Our research broadens the knowledge of kidney disease.

SGLT2 Inhibitors in Diabetic Kidney Disease

Zoungas S, de Boer IH

Type 2 diabetes, increasing in prevalence globally, is a major cause of CKD and kidney failure. Sodium-glucose transport protein 2 inhibitors (SGLT2i) significantly reduced progression of CKD, major adverse cardiovascular events, heart failure, and all-cause mortality in large clinical trials of people with type 2 diabetes.

Prospective cohort study of renin-angiotensin system blocker usage after hospitalized acute kidney injury

Sandeep Brar, Kathleen D. Liu, Alan S. Go, Raymond K. Hsu, Vernon M. Chinchilli, Steven G. Coca, Amit X. Garg, Jonathan Himmelfarb, T. Alp Ikizler, James Kaufman, Paul L. Kimmel, Chirag R. Parikh, Edward D. Siew, Lorraine B. Ware, Hui Zeng, Chi-yuan Hsu and for the ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) study investigators

Background and objectives:The risk-benefit ratio of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy after AKI may be altered due to concerns regarding recurrent AKI. We evaluated, in a prospective cohort, the association between use (versus nonuse) of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and the subsequent risk of AKI and other adverse outcomes after hospitalizations with and without AKI.

Therapeutic transformation for diabetic kidney disease

Katherine R. Tuttle, David Z.I. Cherney

Risks of kidney failure and heart failure are markedly reduced by inhibition of the sodium glucose cotransporter 2 (SGLT2) in patients with diabetic kidney disease. In a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial, drop-in SGLT2 inhibitor usage during the atrasentan enrichment period led to greater reduction in albuminuria compared with atrasentan alone. These data support the hypothesis of greater longer-term kidney protection by combination SGLT2 inhibition and endothelin A receptor antagonism that could be tested in future clinical trials.

Association Between Kidney Clearance of Secretory Solutes and Cardiovascular Events: The Chronic Renal Insufficiency Cohort (CRIC) Study

Yan Chen, Leila R Zelnick, Matthew P Huber Ke Wang, Nisha Bansal, Andrew N Hoofnagle, Rajan K Paranji, Susan R Heckbert, Noel S Weiss, Alan S Go, Chi-Yuan Hsu, Harold I Feldman, Sushrut S Waikar, Rupal C Mehta, Anand Srivastava, Stephen L Seliger, James P Lash, Anna C Porter, Dominic S Raj, Bryan R Kestenbaum, CRIC Study Investigators

Rational & Objective: The clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.

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.