provide a more holistic and person-centered assessment of the quality of dialysis delivered.

Development and evaluation of deep learning–based segmentation of histologic structures in the kidney cortex with multiple histologic stains

Catherine P Jayapandian, Yijiang Chen, Andrew R Janowczyk, Matthew B Palmer, Clarissa A Cassol, Miroslav Sekulic, Jeffrey B Hodgin, Jarcy Zee, Stephen M Hewitt, John O'Toole, Paula Toro, John R Sedor, Laura Barisoni, Anant Madabhushi, Nephrotic Syndrome Study Network (NEPTUNE) including: J. Ashley Jefferson, Katherine Tuttle, Benjamin Freedman, et al.

The application of deep learning for automated segmentation (delineation of boundaries) of histologic primitives (structures) from whole slide images can facilitate the establishment of novel protocols for kidney biopsy assessment. Here, we developed and validated deep learning networks for the segmentation of histologic structures on kidney biopsies and nephrectomies. For development, we examined 125 biopsies for Minimal Change Disease collected across 29 NEPTUNE enrolling centers along with 459 whole slide images stained with Hematoxylin & Eosin (125), Periodic Acid Schiff (125), Silver (102), and Trichrome (107) divided into training, validation and testing sets (ratio 6:1:3). Histologic structures were manually segmented (30048 total annotations) by five nephropathologists. Twenty deep learning models were trained with optimal digital magnification across the structures and stains.

Large-scale, three-dimensional tissue cytometry of the human kidney: a complete and accessible pipeline

Michael J. Ferkowicz, Seth Winfree, Angela R. Sabo, Malgorzata M. Kamocka, Suraj Khochare, Daria Barwinska, Michael T. Eadon, Ying-Hua Cheng, Carrie L. Phillips, Timothy A. Sutton, Katherine J. Kelly, Pierre C. Dagher, Tarek M. El-Achkar, Kenneth W. Dunn & for the Kidney Precision Medicine Project: Katherine Tuttle, Ian de Boer, Jonathan Himmelfarb, Stuart Shankland, Ashveena Dighe, et al

The advent of personalized medicine has driven the development of novel approaches for obtaining detailed cellular and molecular information from clinical tissue samples. Tissue cytometry is a promising new technique that can be used to enumerate and characterize each cell in a tissue and, unlike flow cytometry and other single-cell techniques, does so in the context of the intact tissue, preserving spatial information that is frequently crucial to understanding a cell’s physiology, function, and behavior. However, the wide-scale adoption of tissue cytometry as a research tool has been limited by the fact that published examples utilize specialized techniques that are beyond the capabilities of most laboratories. Here we describe a complete and accessible pipeline, including methods of sample preparation, microscopy, image analysis, and data analysis for large-scale three-dimensional tissue cytometry of human kidney tissues.

Association between goal-striving stress and rapid kidney function decline among African Americans: The Jackson Heart Study

Loretta Cain-Shields, LáShauntá Glover, Bessie Young, Mario Sims

African Americans (AAs) are disproportionately affected by kidney disease and also report higher psychosocial stressors than other racial groups. Goal-striving stress (GSS) is an understudied psychosocial stressor related to attempting to accomplish one's life goals. Given the numerous social determinants that contribute to health inequities among AAs, stress from goal striving may also disproportionately affect the health of AAs and in particular kidney disease outcomes. The objective of this study was to explore the association between GSS and rapid kidney function decline (RKFD) in an AA cohort.

Effects of the Soluble Guanylate Cyclase Stimulator Praliciguat in Diabetic Kidney Disease: A Randomized Placebo-Controlled Clinical Trial

John P. Hanrahan, Ian H. de Boer, George L. Bakris, Phebe J. Wilson, James D. Wakefield, Jelena P. Seferovic, Jennifer G. Chickering, Yueh-tyng Chien, Kenneth Carlson, Michael D. Cressman, Mark G. Currie, G. Todd Milne and Albert T. Profy

Background and objectives: Impaired nitric oxide signaling through soluble guanylate cyclase has been implicated in the pathophysiology of diabetic kidney disease. Praliciguat, a soluble guanylate cyclase stimulator that amplifies nitric oxide signaling, inhibited kidney inflammation and fibrosis in animal models. Design, setting, participants, & measurement: In a phase 2 trial, 156 adults with type 2 diabetes, eGFR 30–75 ml/min per 1.73 m2, and urine albumin-creatinine ratio 200–5000 mg/g treated with renin-angiotensin system inhibitors were randomly allocated 1:1:1 to placebo, 20 mg praliciguat, or 40 mg praliciguat daily for 12 weeks. The primary efficacy and safety outcomes were change from baseline to weeks 8 and 12 in urine albumin-creatinine ratio and treatment-emergent adverse events, respectively. Other outcomes assessed were 24-hour ambulatory BP and metabolic parameters.

Change in Cardiac Biomarkers and Risk of Incident Heart Failure and Atrial Fibrillation in CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

Nisha Bansal, Leila R Zelnick, Elsayed Soliman, Amanda Anderson, Robert Christenson, Christopher DeFilippi, Rajat Deo, Harold I Feldman, Jiang He, Bonnie Ky, John Kusek, James Lash, Stephen Seliger, Tariq Shafi, Myles Wolf, Alan S Go, Michael G Shlipak, CRIC Study Investigators

Circulating cardiac biomarkers may signal potential mechanistic pathways involved in heart failure (HF) and atrial fibrillation (AF). Single measures of circulating cardiac biomarkers are strongly associated with incident HF and AF in chronic kidney disease (CKD). We tested the associations of longitudinal changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), high sensitivity troponin T (hsTnT), galectin-3, growth differentiation factor-15 (GDF-15), and soluble ST-2 (sST-2) with incident HF and AF in patients with CKD.

Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease

Alexander J Kula, Ronit Katz, Leila R Zelnick, Elsayed Soliman, Alan Go, Michael Shlipak, Rajat Deo, Bonnie Ky, Ian DeBoer, Amanda Anderson, Rob Christenson, Stephen L Seliger, Chris Defilippi, Harold I Feldman, Myles Wolf, John Kusek, Tariq Shafi, Jiang He, Nisha Bansal

Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD.