Our faculty research broadens the knowledge of kidney disease.

International consensus definitions of clinical trial outcomes for kidney failure: 2020

Adeera Levin, Rajiv Agarwal, William G Herrington, Hiddo L Heerspink, Johannes F E Mann, Shahnaz Shahinfar, Katherine R Tuttle, Jo-Ann Donner, Vivekanand Jha, Masaomi Nangaku, Dick de Zeeuw, Meg J Jardine, Kenneth W Mahaffey, Aliza M Thompson, Mary Beaucage, Kate Chong, Glenda V Roberts, Duane Sunwold, Hans Vorster, Madeleine Warren, Sandrine Damster, Charu Malik, Vlado Perkovic, participant authors of the International Society of Nephrology’s 1st International Consensus Meeting on Defining Kidney Failure in Clinical Trials, includes Ian H de Boer, among others

Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include...

Angiotensin II type 1 receptor antibodies in kidney transplantation: An evidence-based comprehensive review

Sorohan, B.M., Ismail, G., Leca, N., Tacu, D., Obrișcă, B., Constantinescu, I., Baston, C., Sinescu, I.

Angiotensin II type 1 receptor antibodies (AT1R-Ab) are among the most investigated types of non-HLA antibodies in kidney transplantation. Our aim is to provide an update regarding the clinical relevance of AT1R-Ab by outlining their prevalence, testing methodology, mechanism of graft injury and the association with graft rejection phenotypes, the relationship with HLA-donor specific antibodies (DSA) and some therapeutic aspects. To accomplish these, we performed a literature review between 2005 and 2019, identifying 27 relevant studies for inclusion. The reported prevalence of these antibodies is widely variable in part related to testing variability and lack of a standardized threshold for positivity. Data available suggest that both pre-formed and de novo antibodies are associated with negative graft outcomes.

Longitudinal Changes in Health-Related Quality of Life in Primary Glomerular Disease: Results From the CureGN Study

Murphy, S.L., Mahan, J.D., Troost, J.P., Srivastava, T., Kogon, A.J., Cai, Y., Davis, T.K., Fernandez, H., Fornoni, A,, Gbadegesin, R.A., Herreshoff, E., Canetta, P.A., Nachman, P.H., Reeve, B.B., Selewski, D.T., Sethna, C.B., Wang, C.-S., Bartosh, S.M., Gipson, D.S.,Tuttle, K.R., Gharavi, A., Ahn, W., Appel, G.B., Avasare, R.S., Babayev, R., Batal, I., Bomback, A.S., ....Jefferson, J.A., on behalf of the CureGN Consortium

Prior cross-sectional studies suggest that health-related quality of life (HRQOL) worsens with more severe glomerular disease. This longitudinal analysis was conducted to assess changes in HRQOL with changing disease status. Cure Glomerulonephropathy (CureGN) is a cohort of patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA vasculitis, or IgA nephropathy. HRQOL was assessed at enrollment and follow-up visits 1 to 3 times annually for up to 5 years with the Patient-Reported Outcomes Measurement Information System (PROMIS). Global health, anxiety, and fatigue domains were measured in all; mobility was measured in children; and sleep-related impairment was measured in adults. Linear mixed effects models were used to evaluate HRQOL responsiveness to changes in disease status.

Modelling kidney disease using ontology: insights from the Kidney Precision Medicine Project

Ong, E., Wang, L.L., Schaub, J., O’Toole, J.F., Steck, B., Rosenberg, A.Z., Dowd, F., Hansen, J.h,, Barisoni, L., Jain, S., de Boer, I.H., M.T., Waikar, S.S., Park, C., Crawford, D.C., Alexandrov, T., Anderton, C.R., Stoeckert, C., Weng, C., Diehl, A.D., Mungall, C.J., Haendel, M., Robinson, P.N,, Himmelfarb, J., Iyengar, R., Kretzler, M., Mooney, S., He, Y., Kidney Precision Medicine Project

An important need exists to better understand and stratify kidney disease according to its underlying pathophysiology in order to develop more precise and effective therapeutic agents. National collaborative efforts such as the Kidney Precision Medicine Project are working towards this goal through the collection and integration of large, disparate clinical, biological and imaging data from patients with kidney disease. Ontologies are powerful tools that facilitate these efforts by enabling researchers to organize and make sense of different data elements and the relationships between them.

Photoreactive Carboxybetaine Copolymers Impart Biocompatibility and Inhibit Plasticizer Leaching on Polyvinyl Chloride

Xiaojie Lin, Kan Wu, Qiong Zhou, Priyesh Jain, Mary O’Kelly Boit, Bowen Li, Hsiang-Chieh Hung, Sharon A. Creason, Jonathan Himmelfarb, Buddy D. Ratner, Shaoyi Jiang

Protein and cell interactions on implanted, blood-contacting medical device surfaces can lead to adverse biological reactions. Medical-grade poly(vinyl chloride) (PVC) materials have been used for decades, particularly as blood-contacting tubes and containers. However, there are numerous concerns with their performance including platelet activation, complement activation, and thrombin generation and also leaching of plasticizers, particularly in clinical applications. Here, we report a surface modification method that can dramatically prevent blood protein adsorption, human platelet activation, and complement activation on commercial medical-grade PVC materials under various test conditions.

Microphysiological system modeling of ochratoxin A-associated nephrotoxicity

Tomoki Imaoka, Jade Yang, Lu Wang, Matthew G .McDonald, Zahra Afsharinej, Theo K .Bammler, Kirk Van Ness, Catherine K. Yeung, Allan E. Rettieb, Jonathan Himmelfarb, Edward J. Kelly

Ochratoxin A (OTA) is one of the most abundant mycotoxin contaminants in food stuffs and possesses carcinogenic, nephrotoxic, teratogenic, and immunotoxic properties. Specifically, a major concern is severe nephrotoxicity, which is characterized by degeneration of epithelial cells of the proximal tubules and interstitial fibrosis. However, the mechanism of OTA toxicity, as well as the genetic risk factors contributing to its toxicity in humans has been elusive due to the lack of adequate models that fully recapitulate human kidney function in vitro. The present study attempts to evaluate dose-response relationships, identify the contribution of active transport proteins that govern the renal disposition of OTA, and determine the role of metabolism in the bioactivation and detoxification of OTA using a 3D human kidney proximal tubule microphysiological system (kidney MPS).

How Useful Is an Age-Neutral Model of Chronic Kidney Disease?

In their article, Ravani et al describe the results of a population-based cohort study that used provincial laboratory and administrative data from Alberta, Canada, demonstrating systematic differences in the risks of kidney failure and death across age groups among adults with a severe decrease in estimated glomerular filtration rate (eGFR). Cohort members younger than 65 years were more likely to develop kidney failure than to die, whereas the reverse was true at older ages. Strikingly, the risk of death was 6-fold higher than the risk of kidney failure for those aged 75 to 85 years and 24-fold higher than that of kidney failure for those aged ≥85 years. Although the absolute and relative risks of death and kidney failure also varied by sex, presence or absence of diabetes and cardiovascular disease, and level of albuminuria, marked differences in the relative frequency of death and kidney failure across age groups persisted in all subgroups examined by Ravani et al.

International variation in dialysis discontinuation in patients with advanced kidney disease

Sarbjit V. Jassal, Maria Larkina, Kitty J. Jager, Fliss E.M. Murtagh, Ann M. O’Hare, Norio Hanafusa, Hal Morgenstern, Friedrich K. Port, Keith McCullough, Ronald Pisoni, Francesca Tentori, Rachel Perlman and Richard D. Swartz

Decisions about dialysis for advanced kidney disease are often strongly shaped by sociocultural and system-level factors rather than the priorities and values of individual patients. We examined international variation in the uptake of conservative approaches to the care of patients with advanced kidney disease, in particular discontinuation of dialysis.

Construct validity, ecological validity and acceptance of self-administered online neuropsychological assessment in adults

Chaytor, N.S., Barbosa-Leiker, C., Germine, L.T., Fonseca, L.M., McPherson, S.M., Tuttle, K.R.

The goal of this project was to explore the initial psychometric properties (construct and ecological validity) of self-administered online (SAO) neuropsychological assessment (using the www.testmybrain.org platform), compared to traditional testing, in a clinical sample, as well as to evaluate participant acceptance. SAO assessment has the potential to expand the reach of in-person neuropsychological assessment approaches.

Race, Ancestry and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis

Simon Hsu, Andrew N Hoofnagle, Deepak K Gupta, Orlando M Gutierrez, Carmen A Peralta, Steven Shea, Norrina B Allen, Gregory Burke, Erin D Michos, Joachim H Ix, David Siscovick, Bruce M Psaty, Karol E Watson, Bryan Kestenbaum, Ian H de Boer, Cassianne Robinson-Cohen

Context: A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D-related diseases. Objective: Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry