Chronic Kidney Disease

Our research group is part of the Department of Medicine (Nephrology and Hypertension Service) and is affiliated with the Department of Cell Physiology and Metabolism (PHYM). We investigate the molecular and cellular mechanisms responsible for the onset and progression of chronic kidney disease (CKD). More specifically, we focus on renal tubular cells and their role in disease progression, particularly the role of tubular metabolism in this process. Metabolic disturbances in renal tubular cells directly influence disease progression by altering energy production and activating inflammatory and fibrotic pathways.

RESEARCH OBJECTIVES

Our research aims to better understand how alterations in the energy and mitochondrial metabolism of renal tubular cells contribute to the progression of chronic kidney disease (CKD). In this context, our laboratory focuses particularly on phosphoenolpyruvate carboxykinase 1 (PCK1), a key enzyme in renal metabolism.
PCK1 catalyses the conversion of oxaloacetate to phosphoenolpyruvate, a rate-limiting step in gluconeogenesis — the process by which the kidney synthesises glucose from non-carbohydrate precursors. Beyond its role in gluconeogenesis, PCK1 also plays a part in the cataplerosis of the Krebs cycle, thereby regulating the turnover of metabolites essential for energy metabolism and contributing to the maintenance of acid-base balance within tubular cells.
In the context of diabetes and CKD, PCK1 regulation is disrupted, leading to mitochondrial energy dysfunction, increased oxidative stress, and an exacerbated inflammatory response. These metabolic imbalances contribute to the progressive degradation of renal tissue and the development of fibrosis.
Using a translational approach that combines murine models, omics analyses (transcriptomics, metabolomics), and studies on human clinical samples, we investigate the precise mechanisms by which PCK1 dysregulation influences renal pathophysiology. Our goal is to identify novel therapeutic targets that can modulate PCK1 activity, restore tubular metabolism, slow CKD progression, and prevent end-stage renal disease.

MAIN RESEARCH AREAS

• Investigating the role of PCK1 in kidney disease

• Studying altered signalling pathways and energy metabolism in the kidney

• Analysing the role of mitochondrial dysfunction and inflammation

CORE EXPERTISE

• Renal physiology and pathophysiology

• Biology of tubular cells

• Murine models of chronic kidney disease (CKD)

• Omics approaches: transcriptomics and metabolomics

• Translational research – from bench to bedside

SELECTED PUBLICATIONS

1.      Legouis D., et al. Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality. Nature Metabolism, 2020.

2.      Verissimo T. and Faivre A., et al. Decreased renal gluconeogenesis is a hallmark of chronic kidney disease. Journal of the American Society of Nephrology, 2022.

3.      Faivre A., et al. Tubular cell glucose metabolism shift during acute and chronic injuries. Frontiers in Medicine, 2021.

4.      Verissimo T. and Dalga D., et al. PCK1 is a key regulator of metabolic and mitochondrial functions in renal tubular cells. American Journal of Physiology – Renal Physiology, 2023.

5.      Verissimo T. and de Seigneux S., et al. New evidence of the impact of mitochondria on kidney health and disease. Nature Reviews Nephrology, 2024.

Research