A series of clinical trials demonstrated promising outcomes of sodium glucose co-transporter 2 (SGLT2) inhibitors, a novel class of anti-diabetic drugs, in patients with heart failure (HF), with either reduced ejection fraction or preserved ejection fraction. Of note, these positive outcomes are irrespective of the diabetic status and with rapid onset, suggesting the clinical benefits of SGLT2 inhibition are not fully attributable to glycemic control. Based on various experimental studies, a substantial number of hypotheses have been proposed to explain the beneficial effects of SGLT2 inhibition in HF. These effects can be divided into two groups: indirect systemic effects and
Jeanne A. Ishimwe, Valentina Kon, and Annet Kirabo
Persistent systemic inflammation is a hallmark of chronic kidney disease (CKD) and several of its risk factors, including diabetes and hypertension. The gut microbiome is defined as the microorganisms and their genetic material in the intestinal tract. Emerging evidence has substantiated the gut microbiome as a key mediator of inflammation in various pathophysiologic states, including kidney diseases (1, 2). Patients with kidney failure on dialysis also exhibit bacterial translocation from the intestines to the circulation, contributing to microinflammation (3). Bacterial translocation is reported in other pathologies, including hypertension and autoimmunity (4,
Laura H. Mariani, Laura Barisoni, Debbie S. Gipson, Lawrence B. Holzman, Crystal Gadegbeku, John R. Sedor, and Matthias Kretzler
Patients with newly diagnosed nephrotic syndrome due to minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN) display an impressive amount of variability in disease severity, symptom burden, response to initial therapy, and risk of relapse. Although this heterogeneity is a clinical challenge—frustrating patients and clinicians alike—it is also an opportunity for researchers to partner with patients under routine clinical care to collect the data and bio-samples needed to better define mechanistically relevant subgroups. The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multi-center collaborative consortium that was established to develop such a translational research infrastructure
Ten years ago, human kidney organoids were but twinkles in the eyes of a few intrepid inventors. Now, these tiny collections of cells, which bear a striking resemblance to kidney tissue, are well on their way to becoming a standard research tool. As they spread, kidney organoids are also becoming more diverse and gaining new abilities.
The ability of organoids to mimic features of kidney diseases presents new opportunities to discover medications and exciting possibilities for regenerative medicine. To generate the structures more reproducibly and optimize their shapes and sizes, a technique, called cellular extrusion bioprinting, has recently been introduced
For the greater part of the 20th century, exogenous insulin administration and whole organ pancreatic transplantation served as the predominant therapeutic interventions for patients with type 1 diabetes mellitus. The success of the Edmonton group in achieving insulin independence in the early 2000s via islet cell transplantation in a cohort of patients with autoimmune diabetes led to renewed optimism that this treatment could serve as an alternative to solid organ transplantation (1). However, 16 years later, a shortage of donor pancreatic islet cells remains a major challenge in increasing the scale of human allogeneic islet transplantation.
Basic science is fundamental to advancing medicine and improving health outcomes. It is an exciting time to be engaged in basic and translational research focusing on kidney diseases. Novel research tools and methodologies are available to answer questions that have long eluded scientists. Moreover, we are seeing investments in kidney-related research by pharmaceutical companies, industry, societies, and governments. Examples of these investments include the Kidney Precision Medicine Project (KPMP), funded by the National Institute of Diabetes and Digestive and Kidney Diseases; the Transformative Research in Diabetic Nephropathy (TRIDENT) study, which is a private-public partnership; the Kidney Innovation Accelerator (KidneyX) prize;
The US Preventive Services Task Force (USPSTF) will consider adding screening for chronic kidney disease (CKD) as a potential recommendation in response to a nomination from the Coalition for Kidney Health. The coalition submitted its request in December 2021 and received a response in February 2022, stating that USPSTF has added “Screening for CKD” to its “list of preventive services topics under active consideration.”
The positive response kicks off a thorough, multi-year review, according to Miriam Godwin, health policy director at the National Kidney Foundation (NKF), whom the coalition designated as its contact person in its request to USPSTF. Godwin
The advancements of single-cell and nucleus RNA sequencing (sc/snRNAseq) have shifted our approach to defining cell types and states relevant to human health. These technologies have provided detailed insight into the transcriptome (all of the expressed messenger RNA [mRNA] of a single cell, tissue, or sample) of a single cell. However, this process, requiring dissociation of tissue to the level of the single cell or nucleus, obscures the structural context of each cell within the tissue. Therefore, sc/snRNAseq studies have been limited by their inability to capture data essential to understanding these cellular microenvironments (surrounding cells, extracellular matrix, and signaling
The old tongue-in-cheek maxim that xenotransplantation is, and always will be, the future of transplantation is under withering attack. Three reports within the past few months—one published in a scientific journal (1) and two in the lay press—suggest xenotransplantation success may be at hand. First, a little history.
Xenotransplantation promises an unlimited supply of organs. Conceptually straightforward, the details turn out to be critically important. First attempts at xenotransplantation using pigs were unsuccessful due to, among other issues, the Galα1,3Gal (Gal) epitope on the vascular epithelium. These epitopes induced refractory rejection, leading to organ loss in transplant models.
Congress is staring down a significant number of legislative backlogs as it begins the 2022 calendar year. Congress must still finalize fiscal year (FY) 2022 appropriations before FY 2023 appropriations negotiations can commence, confirm the heads of both the US Food and Drug Administration and National Institutes of Health amid the global COVID-19 pandemic, and confirm a Supreme Court justice to replace retiring Justice Breyer, all with mid-term elections fast approaching this fall. But, there is cause for genuine optimism among the kidney community, as improving kidney health through transformative regulatory and legislative action continues to receive robust bipartisan support