Research

Area 2

Nephro-urological diseases and kidney transplantation

Team leader

Strategic objectives

The multidisciplinary nature of our research group stems from well-balanced collaboration between clinicians and medical researchers, biologists, biochemists, veterinarians and specialist technicians. The LENIT performs translational research to broaden the knowledge of various renal diseases, which sometimes require replacement therapies such as dialysis or kidney transplantation, in addition to side effects caused by the treatments themselves.

This knowledge will enable us to personalize and improve current therapies and to discover new ways of action. Scientific objectives of LENIT are focused on the following areas of research: i) chronic graft dysfunction: etiopathogenic factors and biomarkers in urine; II) mTOR signaling: immunosuppression, proteinuria, cardiovascular disease and side effects of the application of mTOR inhibitors; III) The role of immunosuppression and immunosuppressive medications in posttransplantation oncogenesis; IV) Identification of new uremic toxins; immunology of transplantation (V); cell therapy and renal regeneration (VI) and primary glomerular diseases (VII).

Main lines of research

1. Chronic allograft dysfunction (CAD): etiopathogenic factors and biomarkers in urine

  • The main goal has been the search for urinary biomarkers that allow early diagnosis of CAD. One of the proteins identified was Wnt1 one of the ligands of the Wnt signaling/β-catenin. This line was developed through four FIS projects already completed and Dr. Campistol got new one in which it is intended to modulate Wnt/β-catenin signaling in preventing the progression of CAD in animal models and its potential clinical application in humans.

2. mTOR signaling: immunosuppression, proteinuria, cardiovascular disease and side effects of the application of mTOR inhibitors

  • The objective is to evaluate the pathogenic mechanisms of proteinuria associated with treatment of mTOR inhibitors due to a possible malfunction of the glomerular endothelium using various experimental models of chronic renal failure and renal transplant. The inhibition of mTOR pathway may provide an alternative to calcineurin inhibitorbased therapies, which is associated with increased nephrotoxicity, incidence of cardiovascular disease and cancer in transplant patients. Moreover, the regulation of the mTOR pathway represents a cornerstone in the development of cardiovascular disease.

3. The role of immunosuppression and immunosuppressive medications in posttransplantation oncogenesis

  • The main objective is to study the impact of exosomes from tumor cells on proliferation, angiogenesis and development of premethastatic niche and their involvement in tumor progression, migration and metastasis of malignant tumors in patients undergoing different immunosuppressive regimens after kidney transplantation.

4. Identification of new uremic toxins

  • The main objective is the detection of new uremic toxins using proteomic techniques. Assess the different purification capacity of the dialysis techniques.

5. Immunology of transplantation

  • The objective is to study the role of T and B cell subsets during acute and chronic humoral rejection in kidney transplant patients. Characterization and monitoring of B cell subsets in kidney transplant patients which are treated for an acute antibody-mediated rejection.

6. Cell therapy and renal regeneration

  • The main objective is to analyze the role of mesenchymal stem cells and their microvesicles on in vitro and in vivo models that reproduce the kidney damage by nephrotoxicity or during graft rejection. Moreover, the study of nephrogenesis by the generation of ureteric bud structures and the correction of monogenic kidney diseases in vitro.

7. Primary glomerular diseases

  • The goal is the search for biomarkers plasma and/or urine that allow early diagnosis and non-invasive to improve the management of these patients.

50/50 Program

Translational research in postrasplant neoplasia

Ignacio Revuelta

(HCB-IDIBAPS)

The effect of the immunosuppressive therapy in tumour immune escape and in several oncogenic pathways lead to tumoral progression, angiogenesis and pre-metastatic niche formation. Exosomes released from cancer cells (CaEx) are crucial for intercellular communication between primary tumour, microenvironment and host organs. CaEx role in posttransplant neoplasms is unknown. He aims to characterize CaEx under different immunosuppressive treatments and the relationship with immune, stromal and pre-metastatic cells. Understanding how CaExs work will give us tools for future interventions in posttransplant malignancies without losing effectiveness of immunotherapy, improving patient survival.