Our faculty research broadens the knowledge of kidney disease.

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.

Defining the roles and responsibilities of the kidney transplant medical director: A necessary step for future training, mentoring, and professional development

Alexander C. Wiseman, Enver Akalin, Darshana M. Dadhania, Angelo DeMattos, Mona Doshi, John Friedewald, Christina Klein, Nicolae Leca, Kim Nicoll, Todd Pesavento, Luke Preczewski, Millie Samaniego, Neeraj Singh, Roy Bloom 

The management of a kidney transplant program has evolved significantly in the last decades to become a highly specialized, multidisciplinary standard of care for end‐stage kidney disease. Transplant center job descriptions have similarly morphed with increasing responsibilities to address a more complex patient mix, increasing medical and surgical therapeutic options, and increasing regulatory burden in the face of an ever‐increasing organ shortage. Within this evolution, the role of the Kidney Transplant Medical Director (KTMD) has expanded beyond the basic requirements described in the United Network for Organ Sharing bylaws. Without a clear job description, transplant nephrology trainees may be inadequately trained and practicing transplant nephrologists may face opaque expectations for the roles and responsibilities of Medical Director. To address this gap and clarify the key areas in which the KTMD interfaces with the kidney transplant program, American Society of Transplantation (AST) formed a Task Force of 14 AST KTMDs to review and define the role of the KTMD in key aspects of administrative, regulatory, budgetary, and educational oversight of a kidney transplant program.

Dialysis adequacy reconsidered: The person comes first

Although many nephrologists see value in maximizing clearance and time on dialysis, clinical trials have failed to show a clear and consistent benefit of increasing clearance above the minimum threshold level recommended in clinical practice guidelines or of increasing dialysis session length or frequency. Available evidence suggests that patients and clinicians do not necessarily agree on what matters most when it comes to dialysis care, and that what patients consider to be an adequate dialysis session is highly individual and has little to do with solute clearance. Qualitative studies suggest that patients value spending less time on dialysis, having the dialysis procedure go smoothly, and being treated like an individual by staff members. Because many patients feel that they have little choice but to show up for their dialysis sessions, failing to involve them in decisions about time spent on the machine can contribute to feelings of powerlessness and loss of control, erode their sense of self, and diminish the quality of therapeutic relationships. On the other hand, a flexible and shared approach to decision‐making about time spent on dialysis (and other aspects of care) can help to strengthen relationships, uphold personhood, and align care with what matters most.

Diabetes Management in Chronic Kidney Disease: Synopsis of the 2020 KDIGO Clinical Practice Guideline

Sankar D. Navaneethan, Sophia Zoungas, M. Luiza Caramori, Juliana C. N. Chan, Hiddo J. L. Heerspink, Clint Hurst, Adrian Liew, Erin D. Michos, Wasiu A. Olowu, Tami Sadusky, Nikhil Tandon, Katherine R. Tuttle, Christoph Wanner, Katy G. Wilkens, Lyubov Lytvyn, Jonathan C. Craig, David J. Tunnicliffe, Martin Howell, Marcello Tonelli, Michael Cheung, Amy Earley, Peter Rossing, Ian H. de Boer, Kamlesh Khunti

The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD). The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team.

Vitamin D in human serum and adipose tissue after supplementation

Cora M Best, Devon V Riley, Thomas J Laha, Hannah Pflaum, Leila R Zelnick, Simon Hsu, Kenneth E Thummel, Karen E Foster-Schubert, Jessica N Kuzma, Gail Cromer, Ilona Larson, Derek K Hagman, Kelly Heshelman, Mario Kratz, Ian H de Boer, Andrew N Hoofnagle

Vitamin D occurs in 2 main forms, vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol), and is an essential precursor to the steroid hormone 1,25-dihydroxyvitamin D [1,25(OH)2D]. Humans produce vitamin D3 in the epidermis upon exposure to UVB light and consume both forms (D3 and D2) in foods, beverages, and dietary supplements. Typical daily input from each of these routes and how this varies between individuals are unknown.

Integrating Patient Priorities with Science by Community Engagement in the Kidney Precision Medicine Project

Katherine R. Tuttle, Richard Knight, Paul S. Appelbaum, Tanima Arora, Shweta Bansal, Jack Bebiak, Keith Brown, Catherine Campbell, Leslie Cooperman, Celia P. Corona-Villalobos, Ashveena Dighe, Ian H. de Boer, Daniel E. Hall, Nichole Jefferson, Stacey Jolly, Asra Kermani, Simon C. Lee, Karla Mehl, Raghavan Murugan, Glenda V. Roberts, Sylvia E. Rosas, Jonathan Himmelfarb, R. Tyler Miller and for the Kidney Precision Medicine Project

The Kidney Precision Medicine Project (KPMP) is a multisite study designed to improve understanding of CKD attributed to diabetes or hypertension and AKI by performing protocol-driven kidney biopsies. Study participants and their kidney tissue samples undergo state-of-the-art deep phenotyping using advanced molecular, imaging, and data analytical methods. Few patients participate in research design or concepts for discovery science. A major goal of the KPMP is to include patients as equal partners to inform the research for clinically relevant benefit. The purpose of this report is to describe patient and community engagement and the value they bring to the KPMP.

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Mathias Gorski, Bettina Jung, Yong Li, Pamela R Matias-Garcia, Matthias Wuttke, Stefan Coassin, Chris H L Thio, Marcus E Kleber, Thomas W Winkler, Veronika Wanner, Jin-Fang Chai, Audrey Y Chu, Massimiliano Cocca, Mary F Feitosa, Sahar Ghasemi, Anselm Hoppmann, Katrin Horn, Man Li, Teresa Nutile, Markus Scholz, Karsten B Sieber, Alexander Teumer, Adrienne Tin, Judy Wang, Bamidele O Tayo, Tarunveer S Ahluwalia, Peter Almgren, Stephan J L Bakker, Bernhard Banas, Nisha Bansal, Mary L Biggs, Eric Boerwinkle, Erwin P Bottinger, Hermann Brenner , Robert J Carroll, et al...

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (“CKDi25”; encompassing 19,901 cases, 175,244 controls).

Prediction of Kidney Drug Clearance: A Comparison of Tubular Secretory Clearance and Glomerular Filtration Rate

Yan Chen, Leila R. Zelnick, Andrew N. Hoofnagle, Catherine K. Yeung, Laura M. Shireman, Brian Phillips, Calder C. Brauchla, Ian de Boer, Linda Manahan, Susan R. Heckbert, Jonathan Himmelfarb, Bryan R. Kestenbaum

Although proximal tubular secretion is the primary mechanism of kidney drug elimination, kidney drug dosing strategies are on the basis of eGFR. In a study of 54 participants with or without CKD, measurements of tubular secretory clearance of endogenous secretory solutes predicted the elimination of avidly secreted medications, furosemide and penciclovir. However, GFR’s predictive accuracy (measured by iohexol clearance) resembled that of the secretory solute clearances for predicting furosemide and penciclovir clearance, and the addition of secretory solute clearances yielded only small improvements in predictive accuracy. These findings demonstrate that secretory clearance measurements predict kidney drug elimination but also suggest a tight linkage between GFR and tubular secretory clearance in stable outpatients. This provides some reassurance that GFR is a useful surrogate for secretory drug clearance for drug dosing in such individuals.

Thematic Analysis of the Health Records of a National Sample of US Veterans With Advanced Kidney Disease Evaluated for Transplant

Catherine R. Butler, Aaron Wightman, Claire A. Richards, Ryan S. Laundry, Janelle S. Taylor, Paul L. Hebert, Chuan-Fen Liu, Ann M. O’Hare

Question: What types of clinical care are involved in the kidney transplant evaluation process in real-world clinical settings? Findings: In this qualitative study of the electronic health records of 211 US veterans with advanced kidney disease who were referred for kidney transplant evaluation, 4 dominant themes were identified describing clinical care during the evaluation process: far-reaching and inflexible medical evaluation, psychosocial valuation, surveillance over compliance, and disempowerment and lack of transparency. Meaning: In this study, clinician documentation in the medical record indicated that, to be considered for a kidney transplant, patients were required to participate in a rigid, demanding, and opaque evaluation process over which they and their local clinicians had little control.

Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients

Michael E. Brier, Jessica R. Gooding, James M. Harrington, Jason P. Burgess, Susan L. McRitchie, Xiaolan Zhang, Brad H. Rovin, Jon B. Klein, Jonathan Himmelfarb, Susan J. Sumner, Michael L. Merchant 

Alterations in hemodialysis patients’ serum trace metals have been documented. Early studies addressing associations levels of serum trace metals with erythropoietic responses and/or hematocrit generated mixed results. These studies were conducted prior to current approaches for erythropoiesis stimulating agent (ESA) drug dosing guidelines or without consideration of inflammation markers (e.g. hepcidin) important for regulation of iron availability. This study sought to determine if the serum trace metal concentrations of incident or chronic hemodialysis patients associated with the observed ESA response variability and with consideration to ESA dose response, hepcidin, and high sensitivity C-reactive protein levels.