Our faculty research broadens the knowledge of kidney disease.

Cardiorenal Protection With the Newer Antidiabetic Agents in Patients With Diabetes and Chronic Kidney Disease: A Scientific Statement From the American Heart Association

Janani Rangaswami, Vivek Bhalla, Ian H. de Boer, Alexander Staruschenko, Johanna A. Sharp, Radhika Rajgopal Singh, Kevin Bryan Lo, Katherine Tuttle, Muthiah Vaduganathan, Hector Ventura, Peter A. McCullough, and On behalf of the American Heart Association Council on the Kidney in Cardiovascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Lifestyle and Cardiometabolic Health

Chronic kidney disease (CKD) with type 2 diabetes (T2D) is a major public health problem, resulting in significant cardiovascular and kidney adverse outcomes worldwide. Despite the widespread use of standard-of-care therapies for CKD with T2D over the past few decades, rates of progression to end-stage kidney disease remain high with no beneficial impact on its accompanying burden of cardiovascular disease. The advent of the newer classes of antihyperglycemic agents, including SGLT2 (sodium glucose cotransporter 2) inhibitors and GLP-1 (glucagon-like peptide-1) receptor agonists, has changed the landscape of therapeutic options for patients with CKD with T2D, with demonstration of significant reductions in cardiovascular adverse events and progression to end-stage kidney disease. Several potential mechanisms exist through which these beneficial effects are achieved in both drug classes, which may be independent of their antihyperglycemic effects. This scientific statement summarizes the current literature...

Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets

Matsushita, K., Jassal, S.K., Sang, Y., Ballew, S.H., Grams, M.E., Surapaneni, A, Arnlov, J., Bansal, N., Bozic, M., Brenner, H., Brunskill, N.J., Chang, A.R., Chinnadurai, R., Cirillo, M., Correa, A., Ebert, N., Eckardt, K.-U., Gansevoort, R.T., Gutierrez, O., Hadaegh, F., He, J., Hwang, S.-J., Jafar, T.H., Kayama, T., Kovesdy, C.P., Landman, G.W., Levey, A.S., Lloyd-Jones, D.M., Major, R.W., Miura, K., Muntner, P, Nadkarni, G.N., Naimark, D.M., Nowak, C, Ohkubo, T., Pena, M.J., Polkinghorne, K.R, Sabanayagam, C., Sairenchi, T., Schneider, M.P., Shalev, V., Shlipak, M., Solbu, M.D., Stempniewicz, N., Tollitt, J.j,, Valdivielso, J.M, van der Leeuw, J., Wang, A.Y.-M. , Wen, C.-P. , Woodward, M., Yamagishi, K., Yatsuya, H., Zhang, L., Schaeffner, E., Coresh, J

Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. “CKD Patch” is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures.

US Clinicians’ Experiences and Perspectives on Resource Limitation and Patient Care During the COVID-19 Pandemic

Catherine R. Butler, Susan P. Y. Wong, Aaron G. Wightman, Ann M. O’Hare

Importance: Little is known about how US clinicians have responded to resource limitation during the coronavirus disease 2019 (COVID-19) pandemic. Objective: To describe the perspectives and experiences of clinicians involved in institutional planning for resource limitation and/or patient care during the pandemic. Design, Setting, and Participants: This qualitative study used inductive thematic analysis of semistructured interviews conducted in April and May 2020 with a national group of clinicians (eg, intensivists, nephrologists, nurses) involved in institutional planning and/or clinical care during the COVID-19 pandemic across the United States. Main Outcomes and Measures Emergent themes describing clinicians’ experience providing care in settings of resource limitation. Results: The 61 participants (mean [SD] age, 46 [11] years; 38 [63%] women) included in this study were practicing in 15 US states and were more heavily sampled from areas with the highest rates of COVID-19 infection at the time of interviews (ie, Seattle, New York City, New Orleans)...

Neutrophil Activation and Neutrophil Extracellular Trap Formation in Dialysis Patients

Scott Bieber, Kimberly A. Muczynski, Christian Lood

The removal of metabolic waste by passing blood through synthetic tubing and membranes generates an immune response, even with the most biocompatible materials available. We evaluated blood levels of neutrophil activation and cell death during dialysis to devise a set of markers by which future dialysis interventions might be measured for biocompatibility.

A Targeted Multiomics Approach to Identify Biomarkers Associated with Rapid eGFR Decline in Type 1 Diabetes

Limonte CP, Valo E, Montemayor D, Afshinnia F, Ahluwalia TS, Costacou T, Darshi M, Forsblom C, Hoofnagle AN, Groop PH, Miller RG, Orchard TJ, Pennathur S, Rossing P, Sandholm N, Snell-Bergeon JK, Ye H, Zhang J, Natarajan L, de Boer IH, Sharma K.

Background: Individuals with type 1 diabetes (T1D) demonstrate varied trajectories of estimated glomerular filtration rate (eGFR) decline. The molecular pathways underlying rapid eGFR decline in T1D are poorly understood, and individual-level risk of rapid eGFR decline is difficult to predict. Methods: We designed a case-control study with multiple exposure measurements nested within 4 well-characterized T1D cohorts (FinnDiane, Steno, EDC, and CACTI) to identify biomarkers associated with rapid eGFR decline.

Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study

Hsu S, Zelnick LR, Lin YS, Best CM, Kestenbaum B, Thummel KE, Rose LM, Hoofnagle AN, de Boer IH

The pharmacokinetic clearance of 25-hydroxyvitamin D (25[OH]D) is an essential, yet often overlooked, determinant of the concentration of circulating 25(OH)D, the prevailing marker of vitamin-D status. Observational studies have associated markers of low 25(OH)D clearance with poor clinical outcomes and suggest differences in clearance by kidney function and race. In this study, the authors used gold-standard pharmacokinetic methods to show that reduced 25(OH)D clearance is associated with worsening eGFR. They also found that, among participants with normal eGFR, but not among those with CKD or kidney failure, Black participants had higher 25(OH)D clearance compared with White participants. These findings confirm impaired 25(OH)D clearance as a feature of disordered mineral metabolism in kidney disease, and may provide some insight into racial differences in vitamin-D metabolism.

Interspecies blastocyst complementation

Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas - Volume 2, Pages 447-457, Chapter 32 - Interspecies blastocyst complementation. The complexity of the pancreas poses a challenge for stem cell-based bioengineering. An alternative strategy is to grow human pancreas in a host species, such as a pig. An emerging technique to potentially accomplish this feat is interspecies blastocyst complementation (IBC). In IBC, pluripotent stem cells from a donor species are implanted within a host embryo to fill an organ niche (deficiency). These contribute majorly to the niche organ but negligibly elsewhere in the resulting embryo, which is a chimera. IBC has been used to generate a mostly rat pancreas within a mouse, or vice versa. Mouse pancreas islets grown in rat can rescue diabetic phenotypes in mice after transplantation. Equivalent experiments have not yet been successful in humans, due to both technical and ethical hurdles. Improvements in gene editing and immune regulation may provide a path forward for human organ generation in animal hosts appropriate for clinical transplantation.

Temporal Relationship of Glycemia With Cardiac Arrhythmias in Patients With Type 2 Diabetes and CKD

Nisha Bansal, Leila R Zelnick, Irl B Hirsch, Dace Trence, Nazem Akoum, Ian H de Boer

We demonstrated that hypoglycemia is common in patients with chronic kidney disease (CKD) and T2D;5 and these patients have high rates of cardiac arrythmias.6 However, the association of glycemia with arrythmias in patients with CKD and T2D remains poorly elucidated; and even small relative differences in glucose may be important. Using continuous glucose monitoring (CGM) and mobile cardiac telemetry, there are new opportunities to characterize the temporality of glycemia with onset of an arrhythmia. In this study, we explored the association of glycemia with occurrence of cardiac arrythmias in patients with CKD and T2D.

Global transcriptomic changes occur in aged mouse podocytes

Yuliang Wang, Diana G. Eng, Natalya V. Kaverina, Carol J. Loretz, Abbal Koirala, Shreeram Akilesh, Jeffrey W. Pippin, Stuart J. Shankland

Glomerular podocytes undergo structural and functional changes with advanced age, that; increase susceptibility of aging kidneys to worse outcomes following superimposed glomerular; diseases. To delineate transcriptional changes in podocytes in aged mice, RNA-seq was performed on isolated populations of reporter-labeled (tdTomato) podocytes from multiple young (two to three months) and advanced aged mice (22 to 24 months, equivalent to 70 plus year old humans).

Effects of long-term vitamin D and n-3 fatty acid supplementation on inflammatory and cardiac biomarkers in patients with type 2 diabetes: secondary analyses from a randomised controlled trial

Christine P. Limonte, Leila R. Zelnick, John Ruzinski, Andrew N. Hoofnagle, Ravi Thadhani, Michal L. Melamed, I-Min Lee, Julie E. Buring, Howard D. Sesso, JoAnn E. Manson, Ian H. de Boer 

Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D3 and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes.