Assessing Pharmacokinetics and Safety of Therapeutic Alpha-1-Microglobulin in First-in-Human Kidney Transplantation: A Noncomparative Open-Label Multiple-Dose Phase 1b Study.

Background: RMC-035 is a modified version of alpha-1-microglobulin, an endogenous protein developed as a renoprotective agent. Its intended use is to reduce the risk of irreversible loss of kidney function in cardiac surgery patients and to reduce delayed graft function in kidney transplant recipients. This first-in-human study aimed to evaluate the pharmacokinetics and safety of RMC-035 in kidney transplant recipients.

Early vascular aging in chronic kidney disease: focus on microvascular maintenance, senescence signature and potential therapeutics.

Chronic kidney disease (CKD) is a strong risk factor for cardiovascular mortality and morbidity. We hypothesized that a senescent phenotype instigated by uremic toxins could account for early vascular aging (EVA) and vascular dysfunctions of microvasculature in end stage kidney disease (ESKD) patients which ultimately lead to increased cardiovascular complication. To test this hypothesis, we utilized both in vivo, and ex vivo approaches to study endothelial and smooth muscle function and structure, and characterized markers related to EVA in 82 ESKD patients (eGFR <15 ml/min) and 70 non-CKD controls.

Defining the molecular response to ischemia-reperfusion injury and remote ischemic preconditioning in human kidney transplantation.

Background: Ischemia-reperfusion injury (IRI) inevitably occurs during kidney transplantation and extended ischemia is associated with delayed graft function and poor outcomes. Remote ischemic preconditioning (RIPC) is a simple, noninvasive procedure aimed at reducing IRI and improving graft function. Experimental studies have implicated the kynurenine pathway as a protective mechanism behind RIPC.

Tocilizumab in chronic active antibody-mediated rejection: rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study).

Background: Chronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR.