Publications by authors named "Maria J Ramirez-Bajo"

Background: Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet.

View Article and Find Full Text PDF

Cardiorenal diseases represent a complex interplay between heart failure and renal dysfunction, being clinically classified as cardiorenal syndromes (CRS). Recently, the contributions of altered nicotinamide adenine dinucleotide (NAD) metabolism, through deficient NAD synthesis and/or elevated consumption, have proved to be decisive in the onset and progress of cardiorenal disease. NAD is a pivotal coenzyme in cellular metabolism, being significant in various signaling pathways, such as energy metabolism, DNA damage repair, gene expression, and stress response.

View Article and Find Full Text PDF

Renal ischemia-reperfusion injury (IRI) leads to endoplasmic reticulum (ER) stress, thereby initiating the unfolded protein response (UPR). When sustained, this response may trigger the inflammation and tubular cell death that acts to aggravate the damage. Here, we show that knockdown of the BET epigenetic reader BRD4 reduces the expression of ATF4 and XBP1 transcription factors under ER stress activation.

View Article and Find Full Text PDF

The transplant community is focused on prolonging the preservation time of kidney grafts to allow for long-distance kidney graft transportation, assess the viability of marginal grafts, and optimize a platform for the translation of innovative therapeutics to clinical practice, especially those focused on cell and vector delivery to organ conditioning and reprogramming. We describe the first case of feasible preservation of a kidney from a donor after uncontrolled circulatory death over a 73-h period using normothermic perfusion and analyze hemodynamic, biochemical, histological, and transcriptomic parameters for inflammation and kidney injury. The mean pressure and flow values were 71.

View Article and Find Full Text PDF

Introduction: An increased midnight cortisol (MC) has been described in end-stage kidney disease (ESKD) and type 1 diabetes (T1D). Lower circulating levels of the cytokine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) have been found in T1D and ESKD and associated with cardiovascular (CV) events in the latter. We aimed to study MC and sTWEAK in simultaneous pancreas-kidney transplant (SPKT) recipients, and the association of these markers with CV risk factors and transplant outcomes.

View Article and Find Full Text PDF

Background: Ischemia-reperfusion injury (IRI) upon transplantation is one of the most impactful events that the kidney graft suffers during its life. Its clinical manifestation in the recipient, delayed graft function (DGF), has serious prognostic consequences. However, the different definitions of DGF are subject to physicians' choices and centers' policies, and a more objective tool to quantify IRI is needed.

View Article and Find Full Text PDF

Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent histological examination. Early and sensitive biomarkers of graft damage and alloimmunity are needed to identify graft injury and eventually limit the need for a kidney biopsy.

View Article and Find Full Text PDF

Although the benefits of moderate exercise in patients at high cardiovascular risk are well established, the effects of strenuous exercise remain unknown. We aimed to study the impact of strenuous exercise in a very high cardiovascular risk model. Nephrectomized aged Zucker obese rats were trained at a moderate (MOD) or high (INT) intensity or were kept sedentary (SED) for 10 weeks.

View Article and Find Full Text PDF

The presence of donor-specific antibodies (DSA), mainly against HLA, increases the risk of allograft rejection. Moreover, antibody-mediated rejection (ABMR) remains an important barrier to optimal long-term outcomes after solid organ transplantation. The development of chimeric autoantibody receptor T lymphocytes has been postulated for targeted therapy of autoimmune diseases.

View Article and Find Full Text PDF

Extracorporeal photopheresis (ECP) is an immunomodulatory therapy based on the infusion of autologous cellular products exposed to ultraviolet light (UV) in the presence of a photosensitizer. The study evaluates the ECP efficacy as induction therapy in a full-mismatch kidney transplant rat model. Dark Agouti to Lewis (DA-L) kidney transplant model has been established.

View Article and Find Full Text PDF

Profiling of circulating immune cells provides valuable insight to the pathophysiology of acute rejection in organ transplantation. Herein we characterized the peripheral blood mononuclear cells in simultaneous kidney-pancreas transplant recipients. We conducted a retrospective analysis in a biopsy-matched cohort ( = 67) and compared patients with biopsy proven acute rejection (BPAR; 41%) to those without rejection (No-AR).

View Article and Find Full Text PDF

Several organ allocation protocols give priority to wait-listed simultaneous kidney-pancreas (SPK) transplant recipients to mitigate the higher cardiovascular risk of patients with diabetes mellitus on dialysis. The available information regarding the impact of preemptive simultaneous kidney-pancreas transplantation on recipient and graft outcomes is nonetheless controversial. To help resolve this, we explored the influence of preemptive simultaneous kidney-pancreas transplants on patient and graft survival through a retrospective analysis of the OPTN/UNOS database, encompassing 9690 simultaneous transplant recipients between 2000 and 2017.

View Article and Find Full Text PDF

Background: Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management.

Methods: Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples.

View Article and Find Full Text PDF

Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs). BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles.

View Article and Find Full Text PDF

Aims: Information on the impact of insulin therapy before pancreas donation on pancreas outcomes is scarce. We aim to explore the influence of insulin therapy before donation on recipient and pancreas graft survival.

Methods: Registry study including 12,841 pancreas recipients from the OPTN/UNOS registry performed between 2000 and 2017.

View Article and Find Full Text PDF

According to preliminary data, seroconversion after mRNA SARS-CoV-2 vaccination might be unsatisfactory in Kidney Transplant Recipients (KTRs). However, it is unknown if seronegative patients develop at least a cellular response that could offer a certain grade of protection against SARS-CoV-2. To answer this question, we prospectively studied 148 recipients of either kidney (133) or kidney-pancreas (15) grafts with assessment of IgM/IgG spike (S) antibodies and ELISpot against the nucleocapside (N) and the S protein at baseline and 2 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine.

View Article and Find Full Text PDF

Extracellular vesicles (EVs) are a heterogeneous group of membranous vesicles that differ on their biogenesis and release pathways, such as exosomes, microvesicles and apoptotic bodies. They are involved in cell-to-cell communication delivering signal molecules (proteins, nucleic acids, lipids, ) that can regulate different physiological processes, as well as the development and progression of several diseases. There are different methods and commercial kits to isolate EVs and depending on the methodology one could obtain EVs with different degrees of efficiency, purity and it can be more or less time-consuming.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the effectiveness of murine bone marrow mesenchymal stromal cells (BM-MSCs) and their derived products in treating acute nephrotoxicity caused by cyclosporine (CsA) in a mouse model, focusing on both preventive and curative applications.
  • Results indicate that BM-MSC therapy significantly improved survival rates and renal function, especially when administered after nephrotoxicity was established, while extracellular vesicles (EVs) and conditioned medium (dCM) provided only partial recovery.
  • The authors conclude that BM-MSCs offer promising renoprotective effects in chronic kidney disease contexts, but further research is needed to optimize treatment timing and methods.
View Article and Find Full Text PDF

Objective: Improvement in insulin alternatives is leading to a delayed presentation of microvascular and macrovascular complications of diabetes. The objective of this study was to evaluate the long-term outcomes of older (≥50 years) diabetic patients who receive a pancreas transplantation (PT).

Research Design And Methods: We retrospectively evaluated all 338 PTs performed at our center between 2000 and 2016 (mean follow-up 9.

View Article and Find Full Text PDF
Article Synopsis
  • Mesenchymal stromal cells (MSCs) from adipose tissue and bone marrow have therapeutic potential for kidney transplants, primarily through their immunomodulatory effects and the extracellular vesicles (EVs) they secrete.
  • In a rat kidney transplant model, the study tested the impact of autologous (recipient's own) and donor-derived MSCs and EVs on kidney survival and function, with specific timing for treatment administration.
  • Results showed autologous MSCs improved kidney function and survival, while donor MSCs were detrimental, leading to graft rejection without accelerated rejection from EVs.
View Article and Find Full Text PDF
Article Synopsis
  • * RAPA treatment led to an increase in specific miRNAs (miR-6127, miR-6746-5p, and miR-6787-5p) in extracellular vesicles from metastatic CRC cell lines, unlike CsA and untreated conditions.
  • * The study suggests these miRNAs may regulate gene expression related to cancer progression and could represent a new epigenetic mechanism in managing pre-metastatic CRC in transplant patients.
View Article and Find Full Text PDF
Article Synopsis
  • The study investigated the effectiveness of tofacitinib (TOFA), a Janus kinase 3 inhibitor, in preventing chronic antibody-mediated rejection in kidney transplant rats, compared to traditional treatments like cyclosporin A and rapamycin.
  • Results showed that TOFA improved graft survival and kidney function, reduced humoral damage and donor-specific antibodies, and decreased immune cell infiltration in the treated rats.
  • The findings suggest that TOFA could be a promising option to enhance outcomes in kidney transplants by minimizing immune responses and preserving organ integrity.
View Article and Find Full Text PDF
Article Synopsis
  • Sirolimus (SRL) has been linked to new diabetes onset after transplantation, prompting research on its effects on insulin resistance and pancreatic β-cell function.
  • Experiments with lean and obese Zucker rats showed that SRL impaired glucose tolerance and reduced pancreatic weight and β-cell proliferation, particularly affecting the obese rats.
  • The negative impacts of SRL on insulin production and secretion were evident but reversible once the treatment was stopped, suggesting potential risks for those needing β-cell adaptation post-transplant.
View Article and Find Full Text PDF

A new cell-to-cell communication system was discovered in the 1990s, which involves the release of vesicles into the extracellular space. These vesicles shuttle bioactive particles, including proteins, mRNA, miRNA, metabolites, etc. This particular communication has been conserved throughout evolution, which explains why most cell types are capable of producing vesicles.

View Article and Find Full Text PDF