A highly diverse team imagining the undiscovered

RENAL RESEARCH INSTITUTE

A highly diverse
team imagining
the undiscovered

ABOUT THE RENAL RESEARCH INSTITUTE

The heart of RRI’s capacity for innovation is our ability to examine complex problems through multiple lenses.

The Renal Research Institute (RRI) is an internationally recognized incubator of ideas, treatment processes, and technologies to improve the lives of kidney patients. RRI’s leadership in computational biomedicine and data analytics, as well as our access to a large patient population, accelerates the pace of scientific discoveries and their translation into applied medicine. Our team includes some of the brightest minds from around the world, who, along with their disciplinary expertise, bring a deep understanding of global healthcare issues and challenges.

Our Research

RRI’s pioneering leadership in computational biomedicine and data analytics drives breakthroughs, including the introduction of virtual clinical trials and smartphone-based diagnostics. Not only does our interdisciplinary approach foster wide-ranging research within the global framework of Fresenius Medical Care, it encourages collaboration with academic institutions in the United States, Asia, Europe, Latin America, and Africa.

Latest Research & News

Latest Research

  • Beatriz Akemi Kondo Van Spitzenbergen, Gabriela Bohnen Andrade, Erika Sousa Dias, Júlia Bacarin Monte Alegre, Gabriela Ferreira Dias, Nadja Grobe, Andrea Novais Moreno-Amaral, Peter Kotanko

    RESULTSIncubation of RBCs with CMPF and Jedi1 significantly increased RBC osmotic fragility, an effect prevented by GsMTx-4. At 6.0 g/L NaCl, incubation with CMPF and Jedi1 increased exposure of phosphatidylserine and elevated icCa2+ levels of RBCs, indicating increased eryptosis. Notably, at an isotonic NaCl concentration of 9.0 g/L, CMPF-but not Jedi1-significantly increased RBC phosphatidylserine exposure and icCa2+ levels; both effects were diminished by GsMTx-4.BACKGROUND AND HYPOTHESISIn patients with advanced CKD the lifespan of red blood cells (RBCs) is often shortened, a condition attributed to the 'uremic milieu.' We reported recently that the uremic solute 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) shares structural similarities with Jedi1, a chemical activator of the mechanosensitive cation channel PIEZO1, whose activation increases calcium influx into cells. Against this backdrop, we hypothesized that CMPF may induce premature RBC death (eryptosis) through prolonged CMPF-induced activation of PIEZO1 located on RBCs. To test this hypothesis, we explored if CMPF, at concentrations found in uremia, interacts with PIEZO1 located on RBCs, increases intracellular calcium (icCa2+), and induces eryptosis.CONCLUSIONOur findings support the hypothesis that CMPF may function as an endogenous activator of PIEZO1, increase icCa2+ levels, trigger eryptosis, and, through this pathway, possibly shorten the RBC lifespan. To what extent these in vitro findings are operative in advanced CKD warrants clinical studies.METHODSRBCs from healthy individuals were incubated with CMPF or Jedi1 (both at a concentration of 87 µM), in the presence or absence of the PIEZO1 inhibitor GsMTx-4 (2 µM). We challenged RBCs osmotically through incubation in solutions of NaCl at concentrations between 3.0 and 9.0 g/L and determined their osmotic fragility. Using flow cytometry, we quantified in incubated RBCs icCa2+ levels and phosphatidylserine exposure, a cellular marker of eryptosis.

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Education

LATEST EPISODE

The Gift of Life & Its Impact

March 13, 2025

In this special World Kidney Day episode of Frontiers in Kidney Medicine & Biology, we explore the life-changing power of kidney donation. Dr. Maria E. Ferris, a pediatric nephrologist and kidney donor, shares her personal story alongside her son, Ted Ferris, a three-time kidney transplant recipient, and Chris Ivimey, an altruistic kidney donor.

Join us as we discuss the urgent need for living donors, the impact of transplantation on families, and the power of giving the Gift of Life.