Our research broadens the knowledge of kidney disease.

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.

SGLT2 inhibition and chronic kidney disease outcomes: in diabetes and beyond

Chronic kidney disease (CKD) is a pressing public health concern. CKD attributed to diabetes, known as diabetic kidney disease (DKD), is the most common cause of kidney failure, accounting for half of all cases. As the number of people with diabetes dramatically rises around the world, the burden of diabetic complications will concurrently swell. Occurring in about 30% of patients with type 1 diabetes and 40% of those with type 2 diabetes, DKD is one of most incapacitating and lethal complications of diabetes. Additionally, about a quarter of cases of kidney failure in CKD are attributed to hypertension, followed by various forms of glomerular diseases. It is crucial to recognise that the risks of CKD include a high risk of death that outcompetes risk of progression to kidney failure, particularly in patients with diabetes. Indeed, most people with CKD die before progressing to kidney failure. The largest number of deaths in people with CKD are due to cardiovascular diseases, especially heart failure. In order to meaningfully improve patient outcomes—survival without kidney failure or heart failure—better CKD care is urgently needed.

Perspectives on Conservative Care in Advanced Kidney Disease: A Qualitative Study of US Patients and Family Members

Oestreich, T., Sayre, G., O'Hare, A.M., Curtis, J.R., Wong, S.P.Y.

Rationale & Objective: Little is known about perceptions of conservative care among patients with advanced kidney disease in the United States. Study Design: Qualitative study using cognitive interviewing about attitudes regarding conservative care using decision aids on treatments for advanced kidney disease developed outside the United States. Setting & Participants: 14 patients 75 years or older with advanced kidney disease, defined as estimated glomerular filtration rate ≤ 20 mL/min/1.73 m2 and not receiving maintenance dialysis, and 6 of their family members. Analytical Approach: Thematic analysis of participants’ reactions to descriptions of conservative care taken from various clinical care decision aids.

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant

Naoka Murakami, Patrick Mulvaney, Melissa Danesh, Ala Abudayyeh, Adi Diab, Noha Abdel-Wahab, Maen Abdelrahim, Pascale Khairallah, Shayan Shirazian, Aleksandra Kukla, Itunu O. Owoyemi, Tarek Alhamad, Samir Husami, Madhav Menon, Andrew Santeusanio, Christopher Blosser, Sandra Carias Zuniga, Maria Jose Soler, Francesc Moreso, Zain Mithani, David Ortiz-Melo, Edgar A. Jaimes, Victoria Gutgarts, Erik Lum, Gabriel M. Danovitch, Francesca Cardarelli, Reed E. Drews, Claude Bassil, Jennifer L. Swank, Scott Westphal, Roslyn B. Mannon,Keisuke Shirai, Abhijat Kitchlu, Song Ong, Shana M. Machado, Suraj S. Mothi, Patrick A. Ott, Osama Rahma, F. Stephen Hodi, Meghan E. Sise, Shruti Gupta, David E. Leaf, Craig E. Devoe, Rimda Wanchoo, Vinay V. Nair, Chrysalyne D. Schmults, Glenn J. Hanna, Ben Sprangers, Leonardo V. Riella, Kenar D. Jhaveri, On behalf ofImmune Checkpoint Inhibitors in Solid Organ Transplant Consortium

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs.