Understanding and modulating kidney repair

The kidney is the central regulator of homeostasis and is involved in physiological processes such as blood pressure control, electrolyte and water balance as well as removal of metabolic toxins and waste. The kidney can be damaged by various conditions, including diabetes, ischemia, drug toxicity, and autoimmunity. Since the kidney cannot produce new functional units - called nephrons - after birth, maintaining homeostasis after kidney injury relies on the number of redundant nephrons available at birth, the compensatory adaptation of the remaining nephrons, and kidney repair. Despite the growing global health burden related to kidney disease, the therapeutic options to support kidney repair and avoid kidney failure remain limited, so that kidney replacement therapy by dialysis or transplantation remains the only option for a significant number of patients. Kidney repair depends primarily on cell plasticity: while damaged tubule cells undergo cell death, remaining tubule cells enter a reparative state characterized by the activation of genes involved in cell adhesion, migration, and proliferation. Tubule cell dedifferentiation contributes to altered homeostasis and reduced kidney function following acute kidney injury, but it is a critical initial step of a complex biological process involving the proliferation of reparative cells and their re-differentiation into functional tubule cells. In recent years, we have contributed to fundamental discoveries on the cellular mechanisms of kidney repair. We have characterized the states of epithelial cells involved in kidney repair, elucidated the pivotal role of the transcription factor SOX9 in both kidney repair and fibrosis, and highlighted the central role of altered renal metabolism in acute kidney injury. Our current research aims to identify the critical molecular processes that govern the re-differentiation of reparative tubule cells and to understand the impact of dynamic cell state transitions on the local microenvironment during kidney repair. We are particularly focused on the mechanisms of kidney fibrosis and the interactions between the kidney and the immune system. Our long-term objective is to develop targeted therapies to modulate the repair process and promote kidney regeneration in the contexts of aging, kidney disease, and post-kidney transplantation.

Immunosuppression-free kidney transplantation

Kidney transplantation is the most effective treatment for patients with advanced chronic kidney disease. However, organ transplantation inevitably leads to rejection, necessitating lifelong immunosuppressive therapies. While essential to prevent rejection, these therapies often come with significant side effects. Our research focuses on educating the immune system to accept the kidney allograft without the need for immunosuppression—a concept known as tolerance. Achieving tolerance is the ultimate goal of transplantation immunology. To date, the only strategy that has demonstrated to be effective to achieve tolerance in patients is the combined bone marrow and kidney transplantation from the same donor. However, current protocols to induce tolerance have proven reliable only in selected cases and are associated with potential risks. In recent years, Prof. Cippà has contributed to the first tolerance protocol for HLA-identical kidney transplantation in Europe. Additionally, he pioneered the introduction of BCL2 inhibitors in experimental models of tolerance. Looking ahead, we are committed to establishing a tolerance program at the University Hospital of Basel. Our goal is to leverage new technologies and advanced methodologies to overcome the limitations of current protocols and to further advance the field of tolerance induction.

Connection to clinical practice

Our laboratory is integrated within the division of Transplantation Immunology and Nephrology at the University Hospital of Basel. This integration fosters a close and dynamic interaction between our research team and the clinical division and ensures that our research is aligned with the real needs of our patients. Conversely, our research findings can be rapidly translated into tangible clinical applications. Our commitment to this symbiotic relationship between the lab and the clinic underscores our dedication to improving patient outcomes through cutting-edge research and innovation in nephrology.

Cippà Lab / Nephrology

Head of Research Unit

Prof. Dr. Pietro Ernesto Cippà

Members

Prof. Dr.

Pietro Ernesto Cippà

Professorship / Head of Research Group Department of Biomedicine